Mutsa Bwakura-Dangarembizi presenting at CROI 2013.

Continuing daily cotrimoxazole prophylaxis after starting HIV therapy has significant health benefits for children, according to the results of research conducted in Uganda and Zimbabwe.

Prophylaxis with the antibiotic cotrimoxazole is recommended for people living with HIV who have a weakened immune system. The drug provides important protection against the AIDS-defining pneumonia, PCP.

Prophylaxis is often stopped after people start HIV therapy and their immune system strengthens.

However, cotrimoxazole (Septrin, Bactrim) also provides protection against a range of other infections, including malaria.

Investigators therefore wanted to see if children with HIV in resource-limited settings benefited from continuing treatment with the drug after they started antiretroviral therapy.

The study involved 758 children in Uganda and Zimbabwe. They were randomised to stop or continue cotrimoxazole prophylaxis.

Over two years of follow-up, stopping cotrimoxazole was associated with an increased risk of hospitalisation or death.

Continuing cotrimoxazole reduced the risk of hospitalisation because of infections such as malaria, pneumonia, sepsis and meningitis. 

Kees Brinkman, Onze Lieve Vrouwe Gasthuis, Amsterdam, presenting at CROI 2013. © Liz Highleyman / hivandhepatitis.com

Antiretroviral therapy that includes drugs that work against both HIV and hepatitis B protects against infection with hepatitis B. It seems likely that the drugs act as a form of pre-exposure prophylaxis for hepatitis B.

HIV and hepatitis B have similar modes of transmission. It is recommended that everyone with HIV should be vaccinated against hepatitis B, if they are not already immune. The vaccine is administered in three doses. It is also recommended that antibody levels should be regularly monitored after immunisation and booster doses administered if needed.

However, uptake of the vaccine is often low. Some people do not receive all three doses or do not have a sufficiently strong antibody response to be protected against the infection.

Despite this, doctors at a large HIV clinic in Amsterdam noted that the rate of new hepatitis B infections among people with HIV is low. They wanted to see if this could be explained by the fact that many people are taking antiretroviral drugs which have activity against both HIV and hepatitis B.

These drugs are tenofovir (Viread, also in the combination pills Truvada, Atripla, Eviplera/Complera and Stribild), 3TC (lamivudine, Epivir), and FTC (emtricitabine, Emtriva).

The study involved 3000 people, of whom 871 were found to be susceptible to hepatitis B at the start of the study (not having hepatitis B infection, nor having been vaccinated).

Examining later samples, the researchers found that only 20% of the susceptible group had been vaccinated against hepatitis B infection, 50% were uninfected and 35 (4%) had recent hepatitis B infection.

In contrast, there were 200 new hepatitis C infections. The investigators believe that new hepatitis B infections were indeed ‘rare’.

People who were not taking dually active drugs became infected with hepatitis B sooner than people who were taking such therapy. Tenofovir appeared to be especially protective against infection with hepatitis B.

The researchers think that this reduced rate of new hepatitis B infections may be explained by the use of drugs active against both viruses. They believe their findings have implications for HIV care, and that it may not be necessary to provide booster doses of the hepatitis B vaccine to people taking dually active drugs.

Dr Amina Jindani, St George’s University Medical School, London, presenting at CROI 2013.

Standard TB therapy requires daily treatment for six months. During the first two months, therapy consists of four drugs. This is followed by a four-month continuation phase with two drugs.

Results of a new study suggest that therapy during the continuation phase can be simplified.

Good results were achieved using a new two-drug combination of rifapentine and moxifloxacin taken just once weekly.

This could make treatment much easier to take, and also make it easier for healthcare workers to support adherence and retention in care.

The once-weekly combination worked well in people with HIV. But none were taking HIV therapy so little is known about interactions.

Martin Boeree, St Radboud University, Nijmegen, presenting at CROI 2013.

The key first-line tuberculosis (TB) drug rifampicin can be tolerated at much higher doses than previously thought, new research has shown. This can result in higher drug levels, which could shorten the duration of treatment needed.

