Protease Inhibitor Resistance in the First 3 Years of Second-Line Antiretroviral Therapy for HIV-1 in Sub-Saharan Africa

• Published in: The Journal of infectious diseases Vol. 214; no. 6; pp. 873 - 883
• Main Authors: Boender, T. Sonia, Hamers, Raph L., Ondoa, Pascale, Wellington, Maureen, Chimbetete, Cleophas, Siwale, Margaret, Maksimos, Eman E. F. Labib, Belinda, Sheila N., Kityo, Cissy M., Adeyemo, Titilope A., Akanmu, Alani Sulaimon, Mandaliya, Kishor, Botes, Mariette E., Stevens, Wendy, de Wit, Tobias F. Rinke, Sigaloff, Kim E.
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 15.09.2016
• Subjects: Adolescent; Adult; Africa South of the Sahara - epidemiology; Anti-Retroviral Agents - therapeutic use; Drug Resistance, Viral; Female; HIV Infections - drug therapy; HIV Infections - epidemiology; HIV Infections - virology; HIV Protease Inhibitors - pharmacology; HIV-1 - drug effects; HIV-1 - isolation & purification; HIV/AIDS; Humans; Lentivirus; Male; Middle Aged; Mutation; Prevalence; Prospective Studies; Retroviridae; Young Adult; Africa; HIV-1; protease inhibitor; second-line antiretroviral therapy; sub-Saharan Africa; drug resistance
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/jiw219

Background. As antiretroviral therapy (ART) programs in sub-Saharan Africa mature, increasing numbers of persons with human immunodeficiency virus (HIV) infection will experience treatment failure, and require second- or third-line ART. Data on second-line failure and development of protease inhibitor (PI) resistance in sub-Saharan Africa are scarce. Methods. HIV-1-infected adults were included if they received >180 days of PI-based second-line ART. We assessed risk factors for having a detectable viral load (VL, ≥400 cps/mL) using Cox models. If VL was ≥1000 cps/mL, genotyping was performed. Results. Of 227 included participants, 14.6%, 15.2% and 11.1% had VLs ≥400 cps/mL at 12, 24, and 36 months, respectively. Risk factors for a detectable VL were as follows: exposure to nonstandard nonnucleoside reverse-transcriptase inhibitor (NNRTI)-based (hazard ratio, 7.10; 95% confidence interval, 3.40–14.83; P<.001) or PI-based (7.59; 3.02–19.07; P = .001) first-line regimen compared with zidovudine/lamivudine/NNRTI, PI resistance at switch (6.69; 2.49–17.98; P<.001), and suboptimal adherence (3.05; 1.71–5.42; P = .025). Among participants with VLs≥1000 cps/mL, 22 of 32 (69%) harbored drug resistance mutation(s), and 7 of 32 (22%) harbored PI resistance. Conclusions. Although VL suppression rates were high, PI resistance was detected in 22% of participants with VLs≥1000 cps/mL. To ensure long-term ART success, intensified support for adherence, VL and drug resistance testing, and third-line drugs will be necessary.