In loving memory of Carl Crosco 1979-2012

We are deeply saddened to announce that Carl Crosco passed away today. Carl's passion and energy were the source of countless memories that will last a lifetime. He shared his very personal story and life experiences in hopes to help others. The world is a better place because of Carl. Our hearts go out to his family during this time of loss.

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Obama: US aims to provide HIV drugs for extra 2 million by end of 2013

The United States will aim to provide antiretroviral treatment for 6 million people around the world by 2013, President Barack Obama announced today, increasing the original US target by 2 million.

The United States will also aim to provide antiretroviral drugs to prevent mother to child HIV transmission to 1.5 million women over the next two years, the President said. The US government also aims to support 4.7 million male circumcisions in eastern and southern Africa, and will fund the distribution of at least 1 billion male condoms.

The US government’s decision to increase its investment in antiretroviral treatment follows the results of the HPTN 052 trial, which showed that HIV treatment reduces the risk of transmission to a regular partner by around 96%.

Last month US Secretary of State Hillary Clinton said that the United States was now committed to a policy of creating an AIDS-free generation, and set the use of antiretroviral drugs at the heart of this strategy.

The new treatment target effectively doubles the pace of treatment scale-up through the US government’s President’s Emergency Plan for AIDS Relief (PEPFAR), and the commitment marks a significant turnaround from the Obama administration’s lukewarm attitude towards PEPFAR.

However, the Obama administration says that the expansion of treatment numbers will be achieved without requesting extra funds from Congress.

Instead, the scale-up in specific activities will be achieved through continuing cuts in drug prices and a reorganisation of resources to concentrate on high priority activities.

UNAIDS welcomed the renewed US commitment but highlighted the continuing shortfall in donor commitments to the Global Fund to Fight AIDS, Tuberculosis and Malaria.

The Global Fund announced last week that it has cancelled Round 11 of grant-making to national programmes, scheduled to support new applications from 2012 to 2014, due to lack of payments from donors who had promised money and the failure to make new pledges by other donors.

The Fund will now give money only to programmes already funded in order to allow them to continue providing treatment to people already enrolled.

While welcoming the new US commitment, activists called for swift action to deal with the cash crisis at the Global Fund.

 “We call on the U.S. and all donor countries to hold an emergency donor conference to ensure the Global Fund is open for new business—the business of ending AIDS—this year,” said Asia Russell, Director of International Policy for Health GAP.

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Cardiovascular risks reduced for patients with HIV by therapy with metformin and changes to diet and exercise

Treatment with the anti-diabetes drug metformin helps prevent the progression of sub-clinical cardiovascular disease in patients with HIV, according to the results of a randomised, placebo-controlled study published in the online edition of AIDS.

The study also showed that dietary changes and a thrice-weekly exercise regimen improved lipid profiles and overall cardiovascular fitness.

“We saw an effect of metformin to prevent significant increase in coronary artery calcification and calcified plaque volume over one year of follow up,” write the investigators. “Compliance with the medication was good…Safety and tolerance were good.”

It is now recognised that HIV-positive patients have an increased risk of cardiovascular disease. Sub-clinical cardiovascular disease is also seen with increased frequency in patients with HIV, who generally have a high prevalence of diabetes, dyslipidemia, high blood pressure and abdominal obesity. Such a collection of disorders is often referred to as metabolic syndrome and has been associated with increased calcification of the coronary artery.

HIV care guidelines stress the importance of diet and exercise for the management of metabolic syndrome.

Treatment with the anti-diabetes drug metformin may also have a role. Research in HIV-negative, over-weight patients with diabetes showed that the therapy significantly reduced rates of cardiovascular events. However, data are currently lacking on the drug’s safety and effectiveness in patients with HIV.

Therefore, investigators from the Massachusetts General Hospital designed a study to assess the impact of metformin treatment and lifestyle modification on calcification of the coronary artery and other established cardiovascular risk factors in patients with HIV.

A total of 50 patients, all of whom had metabolic syndrome, were recruited to the study between 2006 and 2010.

The patients were randomised into four arms:

No lifestyle modification and placebo.

Lifestyle modification and placebo.

No lifestyle modification and metformin.

Lifestyle modification and metformin.

The impact of these interventions on calcification of the coronary artery, diet and fitness, metabolic, biochemical and immunological parameters was assessed. Follow-up was for twelve months.

Patients had been infected with HIV for a median of 14 years and had been taking antiretroviral therapy for a median of six years. There were no significant differences between the four study arms in the characteristics of the patients.

Individuals treated with metformin demonstrated significantly less progression of coronary artery calcification than those who received the placebo (p = 0.004).

In contrast, there were no differences in coronary artery calcification scores between patients who changed their diet and exercise habits and those who did not have any lifestyle modification.

Therefore, metformin had a significantly greater effect on calcification of the coronary artery than lifestyle modification (p = 0.01).

In addition, individuals who were treated with metformin also demonstrated less progression of calcified plaque volume than the patients who received the placebo (p = 0.008).

Overall, plaque progression was greatest among the patients randomised to the no lifestyle modification and placebo arm. The median increase in coronary artery calcification among these patients was 56%. In contrast, the smallest increase was among patients in the lifestyle modification and metformin arm (p = 0.03). Significantly less coronary artery calcification was also seen in the group of patients who did not modify their diet and exercise habits, but who were treated with metformin (p = 0.01).

Unsurprisingly, lifestyle modification improved exercise capacity and strength (p < 0.01). However, metformin therapy had no impact on these parameters.

Changes to diet and exercise were also shown to have benefits for HDL-cholesterol levels (p = 0.03). Furthermore, lifestyle modification reduced levels of C-reactive protein (CRP), an important marker of inflammation (p = 0.05).

Treatment with metformin also had some metabolic benefits. Patients who received the drug had significantly better HOMA-IR scores (a marker of insulin resistance) than individuals randomised to receive the placebo (p = 0.05).

Neither of the interventions was associated with serious adverse events. However, lifestyle modification was associated with a small but significant reduction in CD4 cell count (p = 0.04). Two of the metformin-treated patients experienced mild elevations in creatinine levels. These returned to normal after the dose of the drug was modified. Several patients taking the drug also reported mild gastrointestinal side-effects.

“Our data demonstrate that metformin had a robust effect to prevent progression of coronary artery calcification and calcified plaque volume while improving HOMA-IR over one year in HIV patients with metabolic syndrome,” comment the authors. “Lifestyle modification had a lesser effect to prevent plaque progression than metformin.”

They conclude: “Further studies are now needed to understand the mechanisms of metformin to prevent calcified plaque progression and to determine whether metformin, alone or in combination with other strategies, might reduce or prevent cardiovascular disease events in [patients with HIV].”

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LGV cases almost triple in one year; UK public health officials warn against serosorting

The number of gay men infected with the sexually transmitted infection lymphogranuloma venereum (LGV) has almost tripled in one year, and the UK now has the world’s worst epidemic of LGV, the Health Protection Agency reported today. At the same time, the agency is tracking an outbreak in gay men of shigellosis, a bacterial infection that is transmitted through contact with tiny amounts of human faeces.

The HPA suspects that transmission of both infections is being fuelled by serosorting behaviour, in other words men choosing to have unprotected sex with men who have the same HIV status as themselves. While HIV-positive men who serosort may avoid passing on their HIV infection, they still risk acquiring unpleasant and often serious sexually transmitted infections such as LGV, shigella and hepatitis C. Serosorting “is unsafe”, the HPA says.

LGV is a previously rare sexually transmitted infection, seen in UK gay men since 2003. It is caused by specific strains of Chlamydia. If left untreated, symptoms can be complex and severe, including proctitis (inflammation of the anus or rectum).

Diagnoses of LGV increased from 190 in 2009 to 530 in 2010. Of the total 1560 cases seen between 2003 and 2010, more than one third have been diagnosed since the beginning of 2010.

The vast majority (83%) of LGV cases were in HIV-positive gay men. The infection is thought to be transmissible during unprotected anal intercourse, an activity which 84% of infected men report. Two-thirds of diagnoses were in London, but there are cases from across the country, especially Brighton and Manchester.

The public health agency is also concerned about a smaller outbreak of shigellosis. This bacterial infection, caused by either Shigella sonnei or Shigella flexneri has only occasionally been seen in UK gay men. The symptoms of shigellosis can include severe and bloody diarrhoea, but it can be successfully treated with antibiotics.

Shigella is transmitted by contact with tiny amounts of faeces. This can occur as a consequence of poor hygiene, or may be linked to sex, especially rimming, fingering, fisting, anal sex, and handling used sex toys and douching equipment. The bacteria may pass from dirty fingers to the mouth; basic hygiene and handwashing habits reduce the risk of transmission.

There have been 29 cases of infection with Shigella flexneri recorded since May 2011, mostly in London or Manchester. The HPA have not yet identified the key characteristics of the men who have been infected or identified the shared use of specific venues. However some previous shigellosis outbreaks have been concentrated in men with HIV and in men who used sex-on-premises venues.

The HPA report also notes the ongoing epidemic of sexually acquired hepatitis C in gay and bisexual men with HIV - 228 cases of recent infection were recorded at 22 of the larger HIV clinics in 2008-2010.

In addition, new diagnoses of the more widespread infections chlamydia and gonorrhoea are higher than they have been for more than a decade, at around 4500 and 5000 diagnoses respectively.

The HPA believes these figures highlight the dangers for HIV-positive men of ‘serosorting’, in other words having unprotected sex with partners thought also to be HIV-positive. “Serosorting poses a risk of acquiring other STIs and hepatitis, with serious treatment implications,” the agency warns.

It does not encourage HIV-negative men to serosort either, because rates of undiagnosed HIV are high. One quarter of those infected do not know that they have HIV.

