Risk of extended viral resistance in human immunodeficiency virus-1-infected Mozambican children after first-line treatment failure

ABSTRACT

Background: Resistant virus may be selected by sub-optimal control of HIV-1 replication during antiretroviral treatment. The incidence and profile of resistance in children receiving World Health Organization-recommended treatment remains to be evaluated on a large scale. Goals Assessment of the frequency and profile of resistant virus in HIV-1-infected children, treated for at least 6 months with stavudine/zidovudine + lamivudine + nevirapine and presenting virological failure in a large access program in Maputo, Mozambique. Results: Cross-sectional evaluation of plasma HIV-1 viral load (VL) in 495 evaluable children among 512 treated for at least 6 months showed that 360 (72.7%) had a VL of <50 copies/mL of HIV-1 RNA. Genotypic resistance tests were performed in the 84 available samples from the 135 treated children with VL > or = 50 copies/mL 92% of the viruses were resistant to lamivudine and/or nevirapine, and 15% were resistant to stavudine. Twenty children (24%) harbored virus with a extended spectrum of cross-resistance defined as resistance to the 3 drugs of the combination received by the child and/or at least 1 resistance to a drug to which the child had never been exposed (abacavir 5%, tenofovir 6%, didanosine 3.5% and the new generation non nucleoside inhibitor, etravirine 6%). The only factor identified by multivariate analysis as being associated with this extended resistance profile was the duration of treatment (aOR 6.67 [95% CI 1.24-35.93], P = 0.015 for treatment >24 months) with a per month increase of 1.09 (1.02-1.16) P = 0.007.