Rapid ART scale-up in Mozambique began in 2003. As of 2011, >16 000 children were receiving ART in the national program following a standard public health approach. Individual HIVDR genotyping is not routinely available nor recommended; thus, understanding factors associated with successful VL suppression and the prevention of HIVDR in children receiving ART is essential for good program management.
Overall, low levels of HIVDR were observed among children about to initiate ART; however, 4.5% of children did have NNRTI mutations that predicted virologic failure at 12 months. Not unexpectedly, 5 of 6 children with baseline NNRTI resistance had perinatal exposure to NVP (P
= .04). Perinatal exposure to NVP was the only factor significantly associated with baseline HIVDR (OR, 35.7 [95% CI, 4.10–310.61]; P
< .001). This observation has been reported in other studies [22
], in particular, when NVP is administered as a single-dose regimen, which was the case for one-third of the PMTCT-exposed children in our survey.
Findings from this pilot survey show that 12 months after ART initiation, prevention of HIVDR was observed in 77% of children initiating first-line ART during the survey period. Results exceeded the WHO-suggested target of ≥70% [19
]. This rate of virological suppression during the first year of ART is similar to reports from other settings [25
Overall, 8.8% (10 of 113) of the children initiating ART had detected HIVDR-associated mutations at 12 months. Dual class resistance, including combined NRTI and NNRTI, was present in 9 of 113 (7.9%) children. No PI mutations were detected, which reflects the very low use of PIs in this population. The most frequently detected mutations were M184V and Y181C. The mutation M184V selected by the use of 3TC has been found in similar settings in both adults and children in which 3TC is included in the first-line ART. The NNRTI mutation Y181C is frequently found in patients on NVP-containing ART regimens and has been found in infants exposed to NVP single-dose PMTCT for HIV subtypes B and C. The K65R mutation has been found in patients taking d4T and was present in 2 of 96 (1.8%) children. Similar resistance patterns have been reported among patients failing the same first-line regimens used in this cohort [11
]; resistance rates reported were higher than in our cohort, but comparisons are unreliable due to significantly different methods.
Age at ART initiation, perinatal ARV exposure of the mother and newborn, adherence (determined by missing days of medication), HIVDR at ART initiation, and CD4 percentage were associated with HIVDR at 12 months of ART in univariate analyses. However, in the multivariate analysis, only maternal PMTCT exposure, adherence, and baseline HIVDR were associated with HIVDR at 12 months of ART. In this survey, all children failing ART had detected HIVDR-associated mutations, suggesting that in this cohort adherence support and counseling were probably effective.
Recent results of the P1060 study [34
] showed that NVP for PMTCT and treatment with a first-line ART regimen, including a ritonavir-boosted PI, was significantly more effective in treating infants than NNRTI-containing regimens. This has led to a modification of pediatric ART initiation guidelines, which now recommend the use of a PI as first-line therapy. As efforts to eliminate pediatric AIDS are intensified, implementation of ritonavir-boosted PI regimens in children with PMTCT exposure may reduce the risk of virological failure in our setting.