Pretreatment HIV Drug Resistance Increases Regimen Switches in Sub-Saharan Africa

• Published in: Clinical infectious diseases Vol. 61; no. 11; pp. 1749 - 1758
• Main Authors: Boender, T. Sonia, Hoenderboom, Bernice M., Sigaloff, Kim C. E., Hamers, Raph L., Wellington, Maureen, Shamu, Tinei, Siwale, Margaret, Maksimos, Eman E. F. Labib, Nankya, Immaculate, Kityo, Cissy M., Adeyemo, Titilope A., Akanmu, Alani Sulaimon, Mandaliya, Kishor, Botes, Mariette E., Ondoa, Pascale, de Wit, Tobias F. Rinke
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 01.12.2015
• Subjects: Acquired Immunodeficiency Syndrome - drug therapy; Adolescent; Adult; Africa South of the Sahara - epidemiology; Anti-HIV Agents - pharmacology; Anti-HIV Agents - therapeutic use; Antiretroviral drugs; Antiretroviral Therapy, Highly Active - standards; CD4 Lymphocyte Count; Cohort Studies; Drug resistance; Drug Resistance, Viral - genetics; Female; Follow-Up Studies; Genes, pol; Genotype; HIV; HIV Infections - drug therapy; HIV Infections - epidemiology; HIV Infections - mortality; HIV Infections - virology; HIV-1 - drug effects; HIV-1 - genetics; HIV/AIDS; Human immunodeficiency virus; Humans; Male; Medical treatment; Mortality; Mutation; Proportional Hazards Models; Treatment Failure; Treatment Outcome; Viral Load - drug effects; Young Adult; Africa South of the Sahara; Africa; mortality; sub-Saharan Africa; HIV-1 drug resistance; antiretroviral therapy; regimen switch
• ISSN: 1058-4838; 1537-6591
• DOI: 10.1093/cid/civ656

Background. After the scale-up of antiretroviral therapy (ART) for human immunodeficiency virus (HIV) infection in Africa, increasing numbers of patients have pretreatment drug resistance. Methods. In a large multicountry cohort of patients starting standard first-line ART in six African countries, pol genotyping was retrospectively performed if viral load (VL) ≥ 1000 cps/mL. Pretreatment drug resistance was defined as a decreased susceptibility to ≥ 1 prescribed drug. We assessed the effect of pretreatment drug resistance on all-cause mortality, new AIDS events and switch to second-line ART due to presumed treatment failure, using Cox models. Results. Among 2579 participants for whom a pretreatment genotype was available, 5.5% had pretreatment drug resistance. Pretreatment drug resistance was associated with an increased risk of regimen switch (adjusted hazard ratio [aHR] 3.80; 95% confidence interval [CI], 1.49–9.68; P = .005) but was not associated with mortality (aHR 0.75, 95% CI, .24–2.35; P = .617) or new AIDS events (aHR 1.06, 95% CI, .68–1.64; P = .807). During three years of follow up, 106 (4.1%) participants switched to second-line, of whom 18 (17.0%) switched with VL < 1000 cps/mL, 7 (6.6%) with VL ≥ 1000 cps/mL and no drug resistance mutations (DRMs), 46 (43.4%) with VL ≥ 1000 cps/mL and ≥1 DRMs; no HIV RNA data was available for 32 (30.2%) participants. Conclusions. Given rising pretreatment HIV drug resistance levels in sub-Saharan Africa, these findings underscore the need for expanded access to second-line ART. VL monitoring can improve the accuracy of failure detection and efficiency of switching practices.