Pretreatment and Acquired Antiretroviral Drug Resistance Among Persons Living With HIV in Four African Countries

Abstract

Background: Emerging HIV drug resistance (HIVDR) could jeopardize the success of standardized HIV management protocols in resource-limited settings. We characterized HIVDR among antiretroviral therapy (ART)-naive and experienced participants in the African Cohort Study (AFRICOS).

Methods: From January 2013 to April 2019, adults with HIV-1 RNA >1000 copies/mL underwent ART history review and HIVDR testing upon enrollment at 12 clinics in Uganda, Kenya, Tanzania, and Nigeria. We calculated resistance scores for specific drugs and tallied major mutations to non-nucleoside reverse transcriptase inhibitors (NNRTIs), nucleoside reverse transcriptase inhibitors (NRTIs), and protease inhibitors (PIs) using Stanford HIVDB 8.8 and SmartGene IDNS software. For ART-naive participants, World Health Organization surveillance drug resistance mutations (SDRMs) were noted.

Results: HIVDR testing was performed on 972 participants with median age 35.7 (interquartile range [IQR] 29.7-42.7) years and median CD4 295 (IQR 148-478) cells/mm3. Among 801 ART-naive participants, the prevalence of SDRMs was 11.0%, NNRTI mutations 8.2%, NRTI mutations 4.7%, and PI mutations 0.4%. Among 171 viremic ART-experienced participants, NNRTI mutation prevalence was 83.6%, NRTI 67.8%, and PI 1.8%. There were 90 ART-experienced participants with resistance to both efavirenz and lamivudine, 33 (36.7%) of whom were still prescribed these drugs. There were 10 with resistance to both tenofovir and lamivudine, 8 (80.0%) of whom were prescribed these drugs.

Conclusions: Participants on failing ART regimens had a high burden of HIVDR that potentially limited the efficacy of standardized first- and second-line regimens. Management strategies that emphasize adherence counseling while delaying ART switch may promote drug resistance and should be reconsidered.

Keywords: Africa South of the Sahara; acquired immunodeficiency syndrome; drug resistance; public health surveillance.

Figure 1.

HIV-1 subtypes by country. Plasma samples from participants with HIV-1 RNA > 1000 copies/mL at enrollment underwent sequencing of the Pol region with HIV-1 subtype assignment using 4 different tools to achieve a consensus. “Other” subtypes include mixed and recombinant forms.

Figure 2.

Temporal trends in the prevalence of pretreatment antiretroviral drug resistance mutations among viremic ART-naive participants, by country. To evaluate temporal trends in HIVDR prevalence, the study period was dichotomized around the midpoint. The prevalence of specific World Health Organization surveillance drug resistance mutations (Panel A), major NNRTI mutations (Panel B), and major NRTI mutations (Panel C) was compared for participants who underwent genotyping in 2013–2015 and 2016–2019 using Pearson’s Chi-squared test. Statistically significant differences between study periods (P < .05) are shown in bold. Note that in 2016–2019, 3 participants from Tanzania with SDRMs had major mutations conferring resistance to both NNRTIs and NRTIs; this pattern of dual resistance was not present in the earlier period and contributes to the numeric decline in the prevalence of WHO SDRMs despite relatively stable prevalence of NNRTI and NRTI resistance mutations in Tanzania. Abbreviations: NNRTI, non-nucleoside reverse transcriptase inhibitor; NRTI, nucleoside reverse transcriptase inhibitor; WHO, World Health Organization.

Figure 3.

Predicted resistance to individual antiretroviral drugs among viremic ART-naive and ART-experienced participants. Resistance to individual antiretroviral drugs was predicted using the SmartGene Integrated Database Network System to access mutations lists and drug resistance scoring algorithms from the Stanford HIV Drug Resistance Database Version 8.8.0. Abbreviations: 3TC, lamivudine; ABC, abacavir; AZT, azidothymidine (zidovudine); D4T, stavudine; DDI, didanosine; DOR, doravirine; EFV, efavirenz; FTC, emtricitabine; NVP, nevirapine; RPV, rilpivirine; TDF, tenofovir.