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High rate of new diagnoses when gay men phoned and asked to come back for sexual health check-up

It’s feasible for sexual health clinics to take steps to invite ‘high-risk’ patients to come back for re-screening, and doing so leads to a high number of new diagnoses being made, London clinicians report in the December issue of Sexually Transmitted Infections.

When they implemented the strategy with 301 gay or bisexual men who had just been diagnosed with a bacterial sexually transmitted infection (STI), two-thirds came back for a check-up three months later. At the second visit, five new HIV diagnoses and 15 new STI diagnoses were made.

People who have previously been diagnosed with a sexually transmitted infection are a group of patients who have a greater risk of having another STI or HIV in the future. If an effective way of encouraging repeat screening can be identified, this may allow for the early diagnosis of infections.

While a number of organisations recommend that sexually active gay men should test for HIV “at least” once a year, UK clinical guidelines are not clear on the frequency with which gay men who have had an STI should re-screen. Moreover it is likely that only a minority of men come in for a check-up every few months.

In order to increase rates of re-screening, clinicians at the Mortimer Market Centre (a central London clinic popular with gay men) set up a system in which patients were phoned by a health adviser and invited to make an appointment for a check-up, three months after their last visit.

The clinic only invited gay or bisexual men who had been diagnosed with chlamydia, gonorrhoea, syphilis or LGV. Staff made up to three attempts to contact the patient; if an appointment was made but the patient did not attend, the clinic attempted to arrange one more appointment.

The check-up was managed in the same way as for other gay or bisexual men without symptoms. At the time, standard tests were for HIV, syphilis, gonorrhoea (urethra, rectum and throat) and chlamydia (urethra).

During the nine-month evaluation period, 301 men were asked if they would be happy for the clinic to contact them by phone in order to be invited to make a new appointment for a check-up in the future. All men had just been diagnosed with a bacterial STI, 9% were also HIV-positive, half reported unprotected anal sex in the past three months, three-quarters were white, and their average age was 32.

Of the 301 patients:

Half (153 men) came back to the clinic because of the recall programme; 12% of this group had STI symptoms.One in six (53 men) came back to the clinic for another reason; 49% had symptoms.Just under one third (95 men) did not come back to the clinic during the recall period. They either did not want to take part in the programme (30 men), made an appointment but did not turn up (27), could not be reached by telephone (21) or were no longer in the area (17).

Men with HIV were over-represented amongst those who did not come back to the clinic.

On the other hand, men who did come back for re-screening appeared to report more unprotected sex and more sexual partners than non-attenders. However these differences were not statistically significant in this small study.

Several diagnoses of gonorrhoea, chlamydia and syphilis were made at re-screening: nine in those men attending because of the programme, and six in men attending for other reasons.

HIV was diagnosed in four men attending because of the programme and in one man who attended for another reason. Two of these patients had declined testing at their previous appointment; the other three had tested negative at their previous appointment but had not noticed any seroconversion symptoms.

The authors describe the incidence (rate of new infections) as “high” for both bacterial STIs and HIV. They suggest that the identification of recent HIV infections is particularly important as men may otherwise inadvertently pass on their infection.

The results of this study should be considered alongside an Australian study earlier this year which found that sending a text message reminder to ‘high-risk’ gay men every four months increased the numbers who returned for HIV testing during a nine-month period – from 31% to 64%.

Text messages are very simple and cheap to send through automated procedures, while making telephone contact with patients is a more labour-intensive approach. However the London clinicians suggest that phone calls may result in more patients re-screening, and so be more cost-effective.

“This evaluation has demonstrated that recall for re-screening of MSM diagnosed as having a bacterial STI is a feasible strategy both in terms of the high rates of re-screening achieved and the number of new diagnoses made,” they say. Further studies with control groups, which examine cost-effectiveness, are called for, they conclude.

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Adding rituximab to chemotherapy regimens improves outcomes for AIDS-related lymphomas

The addition of rituximab to chemotherapy regimens for the treatment of AIDS-related lymphomas improves both overall survival and progression-free survival, German investigators report in the online edition of AIDS.

Therapy with rituximab appeared to be safe, and no deaths were associated with its use.

“Rituximab was beneficial for AIDS-related lymphoma even in the setting of severe immune deficiency and was not associated with an increased risk of fatal infections,” comment the authors.

Cases of AIDS-related lymphoma have fallen significantly since the introduction of effective antiretroviral therapy. There has also been a marked improvement in the outcomes of individuals diagnosed with the malignancy.

Nevertheless, these cancers are an important cause of the excess mortality that still occurs in HIV-positive patients. Their treatment is controversial and there is some uncertainty about the benefits of adding rituximab – a monoclonal CD20 antibody – to traditional CHOP-based (cyclophosphamide, doxorubicin, vincristine and prednisone ) chemotherapy regimens.

Investigators from Germany therefore analysed the outcomes of patients diagnosed with AIDS-related lymphomas between 2005 and 2008 according to their treatment regimen and the use of the rituximab.

A total of 156 individuals who received care at 25 clinics across Germany were included in the study. These patients had a median age of 45 years, and almost all (92%) were men.

Many of the patients had severe immunosuppression at the time of cancer diagnosis.

Median CD4 cell count was 205 cells/mm3, and a quarter of patients had a CD4 cell below 100 cells/mm3. In two-thirds of patients, the lymphoma was the first AIDS diagnosis. Over half the patients had never taken antiretroviral therapy.

“Thus, a relevant proportion of our patients were late presenters”, emphasise the authors.

Forty-seven per cent of patients were treated with rituximab in addition to their CHOP-based regimen. A median of four rituximab doses were administered.

By the end of 2008, a total of 61 patients (37%) had died after a median of 15 months of follow-up.

After taking into account potentially confounding factors, the investigators found a strong relationship between treatment with rituximab and the chances of survival.

Compared to individuals treated with a traditional CHOP-based regimen, the chances of overall survival were significantly better for patients who also received rituximab (OR = 0.43; 95% CI, 0.21-0.89). The addition of the drug also improved progression-free survival (OR = 0.44; 95% CI, 0.23-0.84).

Expression of CD20 was also a significant predictor of survival (OR = 0.24; 95% CI, 0.12-0.47). A subgroup analysis was therefore performed involving patients with this immune characteristic. This once again showed that rituximab improved both overall survival (OR = 0.42; 95% CI, 0.20-0.87) and progression-free survival (OR = 0.44; 95% CI, 0.23-0.84).

A CD4 cell count above 100 cells/mm3 also predicted the chances of survival in both sets of analysis.

The investigators then turned their attention to the safety of rituximab therapy. As has been noted, 61 patients died. In two-thirds of cases, the cause of death was lymphoma. Infections caused a fifth of deaths, and 11% were due to other causes such as heart attack, liver failure and suicide.

All deaths due to fatal infections were considered to be treatment-related. Three of these twelve deaths involved patients treated with rituximab. Immune suppression appeared to be the main cause of these deaths. Regardless of treatment regimen, the median CD4 cell count at the time of death was in the region of 100 cells/mm3.

“We did observe an increased risk of fatal infections due to use of rituximab,” write the authors. “However, the patients who died from treatment-associated infections had lower CD4 T-cells than the entire group. These findings emphasise the need for prospective trials evaluating the benefits of intensified supportive care.”

They conclude, “the use of rituximab improved overall and progression free- survival.  This effect was seen even in the setting of severe immune deficiency and without an increased risk of fatal infections.”

Noting the substantial mortality rate, the investigators call “for further clinica research in AIDS related lymphomas.”

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New vaccine against pneumococcal disease approved for UK

 A new vaccine that may be more suitable for preventing pneumococcal disease in people living with HIV has been approved in the United Kingdom.

Prevenar 13, manufactured by Pfizer, is targeted at 13 variants of Streptococcus pneumoniae.

Recently published research carried out by the Health Protection Agency shows that among people with HIV, these variants cropped up in 61% of cases of invasive pneumococcal disease diagnosed in 2009. In contrast the PCV7 vaccine would have protected against only 23% of cases.

The Health Protection Agency research also showed that the incidence of invasive pneumococcal disease was 20 times higher among people with HIV compared with the general population.

Illness caused by Streptococcus pneumoniae is a common cause of ill health in the general population. In most people it causes mild health problems such as sinusitis and chest infections, but more severe cases of penumococcal disease can result in septicaemia, severe pneumonia or meningitis.

Tthe risk of invasive and potentially life-threatening pneumococcal disease is higher in the over-50s and in people with suppressed immunity, chronic respiratory conditions such as asthma, heart, liver or kidney disease.

The Prevenar 13 vaccine has been licensed for use in adults aged 50 years and over.

Current UK vaccination policy is to offer the PPV-23 vaccine to adults aged 65 and over, and to adults in specified risk groups, including people living with HIV. The Joint Committee on Vaccination and Immunisations (JCVI) concluded in March 2011, on the basis of unpublished data provided by manufacturer Pfizer, that “there is no conclusive evidence that [the PCV-13] vaccine would be more effective in older adults”.

The JCVI made no specific recommendation regarding vaccination for people living with HIV, despite an initial recommendation from the JCVI’s Pneumococcal sub-committee that people with HIV with controlled viraemia should receive two doses of the PVC-13 vaccine followed by one dose of the PPV-23 vaccine.

2008 guidance from the British HIV Association recommended use of the PPV-23 vaccine in people living with HIV with CD4 cell counts above 200 cells/mm3, and that it should be considered for those with CD4 counts below 200. This recommendation was framed in the light of evidence of lower vaccine efficacy in people with CD4 counts below 200.

The British HIV Association's Immunisation Comittee plans new guidance in 2012 with a view to recommending the PCV-13 vaccine, Dr Anna-Maria Geretti of London's Royal Free and University College Medical School told aidsmap.

