HIV resistance against antiretroviral (ARV) drug tenofovir is increasing, according to a study that called this development disconcerting because: 1) it was previously thought that tenofovir might be less prone to development of drug resistance than other compounds; and 2) tenofovir has been a go-to drug for both treating HIV (as part of ARV cocktail) and preventing HIV (co-formulated with emtricitabine for Truvada) for years now.
The study – by Ravindra Gupta and colleagues, published in The Lancet (Infectious Diseases), and which involved 1,926 people in 36 countries who continued to have uncontrolled HIV despite taking treatment – showed that the number of people with tenofovir-resistant HIV ranged from 20 percent in Europe to over 60 percent in sub-Saharan Africa.
Strong predictors of tenofovir resistance (about 50 percent more) include:
- CD4 cell count of less than 100 cells per μL, suggesting an HIV-damaged immune system; and
- Combining tenofovir with lamivudine (instead of emtricitabine) or nevirapine (instread of efavirenz).
People may also acquire HIV resistance to tenofovir by not taking the drug as intended and the virus mutates, or by getting infected by someone with a resistant form of the virus.
“The finding… indicates a need to develop treatment regimens that will be less prone to this problem, which is one that should probably have been anticipated as an unavoidable outcome of the successful HIV drug rollout programs that have helped to save millions of lives around the world in the past several decades,” the report’s authors stated. “Altogether, the results of this study are a reminder that the problems of HIV drug resistance and transmitted drug resistance are very real, especially in developing country settings, and that there is a need for enhanced, cost-effective tests that can screen for drug resistance in parts of the world in which such tests are often not affordable, as well as for more effective screening for HIV infection in the first place.”
Recommendations include:
- Consideration of a new pro-drug of tenofovir termed tenefovir alafenamide fumarate, which might be less prone to development of drug resistance because of lower toxic effects than tenofovir itself (though the report’s authors also stated that “this might not necessarily translate into lower levels of drug resistance because the same mutation at position K65R in reverse transcriptase causes resistance to both drugs and might be more prone to develop in subtype C viruses that were assessed in this and other studies”);
- Starting treatment early since “drug resistance was more likely to develop in individuals who have low CD4 cell counts due to HIV disease progression”; and
- Identification of individuals as HIV positive as efficiently and as soon as possible so they can start treatment early.
