Background:  Viral resistance is a potential problem for the HIV-infected children exposed to antiretroviral drugs at delivery or after birth. The aim of this study was to evaluate the presence of resistance mutations in children who were diagnosed with HIV infection while receiving antiretroviral prophylaxis for the prevention of  breastfeeding-associated transmission.

Methods:  We studied 25 HIV-infected infants and 22 transmitting mothers of the SIMBA study. In SIMBA, 404 infants of HIV-positive women (in Uganda and Rwanda), who had received zidovudine and didanosine from 36 weeks gestation until 1 week post-partum, were randomized to receive daily lamivudine or nevirapine for the duration of breastfeeding (as long as 6 months) or until HIV infection was confirmed. For this study, we have analyzed samples collected from infants at a median time of 2 weeks after the first detection of HIV and samples collected from mothers at delivery and at enrolment (before the administration of study drugs). The TruGene HIV-1 genotyping kit was used to determine the presence of resistance mutations. 

Results:  Of the 25 children studied, 13 had received prophylaxis with nevirapine and 12 with lamivudine; 24 were diagnosed with HIV infection by week 3; 1 tested HIV-positive at week 6. Of the 13 samples of children who had received nevirapine prophylaxis, 12 (92%) showed the presence of non-nucleoside reverse transcription inhibitor (NNRTI)-resistance mutations (9 Y181C, 3 G190A, 2 K103N, 1 Y188H, 1 V106A); 3 children had multiple mutations. None of these mutations was present in the maternal virus. In the 9 available samples collected 3 to 6 months later, the NNRTI mutations were still present. In 9 of 12 (75%) samples of children who had received lamivudine prophylaxis, the M184V mutation was found. The mutation was no longer present in the 7 available samples collected 3-6 months later. At delivery, 3 of  22 (13.6%) women had NNRTI resistance mutations (K103N, G190A, and V108I) and 1 had the M41L mutation. These mutations were also present at enrolment.

Conclusions:  Post-partum prophylaxis with nevirapine or lamivudine leads almost invariably to the selection of resistance mutations in the children who are diagnosed with the infection while receiving these drugs; this should be considered when choosing the antiretroviral regimen for these children. The presence of resistance-associated mutations in untreated women in Africa needs to be evaluated in a larger sample.

Keywords: drug resistance; mother-to-child transmission; prophylaxis