The PCV-13 is already licensed for use in children and is used routinely in the UK childhood vaccination programme.

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Mild kidney problems in patients with HIV can identify patients with hardening of the arteries

Emergent kidney dysfunction is associated with an increased risk of hardening of the arteries in patients with HIV, Spanish researchers show in the online edition of the Journal of Acquired Immune Deficiency Syndromes.

“Our findings provide support for the hypothesis that mild abnormalities of renal function can independently predict an increased atherosclerotic burden and behave as a useful surrogate marker of subclinical atherosclerosis,” write the investigators.

Kidney disease is an increasingly important cause of serious illness and death in patients with HIV. The exact causes are uncertain but appear to include the effects of HIV, lifestyle factors and possibly the side-effects of some anti-HIV drugs.

Research has established an association between renal dysfunction and an increased risk of cardiovascular disease in HIV-positive patients. However, most HIV-positive individuals with kidney problems experience only mild abnormalities. Nevertheless, studies conducted in the general population have shown that the presence of low-grade albuminuria and a low eGFR are associated with death due to cardiovascular causes.

Investigators in Madrid therefore hypothesised that mild deterioration in kidney function, or incipient renal impairment, would predict hardening of the arteries in HIV-positive patients.

They therefore designed a cross sectional study involving 145 individuals who received HIV care between 2009 and 2010.

Incipient renal impairment was defined as eGFR below 90 ml/min, a rate of eGFR decrease above 3% annually over a three-year period, and an albumin/creatine urine ratio above 5 mg/g. Patients with carotid artery intima media thickness (cIMT) above the 75th percentile or plaques were classified as having sub-clinical atherosclerosis.

Most of the patients (88%) were male and their average age was 41 years. There was a high prevalence of cardiovascular risk factors. The most common was smoking (47%), followed by elevated triglycerides (43%), high cholesterol (39%), hypertension (17%) and diabetes (9%). Nearly all the patients (91%) were taking antiretroviral therapy and 77% had an undetectable viral load.

Plaques were detected in the coronary arteries of 6% of patients and 31% were classified as having sub-clinical atherosclerosis. Incipient renal impairment was identified in almost two-thirds of patients (64%).

The emergence of kidney dysfunction was associated with a number of recognised cardiovascular risk factors, including waist circumference (p = 0.038), diabetes (p = 0.032), high triglycerides (p = 0.013), and metabolic syndrome (p = 0.031).

Some HIV-related factors were also significant. These included lipodystrophy (p = 0.017), nadir CD4 cell count (p = 0.046), a detectable viral load (p = 0.036) and not taking antiretroviral therapy (p = 0.017).

Longer use of all the main classes of antiretrovirals was also associated with the development of mild renal impairment. However, the investigators were unable to find an association with specific drugs, including tenofovir (Viread, also in the combination pills Truvada and Atripla).

Incipient renal impairment was significantly associated with the hardening of the arteries (OR = 4.3; 95% CI, 1.7-10.6; p = 0.001). This association was still highly significant after the investigators controlled for factors known to increase the risk of kidney disease, such as age, and diabetes, as well as cumulative exposure to HIV therapy (OR = 3.8; 95% CI, 1.3-11.0; p = 0.013).

“In our study,” write the authors, “individuals with incipient renal impairment…had a 4-fold higher risk of subclinical atherosclerosis.” They note that this risk was present with even mild kidney dysfunction.

The authors believe their findings have immediate clinical implications and suggest “periodic monitoring of eGFR and albumin/creatine urine ratio might help to better identify subjects at increased risk of cardiovascular disease in order to initiate aggressive management of risk factors.”

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Undiagnosed infections and poor retention in care mean that few US patients fully benefit from HIV treatment

Only a small minority of HIV-positive patients in the United States are gaining the full benefit of antiretroviral therapy, a study published in the November 29th edition of Morbidity and Mortality Weekly Report shows.  Investigators calculated that only a half of all patients are retained in care and that only 28% of people infected with HIV in the US have an undetectable viral load.

“More effort is needed to ensure that…patients remain in care and to eliminate disparities between subgroups who are prescribed ART [antiretroviral therapy] and subsequently achieve viral suppression,” comment the authors.

They warn that the goals of the 2010 US National HIV/AIDS Strategy to increases access to care, improve outcomes and reduce health inequalities can only be met by “achieving high levels of engagement at every stage in the continuum of care.”

The current low proportion of patients with viral suppression would also suggest that the use of HIV treatment as prevention will have only a minimal impact on the continuing epidemic in the US until these issues can be addressed.

An estimated 1.2 million individuals were living with HIV in the US at the end of 2008. With appropriate treatment and care the prognosis of HIV-infected patients can be excellent. Moreover, therapy that suppresses viral load to below the limit of detection significantly reduces the risk of onward transmission of the virus.

To take advantages of the benefits offered by modern HIV medicine it is essential that infected patients are diagnosed, linked and retained in care, prescribed antiretroviral therapy when appropriate, and that this treatment achieves virological suppression.

Using recent surveillance data, the investigators calculated the proportion of patients in the US receiving services at various points in this care continuum.    

They calculated that a fifth of HIV infections in the country were undiagnosed. An analysis of published studies suggested that 77% of diagnosed patients were initially linked with care. However, retention rates were poor and only 51% of individuals continued to regularly access care.

Use of antiretroviral therapy among the patients remaining in care was high, with 89% of individuals taking this treatment. Moreover, 77% of these patients achieved an suppression of the virus (defined as a viral load below 200 copies/ml).

Overall, the high rate of undiagnosed infections and the large proportion of patients dropping out of care meant that only 28% of all HIV-positive patients in the US had an undetectable viral load.

Racial disparities were apparent in the use of HIV therapy and in treatment outcomes.

Of the 92% of whites who were treated with anti-HIV drugs, 84% achieved virological suppression. Use of treatment was less prevalent among Hispanic patients (89%), and the proportion with suppression of the virus was somewhat poorer than those seen in whites (79%). Lower still were rates of treatment utilisation in black patients (86%) and only 70% of these patients experienced a fall in their viral load to below 200 copies/ml.

The study also suggested that HIV prevention efforts needed to be intensified. Only 45% of patients in care had received HIV prevention counselling. There were disparities according to age, with 73% of patients aged 18 to 24 receiving such counselling, compared to 36% of those aged over 55. Over half of black (54%) and Hispanic (52%) of patients were provided with prevention counselling compared to only 29% of whites. The proportion of patients receiving counselling also differed by HIV risk group, and was higher for gay men and other men who have sex with men (MSM) compared to men reporting sex with a woman (50% vs. 39%).

“These low percentages, especially among MSM, who account for most new HIV infections in the United States, indicate a need for health-care providers to deliver HIV prevention more consistently,” suggest the authors.

“Only an estimated 28% of all HIV-infected persons in the United States are virally suppressed, largely because even among those with diagnosed infections, only 51% are receiving regular HIV care,” emphasise the investigators.

They warn: “Without substantial improvement in these percentages, 1.2 million new HIV infections would be expected to occur over the next 20 years.” This could result in $450 billion in health-related expenditure. “Only with success at each step of the continuum of HIV care…can the ultimate goals of improving health, extending lives, and preventing further HIV transmission be achieved.”

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Hepatitis C doesn't affect cognitive function of women, but some evidence HIV does

Infection with hepatitis C does not affect the cognitive performance of women with or at risk of HIV, according to data from the Women’s Interagency HIV Study (WIHS) published in the online edition of the Journal of Acquired Immune Deficiency Syndromes.

“We were unable to show a significant association between the presence of HCV [hepatitis C virus]…and performance on our cognitive battery nor that there is an interaction between HIV and HCV in their effect on cognitive function,” write  the authors.

However, their was some evidence that infection with HIV had an impact on cognition.

A number of earlier studies have suggested that hepatitis C-infected individuals have an increased risk of neurocognitive impairments. Moreover, replicating virus has been found in the brains of patients with the infection. It has also been suggested that co-infection with HIV and hepatitis C could have a worse impact on cognitive function than either virus alone.

Women have been unrepresented in research exploring the impact of hepatitis C on cognition. Therefore, investigators from the WIHS designed a study involving 1338. Just under a fifth (18%) had detectable hepatitis C virus and 67% were infected with HIV.

“To our knowledge this cohort for our study is over twice as large as any previously reported study of the effects of HCV and HIV on cognition,” note the investigators.

The patients were divided into six groups:

Negative for both HIV and hepatitis C RNA (392 individuals).

HIV-negative/hepatitis C RNA-positive (42 individuals).

HIV-positive/hepatitis C RNA-negative (480 individuals).

AIDS/hepatitis C RNA-negative (241 individuals).

AIDS/hepatitis C RNA-positive (88 individuals)

The patients had a battery of four tests to assess their cognitive function. The results were controlled for age, ethnicity, depression, liver disease status and current or past drug and alcohol abuse, all of which have been shown to affect cognitive function.

There were significant differences between the patients according to their hepatitis C and/or HIV-infection status.

Individuals infected with hepatitis C were a significant nine years older than women who did not have hepatitis C (p < 0.001). Rates of injecting drug use were also significantly higher among the women with hepatitis C (85% vs. 12%), and hepatitis C-infected women were also significantly more likely to report recent use of cocaine (p < 0.001).

As expected, liver function was significantly poorer in those infected with hepatitis C, and the women with an AIDS diagnosis had lower CD4 cell counts than other individuals (p = 0.001).

After controlling for potential confounders, the investigators failed to find any association between hepatitis C viraemia and cognitive performance.

In their first set of analysis, they established a significant connection between poorer liver function and poorer cognitive function (p < 0.001). However, this relationship disappeared after controlling for factors such as age, ethnicity, depression and general mental health.

