The impact of the Adolescent Girls Empowerment Program (AGEP) on short and long term social, economic, education and fertility outcomes: a cluster randomized controlled trial in Zambia.

BACKGROUND: Adolescent girls in Zambia face risks and vulnerabilities that challenge their healthy development into young women: early marriage and childbearing, sexual and gender-based violence, unintended pregnancy and HIV. The Adolescent Girls Empowerment Program (AGEP) was designed to address these challenges by building girls' social, health and economic assets in the short term and improving sexual behavior, early marriage, pregnancy and education in the longer term. The two-year intervention included weekly, mentor-led, girls group meetings on health, life skills and financial education. Additional intervention components included a health voucher redeemable for general wellness and reproductive health services and an adolescent-friendly savings account. METHODS: A cluster-randomized-controlled trial with longitudinal observations evaluated the impact of AGEP on key indicators immediately and two years after program end. Baseline data were collected from never-married adolescent girls in 120 intervention clusters (3515 girls) and 40 control clusters (1146 girls) and again two and four years later. An intent-to-treat analysis assessed the impact of AGEP on girls' social, health and economic assets, sexual behaviors, education and fertility outcomes. A treatment-on-the-treated analysis using two-stage, instrumental variables regression was also conducted to assess program impact for those who participated. RESULTS: The intervention had modest, positive impacts on sexual and reproductive health knowledge after two and four years, financial literacy after two years, savings behavior after two and four years, self-efficacy after four years and transactional sex after two and four years. There was no effect of AGEP on the primary education or fertility outcomes, nor on norms regarding gender equity, acceptability of intimate partner violence and HIV knowledge. CONCLUSIONS: Although the intervention led to sustained change in a small number of individual outcomes, overall, the intervention did not lead to girls acquiring a comprehensive set of social, health and economic assets, or change their educational and fertility outcomes. It is important to explore additional interventions that may be needed for the most vulnerable girls, particularly those that address household economic conditions. Additional attention should be given to the social and economic environment in which girls are living. TRIAL REGISTRATION: ISRCTN29322231. Trial Registration Date: March 04, 2016; retrospectively registered.

A Cluster Randomised Trial on the Impact of Integrating Early Infant HIV Diagnosis with the Expanded Programme on Immunization on Immunization and HIV Testing Rates in Rural Health Facilities in Southern Zambia.

BACKGROUND: We assessed the integration of early infant HIV diagnosis with the expanded programme for immunization in a rural Zambian setting with the aim of determining whether infant and postpartum maternal HIV testing rates would increase without harming immunization uptake. METHODS: In an unblinded, location stratified, cluster randomised controlled trial, 60 facilities in Zambia's Southern Province were equally allocated to a control group, Simple Intervention group that received a sensitization meeting and the resupply of HIV testing commodities in the event of a stock-out, and a Comprehensive Intervention group that received the Simple Intervention as well as on-site operational support to facilitate the integration of HIV testing services with EPI. FINDINGS: The average change in number of first dose diphtheria, pertussis, and tetanus vaccine (DPT1) provided per month, per facility was approximately 0.86 doses higher [90% confidence interval (CI) -1.40, 3.12] in Comprehensive Intervention facilities compared to the combined average change in the Simple Intervention and control facilities. The interventions resulted in a 16.6% [90% CI: -7%, 46%, P-value = 0.26] and 10% [90% CI: -10%, 36%, P-value = 0.43] greater change in average monthly infant DBS testing compared to control for the Simple and Comprehensive facilities respectively. We also found 15.76 (90% CI: 7.12, 24.41, P-value < 0.01) and 10.93 (90% CI: 1.52, 20.33, P-value = 0.06) additional total maternal re-tests over baseline for the Simple and Comprehensive Facilities respectively. CONCLUSIONS: This study provides strong evidence to support Zambia's policy of integration of HIV testing and EPI services. Actions in line with the interventions, including HIV testing material supply reinforcement, can increase HIV testing rates without harming immunization uptake. In response, Zambia's Ministry of Health issued a memo to remind health facilities to provide HIV testing at under-five clinics and to include under-five HIV testing as part of district performance assessments. TRIAL REGISTRATION: ClinicalTrials.gov REGISTRATION NUMBER: NCT02479659.

