EVALUATION OF THE PREVENTION OF MOTHER-TO- CHILD TRANSMISSION OF HIV PROGRAM IN ZAMBIA

Transcription

1 EVALUATION OF THE PREVENTION OF MOTHER-TO- CHILD TRANSMISSION OF HIV PROGRAM IN ZAMBIA 30 September 06 This publication was produced for the United States Agency for International Development. It was prepared by Eileen Yam, Tina Moyo, Lyson Phiri, Samuel Kalibala, Karen Foreit, Chipepo Kankasa, Kebby Musokotwane, Mary Chomba Nambao, and Joseph Simbaya.

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3 EVALUATION OF THE PREVENTION OF MOTHER- TO-CHILD TRANSMISSION OF HIV PROGRAM IN ZAMBIA POPULATION COUNCIL: EILEEN YAM, TINA MOYO, LYSON PHIRI, SAMUEL KALIBALA PALLADIUM: KAREN FOREIT ZAMBIA MINISTRY OF HEALTH: CHIPEPO KANKASA, KEBBY MUSOKOTWANE, MARY CHOMBA NAMBAO INDEPENDENT CONSULTANT: JOSEPH SIMBAYA

4 ACKNOWLEDGMENTS We express our gratitude to the women, clinicians, and study staff without whom this study would not have been possible. In addition, we acknowledge the following partners who contributed to the conceptualization and guidance of the study through the Zambia PMTCT Technical Working Group: Department of Pediatrics, University Teaching Hospital; Elizabeth Glaser Pediatric AIDS Foundation; Centers for Disease Control and Prevention; Centre for Infectious Disease Research in Zambia; The Global Fund to Fight AIDS, Tuberculosis and Malaria; Institute of Economic and Social Research, University of Zambia; United Nations Children s Fund; Ministry of Health; World Health Organization (WHO), and the Zambia Prevention Care and Treatment Partnership. This study was funded by United States Agency for International Development Zambia Mission with additional support from the WHO. This report was made possible through support provided by the President s Emergency Plan for AIDS Relief and the U.S. Agency for International Development (USAID) via HIVCore, a Task Order funded by USAID under the Project SEARCH indefinite quantity contract (Contract. AID-OAA-TO ). Published in September The Population Council Inc. Cover photo credit: Manoocher Deghati/IRIN HIVCore improves the efficiency, effectiveness, scale, and quality of HIV treatment, care, and support, and prevention of mother-to-child transmission (PMTCT) programs. The Task Order is led by the Population Council in partnership with Elizabeth Glaser Pediatric AIDS Foundation, Palladium, and the University of Washington. Suggested citation: Yam, Eileen, Tina Moyo, Lyson Phiri, Samuel Kalibala, Karen Foreit, Chipepo Kankasa, Kebby Musokotwane, Mary Chomba Nambao, Joseph Simbaya. 06. Evaluation of the prevention of mother-to-child transmission program in Zambia, HIVCore Final Report. Washington, DC: USAID Project Search: HIVCore.

5 TABLE OF CONTENTS ACRONYMS...5 EXECUTIVE SUMMARY...6 INTRODUCTION...8 METHODOLOGY...0 Study sites and population...0 Sample size calculation... Data collection... KEY FINDINGS...7 Baseline participant characteristics...7 Participant follow-up...8 Facility-based delivery...9 Maternal ART... Infant cotrimoxazole and ARV prophylaxis at 6 weeks, 4 weeks, and 9 months... Exclusive breastfeeding... MTCT rates at 6 weeks, 4 weeks, and 9 months... Characteristics of mother-baby pairs, among infants who seroconverted...3 DISCUSSION...5 RECOMMENDATIONS...7 REFERENCES...8 APPENDIX : ENROLLMENT SURVEY...9 APPENDIX : FOLLOW-UP SURVEY...4 Evaluation of the PMTCT program in Zambia 3

6 ACRONYMS ANC ART ARV CCC CDC CHW DHS DPT EBF EID HEI MTCT PCR PEPFAR PMTCT SM UNICEF USAID Antenatal care Antiretroviral therapy Antiretroviral Child clinic card Centers for Disease Control and Prevention Community health worker Demographic and Health Survey Diphtheria, pertussis, and tetanus Exclusive breastfeeding Early infant diagnosis HIV-exposed infant Mother-to-child transmission of HIV Polymerase chain reaction U.S. President s Emergency Plan for AIDS Relief Prevention of mother-to-child transmission of HIV Safe motherhood United Nations Children s Fund U.S. Agency for International Development 4 Evaluation of the PMTCT program in Zambia