Nevertheless, infection with HIV was associated with impaired speed of information processing and perceptual motor ability (p < 0.001).

The investigators do not regard their findings as definitive: “The question of whether HCV has a direct effect on cognition will require future studies with a complete neuropsychological batter, a large control group and a large group of HCV-mono-infected subjects.” They also believe that such studies would need “a cohort that includes both men and women.”

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Nevirapine and cotrimoxazole prophylaxis safe in HIV-exposed, uninfected infants

Use of nevirapine with cotrimoxazole prophylaxis in HIV-exposed uninfected infants (HIV-EU) until six months of age in Zimbabwe and Uganda was safe with no immediate or long-term adverse effects, researchers on behalf of the HIV Prevention Trials Network (HPTN) 046 protocol trial report in the advance online edition of AIDS.

The findings from this secondary data analysis have important policy implications for HIV-exposed but uninfected infants in resource-poor settings.

The HPTN 046 protocol, a prospective randomised placebo controlled trial, looked at the safety and efficacy of nevirapine prophylaxis against HIV transmission in breast milk with infants followed for 18 months.

Policy makers can now make informed decision regarding the WHO 2010 prevention of mother-to-child (PMTCT) guidelines and the combined use of nevirapine and cotrimoxazole prophylaxis for extended periods of time. Such use is critical in these settings where frequent monitoring is challenging, and where the difficulties of travelling long distances and the high costs of transportation make regular clinic visits difficult.

The guidelines are based on evidence of the effectiveness of the extended use of daily nevirapine in reducing breast milk transmission of HIV. Daily use of nevirapine prophylaxis in HIV-exposed but uninfected infants for PMTCT from birth until one year of age, or until the stopping of breastfeeding (whichever comes first), is recommended.

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The World Health Organization also recommends that HIV-exposed but uninfected infants get cotrimoxazole (CTX) prophylaxis from the age of 4-6 weeks until they are no longer exposed to HIV and have confirmation of being HIV negative. Cotrimoxazole is a highly effective antibiotic against pneumonia and other opportunistic infections.

Side effects with the extended use of nevirapine have included some reports of rash and a decrease in white blood cells (neutropenia); these side effects in addition to anaemia are frequently seen with the use of CTX.

However, the safety of the combined used in HIV-EU is not well understood. The authors note that there are no studies assessing the risks in HIV-EU infants and that safety data is based on HIV-infected individuals, notably adults. Without such data effective public health implementation is handicapped.

So the authors chose to determine the risk and severity of neutropenia and/or anaemia and severe rash in HIV-EU infants randomised to one of two study arms: six months of getting daily nevirapine and cotrimoxazole prophylaxis from six weeks until breastfeeding stopped compared to those getting cotrimoxazole alone.

Following the release in August 2007 of the Six Week Extended Nevirapine (SWEN) trial that showed a 50% reduction in MTCT through breast milk recruitment into HPTN-043 stopped. Analysis was based on a fixed sample size of infants enrolled between February and August 2007.

Among the 293 mother-infant pairs randomised incidence of neutropenia and/or anaemia and skin rash, regardless of the study arm, was highest during the first six weeks of life then from six weeks to six months and lowest in the six to 12 month period.

Most (96%) infants had at least one episode of neutropenia and/or anaemia and about half had the most severe form with relatively few (13%) experiencing skin rash. The authors suggest this may reflect a high background of neutropenia and/or anaemia in this study population. Or, it may reflect an overestimation bias since the ranges used to determine potential toxicity in what is a primarily black-African population are white-based norms.

After six weeks the time to any adverse event was similar in both arms for neutropenia and/or anaemia (all grades); for neutropenia and/or anaemia (grade 3 or above); and skin rash (grade 2 or above: HR, 95% CI: 1.26 (0.96-1.66); 1.27 (0.80-2.03); and 1.16 (0.46-2.90), respectively.

An adverse event in this trial was defined as “any unfavourable or unintended symptom, sign (including an abnormal laboratory finding) or disease temporally associated with the use of the study product (onset after enrolment), regardless of relatedness.”

There were no statistically significant differences in the immediate (six weeks to six months) or long-term (six-12 months) adverse event risks among infants on nevirapine and cotrimoxazole compared to those on cotrimoxazole alone.

The authors note the potential for drug-drug interactions resulting in increased risk of patient illness and death are well documented; taking nevirapine may alter the amount of other drugs absorbed into the blood stream and vice versa.

The authors note that the placebo design of this trial within a setting with routine cotrimoxazole prophylaxis “provided a unique opportunity to assess the immediate and long term adverse events risk associated with concurrent nevirapine and CTX use.” 

Adjustments to eliminate potential confounders (variables such as infants who got zidovudine tail and maternal ARVs found in breastmilk) were made in the time to adverse event and adverse event risk assessments.

The authors conclude that  “extended nevirapine and cotrimoxazole prophylaxis until six months of age among HIV-EU did not appear to increase the immediate or long-term risk of neutropenia, anaemia or skin-rash. However, the safety of concurrent use beyond six months, among HIV-EU breastfed infants, as is currently recommended by WHO needs further evaluation.”

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Earlier deaths in people with HIV due to drugs, alcohol, co-infections, poorly controlled HIV - not rapid ageing

Patients taking antiretroviral therapy have the same mortality risk as individuals in the general population, according to Danish research published in the open-access journal PLoS One. However, this was only the case when the patients responded to treatment and did not have other factors that increased the risk of serious illness and death, such as co-infections or co-morbidities, or drug and alcohol misuse.

“Mortality was associated mainly with well-known HIV and non-HIV-associated risk factors which are identifiable prior to or in the initial phase of HAART [highly active antiretroviral therapy] treatment,” comment the investigators. “Mortality in HIV-infected patients with no identifiable risk factors was almost identical to that of the general population with no risk factors.”

Effective antiretroviral therapy means that many HIV-positive patients have an excellent prognosis. Nevertheless, numerous studies have shown that the overall mortality risk of patients treated with anti-HIV drugs is still higher relative to that observed in the general population.

A number of reasons for this have been proposed including HIV-related illness, co-infections, lifestyle issues, treatment side-effects and accelerated ageing.

Danish investigators wanted to establish a better understanding of this important question.

They therefore designed a study with two aims. The first was to establish the impact on mortality of risk factors that could be identified at the time HIV treatment was started. The second was to estimate the relative risk of death for patients with and without such factors when compared to age- and sex-matched controls from the general population.

The study population comprised 2267 people aged between 25 and 65 who started HIV therapy between 1998 and 2010. The medical records of each patient were checked to see if they had risk factors that could increase the risk of death. These were divided into three broad categories:

Inadequate control of HIV. This was defined as a detectable viral load or a CD4 cell count below 200 cells/mm3.

Co-morbidities and co-infections.

Drug or alcohol abuse.

Each patients was matched with four HIV-negative controls from the general population.

Patients aged between 45 and 65 who had a good response to antiretroviral treatment and who did not have any co-morbidities/co-infections or drug/alcohol problems had a mortality risk ratio (MRR) of 1.14, comparable to that observed in the control population. The risk was somewhat higher for younger patients (25 to 45) who were doing well on therapy, but who had no additional risk factors (MRR = 2.02).

However, the risk of death was increased between four-fold and 20-fold for patients with either co-morbidities/co-infections or problems with drug/alcohol use.

“Increased risk of death was observed only in patients registered with one or more risk factors in the initial phase of HAART treatment,” emphasise the authors.

Individuals in the control group had an 88% probability of surviving until they were 65. The overall chance of survival to this age for patients with HIV was much lower at only 48%.

However, the probability of survival was massively affected by the presence of identifiable risk factors.

Patients with poor response to HIV therapy had a 58% chance of surviving until 65 years of age. This fell to 30% for patients with co-morbidities or co-infections, and to just 3% in those with high levels of drug or alcohol use.

In contrast, patients with none of these risk factors had a chance of survival to age 65 that was comparable to that seen in the general population (86 vs 88%).

“As we did not observe substantially increased mortality among HIV patients without risk factors, our data does not support the theory of premature ageing,” write the authors. “Rather, the data establish that the increased risk of death in the HIV population mainly stems from classic risk factors.”

They conclude: “Future management of the HIV-infected population should focus on early diagnosis, timely and effective HAART, and treatment of co-morbidity and alcohol/drug abuse.”

The authors also believe that it is important to give patients optimistic and accurate information about their potential prognosis, commenting: “Stressing the impact of HIV on mortality after HAART initiation may severely hamper the patients’ quality of life and be at odds with present data.”

View the original article here

Earlier deaths in people with HIV due to drugs, alcohol, co-infections, poorly controlled HIV - not rapid ageing

Patients taking antiretroviral therapy have the same mortality risk as individuals in the general population, according to Danish research published in the open-access journal PLoS One. However, this was only the case when the patients responded to treatment and did not have other factors that increased the risk of serious illness and death, such as co-infections or co-morbidities, or drug and alcohol misuse.

“Mortality was associated mainly with well-known HIV and non-HIV-associated risk factors which are identifiable prior to or in the initial phase of HAART [highly active antiretroviral therapy] treatment,” comment the investigators. “Mortality in HIV-infected patients with no identifiable risk factors was almost identical to that of the general population with no risk factors.”

Effective antiretroviral therapy means that many HIV-positive patients have an excellent prognosis. Nevertheless, numerous studies have shown that the overall mortality risk of patients treated with anti-HIV drugs is still higher relative to that observed in the general population.

A number of reasons for this have been proposed including HIV-related illness, co-infections, lifestyle issues, treatment side-effects and accelerated ageing.

Danish investigators wanted to establish a better understanding of this important question.