Implementation and Operational Research: Reconstructing the PMTCT Cascade Using Cross-sectional Household Survey Data: The PEARL Study.

BACKGROUND: Given the ambitious targets to reduce pediatric AIDS worldwide, ongoing assessment of programs to prevent mother-to-child HIV transmission (PMTCT) is critical. The concept of a "PMTCT cascade" has been used widely to identify bottlenecks in program implementation; however, most efforts to reconstruct the cascade have relied on facility-based approaches that may limit external validity. METHODS: We analyzed data from the PEARL household survey, which measured PMTCT effectiveness in 26 communities across Zambia, South Africa, Cote d'Ivoire, and Cameroon. We recruited women who reported a delivery in the past 2 years. Among mothers confirmed to be HIV infected at the time of survey, we reconstructed the PMTCT cascade with self-reported participant information. We also analyzed data about the child's vital status; for those still alive, HIV testing was performed by DNA polymerase chain reaction testing. RESULTS: Of the 976 eligible women, only 355 (36%) completed every step of the PMTCT cascade. Among the 621 mother-child pairs who did not, 22 (4%) reported never seeking antenatal care, 103 (17%) were not tested for HIV during pregnancy, 395 (64%) reported testing but never received their HIV-positive result, 48 (8%) did not receive maternal antiretroviral prophylaxis, and 53 (9%) did not receive infant antiretroviral prophylaxis. The lowest prevalence of infant HIV infection or death was observed in those completing the cascade (10%, 95% confidence interval: 7% to 12%). CONCLUSIONS: Future efforts to measure population PMTCT impact should incorporate dimensions explored in the PEARL study-including HIV testing of HIV-exposed children in household surveys-to better understand program effectiveness.

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.

Uptake, outcomes, and costs of antenatal, well-baby, and prevention of mother-to-child transmission of HIV services under routine care conditions in Zambia.

BACKGROUND: Zambia adopted Option A for prevention of mother-to-child transmission of HIV (PMTCT) in 2010 and announced a move to Option B+ in 2013. We evaluated the uptake, outcomes, and costs of antenatal, well-baby, and PMTCT services under routine care conditions in Zambia after the adoption of Option A. METHODS: We enrolled 99 HIV-infected/HIV-exposed (index) mother/baby pairs with a first antenatal visit in April-September 2011 at four study sites and 99 HIV-uninfected/HIV-unexposed (comparison) mother/baby pairs matched on site, gestational age, and calendar month at first visit. Data on patient outcomes and resources utilized from the first antenatal visit through six months postpartum were extracted from site registers. Costs in 2011 USD were estimated from the provider's perspective. RESULTS: Index mothers presented for antenatal care at a mean 23.6 weeks gestation; 55% were considered to have initiated triple-drug antiretroviral therapy (ART) based on information recorded in site registers. Six months postpartum, 62% of index and 30% of comparison mother/baby pairs were retained in care; 67% of index babies retained had an unknown HIV status. Comparison and index mother/baby pairs utilized fewer resources than under fully guideline-concordant care; index babies utilized more well-baby resources than comparison babies. The average cost per comparison pair retained in care six months postpartum was $52 for antenatal and well-baby services. The average cost per index pair retained was $88 for antenatal, well-baby, and PMTCT services and increased to $185 when costs of triple-drug ART services were included. CONCLUSIONS: HIV-infected mothers present to care late in pregnancy and many are lost to follow up by six months postpartum. HIV-exposed babies are more likely to remain in care and receive non-HIV, well-baby care than HIV-unexposed babies. Improving retention in care, guideline concordance, and moving to Option B+ will result in increased service delivery costs in the short term.

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.

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.

Analysis of HIV early infant diagnosis data to estimate rates of perinatal HIV transmission in Zambia.