7 EXECUTIVE SUMMARY To assess progress toward meeting the global aim of eliminating mother-to-child transmission of HIV (MTCT), it is critical to evaluate the impact of prevention of mother-to-child transmission (PMTCT) programs. Efforts to evaluate PMTCT programs utilize a range of data sources, including facility registries, cross-sectional surveys of pregnant women, and longitudinal cohort studies. One of the biggest challenges with conducting these evaluations is the attrition of HIV-positive pregnant women over time, with only a small minority being retained in PMTCT care long enough to assess the HIV status of the infant after birth. In Zambia, PMTCT services are supported by the U.S. President s Emergency Plan for AIDS Relief (PEPFAR), with the U.S. Agency for International Development (USAID) supporting the Ministry of Health to deliver PMTCT services in the northern half of the country, and the Centers for Disease Control and Prevention (CDC) supporting such services in the southern half of the country. Local technical support for PMTCT service delivery is provided by the Zambia PMTCT Technical Working Group, which is composed of representatives of the Zambian government, USAID, CDC, implementing partners, and United Nations agencies. In consultation with the Technical Working Group, a national evaluation protocol was developed to be implemented in three northern provinces supported by USAID and in three southern provinces supported by CDC, with the intent of using the same research methods and instruments across sites, as well as conducting coordinated data interpretation, analysis, and dissemination activities. The USAID-supported evaluation activities presented in this report were conducted by HIVCore, a USAID-funded project led by the Population Council. Since the CDCsupported research activities began about four months after the USAID-supported evaluation, at the time of this report, it was not possible to conduct joint analyses or reporting. Between October 04 and May 06, HIVCore conducted a cohort study among 653 HIV-positive pregnant women receiving antenatal care (ANC) in the northern provinces of Central, Copperbelt, and Luapula provinces. Study staff conducted follow-up surveys at 6 weeks, 4 weeks, and 9 months following delivery, collecting self-reported information on PMTCT service utilization and behaviors, including maternal antiretroviral therapy (ART), infant feeding, and infant ART and cotrimoxazole use. In addition, at the same three time points, we administered polymerase chain reaction (PCR) infant testing of participants babies, allowing us to estimate cumulative mother-to-child transmission (MTCT) rates at each point in time. Follow-up interviews and infant testing were conducted in conjunction with routine vaccinations (diphtheria, pertussis, and tetanus vaccine at 6 weeks [DPT ], DPT 3 at 4 weeks, and measles at 9 months). We conducted descriptive and bivariate analyses to examine and compare outcomes of interest at each follow-up period, overall and across districts. To estimate MTCT rates, we utilized a life table technique that accounted for infant seroconversions, withdrawal, death, and loss to follow-up over time. Out of the 653 enrolled women, 667 infants were born, whom we sought to observe in subsequent follow-up periods. Of those infants, 56 infants (77 percent) were retained in the study through the 9-month interview. Of these, 503 received PCR test results. Evaluation of the PMTCT program in Zambia 5

8 Overall, PMTCT service utilization and behaviors were high: y 93 percent of participants delivered in a facility. y 99 percent of women were currently on ART at 9 months. y The proportion of infants ever receiving ARV prophylaxis (reported by mother) increased from 66 percent (6 weeks) to 9 percent (9 months). y The proportion of infants currently taking cotrimoxazole increased from 87 percent (6 weeks) to 99 percent (9 months). y 6 percent of infants were exclusively breastfed at 6 weeks after birth, 40 percent at 4 weeks, and 9 percent at 9 months. The overall cumulative 9-month MTCT rate was.3 percent, ranging from.0 percent in Ndola to 3.4 percent in Nchelenge. This MTCT rate was notably lower than the previously documented estimate of 3 percent (Torpey et al. 0). Among women who initiate and are retained in PMTCT care at study facilities, the program is quite successful at minimizing vertical transmission. Nevertheless, generalizability of these findings to the broader community of HIV-positive pregnant women should be made with caution. Study participants likely had better service access and utilization compared to the broader population; they were women already seeking facility-based ANC who already knew their HIV status. Furthermore, since study staff enlisted local community health workers to proactively follow up with participants and encourage retention in care, the women in our sample benefited from outreach efforts that the general population would not have. 6 Evaluation of the PMTCT program in Zambia

