Effects of antiretroviral exposure through PMTCT strategies on infants in Botswana
Polly Clayden, HIV i-Base
The effects of in antiretroviral (ARV) exposure through PMTCT on HIV-uninfected infants are poorly understood, particularly in resource-limited settings.
Two papers published in JAIDS report findings from sub-studies of the Mashi and Mma Bana randomised controlled PMTCT trials, both conducted in Botswana. [1, 2]
We have covered both these trials extensively in HTB, including early findings from these analyses reported at CROI 2010. 
Increased severe anaemia risk with HAART
Scott Dryden-Peterson and colleagues conducted a post hoc analysis of pooled data from the trials. Infants were grouped by three ARV exposure categories: infants exposed to maternal HAART in utero and during breastfeeding and one month post natal AZT (HAART-BF); infants exposed to maternal AZT in utero and 6 months postnatal AZT during breastfeeding (AZT-BF); and infants exposed to AZT in utero and formula feeding (AZT-FF).
Overall, the investigators analysed data from 1719 infants (691 HAART-BF, 503 AZT-BF and 525 AZT-FF).
They observed severe incident anaemia (grade 3 or 4) in 118 (7.4%) infants from birth through 6 months of age. This occurred in 82 (12.5%) infants in the HAART-BF group, 25 (5.3%) in the AZT-BF and 11 (2.5%) in the AZT-FF groups. Severe anaemia was more frequent in the HAART-BF, group compared to infants in either of the other two groups: OR 2.53 (95% CI 1.59-4.04) and OR 5.96 (95% CI 3.14-11.3) vs AZT-BF and AZT-FF respectively, both p<0.001.
They noted that different frequency of assessment between the groups (AZT-BF group had haemoglobin measured monthly) could create potential bias. There was little evidence of this though, as they did not detect significant differences in the rate of treatment-modifying anaemia between birth, 1, 3-4 or 6-7 month visits among the study groups, p=0.15.
In multivariate analysis, besides HAART-BF exposure, which remained the strongest risk factor: gestational age, per week OR 0.89 (95% CI, 0.82-0.96) p=0.005; male sex OR 1.53 (95% CI 1.03-2.27) and low maternal income <$100 a month OR 2.04 (1.12-3.71) p=0.02, were all associated with severe incident anaemia. The investigators did not find an association with maternal BMI, CD4, viral load or haemoglobin. Nor was there and association with maternal HAART regimen or duration of antenatal HAART. Infants who were small for their gestational age were not at greater risk of severe anaemia.
The majority of episodes of severe anaemia were resolved with multivitamin and iron supplements or stopping AZT but 11 infants from the HAART-BF group needed transfusion. Six infants died (1 HAART-BF, 2 AZT-BF and 3 AZT-FF), three of the infants had severe anaemia reported as cause of death. Two infants were lost to follow up before their severe anaemia was resolved.
Microcytosis and hypochromia occurred in 21.2% and 29.3% of incident anaemias with measurements available. Estimated haemoglobin iron at birth was lower for HAART-BF infants than the other two groups (p<0.001).
The investigators suggested these findings deserve further investigation and emphasised the established benefits of maternal HAART. They wrote: Mitigating strategies such as iron supplementation to HIV-exposed breastfed infants or alternative antiretrovirals should be evaluated to maximise the benefits of maternal HAART while minimising potential risks.
Lower weight HAART-exposed infants catch up by 6 months
Kathleen Powis and colleagues from the same group looked at the effects of in utero ARV exposure on longitudinal growth through 6 months of age in 619 HAART-exposed and 440 AZT-exposed uninfected infants from the two trials.
This was a retrospective analysis of infants carried to 37 weeks gestation or greater.
The investigators used WHOs Child Growth Standards to calculate z-scores for an infants weight for age (WAZ), length for age (LAZ) and weight for length (WLZ).
They reported mean birth weights of 3.01kg and 3.15kg for HAART- and AZT-exposed infants respectively, p<0.001. HAART-exposed infants had lower values for all three z-scores at birth, all p<0.001.
HAART-exposed infants had greater improvement compared to AZT-exposed infants in WAZ from birth through 2 months, p=0.03, but the investigators observed no difference in WAZ between the two exposure groups from 3 through 6 months, p= 0.26.
Similarly, LAZ increased more in the HAART-exposed infants through 2 months, p=0.002, but this difference did not remain significant at 3 to 6 months, p=0.08.
HAART-exposed infants also had a more rapid increase in WLZ through 2 months than AZT-exposed infants, p<0.001. Between 3 and 6 months, the WLZ z-score in HAART-exposed infants declined while the AZT group had small increase. The difference in growth patterns between the two groups was significant, p=0.04.
There was no difference in wasting or stunting between groups, which occurred in about 6% and 5% of infants overall respectively.
The investigators wrote: This analysis is the first to provide reassurance that lower birth weight associated with in utero HAART exposure does not persist during early infancy. It also highlights the importance of early and routinely scheduled health care for HAART- exposed HIV-uninfected infants.
- Dryden-Peterson S et al. Increased risk of severe infant anaemia following exposure to maternal HAART, Botswana. J Acquir Immune Defic Syndr. Volume 56. Number 5. 15 April 2011.
- Powis KM et al. Effects of in utero antiretroviral exposure on longitudinal growth of HIV-exposed uninfected infants in Botswana. J Acquir Immune Defic Syndr. Volume 56. Number 2. February 1, 2011.
- Clayden P. Pregnancy outcomes in infants exposed to maternal antiretrovirals in utero. HTB. Vol 11. No 3/4 March/April 2010.