Breastfeeding in HIV-positive mothers in Botswana did not affect mortality

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A controlled, randomised, prospective trial of 1200 HIV-positive mothers in Botswana found no differences in mortality between those who breastfed and those who formula fed. A trend toward faster declines in CD4 cell count began to emerge several years after cessation of breastfeeding, but this was not statistically significant and its significance is unknown.

The findings were presented to the Sixteenth Conference on Retroviruses and Opportunistic Infections on Wednesday by Shahin Lockman of Brigham and Women's Hospital, Boston, on behalf of a US/Botswana research team.

Several studies have now looked at the effects of breastfeeding on the health of the HIV-positive mother. Results have been conflicting, with the first randomised trial showing that breastfeeding tripled mothers' mortality rates compared to formula feeding.

Glossary

reactive

Because of the possibility that a positive result from a single HIV test is, in fact, a false positive, the result is described as 'reactive' rather than 'positive'. If the result is reactive, this indicates that the test has reacted to something in the blood and needs to be investigated with follow-up tests.

disease progression

The worsening of a disease.

protein

A substance which forms the structure of most cells and enzymes.

trend

In everyday language, a general movement upwards or downwards (e.g. every year there are more HIV infections). When discussing statistics, a trend often describes an apparent difference between results that is not statistically significant. 

ribonucleic acid (RNA)

The chemical structure that carries genetic instructions for protein synthesis. Although DNA is the primary genetic material of cells, RNA is the genetic material for some viruses like HIV.

 

However, most subsequent observational cohort studies have foundno worsening of disease progression in breastfeeding mothers, or faster declines in CD4 cell count and body mass index but no effect on viral load or overall mortality.

Lockman pointed out that in such cohort studies, the sicker women may choose not to breastfeed, biasing the outcomes toward better apparent outcomes for breastfeeding women. Also, many studies have not looked at health outcomes other than the crudest outcome – risk of death.

The study presented by Lockman was a substudy of Botswana's MASHI prevention of mother-to-child transmission (PMTCT) study. In MASHI, 1200 HIV-positive pregnant women were randomised to breastfeeding for six months with prolonged infant AZT prophylaxis (weaning began around five months), or to formula feeding. Women were recruited between 2001 and 2003 and followed for seven years; antiretroviral treatment (ART) became available to eligible participants during recruitment.

In the substudy, the participants' health status was followed for a median of 54 months, including CD4 cell counts, HIV RNA viral loads, and (in a random subsample of 131 women) levels of micronutrients (vitamins B12, A, and E and selenium), albumin, and C-reactive protein (CRP).

Twelve hundred women were randomised, 598 to breastfeeding and 602 to formula feeding, with characteristics very similar between the two groups. Adherence to the study arms was very good, with 93% of formula-feeding mothers not breastfeeding at all, and 95% in the breastfeeding arm initiating breastfeeding. (However, only 18% exclusively breastfed for five months or more.)

The median CD4 cell count at entry was 366 cells/mm3 and median viral load was 4.4 log10. The primary endpoint was time to death, AIDS-defining illness, or CD4 cell count decline to 200 cells/mm3. (Women who became eligible for ART were offered it, and 40% went on treatment.)

Results

Three hundred and seventy-two (31%) of the women progressed to one of the study endpoints – 204 (34%) in the breastfeeding arm and 168 (28%) in the formula-feeding arm. This was not a significant difference (p=0.08).

Mortality rates did not differ between groups: 3% of women in each group died during the study follow-up. The differences that were seen occurred in CD4 declines to 3 (25% breastfeeding vs 21% formula) and AIDS diagnoses (6% vs 3%). Median HIV-1 RNA did not differ between arms at six, twelve or 60 months.

By multivariate analysis, baseline CD4 cell counts ≥ 350 cells/mm3 were protective against progression (adjusted hazard ratio [AHR], 0.54; 95% confidence interval [CI], 0.43 to 0.68; p<.01 a="" as="" ci="" education="" factor="" feeding="" for="" formula="" higher="" hr="" levels="" load="" median="" not="" p="" progression="" risk="" the="" to="" viral="" was="" were="">

A trend toward faster progression began to emerge in breastfeeding mothers, but it was statistically non-significant, and only began to emerge about 30 months after the end of breastfeeding. At six months postpartum, levels of vitamins A, B12, E, selenium and blood albumin were not significantly different between groups. The only significant difference seen was in C-reactive protein (CRP) – an inflammatory marker that appears predictive of disease progression in mothers.

Median CRP levels were higher among breastfeeding than formula-feeding women (2.28 mg/l vs 1.05 mg/l; p

Lockman concluded that breastfeeding was not associated with worsened maternal mortality among women with access to ART, although the team did find higher C-reactive protein levels – an "intriguing" finding that has not previously been investigated. The "puzzling" trend toward faster progression in breastfeeding women, after cessation of breastfeeding, was thought to be either "a spurious finding, or something that reflects a pathology we don't as yet understand." It is also possible that greater differences might have been seen with longer courses of breastfeeding than the rather short five-month period observed in this study.

The investigators plan additional analyses including the incidence of other, non-AIDS-defining diagnoses, body weight, and CRP at later time points.

Reference:

Lockman S et al. The effect of breast feeding vs formula feeding on maternal HIV disease progression, mortality, and micronutrient levels in a 1200-person randomized trial, Botswana. Sixteenth Conference on Retroviruses and Opportunistic Infections, Montreal, abstract 176, 2009.