9 INTRODUCTION The government of Zambia and its partners share the international community s goal of achieving the elimination of mother-to-child transmission of HIV, with the ambitious target of reducing the motherto-child transmission (MTCT) rate to 5 percent by 05. Substantial investments have been made in expanding prevention of mother-to-child transmission (PMTCT) services nationwide, yet little is known about the impact of these programs on HIV transmission from mother to child during pregnancy, labor, delivery, and breastfeeding (i.e., vertical transmission). In Zambia, recent evaluations of PMTCT services have consisted primarily of analyses of service statistics. As a component of a process evaluation, service statistics can shed light on whether and how HIV-positive pregnant women are using available PMTCT services. In addition, among infants born to HIV-positive mothers, an additional source of information is test results from early infant diagnosis (EID) services. EID services refer to HIV testing among HIV-exposed infants (HEIs) between the ages of four and six weeks of age. EID testing typically employs polymerase chain reaction (PCR) testing, a diagnostic technique that tests infant blood for HIV deoxyribonucleic acid (DNA). However, since these studies use program data, they are only applicable to those HIV-positive mothers who are retained and documented in the PMTCT cascade of interventions through delivery and postpartum. HIV-positive mothers and their exposed infants are lost to follow-up at every step of the series of PMTCT and EID services, with some studies suggesting that up to 85 percent of exposed infants are lost to followup within a year of delivery (Sherman et al. 004). Even when HIV-positive pregnant women receive PMTCT services during antenatal care (ANC), facility registries may not accurately reflect PMTCT service utilization. For example, an analysis of program data conducted in public ANC clinics in Lusaka found that among 4,54 live births recorded among HIV-positive mothers during a three-year period, just,83 mother-infant pairs (or 43 percent) had a documented EID HIV test result in the facility records (Chibwesha et al. 0). A 03 data quality assessment carried out in preparation for the current study showed that approximately 60 percent of the polymerase chain reaction (PCR) test registries at the facilities visited did not have the infant s PCR test results, three months after the sample had been taken (Institute of Economic and Social Research 04). EID is essential both to measure vertical transmission of HIV and to initiate pediatric HIV treatment. However, unlike rapid testing for adult HIV which is available at most health facilities EID requires a specialized test that is available only in reference laboratories. EID coverage is limited but growing: service statistics from EID programs in five Zambian provinces (Central, Copperbelt, Luapula, rth Western, and rthern), have reported 7 percent infection rates among HIV-exposed infants between the ages of 0 to 6 weeks, percent between 6 weeks and 6 months, and 0 percent between 6 and months of age. Transmission rates varied based on maternal antiretroviral (ARV) medication regimen, ranging from 4 percent to 0 percent among infants ages 0 to 6 weeks (Torpey et al. 0). However, since not all HIV-positive pregnant women attend PMTCT services, return for EID, or have their service utilization documented in facility registries, the generalizability of these program data is unknown. In Zambia, PMTCT services are supported by the U.S. President s Emergency Plan for AIDS Relief (PEPFAR), with the U.S. Agency for International Development (USAID) supporting PMTCT in Evaluation of the PMTCT program in Zambia 7

10 northern provinces and the Centers for Disease Control and Prevention (CDC) supporting such services in the south. Local technical support and oversight is provided by the Zambia PMTCT Technical Working Group, which is based at the University Teaching Hospital (UTH) in Lusaka and is composed of representatives from the Zambian government, USAID, CDC, implementing partners, and United Nations agencies such as World Health Organization and United Nations Children s Fund (UNICEF). In February 03, the Technical Working Group convened a meeting to develop objectives and study design for a national evaluation of Zambian PMTCT services. At the time, participants agreed that there would be a single evaluation study protocol including identical survey instruments, participant recruitment strategies, and data analysis plans that would be implemented by USAID in three northern provinces, and by CDC in three southern provinces. Furthermore, the intent was to conduct joint data interpretation and dissemination meetings at the end of the respective studies. The USAID-supported evaluation findings presented in this report were conducted through the HIVCore project, which is funded by USAID and led by the Population Council in partnership with the Elizabeth Glaser Pediatric AIDS Foundation, Palladium, and the University of Washington. This study sought to evaluate PMTCT service utilization among a cohort of HIV-positive pregnant women attending ANC facilities in three northern Zambian districts: Kabwe (Central province), Ndola (Copperbelt province), and Nchelenge (Luapula province). Participant service utilization was assessed based on women s selfreported healthcare service uptake and PMTCT-related behaviors at three follow-up interviews: at 6 weeks, 4 weeks, and 9 months following delivery. In addition, to estimate MTCT rates among participants HEIs, the study team performed infant testing of participants babies at approximately the same follow-up periods (i.e., 6 weeks, 4 weeks, and 9 months after delivery). Follow-up interviews and infant testing were conducted in conjunction with routine vaccinations (diphtheria, pertussis, and tetanus vaccine at 6 weeks [DPT ], DPT 3 at 4 weeks, and measles at 9 months). Since USAID and CDC evaluation activities were governed by separate contractual arrangements and timelines, the USAID-supported research started four months before the CDC research. Therefore, as of the time of completion of this USAID-supported report, it was not possible to conduct joint data interpretation or dissemination activities. 8 Evaluation of the PMTCT program in Zambia

11 METHODOLOGY The objectives of this study were to evaluate Zambian PMTCT services by: y Describing PMTCT service utilization and behaviors by Zambian HIV-positive pregnant women and their infants at six weeks, 4 weeks, and nine months, including: y Maternal antiretroviral therapy (ART) use y Infant ARV prophylaxis y Infant cotrimoxazole use y Exclusive breastfeeding (EBF) y Estimating the MTCT rate at 6 weeks, 4 weeks, and 9 months after delivery in a cohort of HIVpositive mothers in PMTCT services in three provinces To accomplish these objectives, the study design was a longitudinal panel beginning with HIV-positive pregnant women enrolled in ANC facilities; their infants were followed for nine months after delivery. STUDY SITES AND POPULATION In consultation with local stakeholders, the study team selected one delivery zone in each of the three study provinces. A delivery zone was defined as a catchment area of health facilities in which pregnant women receive ANC services. Typically, mothers would receive ANC services in any one or more of several lower-level facilities, but then the women deliver at a single higher-level facility (described colloquially as the mother facility). The research team purposively selected zones per province with the greatest number of HIV-positive ANC clients. The selected study facilities are listed in Table. Table Study facilities District, province Mother facility Satellite health centers Kabwe, Central Ndola, Copperbelt Nchelenge, Luapula Polleni Health Center Lubuto Health Center Nchelenge Health Center Chowa Kasanda Makululu Railway Kabushi Kaloko Mushili New Masala Kabuta Kasikishi Province adult female HIV prevalence* 4.8% 0.0%.% *03-4 Zambia Demographic and Health Survey (Central Statistical Office, Ministry of Health, and ICF International 04) Evaluation of the PMTCT program in Zambia 9

