Microbicide success

For the first time a study has shown that a microbicide gel can significantly reduce the risk of male-to-female HIV transmission.

Microbicide advocates are pleased with these findings, but the results of a larger PRO2000 study, due to announce results late this year, will be crucial in determining next steps for microbicide development.

In this study, the PRO2000 microbicide was tested in a clinical trial involving over 3000 women.

Results showed that it reduced the risk of HIV transmission by 30%. This wasn’t quite a statistically significant result. There was an HIV incidence rate of 2.7 per 100 person years amongst women using PRO2000 compared to an incidence of 4 per 100 person years in other arms of the study.

But when the researchers repeated their analysis and took into account the time women weren’t using the gel, their results showed that use of PRO2000 resulted in a statistically significant 36% reduction in the risk of HIV transmission.

Other analysis showed that the more often women used the gel, the higher the level of protection it provided.

The researchers also tried to see how effective PRO2000 was at preventing HIV infections in women who didn’t use condoms. They found an HIV incidence rate of 1% in women whose method of HIV prevention consisted solely of PRO2000. This compared to an incidence of 4% amongst women who were given the placebo gel. They therefore concluded that, amongst women who didn’t use condoms, over 75% of HIV infections appeared to be prevented by PRO2000.

How would PRO2000 be used? One of the study's researchers suggested that it, "may be a niche product for women with no other choices".

Monkey study shows high-dose tenofovir-based microbicides very effective

Research involving monkeys has shown that microbicide gels containing either tenofovir alone or tenofovir plus FTC (emtricitabine) completely protected pigtail macaques from infection with SHIV, an HIV-like virus.

The monkeys were given the microbicides intravaginally 30 minutes before exposure to SHIV. This was done 20 times. None of the monkeys were infected.

The dose of tenofovir was high – 30mg, and when this is translated into human weight, it’s much higher than the 40mg dose of the drug currently being investigated in human trials.

When to start HIV treatment - studies disagree on how early

HIV treatment guidelines, such as those of the British HIV Association, recommend that HIV treatment should be started when a person’s CD4 cell count is around 350 cells/mm³.

Starting treatment at this level has been shown to reduce the risk of not only HIV-related illnesses but also some serious  non-HIV-related illnesses as well, such as heart, kidney and liver disease, as well as some cancers.

Some research has suggested that the risk of illness might be further reduced by starting treatment at even higher CD4 cell counts, for example above 500 cells/mm³.

Two studies presented to CROI have examined the value of early HIV treatment and have yielded conflicting results.

US research involving just over 9000 patients found that people who started treatment when their CD4 cell count was 500 cells/mm³ were 60% less likely to die than individuals who waited to start treatment until their CD4 cell count was lower. However, the study’s design meant that it wasn’t able to address a key question – is there a significant difference between starting treatment in the CD4 cell range 350-500 cells/mm³ compared to starting treatment above 500 cells/mm³.

A second study involved over 20,000 patients. This found that starting HIV treatment at a CD4 cell count above 450 cells/mm³ didn’t reduce the risk of progression to AIDS or death. However, it did show that there were clear benefits of starting treatment when a person’s CD4 cell count was between 350 and 450 cells/mm³ compared to between a count of between 250 and 350 cells/mm³.

There was a lively discussion on the apparently conflicting results of the studies, and it was suggested that a definitive answer would only be provided by a large 'when to start treatment' trial.

Viral load and infectiousness

One of the hottest topics over the last twelve months has been the infectiousness (or otherwise) of people taking HIV treatment who have an undetectable viral load in their blood.

The debate was kick-started a year ago by what’s come to be known as the “Swiss Statement”. This said that individuals taking HIV treatment who had an undetectable viral load and no sexually transmitted infections were essentially non-infectious to their partner in a monogamous heterosexual relationship.

The authors of the Swiss Statement noted that effective HIV treatment suppressed viral load to undetectable levels in both blood and semen.

However, two studies presented to CROI have indicated that HIV can be undetectable in blood, but detectable in semen in a minority of men, even when no sexually transmitted infection is present.

A Canadian study involving 25 men found that after viral load became undetectable in the blood, it was still detectable in 14% of semen samples. Further analysis of the semen sample with the highest viral load found potentially infectious virus.

The study also showed that viral load in semen occasionally “blipped” to detectable levels.

About a third of men who’d been taking long-term HIV treatment that suppressed viral load to undetectable levels in the blood occasionally had detectable HIV in their semen.

A larger French study looked at paired blood and semen samples from 145 men taking HIV treatment. Viral load was undetectable in 85% of these paired samples. But in 3% of samples, HIV was undetectable in blood and detectable in semen – viral load in these samples ranged between 250 and 1200 copies/ml.

Most of these detectable samples were “blips”, and the French researchers found good levels of anti-HIV drugs in the patients’ semen.

There was discussion about the implications of these findings, in particular if the levels of HIV found in semen involved a significant risk of HIV transmission. There was only one case of HIV transmission in the Parisian study, but this involved a patient who wasn’t taking his treatment properly.

However, both sets of researchers concluded that an undetectable viral load in blood doesn’t always mean that viral load is undetectable in semen, and that successful HIV treatment doesn’t eliminate the risk of HIV transmission.

Cell-free virus and transmission

A study presented to CROI looked at the mechanisms of male-to-male HIV transmission.

It showed that cell-free HIV – HIV that’s present in seminal fluid – was responsible for HIV transmission between men. The study only involved four male couples where recent HIV transmission had occurred, but the investigators are confident that the research is so robust that it has much wider implications.

Pre-exposure prophylaxis

The results of monkey studies to test the safety and effectiveness of pre-exposure prophylaxis (PrEP) were also presented to CROI.

The research involved 51 male rhesus macaques. Some were given doses of Truvada  at different intervals, and some were given no treatment. All had rectal exposure to SHIV.

Results of the study showed that Truvada could prevent some infections with SHIV, even if the drug was taken three days before exposure to SHIV and then again two hours later.

Even when infection did occur, it appeared that use of Truvada helped reduce damage to the immune system caused by the virus.

Non-AIDS-defining cancers in people with HIV

US research suggests that people with HIV are more likely to develop non-AIDS-defining cancers than the general population.

The majority of these cancers appeared to be related to infection with human papilloma virus (HPV), which can cause anal and cervical cancer; cancers of the head and neck were also more common.

Researchers compared cancer risk on almost 19,000 people with HIV to about 190,000 HIV-negative individuals.

They found that the rate of infection-related cancers was 30 per 10,000 person years in people with HIV compared to 4 per 10,000 person years in HIV-negative people.

Compared to HIV-negative people, there was an 80-fold increase in the risk of anal cancer amongst people with HIV. There was also a significantly increased risk of other cancers caused by infections, such as liver cancer due to infection with hepatitis B or hepatitis C.

But the researchers also found that the rate of developing non-AIDS-defining cancers had fallen significantly since effective HIV treatment became available.