Universal combination antiretroviral regimens to prevent mother-to-child transmission of HIV in rural Zambia: a two-round cross-sectional study.

OBJECTIVE: To evaluate if a pilot programme to prevent mother-to-child transmission (PMTCT) of the human immunodeficiency virus (HIV) was associated with changes in early childhood survival at the population level in rural Zambia. METHODS: Combination antiretroviral regimens were offered to pregnant and breastfeeding, HIV-infected women, irrespective of immunological status, at four rural health facilities. Twenty-four-month HIV-free survival among children born to HIV-infected mothers was determined before and after PMTCT programme implementation using community surveys. Households were randomly selected and women who had given birth in the previous 24 months were asked to participate. Mothers were tested for HIV antibodies and children born to HIV-infected mothers were tested for viral deoxyribonucleic acid. Multivariable models were used to determine factors associated with child HIV infection or death. FINDINGS: In the first survey (2008-2009), 335 of 1778 women (18.8%) tested positive for HIV. In the second (2011), 390 of 2386 (16.3%) tested positive. The 24-month HIV-free survival in HIV-exposed children was 0.66 (95% confidence interval, CI: 0.63-0.76) in the first survey and 0.89 (95% CI: 0.83-0.94) in the second. Combination antiretroviral regimen use was associated with a lower risk of HIV infection or death in children (adjusted hazard ratio: 0.33, 95% CI: 0.15-0.73). Maternal knowledge of HIV status, use of HIV tests and use of combination regimens during pregnancy increased between the surveys. CONCLUSION: The PMTCT programme was associated with an increased HIV-free survival in children born to HIV-infected mothers. Maternal utilization of HIV testing and treatment in the community also increased.

Declining HIV prevalence among young pregnant women in Lusaka, Zambia.

OBJECTIVE: HIV prevention has been ongoing in Lusaka for many years. Recent reports suggest a possible decline in HIV sero-incidence in Zambia and some neighbouring countries. This study aimed to examine trends in HIV seroprevalence among pregnant and parturient women between 2002 and 2006. METHODS: We analysed HIV seroprevalence trends from two Lusaka sources: (i) antenatal data from a city-wide programme to prevent mother-to-child HIV transmission, and (ii) delivery data from two anonymous unlinked cord-blood surveillances performed in 2003 and again in 2005-2006, where specimens from > 97% of public-sector births in each period were obtained and analysed. FINDINGS: Between July 2002 and December 2006, the Lusaka district tested 243 302 antenatal women for HIV; 54 853 (22.5%) were HIV infected. Over this period, the HIV seroprevalence among antenatal attendees who were tested declined steadily from 24.5% in the third quarter of 2002 to 21.4% in the last quarter of 2006 (P < 0.001). The cord-blood surveillances were conducted between June and August 2003 and again between October 2005 and January 2006. Overall HIV seroprevalence declined from 25.7% in 2003 to 21.8% in 2005-2006 (P = 0.001). Among women < or =17 years of age, seroprevalence declined from 12.1% to 7.7% (P = 0.015). CONCLUSION: HIV seroprevalence appears to be declining among antenatal and parturient women in Lusaka. The decline is most dramatic among women < or = 17 years of age, suggesting a reduction in sero-incidence in this important age group.

Nonvirologic algorithms for predicting HIV infection among HIV-exposed infants younger than 12 weeks of age.

BACKGROUND: Early initiation of antiretroviral therapy has been shown to reduce mortality among perinatally HIV-infected infants, but availability of virologic testing remains limited in many settings. METHODS: We collected cross-sectional data from mother-infant pairs in three primary care clinics in Lusaka, Zambia, to develop predictive models for HIV infection among infants younger than 12 weeks of age. We evaluated algorithm performance for all possible combinations of selected characteristics using an iterative approach. In primary analysis, we identified the model with the highest combined sensitivity and specificity. RESULTS: Between July 2009 and May 2011, 822 eligible HIV-infected mothers and their HIV-exposed infants were enrolled; of these, 44 (5.4%) infants had HIV diagnosed. We evaluated 382,155,260 different characteristic combinations for predicting infant HIV infection. The algorithm with the highest combined sensitivity and specificity required 5 of the following 7 characteristic thresholds: infant CD8 percentage >22; infant CD4 percentage ≤44; infant weight-for-age Z score ≤0; infant CD4 ≤1600 cells/µL; infant CD8 >2200 cells/µL; maternal CD4 ≤600 cells/µL; and mother not currently using antiretroviral therapy for HIV treatment. This combination had a sensitivity of 90.3%, specificity of 78.4%, positive predictive value of 22.4%, negative predictive value of 99.2% and area under the curve of 0.844. CONCLUSION: Predicting HIV infection in HIV-exposed infants in this age group is difficult using clinical and immunologic characteristics. Expansion of polymerase chain reaction capacity in resource-limited settings remains urgently needed.