12 Eligible participants were HIV-positive women attending routine ANC visits at study facilities who were: Age 6+ Pregnant, at least 6 weeks gestational age Had received HIV-positive diagnosis prior to the enrollment date Physically and mentally capable of providing informed consent Residents of the zone and intending to remain a resident through delivery SAMPLE SIZE CALCULATION We calculated the sample size to enroll based on the expected MTCT rate with PMTCT services, as well as the estimated mortality and vaccination coverage rates reported in the 007 Zambia Demographic and Health Survey (DHS) (Central Statistical Office et al. 009). We anticipated that the size of the panel would decrease over time, as we expected some of the original sample would die during the observation period or not return for vaccinations or HEI appointments. We made the simplifying assumption that HEIs would show similar rates of infant/child mortality and vaccination coverage as the general population. 3 Assuming a 6-week vertical transmission rate of 5 percent, we determined that a starting sample of 00 HIV-positive women per province would be sufficient to estimate the nine-month MTCT rate with a 6 percent margin of error at a 95 percent confidence level (Table ). Therefore, our target sample size was 00 pregnant women per province. Table Sample size calculations (number of participants needed per province) Contact period Infant mortality Vaccination coverage Expected MTCT rate (when PMTCT services are utilized) Expected sample ANC 00 DPT (6 weeks) DPT 3 (4 weeks) Measles (9 months) 95% confidence interval for MTCT rate Lower Upper β β β Zambia Demographic and Health Survey (Central Statistical Office et al. 009) β Estimate based on 0 analyses by Torpey and colleagues (Torpey et al. 0) This was the most recent DHS available at the time of study development. 3 Other sources of sample loss include maternal mortality, fetal loss and stillbirth, and mothers moving out of the health zone. They were not included in the sample size calculations because of lack of data. 0 Evaluation of the PMTCT program in Zambia

13 DATA COLLECTION Participant recruitment Throughout the study period, at each study facility in each of the three study districts one paid interviewer worked full-time on-site, available to screen and conduct interviewer-administered surveys of HIV-positive pregnant women who presented for ANC. These same interviewers remained available at the facilities throughout the follow-up period, ready to administer follow-up questionnaires when study participants returned for their infant vaccinations. These study staff were locally recruited from the study districts and underwent a week-long training in Lusaka, which covered study procedures as well as an initial pilot of all instruments at a local ANC facility. During the study enrollment period, the nurse in charge in PMTCT study sites used facility registries and clients safe motherhood (SM) cards to identify clients attending ANC that day who were HIV-positive and at least 6 weeks of gestation. The nurse in charge informed these clients that they may be eligible to participate in a study on pregnancy and infant health and introduced them to the study staff waiting at the exit or waiting area to learn more about the research. Employing quota sampling, study staff were simultaneously deployed to all selected ANC sites. PMTCT clients were consecutively enrolled until at least 00 clients per province consented to and completed the enrollment survey. Prior to initiation of recruitment, the local study coordinator obtained letters of approval from the Ministry of Health and District Medical Officers and presented them to the directors of the health facilities chosen for the study. The Field Study Coordinator met with district health authorities and facility staff to discuss the study s objectives and methodology. Specifically, the local study coordinator introduced research staff to each study facility s nurse in charge and other relevant facility staff, ensuring that they were aware of the upcoming data collection activities and that they were given the opportunity to ask questions or express concerns. Enrollment After obtaining informed consent, the study staff reviewed the client s SM card 4 to ensure that she met the eligibility criteria. That is, they made sure to only enroll mothers who had received a positive HIV test result on a date prior to the date of the current visit, were receiving PMTCT care, and/or had a notation that they were on ART. The study staff then administered a standardized enrollment survey of 0 30 minutes in duration. The interview covered participants baseline reproductive health and HIV-related history, including: Gestational age at first ANC visit Whether she knew her HIV-positive status before the current pregnancy Whether she had previously used ART Previous PMTCT services received during the current pregnancy Contact information for follow-up, including telephone number and address 4 The SM card contains information about services received at every ANC visit as well as information about delivery and postnatal care visits. It is issued to the mother at the first ANC visit and is carried by the mother for all subsequent ANC visits, delivery, and the postnatal care visit at six days after delivery. Evaluation of the PMTCT program in Zambia