They therefore designed a study with two aims. The first was to establish the impact on mortality of risk factors that could be identified at the time HIV treatment was started. The second was to estimate the relative risk of death for patients with and without such factors when compared to age- and sex-matched controls from the general population.

The study population comprised 2267 people aged between 25 and 65 who started HIV therapy between 1998 and 2010. The medical records of each patient were checked to see if they had risk factors that could increase the risk of death. These were divided into three broad categories:

Inadequate control of HIV. This was defined as a detectable viral load or a CD4 cell count below 200 cells/mm3.

Co-morbidities and co-infections.

Drug or alcohol abuse.

Each patients was matched with four HIV-negative controls from the general population.

Patients aged between 45 and 65 who had a good response to antiretroviral treatment and who did not have any co-morbidities/co-infections or drug/alcohol problems had a mortality risk ratio (MRR) of 1.14, comparable to that observed in the control population. The risk was somewhat higher for younger patients (25 to 45) who were doing well on therapy, but who had no additional risk factors (MRR = 2.02).

However, the risk of death was increased between four-fold and 20-fold for patients with either co-morbidities/co-infections or problems with drug/alcohol use.

“Increased risk of death was observed only in patients registered with one or more risk factors in the initial phase of HAART treatment,” emphasise the authors.

Individuals in the control group had an 88% probability of surviving until they were 65. The overall chance of survival to this age for patients with HIV was much lower at only 48%.

However, the probability of survival was massively affected by the presence of identifiable risk factors.

Patients with poor response to HIV therapy had a 58% chance of surviving until 65 years of age. This fell to 30% for patients with co-morbidities or co-infections, and to just 3% in those with high levels of drug or alcohol use.

In contrast, patients with none of these risk factors had a chance of survival to age 65 that was comparable to that seen in the general population (86 vs 88%).

“As we did not observe substantially increased mortality among HIV patients without risk factors, our data does not support the theory of premature ageing,” write the authors. “Rather, the data establish that the increased risk of death in the HIV population mainly stems from classic risk factors.”

They conclude: “Future management of the HIV-infected population should focus on early diagnosis, timely and effective HAART, and treatment of co-morbidity and alcohol/drug abuse.”

The authors also believe that it is important to give patients optimistic and accurate information about their potential prognosis, commenting: “Stressing the impact of HIV on mortality after HAART initiation may severely hamper the patients’ quality of life and be at odds with present data.”

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HIV stigma divides and fragments gay communities

A review of research studies has identified a growing division within gay communities, in which HIV-negative gay men associate mainly with other HIV-negative men, and vice versa. Moreover stigma has negative impacts on the health of both HIV-positive and HIV-negative men, say the authors, writing in the online edition of AIDS Care.

Stigma has been defined as ‘‘a process of devaluation of people either living with, or associated with, HIV and AIDS’’. The majority of the research literature on stigma deals with the attitudes of the general population, but the authors wished to draw attention to and pull together reports concerning the stigmatisation of HIV-positive men within communities of gay men.

They describe this literature as “fragmented and largely anecdotal” – and call for more empirical research – but have identified multiple references to stigma that affects gay and bisexual men.

Seven out of ten gay male respondents to a Dutch survey had experienced stigma on the gay scene.HIV-positive men perceive a ‘‘rift’’ based on HIV status within their gay community.Fear of rejection by potential sexual partners is widely reported and causes long-lasting harm to the self-confidence and self-esteem of men with HIV.Older men with HIV feel particularly under-valued, believing that they are at the “lowest rung” of the “gay social hierarchy”, resented for supposedly being dependent on social benefits that are no longer available to younger men with HIV.Body fat changes and other physical manifestations of HIV and its treatment are regarded as unattractive. Men with such symptoms report a loss of intimacy and the avoidance of particular social spaces because they feel self-conscious or fear rejection.In the United States, black gay men are perceived to be at higher risk of having HIV compared to men of other ethnicities, and are sometimes avoided as sexual partners for that reason.Stigma has a considerable impact on mental and emotional well-being, leading to anxiety, loneliness, depression, thoughts of suicide and avoidance strategies such as social withdrawal.Men who only disclose their HIV-status to a limited support network often feel socially isolated.Some gay men with HIV report keeping social and sexual distance from other HIV-positive men, feeling that being associated with HIV-positive sexual spaces (either online or offline) would compound stigma directed against them.HIV-positive men who identify as ‘barebackers’ tend to report greater stigma, gay-related stress, self-blame and substance abuse coping.Men reporting discrimination from sexual partners and breaches of confidentiality are less likely to adhere to their medication.

The authors note that stigma has negative effects on the health of HIV-negative men too. HIV-negative men who rely on trying to avoid sexual contact with HIV-positive men as a way of avoiding HIV infection put themselves at risk – due to infrequent HIV testing, undiagnosed infection and non-disclosure of HIV status.Moreover stigmatising beliefs are associated with lower rates of HIV testing and poorer knowledge about HIV transmission.

They say that effective strategies, validated by research, to reduce stigma are urgently needed. “Such initiatives should foster a renewed dialogue about living with HIV as a gay man, create opportunities to share understanding and experience among HIV positive and HIV-negative men, and aim to reunite gay communities by reducing stigma and offering integrated medical and social support.”

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Long-term use of HIV drugs is safe, does not raise risk of death, study shows

A large international study has provided persuasive evidence of the long-term safety of antiretroviral therapy. Writing in the online edition of AIDS, investigators from the EuroSIDA study report that prolonged use of antiretroviral therapy did not increase the risk of death from non-AIDS-related illnesses.

“The main finding of our study was that there was no evidence of an increase in the risk of any non-AIDS-related death with prolonged exposure to cART [combination antiretroviral therapy],” comment the authors. “The results are reassuring that so far prolonged use of cART does not appear to be leading to increased risk of death due to some previously identified cumulative effect, or a drug effect whereby there is a long induction period before disease appears.”

It is now well recognised that effective antiretroviral therapy has significantly improved the life expectancy of many patients with HIV.

However, all anti-HIV drugs can cause side-effects, and treatment with some has been linked to an increased risk of cardiovascular disease or kidney dysfunction. Whether prolonged treatment with antiretroviral therapy carries an increased risk of death from these and other diseases is currently unclear.

Therefore investigators from the EuroSIDA cohort study looked at the outcomes of approximately 12,000 patients who received potent combination antiretroviral therapy after 1996.

These patients were categorised according to the duration of treatment (under two years; two to three years; four to six years; six to eight years; and over eight years).

Overall mortality incidence was then calculated according to treatment exposure, as was the incidence of AIDS-related and non-AIDS-related deaths. The investigators adjusted their results to take into consideration factors known to independently affect prognosis including demographics, HIV risk group, co-infection status, CD4 cell count and viral load, and previous history of AIDS-related illnesses.

During 70,000 person years of follow-up, a total of 1297 patients died. A little over two-thirds of deaths (68%) were attributed to non-AIDS-related causes.

AIDS-related mortality accounted for 32% of all deaths. The investigators attributed 9% of deaths to non-AIDS-related infections, 14% to liver-related causes, 10% to non-AIDS-related cancers, 9% to cardiovascular causes, 7% to violence (including suicide) and 7% to other causes. In addition, 12% of non-AIDS-related mortality had an unknown cause.

Incidence of all-cause mortality was 18.3 per 1000 person years; AIDS-related mortality had an incidence of 5.85 deaths per 1000 person years; and the incidence of non-AIDS-related mortality was 12.5 per 1000 person years.

Further analysis showed that the incidence of all-cause mortality and AIDS-related mortality fell significantly as exposure to HIV therapy increased. However, the incidence of non-AIDS-related deaths remained broadly stable.

Each additional year of HIV therapy (after year two) was associated with a 5% reduction in the risk of all-cause mortality (p < 0.0001) and a 14% fall in the risk of AIDS-related deaths (p < 0.0001). The risk of non-AIDS-related deaths fell by 3% each year, a reduction that fell just short of significance (p = 0.06).

“Our analyses confirm the prolonged benefit of cART, with a 5% reduction in the overall risk of death per additional year on treatment, which was mostly attributed to a decrease in the risk of AIDS-related deaths.”

Prolonged use of antiretroviral therapy was also accompanied by a reduction in “the risk of liver-related death, violent, and unknown death.” The investigators speculate that the lower risk of violent death “could relate to stabilised health conditions, life-style changes or improvements in socio-economic status.”

However, longer duration of HIV therapy was accompanied by an increase in mortality attributed to non-AIDS-related cancers. The authors suggest this “may reflect aging of the HIV population…or improvement in cancer screening.”

They conclude: “It is clear that death due to accumulating treatment toxicities is a very uncommon event.”

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3000 UK gay men diagnosed with HIV in 2010 – the highest number ever reported

Whereas there have been falls in the total number of new diagnoses in recent years, 2010’s figure is very similar to that recorded in 2009. A total of 6658 people were diagnosed with HIV.

Half the new diagnoses were in people who acquired HIV through heterosexual sex (around 3350 people). Two thirds of this group are thought to have acquired HIV abroad, and the numbers infected overseas have been falling for several years now. One third of heterosexual infections probably occurred in the UK – this figure has slowly increased over the past decade.

Forty five per cent of the new diagnoses were in gay and bisexual men. With around 3000 men diagnosed in one year, this is the largest annual figure ever recorded. It has gone up from 1820 in 2001, 2660 in 2005 and 2790 in 2009.

Four fifths of newly diagnosed gay men probably acquired HIV in the UK. While the majority of newly diagnosed men are of white ethnicity (83%), one third were born outside the UK.

The HPA also present data from new systems for detecting how recently a person acquired HIV. The procedure, known as RITA (Recent Infection Testing Algorithm) identifies newly diagnosed individuals who were probably infected in the past four or five months. The test is being currently rolled out. 37% of the new diagnoses reported in 2010 could be analysed by RITA.

