HIV-1 drug mutations in children from northern Tanzania

Abstract

Objectives: In resource-limited settings, it is a challenge to get quality clinical specimens due to poor infrastructure for their collection, transportation, processing and storage. Using dried blood spots (DBS) might be an alternative to plasma for HIV-1 drug resistance testing in this setting. The objectives of this study were to determine mutations associated with antiretroviral resistance among children <18 months old born to HIV-1-infected mothers enrolled in prevention of mother-to-child transmission services in northern Tanzania.

Patients and methods: Kilimanjaro Christian Medical Center (KCMC) Clinical Laboratory is the zonal centre for early infant diagnosis using DBS in northern Tanzania. DBS were collected from January 2011 to December 2012. Mothers were kept on triple therapy and single-dose nevirapine before pregnancy and during labour, respectively. Infants were given single-dose nevirapine and most of them were breastfed. Genotypic resistance was determined in those with a viral load of >400 copies/mL.

Results: Genotypic resistance mutations were detected in 13 of 46 children (28%). HIV-1 genotypes were A1 (n = 27), C (n = 10), A/D (n = 4), D (n = 3) and CRF10_CD (n = 2). The median age was 12 weeks (IQR 6-28). The mean log10 viral load was 3.87 copies/mL (SD 0.995). All major mutations were detected in the reverse transcriptase gene and none in the protease gene region. The most frequent mutations were Y181C (n = 8) and K103N (n = 4), conferring resistance to non-nucleoside reverse transcriptase inhibitors.

Conclusions: One-third of infants newly diagnosed with HIV in northern Tanzania harboured major drug resistance mutations to currently used antiretroviral regimens. These mutations were detected from DBS collected from the field and stored at room temperature. Surveillance of drug resistance among this population in resource-limited settings is warranted.

Keywords: antiretroviral therapy; child; dried blood spots; early infant diagnosis; mutations; sub-Saharan Africa.