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High frequency of rapid immunological progression in African infants infected in the era of perinatal HIV prophylaxis

Mphatswe, Wendya; Blanckenberg, Natashaa; Tudor-Williams, Garethb; Prendergast, Andrewc; Thobakgale, Christinaa; Mkhwanazi, Nompumeleloa; McCarthy, Noelc; Walker, Bruce Da,d,e; Kiepiela, Photinia; Goulder, Philipa,c,d

AIDS:
doi: 10.1097/QAD.0b013e3281a3bec2
Basic Science
Abstract

Objectives: To determine the natural history of HIV infection following peripartum single-dose nevirapine (sd-NVP) prophylaxis in a resource-limited country, and to assess implications for antiretroviral therapy (ART) roll-out programmes.

Methods: Infants of HIV-infected mothers in KwaZulu-Natal, South Africa, were tested on days 1 and 28 to detect intrauterine (IU) and intrapartum (IP) infection. Infant follow-up included monthly viral load and CD4 cell measurement. ART was initiated at infant CD4 cell% ≤ 20%.

Results: In 740 infants born to 719 HIV-infected women, mother-to-child transmission (MTCT) was 10.3% (69% IU, 31% IP). Median viral load was higher in mothers of infants infected IP than IU (279 000 versus 86 600 copies/ml; P = 0.039) and lower in mothers of uninfected infants (median 26 750 copies/ml; P < 0.001). Peak viraemia was higher in infants infected IP than IU (5 160 000 versus 984 000 copies/ml; P < 0.001). Median viral load at birth in IU-infected infants (155 000 copies/ml) fell 1.4 log to 6510 copies/ml by day 5 and was beneath the detection limit using dried blood spot analysis in 38% of infants. CD4 cell% declined rapidly, to ≤ 20% in 70% and ≤ 25% in 85% [current World Health Organization (WHO) criteria for initiating ART] of infants by 6 months.

Conclusions: MTCT was reduced by sd-NVP through an effect on IP transmission. Where MTCT occurred despite NVP, two-thirds of transmissions arose IU; IP-infected babies were born to mothers with very high viral load. Disease progression was particularly rapid, 85% infants meeting WHO criteria for ART within 6 months. These findings argue for more effective MTCT-prevention programmes in resource-limited countries.

Author Information

From the aHIV Pathogenesis Programme, The Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa

bDepartment of Paediatrics, Division of Medicine, Imperial College London, UK

cDepartment of Paediatrics, University of Oxford, UK

dPartners AIDS Research Center, Massachusetts General Hospital, Boston, Massachusetts, USA

eHoward Hughes Medical Institute, Chevy Chase, Maryland, USA.

Received 3 January, 2007

Revised 9 March, 2007

Accepted 22 March, 2007

Correspondence to Professor P. Goulder, Department of Paediatrics, Peter Medawar Building for Pathogen Research, South Parks Road, Oxford OX1 3SY, UK. E-mail: philip.goulder@paediatrics.ox.ac.uk

© 2007 Lippincott Williams & Wilkins, Inc.