Highest risk of resistance found in those starting drugs with undiagnosed infection, pointing to importance of screening
The landmark study that found preventive use of antiretroviral medicine by a person who is not infected with HIV can lower the risk of acquiring the virus from his or her infected partner has yielded data showing that the intervention poses lower risks of later resistance to the drugs than previously thought.
The findings, described in the Jan.13 Journal of Infectious Diseases were the result of testing samples from the Partners PrEP clinical trial for mutations associated with resistance to emtricitabine and tenofovir, the two antiretroviral drugs the trial tested. The trial’s 4758 participants in Kenya and Uganda, who tested negative for HIV and whose sexual partners tested positive for HIV, were randomly assigned to take a combination of the two drugs, tenofovir alone, or a placebo. With significantly fewer HIV infections among participants taking the combination, or tenofovir alone than those taking a placebo, the trial showed, in results released in July 2011, the highly effective preventive benefit of pre-exposure prophylactic — or PrEP — use of antiretroviral drugs.
According to the new study, described in the article Risk of Drug Resistance Among Persons Acquiring HIV Within a Randomized Clinical Trial of Single- or Dual-Agent Preexposure Prophylaxis, some of those who were found to be infected during the trial actually had become infected with the virus within weeks before the trial began, when testing did not detect the virus. Among those individuals, the risk of their virus becoming resistant to the drug they were taking appeared higher, particularly if they were taking the combination of tenofovir and emtricitabine, according to the article. But, the authors note, the combination drug also was associated with slightly higher reduction of infection risk than the single drug. In any case, the five cases in which resistance associated with the drugs were found represented less than eight percent of the 63 people in the non-placebo arm of the study who were found to be infected, a much lower rate of resistance than had been estimated in numerous modelling exercises. Those had estimated rates of resistance to the drugs from 25 percent to 44 percent.
The authors note the higher rates of drug-resistance among participants who were already infected as they began the PrEP regimen indicates that careful screening is important to include in the intervention. But they also note that the five cases of HIV-infected individuals in which drug resistance occurred and could be linked to PrEP should be balanced against the 197 HIV infections estimated to have been averted by the intervention.