HIV update - 15th March 2017

Darunavir/ritonavir and heart disease

Darunavir, boosted with ritonavir, is a widely used drug in the protease inhibitor class. New data suggest that long-term use of the drug modestly increases the risk of heart disease (heart attack, stroke, narrowed arteries, etc.).

The data come from the large, observational D:A:D cohort. Analyses from this cohort have previously found that use of older drugs in the protease inhibitor class (as well as use of the drug abacavir) were both associated with a greater risk of heart attack. The older protease inhibitors include saquinavir, indinavir and nelfinavir, each boosted with ritonavir.

Until now, there have been no data to suggest that the newer protease inhibitors were associated with heart disease.

The researchers looked at over 35,000 people taking HIV treatment, contributing data for an average of seven years each. Overall, each year, 5 in 1000 people had heart disease.

In people taking atazanavir boosted with ritonavir (another modern protease inhibitor), rates of heart disease were no higher than average.

But in people taking darunavir/ritonavir they were higher – each year, 14 in 1000 people had heart disease. After taking into account a number of other factors that could influence the results (including CD4 count, other medical conditions and underlying risk of heart disease), the researchers estimated that using the drug for five years was associated with a small but statistically significant increase in the risk of heart attack and stroke (risk ratio 1.5).

They call for more research to understand the reasons for the association. They say that the older protease inhibitors were known to raise cholesterol, but that this is not the case for darunavir/ritonavir.

Case report in the search for a cure

The only person known to be cured of HIV – Timothy Ray Brown, known as the 'Berlin Patient' – stopped HIV treatment when he received a bone marrow transplant to treat leukaemia and has not had detectable HIV for ten years. He received a transplant from a donor with an unusual CCR5 mutation and doctors are unsure whether it is this mutation or another factor that explains his remarkable case.

A few years ago doctors reported on the two ‘Boston patients’ who also had bone marrow transplants and interrupted their HIV treatment. They maintained undetectable viral loads longer than expected, but after three and eight months respectively, had rebounds in their viral loads. The cases showed that bone marrow transplantation is not, in itself, enough to eradicate HIV.

At the recent Conference on Retroviruses and Opportunistic Infections (CROI), researchers reported on another man who had a bone marrow transplant. While the man continued his HIV treatment for more than two years afterwards, he subsequently worked with his doctors to have a carefully monitored treatment interruption. His viral load remained undetectable for nearly ten months, before rebounding. Moreover, it appears that the size of his HIV reservoirs was reduced.

The case will be studied by researchers looking into developing a cure.

Early adherence key to long-term outcomes

Adherence to HIV treatment in the first few months after starting treatment is crucial to the long-term outcomes, a French study suggests. People who took all or nearly all their doses in the first four months after starting treatment were approximately four times more likely to have a persistently undetectable viral load in up to 12 years of follow-up, compared to people who frequently missed doses.

The researchers say this shows the importance of doctors putting particular effort into supporting people at the time of starting HIV treatment to ensure optimum adherence.