Tenofovir can be successfully re-used in people living with HIV (PLWH) who experience virologic failure on a first-line regimen, depending on the other components of that reconstructed regimen , data from a small South African study published in AIDS suggested.
The study featured 60 participants who had two viral load measurements > 1,000 copies/mL while on a regimen consisting of three drugs: tenofovir disoproxil fumarate (TDF, Viread), either lamivudine (3TC, Epivir) or emtricitabine (FTC, Emtriva), and either efavirenz (Sustiva, Stocrin) or nevirapine (Viramune).
Participants were switched to a second-line regimen of lamivudine and dolutegravir (Tivicay, DTG), with during the first two weeks to overcome efavirenz induction. (A second phase of the study will include a control arm to determine whether this addition is necessary.)
At baseline, the virus in 65% of participants had mutations indicating resistance to both TDF and lamivudine. Yet by week 24 post-switch, 85% of participants were virally suppressed (VL < 50 copies/mL), while 10% had low-level viremia (VL 50-100 copies/mL). Additionally, participants who became viremic at some point after week 12 were mostly re-suppressed with enhanced adherence counseling rather than a further change to their antiretroviral therapy, suggesting that loss of viral suppression may be due to poor adherence rather than resistance.
The study authors also speculated that the NRTI mutations present within study participants’ HIV may have crippled the virus enough to show residual antiretroviral activity, and may even protect against the development of dolutegravir mutations, study authors speculated. That said, they noted that since dolutegravir resistance may develop later in the course of treatment, follow-up is continuing through week 96.
Based on these study results and given dolutegravir’s high barrier to resistance, not to mention the limited availability of viral load testing in resource-limited settings, switching people to TDF, lamivudine, and dolutegravir may be feasible without VL measurements if larger studies can confirm these results, the study authors wrote. Such an approach would simplify a wider roll-out of dolutegravir, which the World Health Organization now lists as a preferred HIV treatment option.