Field effectiveness of combination antiretroviral prophylaxis for the prevention of mother-to-child HIV transmission in rural Zambia.

OBJECTIVE: To evaluate the effectiveness of maternal combination antiretroviral prophylaxis for prevention of mother-to-child transmission of HIV (PMTCT) in a program setting. DESIGN: Prospective cohort study. SETTING: Nine primary care clinics in rural Zambia. PARTICIPANTS: Two hundred and eighty-four HIV-infected pregnant women at at least 28 weeks gestation initiating PMTCT services between April 2009 and January 2011 and their newborn infants. INTERVENTION: In four 'intervention' sites, PMTCT comprised universal combination antiretroviral prophylaxis (i.e. irrespective of CD4 cell count) from pregnancy until the cessation of breastfeeding. In five 'control' sites, women received antenatal zidovudine and peripartum nevirapine, the standard of care at the time. Prophylaxis during breastfeeding was not available in control sites. MAIN OUTCOME MEASURE: Cumulative infant HIV infection and death at 12 months postpartum. RESULTS: At 12 month postpartum, one of 104 (1.0%) infants born to mothers at the intervention sites were HIV-infected, compared with 14 of 116 (12.1%) receiving care in the control sites [relative risk (RR): 12.6, 95% CI: 2.2-73.1; P = 0.005]. When we considered the composite outcome of HIV infection or death, similar trends were observed in the overall study population (RR: 3.4, 95% CI: 1.6-7.6; P = 0.002) and in a sub-analysis of women with CD4 cell count more than 350 cells/µl (RR: 3.2; 95% CI: 1.1-9.6; P = 0.04). CONCLUSION: When compared with PMTCT services based on antenatal zidovudine and peripartum nevirapine, the provision of maternal combination prophylaxis imparted measurable health benefits to HIV-exposed infants. Implementation research is needed to further tailor and optimize these strategies for similar field settings.

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, 115552 pregnant women had prenatal and delivery information recorded in ZEPRS. Median gestation age at first prenatal visit was 23weeks (interquartile range [IQR] 19-26). Syphilis screening was documented in 95663 (83%) pregnancies: 2449 (2.6%) women tested positive, of whom 1589 (64.9%) were treated appropriately. 111108 (96%) women agreed to HIV testing, of whom 22% were diagnosed with HIV. Overall, 112813 (98%) of recorded pregnancies resulted in a live birth, and 2739 (2%) in a stillbirth. The median gestational age was 38weeks (IQR 35-40) at delivery; the median birth weight of newborns was 3000g (IQR 2700-3300g). 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.

Comparative outcomes of tenofovir-based and zidovudine-based antiretroviral therapy regimens in Lusaka, Zambia.

BACKGROUND: Although tenofovir (TDF) is a common component of antiretroviral therapy (ART), recent evidence suggests inferior outcomes when it is combined with nevirapine (NVP). METHODS: We compared outcomes among patients initiating TDF + emtricitabine or lamivudine (XTC) + NVP, TDF + XTC + efavirenz (EFV), zidovudine (ZDV) + lamuvidine (3TC) + NVP, and ZDV + 3TC + EFV. We categorized drug exposure by initial ART dispensation by a time-varying analysis that accounted for drug substitutions and by predominant exposure (>75% of drug dispensations) during an initial window period. Risks for death and program failure were estimated using Cox proportional hazard models. All regimens were compared with ZDV + 3TC + NVP. RESULTS: Between July 2007 and November 2010, 18,866 treatment-naive adults initiated ART: 18.2% on ZDV + 3TC + NVP, 1.8% on ZDV + 3TC + EFV, 36.2% on TDF + XTC + NVP, and 43.8% on TDF + XTC + EFV. When exposure was categorized by initial prescription, patients on TDF + XTC + NVP [adjusted hazard ratio (AHR): 1.45; 95% confidence interval (CI): 1.03 to 2.06] had a higher post-90-day mortality. TDF + XTC + NVP was also associated with an elevated risk for mortality when exposure was categorized as time-varying (AHR: 1.51; 95% CI: 1.18 to 1.95) or by predominant exposure over the first 90 days (AHR: 1.91, 95% CI: 1.09 to 3.34). However, these findings were not consistently observed across sensitivity analyses or when program failure was used as a secondary outcome. CONCLUSION: TDF + XTC + NVP was associated with higher mortality when compared with ZDV + 3TC + NVP but not consistently across sensitivity analyses. These findings may be explained in part by inherent limitations to our retrospective approach, including residual confounding. Further research is urgently needed to compare the effectiveness of ART regimens in use in resource-constrained settings.