Does Breastfeeding Negatively Affect the Health and Survival of HIV Positive Mothers?

By Liz Highleyman

HIV positive women in industrialized countries are advised not to breastfeed their infants due to the risk of mother-to-child HIV transmission. In resource-limited countries, however, malnutrition, infections, and other adverse outcomes associated with formula-feeding may be a greater risk. The World Health Organization (WHO) recommends that HIV positive mothers in such settings should breastfeed unless formula-feeding is "acceptable, feasible, affordable, sustainable, and safe."

But how does breastfeeding impact the health of the mother? While some prior research indicated that women who breastfed their babies have a higher mortality rate than those who do not, other studies have not found this effect. In observational studies, women who were already sicker might have been less likely to breastfeed.

As reported at the 16th Conference on Retroviruses and Opportunistic Infections (CROI 2009) this month in Montreal, Shahin Lockman and colleagues assessed outcomes according to infant feeding method in the Mashi trial, a study of prevention of mother-to-child HIV transmission in Botswana.

A total of 1200 HIV positive pregnant women enrolled in the study between 2001 and 2003 and were randomly assigned to breastfeed for 6 months while their infants received a prolonged course of zidovudine (AZT; Retrovir), or to exclusively feed their babies formula. Baseline characteristics did not differ in the 2 arms. At study entry, participants had a median CD4 count of 366 cells/mm3 and median HIV RNA of 4.3 log10.

The women were followed for up to 7 years. During the study, HAART became available to participants who met WHO treatment criteria. Mashi findings on HIV transmission rates were recently reported, showing that breastfeeding with prolonged infant zidovudine prophylaxis was generally safe.

The present sub-study looked at the proportion of women reaching a composite endpoint of CD4 decline to < 200 cells/mm3, AIDS-related illness, or death in an intent-to-treat analysis according to whether they breastfed or formula-fed. Participants were followed for a median 54 months (4.5 years).

Serum samples from 131 randomly selected women (65 breastfeeding, 66 formula-feeding) obtained 6 months post-partum were tested for micronutrients (vitamins B12, A, and E, selenium), albumin, and C-reactive protein (CRP).

Results

93% of mothers in the formula-feeding arm did not breastfeed at all and 95% in the breastfeeding arm started breastfeeding, but only 18% breastfed exclusively for at least 5 months.

Overall, 372 women (31.0%) reached the composite endpoint: 204 of 598 (34.1%) in the breastfeeding arm compared with 168 of 602 (27.9%) in the formula-feeding arm, not a statistically significant difference (P = 0.08).

Looking at the endpoint components:

35 women (2.9%) died during follow-up: 16 (2.7%) in the breastfeeding arm vs 19 (3.2%) in the formula-feeding arm, again not a significant difference;

280 women (23.3%) experienced CD4 decline to < 200 cells/mm3: 151 (25.2%) breastfeeding vs 129 (21.4%) formula-feeding;

25 women (2.1%) were diagnosed with AIDS, and this was about twice as common in the breastfeeding arm: 18 (3.0%) breastfeeding vs 7 (1.2%) formula-feeding.

Individual factors associated with reaching an endpoint were

Younger age (P = 0.02);

Baseline CD4 count < 350 cells/mm3 (P < 0.01);

Baseline HIV viral load higher than the median level (P < 0.01);

Having any income (P = 0.02);

Having no education (P = 0.04);

Being married or co-habiting with a partner (P = 0.01).

In a multivariate analysis, the hazard ratio for reaching an endpoint was 0.82 for formula-feeding, indicating that it did not significantly alter the risk.

Low CD4, higher viral load, and lack of education remained significant predictors of disease progression or death.

A trend toward worse disease progression in the breastfeeding arm emerged about 30 months after the end of breastfeeding.

Median HIV RNA levels did not differ according to study arm at 6, 12, or 60 months.

Median CRP levels were significantly higher among breastfeeding women compared with formula-feeding women (2.28 vs 1.05 mg/L; P < 0.01), and among women who reached an endpoint (1.77 vs 0.77 mg/L; P <0.01).

6 months post-partum, micronutrient and albumin levels did not differ between the 2 study arms.

Based on these findings, the Mashi investigators concluded, "Breastfeeding was not associated with maternal mortality among women with access to HAART."

However, they added, "We found higher CRP and a trend (appearing after cessation of breastfeeding) toward faster progression to AIDS among women randomized to breastfeeding for 6 months (vs to formula-feeding)."

Discussing these results, Lockman said the emerging trend toward worse outcomes in the breastfeeding arm long after breastfeeding had stopped were "puzzling" and require further study.

2/27/09

Reference
S Lockman, M Ghebremichael, R Shapiro, and others. The Effect of Breast Feeding vs Formula Feeding on Maternal HIV Disease Progression, Mortality, and Micronutrient Levels in a 1200-Person Randomized Trial, Botswana. 16th Conference on Retroviruses and Opportunistic Infections (CROI 2009). Montreal, Canada. February 8-11, 2009. Abstract 176.