14 The study staff also reviewed and extracted information from the SM card, such as dates of last menstrual period and expected delivery, ARVs given, and dates of ANC visits made. Follow-up data collection Follow-up data collection (i.e., follow-up surveys and PCR testing) took place at the following events and points in time: y DPT vaccination (~6 weeks after delivery) y DPT3 vaccination (~4 weeks after delivery) y Measles vaccination (~9 months after delivery) To facilitate participant retention, around the time of estimated delivery, study staff attempted to locate participating mothers who had given birth, identify women who had lost their pregnancy/child (miscarriage, stillbirth, early infant death), and identify infants for follow-up. Study staff made daily visits to the maternity site at the time new mothers were discharged as well as the six-day postnatal clinics and identified participating mothers by their SM card number, also recorded in the study log. The study staff checked to see if the mother was given a children s clinic card (CCC) and recorded the child s CCC number in the log. The staff also recorded the infant s date of birth in the study log and encouraged mothers to return for postnatal care and/or infant vaccination. other information was collected during these early post-delivery contacts. To maximize retention during the 6-week, 4-week, and 9-month follow-ups, the study team enlisted community health workers (CHWs), who provided intensive follow-up of mothers in the cohort to ensure that the follow-up rates during the study were enhanced to exceed those observed in the routine immunization program. In addition, study staff were present at maternity wards when mothers were discharged after delivery in order to keep track of mothers who may have been lost to follow-up at the time of delivery. Follow-up surveys At each follow-up period, study staff administered a brief (5-minute) follow-up survey that collected information on maternal ART use, infant ARV prophylaxis, EBF, and infant cotrimoxazole. 5 These surveys served as the data sources for estimating PMTCT service utilization and behaviors over time. At each follow-up period, one survey was administered per baby; mothers who delivered multiples responded to one survey per child. Infant PCR testing Zambian national PMTCT guidelines recommend that HEIs be tested for HIV at six weeks, six months, months, and 8 months (or six weeks after cessation of breastfeeding). Since our study period was limited to nine months of follow-up after delivery, we scheduled PCR testing to correspond with the timing of vaccination visits, as described previously. This meant that our testing protocol was a slight modification of national guidelines, with the second tests occurring at 4 weeks and 9 months (as opposed to at 6 months and months). Infants who tested negative at DPT (6 weeks) were tested 5 Use of daily cotrimoxazole medication is recommended for HEIs to reduce morbidity and mortality (World Health Organization 009). Evaluation of the PMTCT program in Zambia

15 again at DPT 3 (4 weeks), and infants who tested negative at DPT 3 were tested again at measles vaccinations (9 months). The tests were conducted by facility staff, usually in conjunction with these routine vaccination visits. 6 At each vaccination clinic, the nurse in charge provided the required vaccination and other well-child clinic services for the visit and reviewed the infant s child clinic card (CCC) to determine if the infant should be tested for HIV. If testing was indicated, the nurse took a blood sample from the infant and counseled the mother/guardian to return to the facility in one month s time to obtain the infant s test results. After preparing the blood sample for shipment to the laboratory, the nurse registered the test in the facility PCR register. If blood was taken at a previous visit and the results recorded in the facility PCR register, the nurse informed the mother/guardian and recorded the test results on the child s CCC. The nurse then provided post-test counseling and referred HIV-infected infants for ARV treatment. After providing these services, the nurse in-charge identified infants participating in the study by matching the baby s CCC number 7 with the list of CCC numbers in the study log for that clinic and referred them to the study staff. The study staff read the informed consent instructions to the mother/ guardian, answered any questions she may have had, and requested consent to administer a short questionnaire. If the mother/guardian consented, the study staff asked about current infant feeding practices and whether the mother and/or baby were receiving HIV treatment or prophylaxis, and extracted information from the CCC regarding PCR testing and PCR results. If the infant s CCC showed that the infant was HIV-positive, the study staff informed the mother and confirmed that the infant had been referred for treatment. If the CCC review revealed that a scheduled blood draw for PCR testing had not been made, the study staff noted the missing service and then referred the mother back to the clinic staff to complete care. Per national standards, PCR testing is conducted for infants younger than months of age. Before sending blood samples to the reference laboratory, the nurse entered the infant names into the facility PCR registry. Test results were added to the facility PCR registry as soon as they were received back from the laboratory. Ethical considerations and protections The primary risk to the participants was disclosure of confidential information, such as HIV status, and possible discomfort from answering the questionnaire. Possible benefits were feeling encouraged to continue ANC and PMTCT care, as well as infant immunization. To minimize the risk of breach of confidentiality, study staff were trained to be discrete when engaging potential participants in the clinics, taking care to discuss the study and conduct interviews in a private space out of earshot of others. Collected information was stored as securely as possible during the data collection phase. After data 6 On some occasions, study facilities had an erratic supply of filter papers for taking the blood sample, or they ran out of laboratory request forms. In those cases, study staff were unable to obtain the infant blood sample at the time of the scheduled immunization. Later, when supplies became available, data collectors would contact mothers to bring back infants for testing. 7 The CCC is issued at the time of the first vaccination (usually at birth) and is presented at every clinic visit until the child s fifth birthday. Evaluation of the PMTCT program in Zambia 3