Gay men are far more likely to be diagnosed during recent infection than other people. Whereas 7% of heterosexual women and 9% of heterosexual men have recent infection, 24% of newly diagnosed gay men have recent infection.

People who are diagnosed when they are younger are more likely to have recent infection than older people. Among gay men diagnosed under the age of 35, rates of recent infection are high at 31%, whereas in gay men diagnosed over the age of 50, the figure is 13%.

Higher rates of recent infection were also observed in heterosexual women aged 15-24 (14%) and heterosexual men aged 25-34 (14%).

When there are large numbers of people with recent infection, this suggests that HIV transmission is occurring frequently . High rates could also be due to regular HIV testing. The variation by age group may also be due to the fact that younger people have less time to have infections than older people.

The HPA estimates that, at the end of 2010, there were 91,500 people living with HIV in the UK. However one quarter of them are unaware of their infection. Moreover, the epidemiologists anticipate that by the end of 2012, there will be more than 100,000 people living with HIV in the UK.

The HPA now estimate that 1 in 20 gay men in the UK are infected with HIV. In London, where the infection is more common, 1 in 12 are infected. (These figures are based on the assumption that 3.4% of adult men are gay or bisexual). Among black African men and women living in the UK, an estimated 1 in 20 are infected with HIV.

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Hepatitis B genotype B associated with poorer liver-related outcomes in Taiwanese patients co-infected with HIV and hepatitis B

Liver-related outcomes are poorer in HIV-positive patients who are co-infected with hepatitis B virus genotype B compared to co-infected patients with hepatitis B genotype C, Taiwanese investigators report in the online edition of Clinical Infectious Diseases.

The prospective, observational study involved individuals who commenced antiretroviral therapy containing 3TC (lamivudine, Epivir, also in the combination pill Combivir), a drug which has activity against both viruses. The patients were recruited between 1997 and 2008, and followed until 2010.

“Patients with [hepatitis B virus] genotype B co-infection were at higher risk of developing hepatitis flares, liver disease-related deaths, HBeAg seroconversion, and lamivudine resistance mutations than those with genotype C coinfection,” write the authors. Genotype did not affect HIV-related outcomes.

HIV and hepatitis B share transmission modes. Therefore, large numbers of patients are co-infected with these viruses. There are eight hepatitis B genotypes (A – H). The distribution of genotypes varies according to geographical region, and genotypes B and C predominate in Asia.

Little is known about the differential impact of these two genotypes on liver-related outcomes in patients co-infected with HIV and hepatitis B.

Therefore, investigators in Taiwan recruited 145 co-infected patients starting antiretroviral therapy to a study analysing the clinical, immunological and virological outcomes of patients according to hepatitis B genotype.

The hepatitis B-related outcomes included the risk of hepatitis flares, liver disease-related death, hepatitis B e antigen (HBeAg) seroconversion, and the development of strains of hepatitis B with resistance to 3TC. Changes in CD4 cell count and HIV viral load were also compared according to genotype.

A total of 96 patients were co-infected with genotype B and 49 with genotype C were recruited. There were no significant baseline differences between the patients.

However, they had severe immune suppression at the time they started HIV treatment, and their median CD4 cell count was just 117 cells/mm3. Median baseline HIV viral load was approximately 125,000 copies/ml. Median hepatitis B viral load at the start of the study was 63,000 copies/ml.

Patients were treated with 3TC-containing antiretroviral therapy for a median of 2.8 years. During this time, none of the patients received any other antiretroviral drugs with activity against hepatitis B.

Compared to patients with genotype C, those with genotype B co-infection were significantly more likely to experience hepatitis flares (44% vs. 27%, p = 0.04), die of liver-related causes (9% vs. 0%, p = 0.03), have HBeAg seroconversion (62% vs. 25%, p = 0.03), and developed strains of hepatitis B with resistant to 3TC (31% vs. 12%, p < 0.001).

Analysis that controlled for potentially confounding factors confirmed the relationship between genotype B co-infection and a number of liver-related outcomes.

Compared to individuals with genotype C, those with genotype B had a higher risk of hepatitis flares (AHR = 4.13; 95% CI, 2.87-5.39; p = 0.01) and were also more likely to develop 3TC-resistant hepatitis B (AHR = 8.67; 95% CI, 6.37-10.98, p = 0.001).

However, there was no significant difference in mortality risk between the genotypes. Nor did HIV-related outcomes differ between the two groups of patients, who had similar falls in viral load and increases in CD4 cell count.

“Hepatitis B genotype B is the most predominant genotype in hepatitis B virus and HIV-co-infected Taiwanese patients,” conclude the investigators. “Patients with genotype B co-infection are more likely to experience acute exacerbations of hepatitis, HBeAg seroconversion, lamivudine resistance, and liver disease-related death than those with genotype C coinfection when they receive [HIV therapy] containing lamivudine as the only active agent against hepatitis B virus.”

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Patients on HIV therapy have an increased risk of stress and fragility fractures; no link to specific drug

Patients taking antiretroviral therapy have an increased risk of fractures typically associated with low bone mineral density, Danish investigators report in the online edition of AIDS.

However, the most important risk factors were the presence of other chronic illnesses and smoking. Treatment with tenofovir (Viread, also in the combination pills Truvada and Atripla) did not increase the risk of fractures, nor did CD4 cell count.

“We found an association between HAART [highly active antiretroviral therapy]-exposure and increased risk of low-energy fractures but cannot determine whether this increased risk is induced by alterations in BMD [bone mineral density] observed after HAART initiation or by differences between HAART-treated and HAART-naïve patients,” write the investigators.

It is now well established that HIV-positive patients have an increased risk of developing low bone mineral density. The inflammation caused by HIV, and the low body weight seen in many patients with HIV, are known risk factors for this condition.

However, low bone mineral density has also been seen in patients treated with antiretroviral drugs and has been especially associated with tenofovir.

The clinical consequences of this reduction in bone density are unclear.

Studies examining the incidence of fractures in HIV-positive patients in the modern treatment era have produced conflicting results. Moreover, the research has been limited by small sample sizes, and the failure to take into account some factors that can increase the risk of fractures, such as injecting drug use and co-infection with hepatitis C virus.

To establish a clearer understanding of this important aspect of HIV medicine, Danish investigators therefore checked the records of over 5000 HIV-positive patients who received HIV care between 1995 and 2009. Each patient was matched with five HIV-negative controls of the same sex and a similar age.

Information was obtained on the overall incidence of fractures.

These were categorised as low- or high-energy fractures.

Low energy fractures were typically stress or fragility fractures and were therefore consistent with the presence of low bone mineral density. In contrast, high-energy fractures were unlikely to be due to problems with bone mineral density and were of a sort associated with traumatic injury.

The patients had a median age of 37 years. Three-quarters were men, 11% had a history of injecting drug use and 16% were co-infected with hepatitis C. The majority of patients (62%) were diagnosed after 1995 and 78% received therapy with antiretroviral drugs.

Overall incidence of any fracture among the HIV-positive patients was 21 per 1000 person years. This compared to an incidence of 13.5 per 1000 person years among the HIV-negative controls.

The investigators calculated that HIV-positive individuals were 50% more likely to experience a fracture than age- and sex-matched controls. This risk of facture was 40% higher for patients who were antiretroviral naïve and 60% higher for those with experience of HIV therapy.

Incidence of fractures consistent with low bone mineral density was 17.7 per 1000 person years among patients co-infected with HIV and hepatitis C. This compared to an incidence of only 7.4 per 1000 person years for HIV-mono-infected patients.

However, these mono-infected individuals were still 60% more likely to experience a fragility or stress fracture than matched controls.

Rates of high-energy fracture were comparable between the HIV-mono-infected patients and the HIV-negative controls (9.5 vs. 8.7 per 1000 person years). Among co-infected patients the incidence was 22.7 per 1000 person years.

The investigators suggest that this higher incidence “may be associated with the consequences of intravenous drug use or increased alcohol use including increased fall or trauma risk.”

Because of the association of co-infection with the increased risk of traumatic fractures, the investigators limited their analysis of the risk factors associated with low-impact fractures to HIV-mono-infected patients.

Patients who had not taken HIV therapy had the same risk of a low impact fracture as the HIV-negative controls.

In contrast, antiretroviral-experienced patients were approximately 80% more likely to have a fragility or stress fracture than the controls (IRR = 1.8; 95% CI, 1.5-2.1). This risk fell when the researchers controlled for the presence of other chronic illnesses (IRR = 1.6; 95% CI, 1.36-1.87).

Incidence of low-energy fractures among mono-infected patients increased from 3.5 per 1000 person years in the period before HIV therapy became available to 8.3 per 1000 person years between 1997 and 2003, and then remained relatively stable at 7.5 per 1000 person years in the period up to 2009.

“The risk of low-energy fracture associated with HAART exposure was moderate and did not increase over time,” comment the investigators.

The investigators then attempted to establish the specific risk factors for low-energy fractures among treatment-experienced patients. Smoking was strongly associated with the risk of such fractures (IRR = 2.0).

However, the use of tenofovir did not increase the risk of such fractures (IRR = 1.2; 95% CI, 0.8-1.7).

“HIV-infected patients without HCV-coinfection had increased risk of low-energy fractures,” conclude the researchers. “Future research should explore mechanisms behind the HAART-associated initial BMD loss and investigate possible interventions in patients at high risk of osteoporosis.”

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Raltegravir kinder to bones and body fat than boosted protease inhibitors in Spanish trial

Raltegravir (Isentress)-based treatment appears to have a more favourable impact on fat accumulation and bone metabolism compared to therapy based on a ritonavir-boosted protease inhibitor, according to Spanish research published in the online edition of AIDS.

