Population-based surveillance of HIV drug resistance emerging on treatment and associated factors at sentinel antiretroviral therapy sites in Namibia

Abstract

Objective: The World Health Organization (WHO) prospective surveys of acquired HIV drug resistance (HIVDR) evaluate HIVDR emerging after the first year of antiretroviral therapy (ART) and associated factors.

Methods: Consecutive ART starters in 2009 were enrolled at 3 sentinel sites in Namibia. Genotyping was performed at start and after 12 months in patients with HIV viral load (VL) >1000 copies per mL. HIVDR outcomes were: HIVDR prevention (VL ≤1000 copies/mL), possible HIVDR (VL >1000 copies/mL without detectable HIVDR or loss to follow-up or ART stop), and HIVDR (VL >1000 copies/mL with detectable HIVDR). Adherence was assessed using medication possession ratio (MPR).

Results: Of 394 starters, at 12 months, 80% were on first-line ART, 1% died, 4% transferred out, 1% stopped ART, <1% switched to second-line, and 15% were lost to follow-up. Among patients on first-line, 77% had VL testing, and 94% achieved VL ≤1000 copies per mL. At baseline, 7% had HIVDR. After 12 months, among patients with VL testing, 5% had HIVDR. A majority of patients failing therapy had high-level resistance to nonnucleoside reverse transcriptase inhibitors but none to protease inhibitors. All sites achieved the WHO target of ≥70% HIVDR prevention. Factors associated with not achieving HIVDR prevention were: baseline resistance to nonnucleoside reverse transcriptase inhibitors [odds ratio (OR) 3.0, P = 0.023], WHO stage 3 or 4 at baseline (OR 2.0, P = 0.012), and MPR <75% (OR 4.9, P = 0.021).

Conclusions: Earlier ART initiation and removal of barriers to on-time drug pickups may help to prevent HIVDR. These data inform decisions at national and global levels on the effectiveness of first- and second-line regimens.

FIGURE 1. Flow diagram of individuals enrolled in survey: from baseline to 12-month endpoints

SDRM= WHO surveillance drug resistance mutations list ART=antiretroviral therapy VL=viral load cp/mL=copies/mL HIVDR=HIV drug resistance

FIGURE 2. Baseline HIVDR classifications, drug resistance and mutation prevalence

Figure 2a. Denominator = classifiable baseline genotype HIVDR=HIV drug resistance DR=drug resistance ARV=antiretrovirals Figure 2b. Excludes resistance to unboosted PIs Predicted HIVDR per Stanford HIVdb Mutations as defined by 2009 WHO surveillance drug resistance mutations (SDRM) list NNRTI=non-nucleoside reverse transcriptase inhibitors NRTI=nucleoside/nucleotide reverse transcriptase inhibitors PI=protease inhibitors

FIGURE 3. Endpoint HIVDR classification and drug resistance

Figure 3a. Denominator = classifiable endpoint genotype + LTFU + stopped ART – (died + transferred out) HIVDR=HIV drug resistance VL=viral load DR=drug resistance LTFU=lost to follow-up c/mL=copies/mL Figure 3b. Predicted HIVDR per Stanford HIVdb ZDV+TDF+3TC+LPV/r is the recommended second-line regimen in Namibia NNRTI=non-nucleoside reverse transcriptase inhibitor NRTI=nucleoside/nucleotide reverse transcriptase inhibitor PI=protease inhibitor NVP=nevirapine; EFV=efavirenz, ETR=etravirine, RPV=rilpivirine, TDF=tenofovir; 3TC=lamivudine; ABC=abacavir, ZDV=zidovudine; d4T=stavudine; DDI=didanosine, FTC=emtricitabine, LPV/r=lopinavir/ritonavir