Growth of human immunodeficiency virus-uninfected children exposed to perinatal zidovudine for the prevention of mother-to-child human immunodeficiency virus transmission

BACKGROUND: Perinatal human immunodeficiency virus (HIV) prevention programs have been implemented in several countries, and many children have been or will be exposed to antiretrovirals in utero and during their first weeks of life. Although reducing substantially the number of infected children, the potential adverse consequences of these treatments on the health of HIV-uninfected children need to be assessed. OBJECTIVE: To investigate the impact of in utero and postnatal zidovudine exposure on the growth of HIV-uninfected children born to HIV-infected women. METHODS: We used data prospectively collected in 1408 live born children participating in a clinical trial comparing zidovudine regimens of different durations to prevent perinatal transmission in Thailand (PHPT-1). We used a linear mixed model to analyze the anthropometric measurements (weight for age, height for age and weight for height Z-scores) until 18 months of age according to zidovudine treatment duration (mothers, <7.5 weeks versus more; infants, 3 days versus >4 weeks). RESULTS: Children exposed in utero for >7.5 weeks had a slightly lower birth weight (Z-score difference, 0.08; P = 0.003). However, zidovudine exposure had no effect on the evolution of Z-scores from 6 weeks to 18 months of age. CONCLUSIONS: Although a longer in utero zidovudine exposure may have had a negative impact on birth weight, the magnitude of this effect was small and faded over time. Neither the total nor the postnatal duration of exposure was associated with changes in infant Z-scores from 6 weeks to 18 months of age.     

Uptake of early infant diagnosis in Thailand’s national program for preventing mother-to-child HIV transmission and linkage to care, 2008–2011

Introduction

Early infant diagnosis (EID) has been a component of Thailand''s prevention of mother-to-child HIV transmission (PMTCT) programme since 2007. This study assessed the uptake, EID coverage, proportion of HIV-exposed infants receiving a definitive HIV diagnosis, mother-to-child transmission (MTCT) rates and linkage to HIV care and treatment.

Methods

Infant polymerase chain reaction (PCR) testing data from the National AIDS Program database were analyzed. EID coverage was calculated as the percentage of number of HIV-exposed infants receiving ≥1 HIV PCR test divided by the number of HIV-exposed infants estimated from HIV prevalence and live-birth registry data. Definitive HIV diagnosis was defined as having two concordant PCR results. MTCT rates were calculated based on infants tested with PCR and applied as a best-case scenario, and a sensitivity analysis was used to adjust these rates in average and worst scenarios. We defined linkage to HIV care as infants with at least one PCR-positive test who were registered with Thailand''s National AIDS Program. Chi-squared tests for linear trend were used to analyze changes in programme coverage.

Results

For 2008 to 2011, the average EID coverage rate increased from 54 to 76% (p<0.001), with 65% coverage (13,761/21,099) overall. The number of hospitals submitting EID samples increased from 458 to 645, and the percentage of community hospitals submitting samples increased from 75 to 78% (p=0.044). A definitive HIV diagnosis was made for 10,854 (79%) infants during this period. The adjusted MTCT rates had significantly decreasing trends in all scenarios. Overall, an estimated 53% (429/804) of HIV-infected infants were identified through the EID programme, and 80% (341/429) of infants testing positive were linked to care. The overall rate of antiretroviral treatment (ART) initiation within one year of age was 37% (157/429), with an increasing trend from 28 to 52% (p<0.001).

Conclusions

EID coverage increased and MTCT rates decreased during 2008 to 2011; however, about half of HIV-infected infants still did not receive EID. Most HIV-infected infants were linked to care but less than half initiated ART within one year of age. Active follow-up of HIV-exposed infants to increase early detection of HIV infection and early initiation of ART should be more widely implemented.     

Revisiting the role of neutralizing antibodies in mother-to-child transmission of HIV-1

We analyzed the association between mother-to-child transmission (MTCT) of human immunodeficiency virus type 1 (HIV-1) and maternal neutralizing antibodies to heterologous primary isolates of various HIV-1 clades, to test the hypothesis that protective antibodies are those with broad neutralizing activity. Our study sample included 90 Thai women for whom the timing of HIV-1 transmission (in utero or intrapartum) was known. The statistical analysis included a conditional logistic-regression model to control for both plasma viral load and duration of zidovudine prophylaxis. The higher the titer of neutralizing antibodies to a heterologous strain of the same clade, the lower the rate of MTCT of HIV-1. More specifically, high levels of neutralizing antibodies to the MBA (CRF01_AE) strain were associated with low intrapartum transmission of HIV-1. This suggested that such heterologous neutralizing antibodies may be involved in the natural prevention of late perinatal HIV transmission. These data are consistent with the hypothesis that the use of some antibodies might help to prevent perinatal HIV transmission, through passive immunoprophylaxis. Moreover, the study of humoral factors associated with MTCT of HIV-1 may identify correlates of protection that should help in the design of efficient HIV/acquired immunodeficiency syndrome vaccines.