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Early virological suppression despite high frequency NNRTI resistance following perinatal prophylaxis in HIV-infected African infants


Infants infected with HIV-1 perinatally, despite single-dose nevirapine (sd-NVP) prophylaxis, progress rapidly. Furthermore, non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance mutations, following exposure to sd-NVP, may have deleterious effects on efficacy of antiretroviral therapy (ART). Data on treatment outcome in sub-Saharan African infants exposed to sd-NVP are therefore urgently required.


Infants born to HIV-infected mothers in Durban, South Africa, were tested on days 1 and 28 of life to determine intrauterine and intrapartum HIV infection, respectively. HIV-infected infants received randomised immediate or deferred (once CD4≤0%) 4-drug ART (zidovudine, lamivudine, nelfinavir and nevirapine) in a dedicated study clinic, with free outpatient and inpatient treatment of illness. Genotyping for NNRTI resistance mutations was undertaken pre-ART. Monthly follow-up to 1-year post-ART included viral load (VL) and CD4 count measurement. Adherence was assessed at every appointment by caregiver verbal recall and by measured medication returns.


All 63 HIV-infected infants were exposed to sd-NVP. 20/51 (39%) infants with baseline genotyping results had NNRTI resistance (most frequently Y181C; 20%). Median pre-ART viral load was 952,000 copies/mL. 43 infants were randomised to immediate ART. Of these, 3 were lost to follow-up pre-ART; 40 started ART (on median day 28; range 8-164) and 36/40 completed 1 year of ART. 20 infants were randomised to deferred ART. 16 reached the treatment threshold of CD4≤20% (at median day 99) and 13/16 started ART during infancy (on median day 142; range 81-227). Verbal and measured adherence was 99% and 95%, respectively. One year post-ART, 49/49 (100%) infants had VL<400 copies/mL and 46/49 (94%) had VL<50 copies/mL; 9 infants (18%) required second-line ART due to virological failure (n=4), TB treatment (n=4) or both (n=1). Time to VL<50 correlated with maternal CD4 (r=−0.42; P=0.005) and infant pre-ART VL (r=0.64; P<0.001). NNRTI mutations had no significant effect on virological suppression. Infants starting immediate compared to deferred ART had fewer illness episodes (median 7 vs 12 illness episodes per infant; P=0.003), but no significant difference in mortality, virological suppression or CD4 repletion.


Excellent adherence and virological suppression are achievable in infants, despite high-frequency NNRTI mutations, high viral loads and rapid disease progression. Infants are currently relatively neglected in roll-out programmes and ART provision must be expanded. Immediate therapy may be preferable to delayed ART, to reduce morbidity and prevent loss to follow-up.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution 2.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Prendergast, A., Mphatswe, W., Tudor-Williams, G. et al. Early virological suppression despite high frequency NNRTI resistance following perinatal prophylaxis in HIV-infected African infants. Retrovirology 5 (Suppl 1), O27 (2008).

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