New anti-HIV drugs

A large medical conference in the United States has provided an opportunity for researchers to present their findings about several new anti-HIV drugs.

Modern HIV treatment is very effective, safe and easy to take. Treatment is lifelong, so it’s important that new drugs continue to be developed to make sure that people don’t run out of options for changing treatment if they need to, perhaps because of side-effects or drug resistance.

Dolutegravir works well in people starting HIV treatment

Research presented to the conference showed that treatment based on the new integrase inhibitor dolutegravir is safe and effective for people starting HIV therapy.

Dolutegravir has been approved in the US with the trade name Tivicay and is currently awaiting approval in Europe.

In the latest research, doctors compared the safety and effectiveness of dolutegravir therapy to treatment based on ritonavir-boosted darunavir (Prezista).

The study involved approximately 500 people.

A year after starting treatment, 90% of participants in the study taking dolutegravir had an undetectable viral load, compared to 83% of participants taking darunavir/ritonavir.

The difference in the rate of viral load suppression was especially notable for people who had a high viral load before they started treatment: 93% for dolutegravir versus 70% for darunavir/ritonavir. For people with lower viral loads, the rate of viral suppression was very similar: 88 vs 87%.

CD4 cell gains were similar between the two drugs.

Only 1% of people taking dolutegravir and 4% of those taking darunavir/ritonavir stopped taking treatment because of side-effects.

The most common side-effects were diarrhoea, nausea and headache.

Dolutegravir had a slightly more favourable cholesterol profile.

A separate study showed that dolutegravir worked well in study participants irrespective of their sex, ethnicity or age.

New tenofovir formulation

A new formulation of the anti-HIV drug tenofovir (Viread, also in the combination pills Truvada, Atripla and Eviplera) has a powerful anti-HIV effect but is less likely to cause kidney or bone side-effects, new research shows.

Tenofovir is one of the drugs recommended for first-line HIV therapy. It is potent against HIV, easy to take and has a generally mild side-effect profile. However, it has been associated with a deterioration in kidney function and also changes in bone metabolism.

Researchers have developed a new formulation of the drug called tenofovir alafenamide (TAF). It achieves much higher concentrations than the existing formulation of the drug (tenofovir disoproxil fumarate, TDF) in cells that harbour HIV, but blood concentrations are lower. This means that dosing of the drug can be reduced. Researchers wanted to see what effect this had on bone and the kidneys.

Their study involved 170 people starting HIV treatment for the first time.

They were randomised to receive treatment based on TAF or TDF and monitored for 48 weeks.

Equal proportions of participants in the study achieved an undetectable viral load (88 vs 88%). CD4 cell gains were also similar.

In terms of side-effects, a higher proportion of people taking TAF reported nausea (21 vs 12%).

TAF was associated with smaller declines in kidney function and bone density than TDF.

Research into this new formulation of tenofovir is continuing.

Kidney function and bone metabolism are monitored as part of routine HIV care. This means that problems can be spotted early to allow you and your doctor to discuss possible options.

Experimental NNRTIs

Early research shows that AIC292, an experimental drug in the NNRTI class, has a powerful anti-HIV effect, a high barrier to resistance and a good safety profile.

The drug is in the early stages of development. Laboratory research suggests that it will work well against both drug-sensitive and drug-resistant virus and has a high barrier to resistance. It does not appear to interact with any of the existing anti-HIV drugs and research involving HIV-negative volunteers showed it has a mild side-effect profile.

The product will be examined in further research.

MK-1439 is another NNRTI currently in clinical trials. The latest data show that levels of this drug are boosted by ritonavir, but tenofovir has no effect on blood levels of MK-1439.