Prevalence and characteristics of HIV drug resistance among antiretroviral treatment (ART) experienced adolescents and young adults living with HIV in Ndola, Zambia

• Published in: PloS one 2020-08, Vol.15 (8), p.e0236156
• Main Authors: Miti, Sam, Handema, Ray, Mulenga, Lloyd, Mwansa, Jonathan K, Abrams, Elizabeth, Frimpong, Christiana, Burke, Virginia M, Zulu, Mangani, Siwingwa, Mpanji, Mwakazanga, David, Kalibala, Sam, Denison, Julie A
• Format: Article
• Language: English
• Subjects: Adolescent; Adolescents; Anti-HIV Agents - pharmacology; Anti-HIV Agents - therapeutic use; Antiretroviral agents; Antiretroviral drugs; Antiretroviral therapy; Biology and Life Sciences; Children & youth; Clinical Decision-Making; Clinical trials; Clinics; Control methods; Cross-Sectional Studies; Decision making; Demographic aspects; Disease control; Drug resistance; Drug Resistance, Viral - genetics; Drug therapy; Efavirenz; Emtricitabine; Epidemics; Failure analysis; Female; Health aspects; Health facilities; Highly active antiretroviral therapy; HIV; HIV infections; HIV Infections - drug therapy; HIV Infections - epidemiology; HIV-1 - genetics; HIV-1 - isolation & purification; Human immunodeficiency virus; Humans; Infectious diseases; Lamivudine; Male; Medicine and Health Sciences; Mutation; Nevirapine; Non-nucleoside reverse transcriptase inhibitors; Nucleoside reverse transcriptase inhibitors; Nucleosides; People and Places; Prevalence; Protease; Protease inhibitors; Proteinase inhibitors; Public health; Randomized Controlled Trials as Topic; RNA, Viral - genetics; RNA, Viral - isolation & purification; RNA-directed DNA polymerase; Statistics; Stavudine; Studies; Supervision; Teaching hospitals; Teenagers; Tenofovir; Thymidine; Thymidine - genetics; Tropical diseases; Viral Load - drug effects; Young Adult; Young adults; Youth; Zambia; Zidovudine
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0236156

HIV drug resistance (HIVDR) poses a threat to the HIV epidemic control in Zambia especially in sub-populations such as the 15-24 years where there is poor virological suppression. Understanding the prevalence and patterns of HIVDR in this population (15-24 years) will contribute to defining effective antiretroviral therapy (ART) regimens, improving clinical decision making, and supporting behavioral change interventions needed to achieve HIV epidemic control. A cross-sectional analysis of study enrollment data from the Project YES! Youth Engaging for Success randomized controlled trial was conducted. Participants were 15 to 24 years old, who knew their HIV status, and had been on ART for at least 6 months. All participants completed a survey and underwent viral load (VL) testing. Participants with viral failure (VL ≥1,000 copies/mL) underwent HIVDR testing which included analysis of mutations in the protease and reverse transcriptase genes. A total of 99 out of 273 analyzed participants receiving ART had VL failure, of whom 77 had successful HIVDR amplification and analysis. Out of the 77, 75% (58) had at least one drug resistant mutation, among which 83% (48/58) required a drug change. Among the 58 with HIVDR mutations, the prevalence of at least one HIVDR mutation to nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs) were 81%, 65.5% and 1.7%. The mutation M184V which confers resistance to NRTI drugs of lamivudine (3TC) and emtricitabine (FTC) was the most common (81%) among NRTI associated mutations followed by K65R (34.5%) which is associated with both tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide fumarate (TAF) resistance. Thymidine analogue mutations (TAMs) which confer resistance primarily to zidovudine (AZT), stavudine (d4T) and other NRTIs were observed at 32.8%. Common TAMs were K70RTQNE (32.8%), K219QE (22.4%), D67N (17.2%) and T215IT (15.5%). The most common NNRTI associated mutation was the K103N (65.5%) which confers resistance to both efavirenz (EFV) and nevirapine (NVP). There was a relatively high occurrence of other NNRTI mutations V106A (36.2%), as well as Y188C (36.2%) and Y181C (36.2%) which confer resistance to etravirine. There is a high prevalence of HIVDR including TAMs despite majority of these patients (90.48%) being on AZT or d4T sparing first line ART among the youth. Emergence of these mutations including the NNRTI associate