Virological Failure and Drug Resistance in Patients on Antiretroviral Therapy After Treatment Interruption in Lilongwe, Malawi

TLDR: Virological failure combined with drug resistance after resumption of first-line ART occurred in 24.1% of the patients with treatment interruption, requiring a switch to protease inhibitor-based second-line therapy.

Abstract: Background. Since 2004, Malawi has rapidly scaled up access to antiretroviral therapy (ART) in the national program following a public health approach with limited laboratory monitoring. We examined virological outcomes in patients with treatment interruption at 2 clinics of the Lighthouse Trust, Lilongwe, Malawi. Methods. We evaluated patients who resumed first-line ART after having at least 1 treatment interruption documented in the electronic data system in 2008–2009. Viral load (VL) was analyzed at least 2 months after resumption of ART. For VL ≥1000 copies/mL, drug-resistance genotype was characterized using the Stanford database. Results. Between June and November 2009, we enrolled 133 patients (58.7% female) with a mean age of 38.4 years. Mean duration of ART prior to treatment interruption was 14.3 months. After a minimum of 2 months following ART resumption, VL was undetectable in 81 (60.9%) patients, was 400–1000 copies/mL in 12 (9.0%) patients, and was ≥1000 copies/mL in 40 (30.1%) patients. Genotyping and drug-resistance testing were successfully performed for 36 of 40 patients, all carrying human immunodeficiency virus type 1 subtype C. Relevant mutations affecting nonnucleoside reverse transcriptase inhibitors were found in 32 of 133 (24.1%) patients and combined with relevant nucleoside reverse transcriptase mutations in 27 of 133 (20.3%) patients. Conclusions. Virological failure combined with drug resistance after resumption of first-line ART occurred in 24.1% of the patients with treatment interruption, requiring a switch to protease inhibitor–based second-line therapy. Patients with treatment interruption should receive VL assessment after resumption of ART to detect treatment failure and to reduce development and spread of drug resistance.