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  • Oral presentation
  • Open Access

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

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Retrovirology20085 (Suppl 1) :O27

https://doi.org/10.1186/1742-4690-5-S1-O27

  • Published:

Keywords

  • Viral Load
  • Lamivudine
  • Nevirapine
  • Nelfinavir
  • Virological Suppression

Background

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.

Methods

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.

Results

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.

Conclusions

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.

Authors’ Affiliations

(1)
Department of Paediatrics, University of Oxford, Oxford, UK
(2)
HIV Pathogenesis Programme, University of KwaZulu-Natal, Durban, South Africa
(3)
Department of Paediatrics, Imperial College London, London, UK
(4)
National Institute for Communicable Diseases, Johannesburg, South Africa
(5)
Partner AIDS Research Center, Boston, MA, USA
(6)
Howard Hughes Medical Institute, Chevy Chase, MD, USA

Copyright

© Prendergast et al.; licensee BioMed Central Ltd. 2008

This article is published under license to BioMed Central Ltd.

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