A report by George Beatty, MD, MPH, associate clinical professor of medicine, UCSF Positive Health Program at San Francisco General Hospital and Trauma Center:
The prevalence and patterns of HIV drug resistance in resource-limited settings are not yet well understood, but this understanding is critically important in maintaining the initial success of ART. An oral session on resistance today added some helpful information.
In response to changing [World Health Organization (WHO)] guidelines, most countries in Africa have begun to use tenofovir in their first line regimens. As it has become clearer that the predominant viral strain there (subtype C) has a higher predilection for developing the K65R mutation, associated with TDF resistance, there has been concern about possible increases in failure of first line TDF-containing regimens.
Two separate studies from South Africa described resistance in patients on TDF. In the first, 26/60 (43%) of patients failing on TDF had K65R. In another study, significantly more patients failing NVP/TDF/3TC developed K65R (7/8 or 88%) than did those taking EFV/TDF/3TC (40/105 or 38%). (The good news was that in patients failing second-line therapy with LPV/r, PI mutations were low (~10%), and only 4% of these were major DRV mutations.) This adds to the growing number of reasons, including hepatotoxicity and efficacy concerns, why efavirenz may be the better drug to pair with TDF and 3TC/FTC in Africa.
WHO presented data on the prevalence of drug mutations at time of initiation of ART, and at 12 months, in Africa and southeast Asia. About 5% of patients overall had resistance at the time they started therapy; most of this was NNRTI resistance. Among those failing at 12 months, 72% had drug resistance (69.5% NNRTI, 62.5% NRTI, and 60% with both). Transmitted resistance to NNRTIs will need to be monitored closely, and the high rates of dual-class resistance at first line failure continue to support the use of a boosted-PI in standard second line regimens.