Frequency of resistant virus and options for a second-line treatment for HIV-1 infected children under HAART in Mozambique
ABSTRACT Background: Resistance outcome for treated children in low resource countries is scarce. We aimed to describe the type and frequency of viral resistance in children with > 12 months of WHO advised highly active antiretroviral therapy (HAART) in a large access program in Mozambique.
Methods: Between Dec 2003 and Dec 2006, 515 children (median age: 36.8 m) were included, 97% received a combination of d4T plus 3TC and nevirapine. HIV-1 RNA was transversally performed once using the Roche Amplicor v1.5 test. HIV-1 genotypic resistance tests were performed on available plasma samples when HIV-1 RNA was > 3 log10 copies/ml. Drug resistance was interpreted according to the 2007 French ANRS algorithm.
Results: Viral load was available for 498 out of the 515 children. Among them, 134 had a viral load > 3 log10 copies/ml and genotypic resistance test could be performed for 87 children. The overall frequency of viruses showing genotypic resistance to at least 1 antiretroviral drug was 90%. The prevalences of children with ≥ 1 major mutation conferring drug resistance to NRTIs and NNRTIs were 85% and 90%, respectively. M184V was the most common NRTI mutation. Thymidine analogs mutations (TAMs) conferring resistance to ZDV or d4T were observed in 15%. Resistance to Tenofovir, Abacavir and ddI were described in 6%, 5% and 3.5% respectively. The NRTIs Multi Drug Resistance complex (Q151M) was found in 3 cases. Unexpectidely, five children (6%) had developed extensive resistance to NNRTIs inducing resitance to the new NNRTI etravirine.
Conclusions: After experiencing failure with HAART containing 2 drugs with low genetic barrier, almost all children have at least lamivudine and NNRTI resistance. Broad spectrum resistances to second NRTIs line (ddI, ABC,TDF) concerned 6% of children. Multi drug resistance to all NRTIs was found in 3.5%.