HIV update - 19th March 2014

Transmission risks

What are the chances of someone with an undetectable viral load passing HIV on to a sexual partner? “Our best estimate is it’s zero,” said investigators presenting research from the first two years of the PARTNER study, involving couples in which one partner has HIV and the other does not.

Final results from the study are due in 2017 but, so far, there have been no transmissions when the HIV-positive partner in a couple has an undetectable viral load.

The data were presented at the recent Conference on Retroviruses and Opportunistic Infections in Boston.

British and European researchers recruited couples, gay or straight, in which one person has HIV and the other does not. All recruited couples were already using condoms inconsistently or not at all. All HIV-positive partners were taking treatment.

The aim of the study is to quantify the risk of transmission in these circumstances. It is the first study of its type to include a large number of gay couples, so can produce estimates of the risk during anal as well as vaginal sex.

The study is ongoing, and more definitive results will be available later. The current analysis includes data on almost 800 couples who reported just under 45,000 acts of penetrative sex, around half of which were anal sex.

The key news is that so far there have been no transmissions within couples from a partner with an undetectable viral load.

Without treatment, the researchers would have expected that around 100 partners would have acquired HIV.

Although some of the partners did become HIV positive, genetic testing of the HIV revealed that in all cases the virus came from someone other than the main partner.

Also, a number of people with HIV whose viral load rose above 200 copies/ml were excluded from this analysis.

Based on the current data, the transmission rate appears to be zero. However, the researchers and statisticians say that they do not yet have enough data to state this with confidence.

In particular, they are not confident about the transmission risk if a couple continues to have unprotected sex regularly over many years. In order to provide more precise estimates, the researchers are continuing to collect data and are recruiting more gay couples – including at several UK clinics.

These findings are preliminary. The final results, due in 2017, will help couples weigh up choices about using condoms during sex.

Treatment for hepatitis C

A lot of encouraging research on the treatment of hepatitis C was presented at the recent Conference on Retroviruses and Opportunistic Infections. In particular, three studies showed good outcomes for people who have both hepatitis C and HIV.

It was previously thought that people with HIV co-infection usually have a poorer response to hepatitis C treatment. In fact, it now appears that when a potent combination of two or three hepatitis C drugs is taken, people with HIV co-infection can have results that are comparable to people who only have hepatitis C.

Moreover, some of these drug combinations do not include pegylated interferon, the injectable drug that gives some people side-effects. A study examined a two-drug combination of sofosbuvir and ribavirin.

Sofosbuvir (Sovaldi) is a recently licensed drug, manufactured by Gilead, which has already been shown to give excellent results in people with hepatitis C mono-infection. Importantly, it can be taken safely with most anti-HIV drugs.

In the study, 24 weeks’ treatment led to a sustained virological response (cure) in 75% of people with hepatitis C genotype 1 who had not been treated before. (The majority of people with HIV and hepatitis C co-infection in the UK have genotype 1.) People with genotypes 2 or 3 also had good results.

Two further studies examined use of the new drugs simeprevir and faldaprevir. Each study recruited people with HIV and hepatitis C genotype 1, including people who have had problems taking treatment before and people with cirrhosis (a scarred liver).

In these studies, the new drug was taken for 12 or 24 weeks, together with pegylated interferon and ribavirin. Patients then continued to take pegylated interferon and ribavirin for a number of weeks. The total duration of treatment was between 24 and 48 weeks.

In both studies, over 70% of those treated had a sustained virological response (cure for hepatitis C), with rates as high as 85% for some groups.

The new drugs, simeprevir and faldaprevir, caused relatively few side-effects, although many people had side-effects from pegylated interferon. However, the new drugs can only be taken safely with some anti-HIV drugs – there are interactions with many antiretrovirals.

Many other hepatitis C drugs are in the pipeline.

Starting HIV treatment

A study has shown the integrase inhibitor raltegravir (Isentress) to be superior, in terms of the overall likelihood of treatment failure and safety, when compared with two ritonavir-boosted protease inhibitors – atazanavir (Reyataz) and darunavir (Prezista).

These findings are likely to be taken into account the next time treatment guidelines are revised.

In the study, 1809 people living with HIV, who had not taken HIV treatment before, were randomised into three groups and received one of the three drugs, alongside tenofovir and FTC (co-formulated in Truvada).

After 96 weeks, slightly more of those taking raltegravir had an undetectable viral load (94%) than those taking one of the boosted protease inhibitors (88-89%).

More important differences were seen in terms of side-effects. Very few people taking raltegravir (1%) or darunavir (5%) changed drugs because of side-effects. In contrast, 16% of those on atazanavir did so, often because of jaundice (a usually harmless yellowing of the skin and whites of the eyes).

The results are useful because they compare three of the drugs which are currently proposed as choices for people beginning HIV treatment. Additionally, a previous study has shown that raltegravir performs better than efavirenz (Sustiva) in people starting HIV treatment.

The risk of a heart attack

Cardiovascular disease has become a major cause of serious illness and death in people living with HIV. The exact reasons are unclear, but could include the damage caused by untreated HIV infection, the side-effects of some antiretroviral drugs and well-known risk factors such as an unhealthy diet and smoking.

But a recent study from California suggests that improvements in HIV treatment could be normalising rates of heart attack among people living with HIV. Researchers compared rates of heart attack in almost 25,000 people living with HIV and 250,000 HIV-negative people of the same age and sex, between 1996 and 2011.

Overall, those with HIV were 40% more likely to have a heart attack. But the relationship between HIV and heart attack risk diminished over the course of the study, and in 2010-11 people living with HIV and HIV-negative people had a similar level of risk.

But the study population was made up of individuals who had health insurance (and so excludes some less affluent people) and 91% were male. The findings might not be applicable to other groups.

In fact, a separate study involving over 2000 women has had very different results. Of note, these women were all either military veterans or the partners of military veterans, and are likely to include more people who could not afford health insurance. This study found that having HIV was associated with a threefold increase in the risk of heart attack. Heart attacks occurred at a younger age in women with HIV.

Have these studies clarified the relationship between HIV and cardiovascular risk? The startlingly contrasting results suggest that the effects of poverty as well as risk factors such as smoking and an unhealthy diet may be important in determining which people living with HIV have an increased risk of heart attack.