Multivariate longitudinal analysis showed that after adjusting for age, the weight-for-age Z score was lower in ENIC than in UEC (difference between means: −0.27; 95% CI: −0.53 to 0.00; P = 0.049). The proportions of moderate and severe wasting, stunting, and underweight were similar among ENIC and UEC (data not shown).
The findings of this study show that compared with UE infants, HIV ENI infants had an increased frequency of anemia, poorer nutritional status, and alterations in some immunologic profiles. In addition, although the risk of outpatient attendances was lower in ENIC, the risk of severe pneumonia was increased in these children compared with UE infants.
Children born to HIV-positive mothers with CD4 <200 cells per microliter are more likely to have a poor birth outcome and increased infant morbidity and mortality.7,11,15,45,46 In this study, the prevalence of LBW and prematurity in ENIC was not significantly higher than in UEC. This is probably because of the few HIV-positive women with CD4 counts below 200 cells per microliter in this study.
Interestingly, ENIC had a significantly lower risk of OPD visits than did UEC, mainly because of a decreased risk of diarrhea and AURI episodes. This lower OPD attendance is probably related to the antibacterial effect of CTXP that ENIC routinely receive through a special clinic at the MDH. Alternatively, this additional clinical follow-up might have affected the health-seeking behavior of mothers of ENIC reducing their attendance to the OPD. It is important to note that previous studies documenting an increased morbidity in ENIC were performed in contexts where CTXP was not available.3,9,11 Contrary to the other reports suggesting a nonsignificant increased risk of diarrhea with CTXP,47–49 the findings of this study showed a significant effect of CTXP in decreasing the risk of AURI (by 30%) and diarrhea (by 50%). This was observed even in the presence of high levels of bacterial resistance to CTX in this setting.50 The contribution of CTXP to these findings is also supported by the lack of difference in the incidence of OPD visits between the 2 groups of infants in the first month of life before the initiation of CTXP. Discrepancies between this and other reports regarding the effect of CTXP on morbidity in ENIC might be explained by the differences in age, feeding modes, duration of CTXP, or follow-up. It has been shown that CTXP confers protection against malaria.49,51 However, we were unable to assess the effect of CTXP on malaria incidence because of the small number of malaria episodes registered during the follow-up. We did, however, observe a borderline significant increased incidence of hospital admissions for CSP in ENIC. This could be explained by a misdiagnosis of tuberculosis.12 Tuberculosis is frequent among infants born to HIV-positive mothers,2 but it is difficult to diagnose in small children in poor resource settings,52 and it is not preventable by CTXP. Alternatively, it may be possible that CTXP is less effective in preventing CSP than mild respiratory infections53 or that those ENIC with CSP were poor compliers for CTX. Larger studies will be necessary to elucidate CSP risk in ENIC.
CTXP for ENIC is being reconsidered because of the concerns regarding the development of bacterial resistance.24,25 In the current study, despite an established PMTCT program, the rate of vertical transmission at 12 months of age was 27%, which illustrates the shortcomings of the health-care system. It might be premature to discontinue the CTXP in ENIC in the current context of continued breast-feeding up to 12 months of age and poor uptake of antiretrovirals.1 More information is needed on the impact of CTXP on infant health and uptake of PMTCT interventions before changing the current policy.
The authors are grateful to all the mothers and their infants who participated in the study, also to the dedicated staff of the Manhiça District Hospital, and to the field, clinic, and data management staff at the Manhiça Health Research Centre, Mozambique.
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