Data from a large Africa Health Research Institute (AHRI) clinical trial shows that high levels of HIV drug resistance are emerging, but do not immediately pose a threat in the context of current first-line drug therapies. The findings were presented at the recent Conference on Retroviruses and Opportunistic Infections (CROI) 2017 in Seattle, USA.
The study worked within the ANRS TasP Trial – in which 28 155 people living in rural KwaZulu-Natal were offered rapid HIV screening in their homes every six months and were helped to access care – and specifically focussed on resistance. Researchers set out to answer how many people were infected with a resistant virus before they started treatment, and what impact this had on treatment efficacy.
These questions are vital in the context of new World Health Organisation HIV treatment guidelines, which recommend a ‘treat-all’ approach. Research has shown that early use of antiretroviral therapy (ART) improves health and reduces the risk of transmitting HIV to partners. However, there is concern that by expanding ART access we may see an increase in transmitted drug resistance to first-line HIV drugs. Second-line drugs often have more side-effects, and are also four to 12 times more expensive than the first-line regimen.
Using next generation sequencing, AHRI scientists sequenced the HIV genome of more than 1 300 ART naïve, HIV positive participants. Deep sequencing allows scientists to detect mutations down to 2% of the viral population, giving a more detailed perspective than the gold standard for drug resistance testing, called ‘Sanger Sequencing’.
Their results show around 17% of the participants were infected with a resistant strain of HIV. This figure is consistent with ART roll-out for more than a decade in South Africa. However, the study findings show that these resistances didn’t necessarily affect treatment outcomes. 95% of participants on treatment successfully suppressed the virus. This is higher than the UNAIDS target of 90%.
AHRI’s Dr Anne Derache, who led the research, suggests there were two factors that likely played a role in good response to ART. Firstly, there was a high level of adherence to treatment. This was most likely thanks to the fixed dose combination ARVs that were provided, which makes them easier to take, and also to the regular adherence counselling within the trial setting. Secondly, the combination of two of the drugs in this fixed dose are potent enough to achieve viral suppression in the short term, even if participants have resistance to the third drug. But these results still need to be confirmed with longer follow-up times, as this study had a median time on ART of 16 months.
“It’s great news that we have potent, cheap, fixed dose combination drugs that are easy to take with few side effects, and resistance is not yet compromising this particular therapy,” says Derache. “But it’s much too early to conclude anything. In 10 to 15 years’ time drug resistance may still become a major issue.”