Rifampicin (rifampin, Rifadin, Rimactane) is used in first-line TB therapy. The dose is 600mg per day throughout the six-month course of treatment.

However, the maximum dose of rifampicin has never been determined.

Doctors therefore designed a study involving people with active TB in South Africa. They were divided into five dosing groups.

Treatment for the first seven days consisted of rifampicin monotherapy. Doses of the drug were related to weight, escalating from 10mg/kg for people in the first group to 35mg/kg for group five.

There was no evidence that higher doses of rifampicin increased the risk of side-effects. Higher doses of the drug also appeared to reduce TB bacteria levels.

Research is now planned to further evaluate the safety and effectiveness of the 35mg/kg doses, as well as 40 and 45mg/kg doses.

A matter that requires attention is the interaction between rifampicin and the anti-HIV drug efavirenz (Sustiva, Stocrin, also in Atripla). When rifampicin is used at a 600mg dose, the daily dose of efavirenz is increased to 800mg. It is unclear if increasing the dose of rifampicin will require a corresponding increase in efavirenz dose.

Hyman Scott, University of California, San Francisco, presenting at CROI 2013.

Researchers analysing several studies of sexual risk and HIV infection in US gay men found that black gay men were at much higher risk of HIV infection per sexual contact than other groups within the population.

But they were unable to find a reason for the increase in new infections in this group.

Young men who have sex with men (MSM), and MSM of colour, have the highest HIV incidence rates in the US. In recent years, new HIV diagnoses stayed steady amongst most population groups, but they increased by 48% in young black gay men.

Researchers from the US Centers for Disease Control looked at four studies to see if the increased risk for young men and black men was due to other behavioural or demographic factors, or another reason altogether.

The CDC researchers looked at how, in the four different studies, the number of sexual contacts varied the risk of acquiring HIV and related these to the kind of sex the participants had and their partners’ HIV status. They also asked about injecting drug use.

Without taking other factors into account, men under 25 had a 31% higher per-contact risk of being infected with HIV, and black men had a 78% higher risk. However, the studies showed that black men had fewer unprotected sexual contacts. The study wasn’t able to provide an explanation for the higher risk, but some possible factors were suggested, including higher HIV prevalence amongst black men in the US and people choosing partners from a smaller group of men.

The CDC also reported to CROI on the first estimate of the efficacy of condoms in preventing HIV transmission during anal sex since 1989. It found condoms stop seven out of ten anal transmissions – the same efficacy found by the 1989 study.

However, this was only true in situations where men used condoms consistently – that is, every time they had sex. The study also showed that only small numbers of men managed this – one in six over the period of the study. And the analysis revealed that sometimes using a condom was no more effective at preventing HIV than not using one at all. The researchers are now going to do further research to split ‘sometimes’ into different frequencies of use to find out below which level condom use ceases to be protective.

These more recent data about condom efficacy provide a useful benchmark to compare condom efficacy to some of the newer HIV prevention technologies.

Andrew Zolopa, Stamford University, presenting at CROI 2013. © Liz Highleyman / hivandhepatitis.com

A new pro-drug of tenofovir reaches HIV-infected cells more easily than the existing formulation of the drug, research shows. The pro-drug, which is called tenofovir alafenamide fumarate or TAF, had the same potency as the existing formulation (tenofovir disoproxil fumarate, TDF). However, a smaller dose was required and it was less toxic to the bones and kidneys.

Tenofovir is now an established mainstay of HIV therapy. It has powerful anti-HIV effect and has a mild side-effect profile. However, it has been associated with kidney toxicities and reduced bone mineral density.

The way in which the new pro-drug is metabolised allows it to reach higher concentrations in CD4 cells. Adequate concentrations of the drug can be achieved with lower doses, which could reduce the risk of toxicities.

Investigators compared the safety and efficacy of TAF with the existing tenofovir formulation in combination with other antiretroviral drugs.

They study involved 170 people starting HIV therapy for the first time.

Results showed that TAF was as potent as the existing tenofovir formulation.

The overall side-effect profiles of the two formulations were broadly similar. However, TAF was associated with fewer kidney and bone toxicities.

Phase 3 studies involving TAF are now planned.