16 collection was completed and identities confirmed for data entry, participants were de-identified by physically removing their SM and the CCC number and name from the study logs and questionnaires, leaving only the unique study number. During any follow-up visits to homes that were necessary, interviewers took care to avoid providing any details about the study or eligibility criteria to residents other than the study participant, minimizing the possibility of disclosing her HIV status by conducting all conversations in a private space. If the study participant was not available, the interviewers only divulged that the woman was part of a health study and that the purpose of the home visit was to discuss health behaviors and service utilization. All hard copies of questionnaires, study logs, and data extraction forms were stored under lock and key, first with the study staff and then transferred to the Population Council s Lusaka office, accessible only to the study coordinator or other staff delegated by her. Signed consent forms and face sheets with identifiable information were stored in a locked location separately from the questionnaires and results reports, and they were available only to the study coordinator and authorized study staff. Presentations, reports, and papers on study findings did not reveal the identities of any participants. Data analysis To start, we conducted bivariate analyses with chi-square tests to describe baseline demographic and HIVrelated characteristics of enrolled women and identify significant differences between districts. To describe the PMTCT service utilization and behaviors among mother-baby pairs over time, we then analyzed the mothers self-reported responses to follow-up survey questions related to place of delivery, maternal ART use, EBF, infant ART use, and infant cotrimoxazole use. We calculated descriptive statistics comparing these indicators across the three follow-up periods. To assess differences across districts at each time point, we conducted bivariate analyses of these outcomes at each follow-up period using Pearson s chi-square tests. For infant-level outcomes (ART use and cotrimoxazole use), we used the Rao-Scott adjusted chisquare test to account for correlation between twins. Based on infant PCR test results obtained at each of the three follow-up periods, we estimated cumulative MTCT rates at 6 weeks, 4 weeks, and 9 months. This estimate was calculated for the total sample as well as for each district. We constructed life tables based on the number of reactive cases per district at each follow-up period. The life table approach is a survival analysis technique for examining time to event outcomes such as HIV-free survival after birth. Life table analysis takes into account withdrawal of infants from the study at various follow-up points, due, for example, to loss to follow-up, study withdrawal, infant death, or seroconversion. Specifically, for each follow-up period, rather than restricting analyses to infants retained in the study during that interval, the number of infants considered at risk included the number of infants who survived up until the beginning of that interval plus half the number of infants who withdrew during that interval. We employed this standard convention of counting half the number of missing infants in the denominator at each time period, making the simplifying assumption that any departures of study infants due to the reasons listed above would be evenly distributed throughout the interval in which they are lost. The arithmetic formulas for constructing these cumulative MTCT rates are illustrated in Figure. 4 Evaluation of the PMTCT program in Zambia

17 Figure Arithmetic formulas for constructing cumulative MTCT rates Follow-up interval # at start of interval (N) # of positive PCR during interval (H) # missing during interval (L)* Adjusted number at risk (N-0.5L) Probability of positive PCR during interval (P = H/N-0.5L) Probability of HIV-free survival through interval (-P) Cumulative HIV-free survival to end of time interval Cumulative MTCT rate at end of time interval Enrollment-6 weeks A A -A 6-4 weeks B A*B -(A*B) 4 wks-9 mos C A*B*C -(A*B*C) * This would include participants who withdrew from the study, died, or were lost to follow up. Evaluation of the PMTCT program in Zambia 5

18 KEY FINDINGS BASELINE PARTICIPANT CHARACTERISTICS Across the three districts, 653 women enrolled in the study. Baseline demographic characteristics are displayed in Table 3. The age distribution of enrolled women was similar across districts. A significantly larger proportion (95 percent) of Ndola women were married compared to those in the other two districts (86 percent in Kabwe, 87 percent in Nchelenge). A larger proportion (8 percent) of Kabwe women had no living children, compared to women from Ndola (4 percent) or Nchelenge (4 percent). Overall, about half of participants had completed some primary education, with 46 percent achieving secondary education or more. Women in Nchelenge had lower education levels than those in Kabwe and Ndola, with 9 percent having at least some secondary education, compared to 53 percent in Kabwe and 55 percent in Ndola. Compared to education levels in the general adult female population in the study provinces, study participants had slightly higher education levels, with at least some secondary education for 53 percent of study participants versus 34 percent for the general public in Central, 55 percent versus 5 percent in Copperbelt, and 8 percent versus 3 percent in Luapula (Central Statistical Office, Ministry of Health, and ICF International 04). Table 3 Baseline characteristics of enrolled mothers (N = 653) Kabwe (n = 9) Ndola (n = 6) Nchelenge (n = 8) Total (N = 653) % n % n % n % n Age < Marital status** Single Married/cohabiting Separated/divorced/widow Education*** ne Primary Secondary > secondary Living children** ne to Observations for individual variables may not sum to total sample size due to missing values. *p < 0.05, **p < 0.0, ***p < Evaluation of the PMTCT program in Zambia