BACKGROUND: Mother-to-child transmission of HIV (MTCT) remains the most prevalent source of pediatric HIV infection. Most PMTCT (prevention of mother-to-child transmission of HIV) programs have concentrated monitoring and evaluation efforts on process rather than on outcome indicators. In this paper, we review service data from 28,320 children born to HIV-positive mothers to estimate MTCT rates. METHOD: This study analyzed DNA PCR results and PMTCT data from perinatally exposed children zero to 12 months of age from five Zambian provinces between September 2007 and July 2010. RESULTS: The majority of children (58.6%) had a PCR test conducted between age six weeks and six months. Exclusive breastfeeding (56.8%) was the most frequent feeding method. An estimated 45.9% of mothers were below 30 years old and 93.3% had disclosed their HIV status. In terms of ARV regimen for PMTCT, 32.7% received AZT+single dose NVP (sdNVP), 30.9% received highly active antiretroviral treatment (HAART), 19.6% received sdNVP only and 12.9% received no ARVs. Transmission rates at six weeks when ARVs were received by both mother and baby, mother only, baby only, and none were 5.8%, 10.5%, 15.8% and 21.8% respectively. Transmission rates at six weeks where mother received HAART, AZT+sd NVP, sdNVP, and no intervention were 4.2%, 6.8%, 8.7% and 20.1% respectively. Based on adjusted analysis including ARV exposures and non ARV-related parameters, lower rates of positive PCR results were associated with 1) both mother and infant receiving prophylaxis, 2) children never breastfed and 3) mother being 30 years old or greater. Overall between September 2007 and July 2010, 12.2% of PCR results were HIV positive. Between September 2007 and January 2009, then between February 2009 and July 2010, proportions of positive PCR results were 15.1% and 11% respectively, a significant difference. CONCLUSION: The use of ARV drugs reduces vertical transmission of HIV in a program setting. Non-chemoprophylactic factors also play a significant role in HIV transmission. The overall change in the proportions of positive PCR results over time is more likely an indication of better PMTCT implementation. Determination of the outcomes of PMTCT in program settings is feasible but requires accurate documentation and analysis.

Early infant diagnosis of HIV infection in Zambia through mobile phone texting of blood test results.

OBJECTIVE: To see if, in the diagnosis of infant infection with human immunodeficiency virus (HIV) in Zambia, turnaround times could be reduced by using an automated notification system based on mobile phone texting. METHODS: In Zambia's Southern province, dried samples of blood from infants are sent to regional laboratories to be tested for HIV with polymerase chain reaction (PCR). Turnaround times for the postal notification of the results of such tests to 10 health facilities over 19 months were evaluated by retrospective data collection. These baseline data were used to determine how turnaround times were affected by customized software built to deliver the test results automatically and directly from the processing laboratory to the health facility of sample origin via short message service (SMS) texts. SMS system data were collected over a 7.5-month period for all infant dried blood samples used for HIV testing in the 10 study facilities. FINDINGS: Mean turnaround time for result notification to a health facility fell from 44.2 days pre-implementation to 26.7 days post-implementation. The reduction in turnaround time was statistically significant in nine (90%) facilities. The mean time to notification of a caregiver also fell significantly, from 66.8 days pre-implementation to 35.0 days post-implementation. Only 0.5% of the texted reports investigated differed from the corresponding paper reports. CONCLUSION: The texting of the results of infant HIV tests significantly shortened the times between sample collection and results notification to the relevant health facilities and caregivers.

Infant feeding options, other nonchemoprophylactic factors, and mother-to-child transmission of HIV in Zambia.

BACKGROUND: The role of antiretroviral drugs in the prevention of mother-to-child transmission (PMTCT) of HIV is well known. The objective of this study is to explore how nonchemoprophylactic factors, including infant feeding practices, mother's HIV status disclosure, mode and place of delivery, infant gender, and maternal age, are related to MTCT. METHODS: The study analyzed program data of DNA polymerase chain reaction (PCR) results from dried blood spot samples and selected client information from perinatally exposed infants aged 0 to 12 months. RESULTS: A total of 8237 samples were analyzed. In all, 84% of the mothers ever breast-fed their children. In instances where both mother and baby received intervention, the transmission rates of HIV were higher among those who are still breast-feeding after 6 to 12 months. Disclosure, location, and mode of delivery did not have an effect on the transmission rates of HIV when both mother and baby received prophylaxis. CONCLUSION: Nonchemoprophylaxis factors, especially breast-feeding, play a key role in perinatal transmission of HIV.

