High frequency of rapid immunological progression in African infants infected in the era of perinatal HIV prophylaxis.
OBJECTIVE
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% < or = 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 < or = 20% in 70% and < or = 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.
Mphatswe
Wendy
W
HIV Pathogenesis Programme, The Doris Duke Medical Research Institute, University of KwaZulu-Natal, Durban, South Africa.
Blanckenberg
Natasha
N
Tudor-Williams
Gareth
G
Prendergast
Andrew
A
Thobakgale
Christina
C
Mkhwanazi
Nompumelelo
N
McCarthy
Noel
N
Walker
Bruce D
BD
Kiepiela
Photini
P
Goulder
Philip
P
D019380:Anti-HIV Agents / Q000008:administration & dosage*; D018791:CD4 Lymphocyte Count; D018450:Disease Progression; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000453:epidemiology / Q000276:immunology* / Q000517:prevention & control; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical; D009017:Morbidity; D009035:Mothers; D019829:Nevirapine / Q000008:administration & dosage*; D018743:Perinatal Care / Q000379:methods; D013019:South Africa / Q000453:epidemiology; D019562:Viral Load; D014766:Viremia / Q000276:immunology
D019380:Anti-HIV Agents; D019829:Nevirapine