19 At baseline, overall, nearly two-thirds of women were enrolled between 6 and 30 weeks gestation, and two-thirds had attended either two or three ANC visits. Across districts, roughly half of enrolled women first learned their HIV status during the current pregnancy. Between 79 and 88 percent had ever had a CD4 blood test, and between 89 and 9 percent had ever received ART. Women in Nchelenge were significantly less likely to have been taking ART when they got pregnant (68 percent compared to 80 percent in Ndola and 99 percent in Kabwe). Among those with partners, Nchelenge participants were significantly less likely to know their partner s HIV status (63 percent compared to 7 percent in Ndola and 76 percent in Kabwe) (Table 4). Table 4 Baseline HIV and PMTCT history (N = 653) Kabwe (n = 9) Ndola (n = 6) Nchelenge (n = 8) Total (N = 653) % n % n % n % n Gestational age at enrollment (weeks) Number of ANC visits** to When first found out HIV status During this pregnancy Before this pregnancy Ever had CD4 blood test* Ever received ART When first received ART** This pregnancy Before this pregnancy Was taking ART when became pregnant*** Knows partner status* Observations for individual variables may not sum to total sample size due to missing values. *p < 0.05, **p < 0.0, ***p < 0.00 PARTICIPANT FOLLOW-UP Fourteen of the 653 enrolled women had twins, yielding 667 infants that we sought to observe in subsequent follow-up periods. We conducted follow-up surveys and reviewed PCR test result documentation at six weeks, 4 weeks, and nine months. Figure displays the number of surveys and PCR test results obtained as of each follow-up period. In some cases, women completed follow-up surveys but were unable to undergo infant PCR testing, due Evaluation of the PMTCT program in Zambia 7

20 to shortage of supplies at the clinic. Therefore, there were fewer infant PCR test results than follow-up surveys at each time period (Figure ). There were a total of 5 mother-baby pairs for whom survey data were not available at the nine-month follow-up period: five withdrawals, 7 infant deaths, 48 relocations, and 7 who were untrackable. When comparing these 5 mother-baby pairs to the 56 who responded to the nine-month follow-up survey, there were some statistically significant differences in demographic characteristics. Those who were retained were slightly older, with 45 percent aged 30 or older (compared to 30 percent among those missing, p < 0.0). A slightly larger proportion of the missing women had no children (8 percent vs. 4 percent, p < 0.05). Among those who were retained in the study over time, a larger proportion had first received their positive diagnosis more than a year ago as opposed to more recently (0 percent vs. 7 percent, p < 0.05). In terms of PMTCT-related behaviors or service utilization, there were no other significant differences between women who were retained at nine months and those who were not. Figure Completed surveys and infant PCR test results, per follow-up period Number Completed follow-up survey Documented infant PCR results Maternal enrollment 6 weeks 4 weeks 9 months There were 653 enrolled women, 4 of whom had twins. Therefore, at each follow-up period, the highest possible number of observations was 667. FACILITY-BASED DELIVERY A very large proportion of enrolled mothers (93 percent) delivered in a facility, ranging from 9 percent in Ndola to 97 percent in Nchelenge (p < 0.05). Figure displays the facility-based delivery rates among study participants. In contrast, in the general population in Zambia, levels of facility-based delivery are notably lower: 50 percent in Central, 73 percent in Luapula, and 84 percent in Copperbelt provinces (Central Statistical Office et al. 04). 8 Evaluation of the PMTCT program in Zambia

21 Figure Facility-based delivery, as reported at 6-week follow-up Percentage Kabwe (n = 7) Nchelenge (n = 99) Ndola (n = 93) Total (n = 563) Facility-based delivery rates were significantly different across districts (p < 0.05). MATERNAL ART We analyzed the proportion of women who were currently using ART, among those mothers for whom these data were available for all three follow-up periods (n = 465). At each point in time, ART use was nearly universal, higher than 96 percent across districts at each time period. There were no significant differences in ART utilization across districts. These high levels of ART use are comparable to those observed in previous reports of ART utilization by Zambian HIV-positive pregnant women (9 percent in 04) (National AIDS Council 05). INFANT COTRIMOXAZOLE AND ARV PROPHYLAXIS AT 6 WEEKS, 4 WEEKS, AND 9 MONTHS According to national guidelines, HEIs whose mothers are on ART should receive ARV prophylaxis until they are six weeks old (Ministry of Health 04). In addition, daily cotrimoxazole medication is recommended for HEIs through cessation of breastfeeding (World Health Organization 009). To examine changes in infant ARV and cotrimoxazole prophylaxis utilization over time, we analyzed these outcomes just among infants whose mothers reported on these two indicators at all three follow-up periods (n = 469 for cotrimoxazole, and n = 470 for ARV). Generally, there were successively higher proportions of babies who reportedly were taking cotrimoxazole or had ever used ARV (Figures 3 and 4). Evaluation of the PMTCT program in Zambia 9

