Background:  The development of resistance to nucleoside analogs in HIV-2 has shown some differences with respect to HIV-1, mainly a higher rate of selection of mutation Q151M, which unfortunately results in multi-nucleoside resistance. However, since most series of HIV-2 patients on ART are small, information on drug resistance patterns is often inaccurate. In drug-naive HIV-1 patients, selection of K65R in the reverse transcriptase (RT) is generally restricted to patients failing tenofovir (TDV), although in the presence of K65R the susceptibility to other drugs such as lamivudine (T3C), didanosine (ddI), or abacavir (ABC) may be diminished. Herein, we provide the first evidence for selection of K65R in HIV-2 patients failing ABC and never exposed to TDV.

Methods:  In Bissau, 22 HIV-2 patients attending a clinic initiated ART as part of the DREAM program were identified and followed for 12 months. Plasma HIV-2 RNA was measured using EasyQ v1.1. The RT gene was amplified from plasma RNA and sequenced for genotypic resistance analysis.

Results:  All patients were HIV-2 subtype A. Most patients (15 of 22, 68%) were treated with aidovudine (AZT)+3TC+ABC as first-line therapy. The rest received AZT+3TC+nevirapine (NVP) and indinavir (IDV) +ABC+ddI, according to drug availability. Mean baseline plasma HIV-2 RNA was 4.06 log copies/mL (range 1.9 to 6.36). Overall, 68% of patients never reached undetectability (<200 copies/mL) and 19 of 22 (86%) failed therapy within 12 months of treatment. As expected, the majority (84%) developed M184V in the RT. Interestingly, K65R was selected in 3 patients, 2 of whom were failing AZT+3TC+ABC and 1 receiving IDV+ABC+ddI. Surprisingly, none of these patients developed Q151M, which has been reported to be frequently seen in HIV-2 patients failing AZT.

Conclusions:  Complete viral suppression in HIV-2 is not readily achieved and sustained over 1 year with triple antiretroviral regimens and drug resistance develops rapidly. Different patterns of resistance mutations in the RT of HIV-2 compared to HIV-1 seem to exist. In this study, K65R was selected in the absence of TDF in patients failing ABC. Clearly, selection of drug combinations and treatment strategies for HIV-2 merits a differential consideration than for HIV-1.