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

Trevor A Crowell; Brook Danboise; Ajay Parikh; Allahna Esber; Nicole Dear; Peter Coakley; Alex Kasembeli; Jonah Maswai; Samoel Khamadi; Emmanuel Bahemana; Michael Iroezindu; Francis Kiweewa; John Owuoth; Joanna Freeman; Linda L Jagodzinski; Jennifer A Malia; Leigh Ann Eller; Sodsai Tovanabutra; Sheila A Peel; Julie A Ake; Christina S Polyak; AFRICOS Study Group

doi:10.1093/cid/ciaa1161

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

Clin Infect Dis. 2021 Oct 5;73(7):e2311-e2322. doi: 10.1093/cid/ciaa1161.

Authors

Trevor A Crowell^{1

2}, Brook Danboise¹, Ajay Parikh^{1

2}, Allahna Esber^{1

2}, Nicole Dear^{1

2}, Peter Coakley^{1

2}, Alex Kasembeli^{1

3}, Jonah Maswai^{1

3}, Samoel Khamadi^{1

4}, Emmanuel Bahemana^{1

4}, Michael Iroezindu^{1

5}, Francis Kiweewa⁶, John Owuoth^{1

7}, Joanna Freeman^{1

2}, Linda L Jagodzinski¹, Jennifer A Malia¹, Leigh Ann Eller^{1

2}, Sodsai Tovanabutra^{1

2}, Sheila A Peel¹, Julie A Ake¹, Christina S Polyak^{1

2}; AFRICOS Study Group

Affiliations

¹ US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
² Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, Maryland, USA.
³ HJF Medical Research International, Kericho, Kenya.
⁴ HJF Medical Research International, Mbeya, Tanzania.
⁵ HJF Medical Research International, Abuja, Nigeria.
⁶ Makerere University Walter Reed Project, Kampala, Uganda.
⁷ HJF Medical Research International, Kisumu, Kenya.

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.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Adult
Anti-HIV Agents* / pharmacology
Anti-HIV Agents* / therapeutic use
Cohort Studies
Drug Resistance, Viral / genetics
HIV Infections* / drug therapy
HIV Infections* / epidemiology
HIV-1* / genetics
Humans
Mutation
Uganda
Viral Load

Substances

Anti-HIV Agents

Abstract

Publication types

MeSH terms

Substances

Grants and funding