The study involved 74 patients who were taking HIV therapy including a ritonavir-boosted protease inhibitor. Approximately half were randomised to switch to the integrase inhibitor raltegravir. Changes in body fat composition and bone mineral density were assessed one year after randomisation and generally favoured raltegravir.

“In our study, raltegravir showed a more neutral effect on body fat,” write the investigators. “To our knowledge our study provides the first published data about the effects of raltegravir on bone composition. Patients switching…to raltegravir showed improvements in virtually all locations.”

Effective antiretroviral therapy means that many HIV-positive patients have a near normal life expectancy.

However, HIV treatment can cause long-term side-effects, and it is arguable that one of the most feared is the syndrome of body fat changes known as lipodystrophy.

There are two components to lipodystrophy. The first is fat loss, or lipoatrophy. This is associated with older drugs in the nucleoside reverse transcriptase inhibitor (NRTI) class. The second component involves the accumulation of visceral fat, or lipohypertrophy, especially around the trunk. This side-effect may be caused by protease inhibitors. However, little is known about the impact of raltegravir on body composition.

In addition, there are concerns that antiretroviral therapy may have an impact on bone metabolism. Studies have yielded conflicting results concerning protease inhibitor therapy and bone loss, and the effect of raltegravir on bone metabolism has received little attention.

Therefore, between June and December 2008 investigators from the SPIRAL clinical trial in Barcelona designed a sub-study involving 74 patients who were taking long-term virologically suppressive HIV therapy based on a ritonavir-boosted protease inhibitor (median of 32 months).

The patients were randomised on an equal basis to either to continue their current therapy or to switch from a protease inhibitor to raltegravir.

Both DEXA and CT scans were performed at baseline. These were repeated 48 weeks later in order to assess the impact of the alternative regimens on body composition and bone density.

A significant increase in visceral adipose tissue (p = 0.002) and total adipose tissue (p = 0.01) was seen in the patients who remained on a ritonavir-boosted protease inhibitor.

The investigators found these outcomes “striking”, and comment: “Despite long-term protease inhibitor use, patients continuing the same protease inhibitor/ritonavir had a significant increase in visceral adipose tissue and total adipose tissue after 48 weeks, suggesting that fat changes probably continue over time with protease inhibitors/ritonavir.” They believe these data show “a class effect of protease inhibitors on increasing abdominal fat.”

In contrast, no significant changes were seen in the visceral fat levels of patients treated with raltegravir.

The scans also revealed the different impact of the two regimens on bone mineral density.

There were no significant changes in the bone mineral density of the patients who continued to take therapy based on a ritonavir-boosted protease inhibitor.

However, total bone mineral density increased significantly (p = 0.02), as did total hip bone mineral density (p = 0.01).

“Switching from a protease inhibitor/ritonavir to raltegravir showed improvements in bone mineral density…while maintaining the protease inhibitor/ritonavir showed an increase in visceral adipose tissue and total adipose tissue,” conclude the authors.

They believe their findings could have implications for HIV treatment strategies: “Raltegravir might be considered a safe treatment option in certain patients, especially in the HIV-infected aging population, because of its already known lipid effects and now because of its potential beneficial bone effects.”

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Treatment switches after CD4 count decline reduce risk of death by 75% in Zambia, Malawi

Mortality was reduced by about 75% among adults experiencing immunological failure according to the World Health Organization (WHO) criteria who switched to a second-line regimen compared to those who remained on a failing regimen in two public sector ART programmes without access to routine viral load monitoring in Zambia and Malawi, researchers report in the advance online edition of AIDS.

Additionally in this collaborative analysis Thomas Gsponer and colleagues on behalf of the Southern African region of the International epidemiological databases to evaluate AIDS (IeDEA-SA) showed the less time spent on a failing regimen the lower the risk of death, HR:0.70 (95%  credible intervals (CI): 0.44-1.09), p=0.11 for each six months of shorter exposure.

An estimated 6.6 million people are now getting ART in resource-poor settings. As access to treatment increases so does the number of people experiencing treatment failure with a corresponding increase in the use of second-line treatment regimens.

Cost and the absence of the necessary laboratory infrastructure preclude the regular use of viral load monitoring in resource-poor settings, especially in rural areas.

Without viral load monitoring immunological (CD4 cell counts) and clinical criteria are used to determine treatment failure. However, the accuracy of such criteria to detect virological failure is poor. This may lead to unnecessary switching with many health care providers reluctant to switch using these criteria. So people are switched later and at lower CD4 cell counts compared to programmes where viral load monitoring is available, note the authors.

The authors chose to examine further the effect of switching to second-line ART on mortality in settings without viral load monitoring.

All adult patients experiencing treatment failure according to WHO immunological criteria from two public sector ART programmes in Lusaka, Zambia and Lilongwe, Malawi were included in the analysis. Clinical and immunological monitoring was done every three to six months. In both sites viral load testing is limited because of cost and operational difficulties.

Criteria for inclusion: all patients 16 years of age and over with immunological failure after January 1, 2004 based on any of the three WHO criteria: 1) CD4 cell counts staying persistently under 100 cells/mm3 2) a fall of CD4 cell counts below the baseline count and 3) a fall greater than 50% from the peak value.

Marginal structural models and inverse probability weighting of switching to compare mortality between patients who switched and those who did not and between those who switched immediately and those who switched later were used. The authors believe this to be the first study of its kind using this model in a resource-poor setting.

From 2004 to 2009 of the 80,937 patients who started ART, 2411 met the eligibility criteria and experienced failure; 96.1% (2317) from Zambia and 3.9% (94) from Zambia.

Of these 324 (13.4%) were switched to second-line ART during a median of 1.7 years of follow-up.

Median CD4 cell count in those who switched was lower at the start of ART and failure compared to those who did not: 80 cells/mm3 compared to 155 cells/mm3, p<0.001 and 77 cells/mm3 compared to 146 cells/mm3, p<0.001, respectively.

In addition to lower mortality, loss to-follow-up was also lower among people who switched compared to those who did not: 14.2 (6.8-25.9) compared to 50.5 (43.2-58.5) per 1000 person years, p<0.001, respectively.

After adjusting for baseline and time-dependent confounders the risk of death among those who switched to a second-line regimen immediately after failure was significantly lower than those who remained on a failing regimen (HR 0.25, 95% CI: 0.09-0.72, p=0.01).

27.2% (655) patients had at least one viral load measured between six months after starting ART and immunological failure. Viral load measurement was more common among those who switched compared to those who did not, but was not statistically significant.

The authors note that ideally a randomised clinical trial should be used to determine the causal effect of switching to second-line treatment among immunologically failing patients. But they caution this is highly improbable since it raises ethical concerns.

So observational data as provided in this study offer the best available evidence to guide and inform clinical practice and public health decisions on when and if to switch, they add.

The authors note that prognostic factors can distort results from observational studies. Inverse probability of treatment weighting was used to adjust for confounding by time-updated CD4 cell counts.

The authors note that while the reduction in death was significant it may have unknowingly included patients who met the immunological failure criteria but had an undetectable viral load.

While two public sector programmes were involved, the authors question how generalisable their findings are. These programmes are equipped with electronic medical records systems, have access to regular CD4 cell counts and are involved in an international collaboration of HIV cohorts. Yet, they nonetheless follow national guidelines for the public health approach common to many programmes in the region.

The authors conclude, “in ART programmes [in sub-Saharan Africa] switching patients to second-line regimens based on WHO immunological failure criteria appears to reduce mortality, with the greatest benefit in patients switching immediately after failure is diagnosed.”  

Adding that targeted viral load may further reduce unnecessary switching and recommend that future studies “investigate at what CD4 cell count levels patients should ideally be switched and should examine long-term outcomes including after second-line failure.”

Reference

Gsponer T et al. The causal effect of switching to second-line ART in programmes without access to routine viral load monitoring. AIDS, advance online edition, doi: 10.1097/QAD.0b013e32834e1b5f, 2011.

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Co-infection with hepatitis B worsens HIV-related outcomes

Co-infection with hepatitis B virus increases the risk of AIDS or death for patients newly diagnosed with HIV, investigators from the US military report in the online edition of the Journal of Infectious Diseases.

Individuals with chronic hepatitis B infection were twice as likely to progress to AIDS/death compared to patients who were only infected with HIV.

“With compelling data confirming the risk for persons with co-infection, it is imperative that we commit to implement…additional steps to combat hepatitis B now,” write the authors of an accompanying editorial.

HIV and hepatitis B share modes of transmission. These include sexual exposure, injecting drug use and mother-to-child transmission. Therefore a significant proportion of HIV-positive patients are co-infected with HIV.

Infection with HIV can accelerate the course of hepatitis B disease.

“HIV co-infection is known to influence the natural history and course of hepatitis B by impairing the quantity and quality of the innate and adaptive immune response,” explain the authors.

There is no cure for hepatitis B, but a number of antiretroviral drugs are active against both HIV and hepatitis B and can thus help prevent liver damage and disease progression.

Studies exploring the impact of hepatitis B on HIV-related outcomes have yielded conflicting results. However, these studies were limited by their inability to control for a number of factors, including duration of infection with HIV.

In order to overcome this limitation, investigators from the US military designed a retrospective study, involving patients with an approximate date of HIV-seroconversion who were categorised according to their hepatitis B infection status. A series of analysis were then conducted to assess the impact of co-infection on the risk of progression to AIDS and death.

Patients diagnosed with HIV since 1986 were included in the study. All had been repeatedly screened for the infection and it was possible to estimate the date of their seroconversion within three years.

Their routine care involved testing for hepatitis B. This screening showed that 74% had never been infected with the virus; 20% had resolved hepatitis B infection; 4% had isolated hepatitis B core antigen (HBcAb); and 3% had chronic hepatitis B infection.  

