In this study of 296 HIV-1–infected postpartum women, there were significant differences in CD4 cell count decline and BMI between breast-feeding and non–breast-feeding women but no differences in HIV-1 RNA levels or mortality over the 2-year postpartum period. Thus, although lactation appeared to have effects on CD4 cell count, there were no long-term effects of lactation on either HIV-1 RNA level or mortality. Our finding of a more rapid CD4 cell count decline during breast-feeding may explain our earlier observation of significantly increased mortality in a randomized clinical trial of breast-feeding [1
]. Our finding of negligible long-term effects of breast-feeding on HIV-1 RNA levels and mortality are consistent with the findings of other observational studies [2
The mothers in this study had a significant decrease in CD4 cell count between months 1 and 24 postpartum (an estimated decrease of 3.9 cells/µL/month, or ~48 cells/µL/year). This is comparable with findings in cohorts of nonimmunosuppressed US men and women (~30 to >1100 cells/µL/year) [14
]. CD4 cell count decline was highest among the current breast-feeding women in the present study (−7.7 cells/µL/month), and this decrease was significantly higher than that for the never breast-feeding women (−4.4 cells/µL/month). Women who stopped breast-feeding did not continue at the same rate of decline (−3.2 cells/µL/month) as during breast-feeding, suggesting that the breast-feeding effect on CD4 cell count decline is a non-sustained process related to active breast-feeding. The accelerated CD4 cell count decline during breast-feeding may result from hormonal effects, nutritional/metabolic effects, or the numeric loss of CD4 cells as part of increased cellular egress to infants via breast milk.
We were not surprised to observe significant decreases in BMI in current versus never breast-feeding mothers. The process of lactation entails caloric costs that translate into increased energy requirements and/or weight loss. Demonstration of this effect in the breast-feeding duration–adjusted mixed-effects model but not in the spline models comparing ever versus never breast-feeding mothers supports the superiority of statistical models that include duration of breast-feeding to determine the effect of breast-feeding. Breast-feeding had an effect on BMI but was not associated with postpartum body cell mass changes in women. It is possible that changes in body cell mass may have more influence on HIV-1 progression than changes in weight or BMI. Despite significant decreases in CD4 cell count and BMI attributable to breast-feeding, HIV-1 RNA levels remained remarkably stable in this cohort of women overall, and there were no discernible differences between the 2 feeding groups over time in any of the models used. Thus, although breast-feeding modified CD4 cell count decline and BMI, viral replication was not significantly altered despite these immune and nutritional changes due to lactation. It is possible that the process of lactation may affect lymphocyte production in a way that does not alter the replication of HIV-1. In addition, the levels of CD4 cell count decline we observed, although significant, may not be clinically relevant, particularly for women with short breast-feeding durations. The CD4 cell count decline in women who breast-fed for 6 months did not differ significantly from the decline in those who never breast-fed. The World Health Organization currently recommends 6 months of exclusive breast-feeding for HIV-1–infected women who elect to breast-feed. For this duration of breast-feeding, our data suggest that breast-feeding would have a minimal adverse effect on CD4 cell count.
Mortality in the cohort did not differ between the women who ever breast-fed and the women who never breast-fed. Several factors may explain the differing results we observed regarding the effect of breast-feeding on mortality between our present and previous study [1
]. Both studies were based in Nairobi and involved the same recruitment clinics and study clinic. The first study, a randomized clinical trial, had a more ideal study design for comparing feeding groups in that feeding was randomized. The importance of randomization is evident, given the highly significant differences at baseline between the 2 self-selected feeding groups in our present study. Here, although formula was provided, the women who chose to formula feed had more education, were more likely to have access to flush toilets, and were more likely to report a history of HIV-1–related illness. In addition, unmeasured differences in counseling, stress, and nutrition between the formula-feeding and breast-feeding women may have contributed to HIV-1 disease progression and confounded our assessment of the effect of breast-feeding. Our first study had greater power to assess mortality, with >200 women in each feeding group and higher postpartum mortality. In the first study, adverse effects of breast-feeding were most notable in severely immunosuppressed women. Our present cohort received interventions that were unavailable during the first study, including short-course zidovudine, CD4 cell count–based provision of cotrimoxazole prophylaxis, multivitamin supplementation for 6 months postpartum, and referral for provision of HAART when severely immunosuppressed. It is plausible that the availability of these options for mothers attenuated the potential adverse effects of breast-feeding on maternal HIV-1 disease progression.
The present study has several strengths and limitations. This study had the benefit (in contrast to previous studies of maternal HIV-1 disease progression) of being designed primarily to assess maternal HIV-1 disease progression. Thus, we comprehensively delineated HIV-1 disease progression by looking in detail at several key markers of progression in addition to mortality, including CD4 cell count, HIV-1 RNA level, weight, and body cell mass changes. Monthly assessment of feeding status by self-report and physical examination enhanced the accuracy of the assessment of true feeding status. Analytical techniques adjusting for baseline confounding variables were used to determine the effects of ever breast-feeding. In addition, because lactation effects were likely to differ between the women who breast-fed for only a few days and those who breast-fed for longer periods, additional mixed-effects models incorporating duration of breast-feeding enabled the comparison of effects between current breast-feeding women, former breast-feeding women, and women who never breast-fed.
The limitations of this study include the nonrandomized design; the relatively high prevalence of censoring in the study because of a second pregnancy or HAART initiation; differing rates of losses to follow-up, with a higher loss among the breast-feeding mothers than among the non–breast-feeding mothers; and evaluation of the rate of CD4 cell count decline starting at month 1 postpartum rather than at delivery. Higher losses to follow-up among the breast-feeding mothers may have led to the underestimation of adverse maternal effects due to breast-feeding if the losses were the result of mortality or illness. However, losses to follow-up among the breast-feeding mothers was not statistically significantly higher than among the never breast-feeding mothers, and baseline CD4 cell counts did not differ significantly between the women who were lost and those who remained in follow-up. Censoring because of second pregnancies and HAART initiation is a phenomenon that is not unique to our cohort of postpartum HIV-1–infected women, and these levels of censoring are likely to be similar to those in other postpartum maternal cohorts in Africa during the era of expanded HAART access. To gain from informative censoring due to HAART initiation, we analyzed both time to death and time to death or HAART initiation.
In summary, our interpretation of the data suggests that, with good maternal follow-up—including monitoring for immunosuppression and management of immunosuppressed women via both the use of cotrimoxazole prophylaxis and referral to HAART programs—the potential effects of breast-feeding on CD4 cell count and nutrition are attenuated and the risks of increases in HIV-1 RNA level or mortality are minimized. Our study suggests that, although breast-feeding may affect CD4 cell count and BMI in HIV-1–infected women, with extended maternal HIV-1 care, lactation may not be associated with a significant compromise in maternal health.