Reducing pediatric HIV infection: estimating mother-to-child transmission rates in a program setting in Zambia.

BACKGROUND: Vertical transmission of HIV remains the main source of pediatric HIV infection in Africa with transmission rates as high as 25%-45% without intervention. Even though effective interventions to reduce vertical transmission of HIV are now available and remarkable progress has been made in scaling up prevention of mother-to-child transmission (PMTCT) services, the effectiveness of PMTCT interventions is unknown in Zambia. In this study, we estimate HIV vertical transmission rates at different age bands among perinatally exposed children. METHODS: The study analyzed program data of DNA polymerase chain reaction results and selected client information on dried blood spot samples from perinatally exposed children aged 0-12 months sent to the polymerase chain reaction laboratory from 5 provinces between September 2007 and January 2009. RESULTS: Samples of 8237 babies between 0 and 12 months were analyzed, with 84% of the mothers having ever breastfed their children. The observed transmission rate was 6.5% (5.1%, 7.8%) among infants aged 0-6 weeks when both mother and infant received interventions compared with 20.9% (12.3%, 29.5%) where no intervention was given to either mother or baby. Observed HIV transmission with single-dose nevirapine (sdNVP) was 8.5% (5.9%, 11.0%) among infants aged 0-6 weeks, whereas zidovudine with sdNVP (zidovudine + NVP) and highly active antiretroviral therapy were associated with observed transmission rates of 6.8% (4.5%, 9.1%) and 5.0% (3.0%, 7.0%), respectively; whereas these estimates were not significantly different from one another, they were all significantly lower than no intervention for which the estimated rate was 20.9%. Regardless of the intervention, the observed transmission rates were higher among infants aged 6-12 months. CONCLUSIONS: PMTCT interventions, including sdNVP, are working in program settings. However, postnatal transmission especially after 6 months through suboptimal feeding practises remains an important challenge to further reduce pediatric HIV.

Antiretroviral therapy in antenatal care to increase treatment initiation in HIV-infected pregnant women: a stepped-wedge evaluation.

BACKGROUND: The objective of the study was to evaluate whether providing antiretroviral therapy (ART) integrated in antenatal care (ANC) clinics resulted in a greater proportion of treatment-eligible women initiating ART during pregnancy compared with the existing approach of referral to ART. ANALYSIS DESIGN AND METHODS: The evaluation used a stepped-wedge design and included all HIV-infected, ART-eligible pregnant women in eight public sector clinics in Lusaka district, Zambia. Main outcome indicators were the proportion of treatment-eligible pregnant women enrolling into HIV care within 60 days of HIV diagnosis, and of these, the proportion initiating ART during pregnancy. Adjusted odds ratios (AORs) and confidence intervals (CIs) for enrollment and initiation proportions were estimated through a logistic regression model accounting for clinical site cluster and time effects. RESULTS: Between 16 July 2007 and 31 July 2008, 13,917 women started antenatal care more than 60 days before the intervention rollout and constituted the control cohort; 17 619 started antenatal care after ART integrated into ANC and constituted the intervention cohort. Of the 1566 patients found eligible for ART, a greater proportion enrolled while pregnant and within the 60 days of HIV diagnosis in the intervention cohort (376/846, 44.4%) compared with the control cohort (181/716, 25.3%), AOR 2.06, 95% CI (1.27-3.34); and initiated ART while pregnant in the intervention cohort (278/846, 32.9%) compared with the control cohort (103/716, 14.4%), AOR 2.01, 95% CI (1.37-2.95). CONCLUSION: An integrated ART in ANC strategy doubled the proportion of treatment-eligible women initiating ART while pregnant.