Importantly, 48% of patients were diagnosed with HIV before the advent of effective HIV therapy in 1996.

The investigators had 16, 946 person years of follow-up available for analysis. During this time, 305 patients developed AIDS and 164 died.

Initial analysis showed that hepatitis B infection status was significantly associated with these outcomes.

Compared to individuals with no hepatitis B infection, patients with chronic hepatitis B were over twice as likely to develop AIDS or die (RR = 2.23; 95% CI, 1.51-3.28). The risk of these outcomes was also significantly increased for patients with isolated HBcAb (RR = 1.54; 95% CI, 1.02-2.34), and for those with resolved hepatitis B infection (RR = 1.35; 95% CI, 1.09-1.66).

Subsequent analysis that controlled for potential confounding factors, such as year or diagnosis and use of potent HIV therapy showed that showed that chronic hepatitis B infection remained associated with a significant risk of AIDS or death (HR = 1.80; 95% CI, 1.20-2.69). There was also a non-significant trend suggesting that resolved hepatitis B infection (HR = 1.17; 95% CI, 0.94-1.46) and isolated HBcAb (HR = 1.14; 95% CI, 0.75-1.75) were also associated with AIDS or death.

“We found that hepatitis B virus infection has a significant impact on HIV outcomes,” comment the investigators. “We also found an increased risk of AIDS or death in the HAART [highly active antiretroviral therapy] era, despite the fact that the majority of participants received an hepatitis B-active drug as part of their regimen.”

Only a fifth of patients had been vaccinated against hepatitis B, leading the investigators to suggest: “Our findings underscore the need to prevent hepatitis B in those with HIV and also in cohorts of HIV-negative individuals with risk factors for HIV acquisition.”

However, the study had a number of limitations. Most notably, it did not differentiate the causes of death, and many of the deaths in co-infected patients could have been due to factors other than hepatitis B.

Nevertheless, the authors of an accompanying editorial believe the research “adds to the weight of evidence that co-infection is deleterious by demonstrating that in a well-characterised cohort, it doubles the risk of AIDS-defining illness and death.”

They believe this underscores the importance of vaccinating individuals with or at risk of HIV against HIV and the inclusion of drugs that work against both infections in the antiretroviral therapy of co-infected patients.

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UK considering lifting restrictions on health workers with HIV – as long as viral load is undetectable

The Department of Health has opened a consultation on possible changes to its policy on the employment of people with HIV. The current ban on people with HIV performing specific procedures in surgery, dentistry and gynaecology may be lifted, so that staff who are taking antiretroviral therapy and have a viral load below 200 copies/ml could work in the NHS.

Implementation of the proposal will, in part, depend on the responses received during the public consultation that is open until 9 March 2012. Patient safety in the NHS is a sensitive political issue and if public discussion is not informed by scientific evidence, the proposals could be controversial.

Current UK policy is for a total ban on HIV-positive healthcare workers performing ‘exposure-prone procedures’. As a result, a number of medical jobs are not open to people with HIV and the consequences for someone diagnosed in the middle of their career can be devastating.

An exposure-prone procedure is one in which injury to the healthcare worker could result in the worker’s blood contaminating the patient’s open tissues. These procedures involve a combination of sharp objects and the worker’s hands being in a body cavity. Surgery is the most obvious example, but many dental procedures are also considered ‘exposure-prone’.

Only a few other developed countries (including Australia, Ireland and Italy) have a policy as restrictive as that of the UK. It is more common for the management of an HIV-positive healthcare worker to be determined on a case-by-case basis. This is the situation in Austria, Belgium, Canada, France, New Zealand and Sweden, for example.

A current court case, in which a dentist with HIV is claiming the current ban is discriminatory and unlawful, helps explains why the government is considering the change.

A working group of experts examined the evidence on the risk of transmission occurring in healthcare settings, especially when patients have been treated by an HIV-positive health worker. Internationally, there have only been four cases of transmission, none of them in the UK. In the United States, testing of 22,171 patients who had been treated by 51 different HIV-positive workers, including surgeons, obstetricians and dentists, did not identify any new HIV infections. 

During some of the less invasive ‘exposure-prone procedures’ (such as a local anaesthetic injection or a routine tooth extraction), the experts consider the transmission risk to be “negligible”. During the most invasive procedures (such as a caesarean section or open cardiac surgery), they consider the risk to be “extremely low”.

But the experts consider that the risk of HIV transmission will vary, depending on the infectiousness of the health worker, as measured by viral load.

They therefore recommend that HIV-positive workers should be allowed to perform exposure-prone procedures as long as:

They are taking combination antiretroviral therapyTheir viral load is consistently below 200 copies/ml (tests taken every three months)They are under the joint supervision of a consultant in occupational medicine and their usual doctor.

The recommendations therefore open the possibility of individuals taking HIV treatment for occupational health reasons, when it would not otherwise be recommended.

Workers whose viral load rebounded or who ceased to comply with the testing requirements would be asked not to perform exposure-prone procedures until the situation was resolved.

Based on the prevalence of HIV in the England and the number of NHS employees who perform exposure-prone procedures, the experts estimate that the measures could affect around 110 HIV-positive workers (including those with undiagnosed infection).

England’s Chief Medical Officer, Dame Sally Davies, commented: "We need to ensure that the guidelines and restrictions imposed are evidence-based and achieve a fair balance between patient safety and the rights and responsibilities of healthcare workers with HIV. This consultation will seek wide views on the expert advice and whether it should be accepted."

The chairman of the Expert Advisory Group on AIDS, Professor Brian Gazzard, said: "Our careful review of the evidence suggests that the current restrictions on healthcare workers with HIV are now out of step with evidence about the minimal risk of transmission of infection to patients and policies in most other countries. This risk can be reduced even further if the healthcare worker is taking effective drug therapy for HIV and being monitored by HIV and occupational health specialists."

As healthcare is a responsibility of the devolved administrations in the United Kingdom, there are likely to be parallel consultations in the four countries. England and Scotland have already issued consultation documents, both of which are open until 9 March 2012.

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Electrocautery ablation: safe and effective treatment of high-grade pre-cancerous anal lesions in gay men

A clinic-based intervention offers safe and effective treatment for high-grade pre-cancerous anal lesions, US investigators report in the online edition of the Journal of Acquired Immune Deficiency Syndromes.

Doctors at the Mount Sinai School of Medicine, New York, used a technique called electrocautery ablation to treat pre-cancerous anal lesions in 232 gay men, 132 of whom were HIV-positive.

Eighteen months after treatment, 83% of HIV-negative men and 69% of those with HIV were free of high-grade pre-cancerous anal lesions.

“Electrocautery ablation of high-grade anal squamous intraepithelial lesions is a safe and effective office-based procedure comparable to other available treatments,” comment the investigators.

Incidence of anal cancer has increased dramatically among gay men in recent years. HIV-positive gay men appear to be especially vulnerable to the disease, and its incidence is five-times higher in these patients compared to HIV-negative men.

Infection with high certain high-risk strains of human papillomavirus can cause cell changes in the anus, resulting in the formation of lesions. The severity of these changes is graded, and between 9% and 13% of high-grade lesions progress to anal cancer.

There are a number of treatments for these pre-cancerous lesions including infrared coagulation and topical creams such as imiquimod.

Another therapy is electrocautery ablation. The investigators described the procedure thus: “Using a gentle brushing technique the lesion was ablated [worn down] by moving [a] blade lightly across the surface like a paint-brush.” The therapy has a number of advantages and can be performed in clinics without the need for anaesthetic or sedation.

Investigators wished to assess the safety and effectiveness of this procedure. They therefore retrospectively analysed the notes of gay men who had the treatment between 2006 and 2010. The patients received an initial treatment and were then followed at intervals of three to six months and were provided with additional treatment if necessary.

At the first treatment session, a total of 375 lesions were treated in HIV-infected men compared to 226 lesions in the HIV-negative patients, a significant difference (p = 0.006).

Lesions recurred in 53% of HIV-negative men (mean number of lesions, 1.6) and in 61% of HIV-positive men (mean number of lesions, 1.9).

The number of lesions present at the time of the initial treatment session was associated with the risk of recurrence. Patients with only one lesion at this time were 55% and 73% less likely to experience a recurrence than individuals with two or three lesions (p = 0.008 and p < 0.001 respectively).

The persistence of individual lesions after the initial session of treatment was also examined by the researchers. They found a cure rate of 85% in HIV-negative individuals and 75% in HIV-positive patients.

The first treatment session appeared to offer the best chance of eradicating lesions. In HIV-negative patients the persistence rate after a second ablation treatment was 3.03 times greater than that observed after the first session.

Further analysis showed that lesions were a significant 2.34 times more likely to recur in HIV-positive men compared to HIV-negative men after a second treatment (p = 0.008).

“Extensive dysplastic tissue may indicate either infection with more oncogenic virus or a more immune compromised host,” suggest the investigators.

Nevertheless, at the last follow-up visit, 83% of HIV-negative individuals and 69% of men with HIV were free of high-grade anal lesions.

Such a level of efficacy is comparable to that achieved with alternative therapies.

“Given that infrared coagulation and electrocautery ablation have similar outcomes when treating high-grade anal squamous intraepithelial lesions, the choice of modality should be based on clinician comfort and preference,” comment the authors. “In our hands the overall impression was that electrocautery ablation seemed faster, more hemostatic and allowed more extensive disease to be treated in office.”

Pain after treatment was the most commonly reported side-effect. However, this was adequately controlled with mild painkillers. One HIV-positive patient progressed to anal cancer, despite multiple ablation treatments.

“While we documented a single progression (0.4%), rates were far lower tan series advocating a ‘watch and wait’ approach,” conclude the authors.

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