CROI: HAART use in mothers substantially reduces HIV infections in breastfeeding infants in Kisumu, Kenya

In a Monday afternoon session at the Fifteenth Conference on Retroviruses and Opportunistic Infections in Boston, several investigators reported successes in preventing of mother-to-child transmission (PMTCT). In the Kisumu Breastfeeding Study, low rates of HIV infection were seen in children when mothers were kept on three-drug HAART regimens from late pregnancy through six months of breastfeeding.

Although breastfeeding from an HIV-positive mother poses a risk of HIV transmission to the infant, breastfeeding is still recommended for HIV-positive women until their child is six months old, based on evidence that it provides better health outcomes for the child than formula feeding. Trials are therefore underway to find ways of reducing the risk of mother-to-child transmission (MTCT) during breastfeeding.

The Kisumu Breastfeeding Study (KiBS) was a phase IIb PMTCT trial which aimed to reduce MTCT by using HAART to suppress viral load in HIV-positive pregnant and nursing mothers, regardless of whether the mothers qualified for treatment by current access guidelines.

KiBS was a one-arm study with no control arm. Enrolment began in July 2003 and continued until November 2006; publication of complete results is expected by January 2009. Women were included if they were HIV-positive, pregnant, and had decided to breastfeed their babies after counselling on the risks and benefits of breastfeeding. They had to be not on antiretrovirals and to have no medical contraindications.

The mothers received HAART from 34 weeks into pregnancy, until six months after giving birth, and the infants received single-dose nevirapine (2 mg/kg) within 72 hours of birth. The women were advised to exclusively breastfeed and to wean their children rapidly at six months. From July 2003 to January 2005, the HAART regimens consisted of Combivir (300 mg zidovudine / 150 mg lamivudine) twice daily, plus nevirapine. In January 2005, a nevirapine safety warning was issued regarding hepatotoxicity risk for women with CD4 cell counts greater than 250 cells/mm³; at that point any such women in the study were switched to nelfinavir, 250 mg twice daily.

Mothers and children were followed for two years after birth. Infants were tested for HIV via dried blood spots collected within one week of delivery, at two and six weeks, and at three, six, nine, twelve, eighteen, and twenty-four months. PCR testing was done on all samples and ELISA at 18 and 24 months. Kaplan-Meier methods were used to estimate rates of HIV infection overall, by infant sex, by maternal enrolment CD4 cell count (≤ 250, or >250 cells/mm³), and by initial regimen (nevirapine or nelfinavir) for mothers with CD4 cell counts > 250 cells/ mm³.

From 601 women screened, 522 were enrolled in the study. Their median age was 23 years, median CD4 cell count was 392 cells/mm³, and median viral load was 4.5 log₁₀. Only 16% were at WHO disease stage 2 or greater.

HIV infection data were available for 502 live-born babies. Of these, 12 (2.4%) became infected in the first week, 19 (3.9%) after six weeks, 20 (4.1%) after three months, 27 (5.9%) after twelve months, and 29 (6.7%) after eighteen months. No differences in infection rates were found by maternal CD4 (p = 0.89) or by HAART regimen (p = 0.83). The overall rate at 12 months for females was 7.4 (95% CI, 4.6 - 11.9), and for males, 4.5 (95% CI, 2.5 - 8.1) (p = 0.15).

Conclusions

A low 12-month infant HIV transmission rate of 5.9% was achieved using maternal HAART from 34 weeks of gestation through six months of breastfeeding. When excluding the children presumed infected during delivery, the transmission attributable to breastfeeding was only 3.5% by twelve months. There was no difference in transmission based on maternal CD4 or regimen. HIV transmission did occur after HAART was discontinued at six months, presumably due to continued breastfeeding after HAART cessation.

The researchers state that further assessment—of adherence, optimal timing for breastfeeding cessation, HIV-free survival time, and drug resistance in mothers and infants—is necessary to determine whether HAART is a feasible, acceptable, safe, and efficacious strategy for PMTCT among breastfeeding women, particularly those who do not meet WHO treatment criteria.

The findings on maternal antiretroviral treatment stand as a contrast to other findings presented yesterday, which looked at the use of extended nevirapine prophylaxis in infants. Those studies, although not strictly comparable, found slightly higher rates of HIV transmission after six or nine months, and this group of findings are likely to provoke debate about the best way of reducing the risk of HIV transmission through breastfeeding.