Rapid progression in infants infected with HIV despite single dose nevirapine prophylaxis
Polly Clayden, HIV i-Base
A paper in AIDS authored by Wendy Mphatswe and coworkers reported findings from a study conducted in KwaZulu Natal, South Africa, to evaluate MTCT in a cohort of mothers and infants receiving single-dose NVP and disease progression in a subset of infants that were HIV-positive despite the NVP prophylaxis.
The infants form part of a study designed to assess the feasibility of ART delivery and to compare immediate versus delayed ART in early infancy.
In the study HIV-positive infants were randomised at enrolment (2:1) to immediate versus delayed ART (the results will be reported upon completion of the study). This report looks at transmission across the whole cohort and also the natural history of disease progression in the 20 infants randomised to delayed ART.
Infants were tested (whole blood) on days 1 and 28 to establish intrauterine (IU) and intrapartum (IP) infection. Follow up included monthly viral load and CD4 cell measurement. ART was initiated at infant CD4% of 20% in infants randomised to deferred treatment.
A total of 740 babies born to 719 HIV-positive mothers between July 2003 and September 2005 were included in the MTCT analysis. The investigators reported 75 transmissions at time of analysis, giving an overall MTCT rate of 10.3% (69% IU, 31% IP). The calculated IU MTCT rate was 7.1% and the IP MTCT rate 3.2%.
They found the median viral load in mothers of HIV-positive infants was higher than in mothers of HIV-negative infants (99,650 vs 26, 750 copies/mL, p<0.001). Median viral load was higher in mothers of IP-infected than IU-infected infants (279,000 versus 86, 600 copies/mL, p=0.039). Viral loads in mothers of both groups of infected infants were significantly higher than in mothers of uninfected infants (IU vs no transmission, p=0.002; IP vs no transmission, p<0.001).
Additionally median CD4 cell counts in mothers of IP-infected infants were significantly lower than in mothers of uninfected infants (200 vs 394 cells/mm3, p<0.001). Those in mothers of IU-infected infants were lower than those in mothers of uninfected infants (327 versus 394 cells/mm3, p=0.05).
Viral load data were analysed from both the 20 infants randomised to deferred ART and from the 43 randomised to immediate ART before treatment was initiated. The median viral load of IU-infected infants on day 01 was 155,000 copies/mL and 6,510 copies/mL at confirmatory testing (median day 5).
Where the timing of infant NVP administration was recorded (59/61 IU infected infants), this was a median 5 days before the confirmatory test and was, likely to have caused the fall in viral load in the first week of life. The investigators noted that in 13/34 (38%) infants, this day 5 viral load was beneath the limit of detection (3.6 log10 or 4000 copies/mL) that would have been measured had the analysis used dried blood spots (50mL whole blood) and in one infant was undetectable (<50 copies/mL).
Concerning this the investigators wrote: The NVP-induced 25-fold reduction of viral load in IU-infected infants in the first days of life is of significance where filter paper methods of HIV diagnosis using dried blood spots are employed. They suggest that, Collection of dried blood spots should, therefore, either be undertaken prior to infant NVP administration or delayed until the potential effects of NVP have passed in order to reduce under diagnosing of IU-infected infants. Use of dried blood spots testing to diagnose IP infection at day 28 does not suffer from the same limitation.
In IP-infected infants the first median viral load (day 28) was higher than in IU-infected infants (585, 000 vs 155,000 copies/mL). The highest viral load in the first 6 months of life, was significantly higher in IP-infected infants than in IU-infected infants (5,160,000 vs 984, 000 copies/mL, p<0.001).
In the group of 20 infants randomised to deferred treatment the median CD4 cell% at birth was 47% and 7 infants (35%) had progressed to a CD4% of 20% by 3 months; this increased to 14 (70%) by 6 months and 16 (80%) by 1 year. Time to CD4% 20% was directly related to maternal CD4 cell count, r=0.51, p=0.02, Spearman.
The investigators wrote: It is critical, therefore, that women have access to CD4 cell count testing in pregnancy and that ART is made available for women with advanced disease, both to improve their own health and to prevent transmission more effectively than current perinatal regimens.
Again these authors are absolutely right!
Mphatswea W, Blanckenberg N, Gareth Tudor-Williams G et al. High frequency of rapid immunological progression in African infants infected in the era of perinatal HIV prophylaxis. AIDS 2007, 21:12531261.