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

Journal article

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.

Authors: Boender, T; Hamers, R; Ondoa, P; Wellington, M; Chimbetete, C

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Oxford University Press
• Journal: Journal of Infectious Diseases
• Volume: 214
• Issue: 6
• Pages: 873-883
• Publication date: 2016-07-11
• Acceptance date: 2016-05-19
• DOI: 10.1093/infdis/jiw219
• EISSN: 1537-6613
• ISSN: 0022-1899
• Keywords: second-line antiretroviral therapy; protease inhibitor; HIV-1; sub-Saharan Africa; drug resistance