Issues in the design of a clinical trial with a behavioral intervention--the Zambia exclusive breast-feeding study

PURPOSE: We present the rationale and design of the Zambian Exclusive Breast-feeding Study (ZEBS), a randomized trial evaluating the efficacy of short-duration exclusive breast-feeding (EBF) as a strategy to reduce postnatal human immunodeficiency virus (HIV) transmission while preserving the other health benefits of this important mode of infant feeding. METHODS: One thousand two hundred HIV-positive pregnant women were recruited in Lusaka, Zambia, and followed with their infants for 24 months. In addition to Nevirapine (NVP), all women received intensive and frequent clinic- and home-based counseling to support exclusive breast-feeding. When the infant was 1 week of age, half of the women were randomly assigned to a group encouraged to abruptly (<24 h) cease all breast-feeding at 4 months. The primary outcome of the experimental (randomized) comparison is HIV-free survival at 24 months. The design is also observational and will compare HIV transmission rates between those who do and do not adhere to the counseling intervention promoting exclusive breast-feeding. CONCLUSION: Our study aims to quantify the benefit-risk ratio of early cessation of exclusive breast-feeding to interrupt mother-to-child transmission of HIV with an intensive behavioral intervention and has both observational and experimental analytic approaches. Our study design assesses efficacy and also has a prominent applied component that if the intervention is effective, it will permit rapid and sustainable adoption within low-resource communities.     

Modified Kigali combined staging predicts risk of mortality in HIV-infected adults in Lusaka, Zambia

We assessed the utility of the modified Kigali combined (MKC) staging system for predicting survival in HIV-infected Zambian adults in a prospective, longitudinal, open cohort. From 1995 to 2004, HIV-discordant couples (one HIV-infected partner and one HIV-negative partner) were recruited from couples' voluntary counseling and testing centers in Lusaka, Zambia and followed at 3-month intervals. MKC stage, which incorporates clinical stage with erythrocyte sedimentation rate (ESR), hematocrit, and body mass index (BMI), was determined at enrollment. Kaplan-Meier survival and Cox proportional hazard methods were used to calculate median survival and relative hazards. We enrolled 1479 HIV-discordant couples with a combined 7305 person-years of follow-up. Among HIV-infected participants over the 9-year study period, there were 333 confirmed deaths. The time to 50% mortality was 8.5 years with MKC stage 1 and 2 disease compared to 3.7 years with MKC stage 4 disease at enrollment. Survival rates at 3 years were 85% with MKC stage 1 and 2 disease, 74% with MKC stage 3 disease, and 51% with MKC stage 4 disease. A total of 275 HIV-negative partners seroconverted during follow-up. In comparison, survival rates at 3 years were 94% for HIV-negative participants and 92% for participants who seroconverted during follow-up. In multivariate analysis, MKC stage 4 disease (HR = 3.7, 95% CI = 2.7-5.0) remained a strong predictor of mortality. Incorporating ESR, hematocrit, and BMI with clinical staging is a powerful, low-cost tool to identify HIV-infected adults at high risk for mortality.     

Cost of abortions in Zambia: A comparison of safe abortion and post abortion care

Unsafe abortion is a significant but preventable cause of maternal mortality. Although induced abortion has been legal in Zambia since 1972, many women still face logistical, financial, social, and legal obstacles to access safe abortion services, and undergo unsafe abortion instead. This study provides the first estimates of costs of post abortion care (PAC) after an unsafe abortion and the cost of safe abortion in Zambia. In the absence of routinely collected data on abortions, we used multiple data sources: key informant interviews, medical records and hospital logbooks. We estimated the costs of providing safe abortion and PAC services at the University Teaching Hospital, Lusaka and then projected these costs to generate indicative cost estimates for Zambia. Due to unavailability of data on the actual number of safe abortions and PAC cases in Zambia, we used estimates from previous studies and from other similar countries, and checked the robustness of our estimates with sensitivity analyses. We found that PAC following an unsafe abortion can cost 2.5 times more than safe abortion care. The Zambian health system could save as much as US$0.4 million annually if those women currently treated for an unsafe abortion instead had a safe abortion.     

Alpha-defensins in the prevention of HIV transmission among breastfed infants

Alpha-defensins have been observed to have anti-HIV activity but have not been investigated in relation to mother-to-child HIV transmission. We measured the concentration of alpha-defensins in breast milk of HIV-positive mothers and tested whether the concentrations were associated with HIV transmission. A nested case-control study of 32 HIV-positive women who transmitted HIV to their infants and 52 randomly selected HIV-positive women who did not transmit HIV to their infants was conducted in Lusaka, Zambia. alpha-Defensins were detected in most (79%) of the milk samples tested. Concentrations of alpha-defensins increased as breast milk HIV RNA quantity increased, and breast milk HIV RNA quantity was, in turn, a strong and significant predictor of HIV transmission. After adjustment for milk HIV RNA quantity, however, alpha-defensin concentration was significantly associated with a decreased risk of intrapartum and postnatal HIV transmission (odds ratio = 0.3, 95% confidence interval: 0.09-0.93). Our data suggest that there may be a role for alpha-defensins in prevention of HIV transmission to breastfed infants.     

Implementation of the Zambia Electronic Perinatal Record System for comprehensive prenatal and delivery care

Objective

To characterize prenatal and delivery care in an urban African setting.

Methods

The Zambia Electronic Perinatal Record System (ZEPRS) was implemented to record demographic characteristics, past medical and obstetric history, prenatal care, and delivery and newborn care for pregnant women across 25 facilities in the Lusaka public health sector.

Results

From June 1, 2007, to January 31, 2010, 115 552 pregnant women had prenatal and delivery information recorded in ZEPRS. Median gestation age at first prenatal visit was 23 weeks (interquartile range [IQR] 19-26). Syphilis screening was documented in 95 663 (83%) pregnancies: 2449 (2.6%) women tested positive, of whom 1589 (64.9%) were treated appropriately. 111 108 (96%) women agreed to HIV testing, of whom 22% were diagnosed with HIV. Overall, 112 813 (98%) of recorded pregnancies resulted in a live birth, and 2739 (2%) in a stillbirth. The median gestational age was 38 weeks (IQR 35-40) at delivery; the median birth weight of newborns was 3000 g (IQR 2700-3300 g).

Conclusion

The results demonstrate the feasibility of using a comprehensive electronic medical record in an urban African setting, and highlight its important role in ongoing efforts to improve clinical care.