Extended use of nevirapine or zidovudine and nevirapine in infants can reduce the risks of HIV transmission through breastmilk by over 70%, Charles van der Horst reported in a late breaker session at the International AIDS Society conference (IAS 2011) in Rome last week.
Dr van der Horst presented findings, on behalf of a collaboration of study investigators from the US, Ethiopia, India, Uganda and Malawi, from a pooled analysis of data from 5396 mother-infant pairs who participated in five randomised trials to estimate the effectiveness of infant nevirapine prophylaxis in preventing breast-milk HIV transmission in HIV-negative infants at birth.
In resource-poor settings mother-to-child transmission (MTCT) of HIV continues to be a major cause of death and disease. Breastfeeding accounts for about a third of the estimated 420,000 children infected each year. Fifty percent of these children will die before they reach two years of age.
Women are faced with a dilemma. While breastfeeding provides protection and is associated with decreased mortality and disease in the first year of life compared to formula feeding, the longer they breastfeed the greater the risk of HIV transmission: 68% of all HIV infections among infants who breastfeed happen after six months of age.
Since safe and affordable replacement options to breastfeeding are severely limited in most resource-poor settings, effective strategies to prevent transmission through breastfeeding are critical.
Maternal antiretroviral therapy (ART), when available, can be protective against transmission. In 2009 an estimated 53% of identified pregnant HIV-positive women in low- and middle-income countries received ART. Lower maternal CD4 cell counts are associated with a greater probability of MTCT and death, and many women in resource-poor settings present late for antenatal care. For ART to be effective in preventing MTCT, viral loads need to be undetectable, which may take several weeks after starting antiretroviral treatment.
Maternal and infant single-dose and infant extended-dose nevirapine offer important alternative means of protection for the infants of HIV-positive breastfeeding mothers.
Results from these randomised clinical trials have shown daily nevirapine to be effective in preventing HIV transmission through breastmilk. These results, among others, led the World Health Organization (WHO) to change its guidelines in 2010.
Exclusive breastfeeding for six months with the introduction of complementary foods for the next six months is now recommended. Breastfeeding should stop at the end of 12 months, if feasible. Rapid weaning is no longer advised.
The trials included in the pooled analysis comprised:
- Six-week extended nevirapine (SWEN): Three separate but comparable studies in Ethiopia, India and Uganda where six weeks of daily infant nevirapine was used for prophylaxis but no maternal antenatal prophylaxis;
- Post-exposure prophylaxis of infant (PEPI) in Malawi: in all three arms of the study, during birth the mothers received single-dose nevirapine and their infants received single-dose nevirapine and one week of zidovudine; in one group the infants also received daily nevirapine for 14 weeks and in another group infants received daily nevirapine and zidovudine for 14 weeks;
- Breastfeeding, antiretrovirals and nutrition (BAN) trial in Malawi: Daily infant nevirapine given for 28 weeks was compared to maternal ART; at delivery all infants and mothers got single-dose nevirapine and one week of zidovudine and lamivudine.
The SWEN and PEPI trials included women of all CD4 cell counts, whereas the BAN trial only included women with CD4 cell counts over 200 cells/mm3.
In the analysis Dr van der Horst and colleagues compared the four daily regimens: nevirapine for 6 weeks, 14 weeks, or 28 weeks, or nevirapine plus zidovudine for 14 weeks.
"...the longer the duration of prophylaxis, the greater the reduction in the risk of infection." Charles van der Horst
In the six-week regimen (SWEN) the estimated risk for transmission was 1.6% compared to 3.4% for the control at the end of treatment at the age of six weeks.
In the 14-week regimens (PEPI) the estimated risks for transmission for nevirapine alone and nevirapine plus zidovudine were 1.9% and 2.3%, respectively compared to 7.3% for the control.
Infants infected within the first week, those with indeterminate specimens at birth or six months, those who died within the first week after birth and those whose mothers’ CD4 cell counts were under 200 cells/mm3 were excluded from the pooled analysis.
The primary outcome of the analysis was infection or death by 203 days.
The estimated cumulative risk of HIV infection among infants uninfected at birth was 5.8% (95% CI: 4.0 to 7.6), 3.7% (95% CI: 2.3 to 5.1), 4.8% (95% CI: 3.2 to 6.4) and 1.8% (95% CI: 0.8 to 2.8), p<0.001 for the six week, 14 week nevirapine alone, 14 week dual-prophylaxis regimen and 28 week nevirapine regimen, respectively.
Women with a baseline CD4 cell count between 200 cells/mm3 and 350 cells/mm3 had a two-fold higher rate of their infants becoming infected than those with CD4 cell counts over 350 cells/mm3. In addition the more the infant weighed at birth, the less likely they were to become infected.
After adjusting for maternal baseline CD4 cell count and infant birth weight according to trial site, nevirapine reduced the rate of HIV infection by 71% (95% CI: 58-80, p<0.001) and the rate of HIV infection or death by 58% (95% CI: 45-69, p<0.001).
Dr van der Horst concluded “extended prophylaxis with nevirapine or with nevirapine and zidovudine significantly reduces postnatal HIV-infection; the longer the duration of prophylaxis, the greater the reduction in the risk of infection.”
Hudgens M et al. Pooled individual data analysis of five randomized trials of infant nevirapine prophylaxis to prevent HIV-1 transmission through breast milk. The Sixth IAS Conference on HIV Pathogenesis, Treatment and Prevention, Rome, 2011, abstract WELBC03.