22 Figure 3 Infant currently taking cotrimoxazole Percentage weeks *** 4 weeks *** 9 months Kabwe (n = 33) Ndola (n = 48) Nchelenge (n = 88) Total (n = 469) ***p < 0.00 Figure 4 Infant ever taken ARV prophylaxis Percentage weeks *** 4 weeks *** 9 months *** Kabwe (n = 33) Ndola (n = 48) Nchelenge (n = 88) Total (n = 469) ***p < Evaluation of the PMTCT program in Zambia

23 EXCLUSIVE BREASTFEEDING National and global PMTCT guidelines recommend EBF for HEIs through six months of age (Ministry of Health 04). Overall 6 percent of women reported that they were exclusively breastfeeding their infants at the six-week follow-up visit. The lowest proportion was reported in Kabwe (3 percent), followed by Nchelenge (6 percent) and Ndola (90 percent). At 4 weeks, 40 percent of participants reported EBF, dropping to 9 percent at 9 months. EBF was defined as feeding the baby nothing other than breastmilk in the day before the survey. MTCT RATES AT 6 WEEKS, 4 WEEKS, AND 9 MONTHS Overall, there were 4 infants who received reactive PCR tests during the follow-up period, with progressively fewer cases identified in successive follow-up periods (Table 5). Table 5 Reactive PCR tests, by time period and district (n = 4) 6 weeks 4 weeks 9 months Total Kabwe Ndola 0 Nchelenge Total Based on life table analysis, the overall cumulative MTCT rates at 6 weeks, 4 weeks, and 9 months were.3 percent,. percent, and.3 percent, respectively. The highest nine-month cumulative MTCT rate was estimated in Nchelenge (3.4 percent), followed by Kabwe (.6 percent) and Ndola (.0 percent) (Table 6). Table 6 Cumulative MTCT rates, by time period and district 6 weeks % 4 weeks % 9 months % Kabwe Ndola Nchelenge Total.3..3 CHARACTERISTICS OF MOTHER-BABY PAIRS, AMONG INFANTS WHO SEROCONVERTED All but one of the 4 mothers of the infants who seroconverted was married or cohabiting, and 5 of 4 had some secondary education (Table 7). All 4 mothers delivered in a facility, and of the 4 were first diagnosed with HIV during the current pregnancy. Likewise, first initiated ART during the current pregnancy. At 6 weeks of age, 6 of 3 mothers reported EBF. Infant ARV prophylaxis had ever been taken by 0 infants at 6 weeks, increasing to all 4 at 9 months. Evaluation of the PMTCT program in Zambia

24 Table 7 Characteristics of mother-baby pairs, among seroconversions (n = 4) Maternal age < Marital status Single Married/cohabiting Separated/divorced/widowed n (among infants who seroconverted) 3/4 6/4 5/4 0/4 3/4 /4 Knew partner HIV status (among 3 married/cohabiting women) 7/3 Education ne Primary Secondary More than secondary 0/4 9/4 4/4 /4 Facility delivery 4/4 Diagnosed with HIV during current pregnancy /4 Mother initiated ART during current pregnancy* /3 Infant EBF* At 6 weeks At 4 weeks Ever taken infant ARV At 6 weeks At 4 weeks At 9 months Current infant cotrimoxazole prophylaxis* At 6 weeks At 4 weeks At 9 months *Some cases had missing values for selected indicators. 6/3 4/ 0/4 /4 4/4 /4 0/ 0/ Evaluation of the PMTCT program in Zambia

25 DISCUSSION At nine months post-delivery, we observed a.3 percent overall MTCT rate among study participants, which was notably lower than previous estimates. The low MTCT rate was accompanied by high rates of maternal ART use as well as infant ARV and cotrimoxazole use. Based on these findings, among those women who receive PMTCT services and are retained in care at the study facilities, the PMTCT program is quite successful at minimizing vertical transmission. The study team was able to retain a larger than expected proportion of enrolled mothers and infants. In our sample size calculation, we estimated that we would retain about 363 infants through nine months post-delivery; however, we were able to obtain PCR test results for 503 infants over this study period. We attribute this retention to the diligence of the CHWs who were tasked with tracking down participants who were late for follow-up visits. Since these women essentially received these cues to action by the CHWs, the study activities may have served as an intervention that compelled women to receive care that they otherwise may not have received. We noted few significant differences between women who were not retained in the study compared to those who remained in the study for the duration. Therefore, we feel confident that the cumulative MTCT rates presented here are reasonable estimates of the true rate in the enrolled study population. The cumulative nine-month MTCT rate in Nchelenge (3.4 percent) was substantially higher than that of the other two districts, which may partly reflect that significantly fewer Nchelenge women had initiated ART prior to the current pregnancy, and that they tended to have lower education levels than participants from the other provinces. In addition, the Nchelenge sites were more rural and remote, with poor road infrastructure, which may further inhibit health care access and utilization. Half of the participants (and of 4 mothers of infants who seronconverted) did not know their HIV status until the current pregnancy, which indicates a critical missed opportunity to identify these women earlier and meet their care and treatment needs before they get pregnant. Furthermore, nearly 30 percent of those with partners did not know the partner s status at the time of enrollment in this study by which time they were already pregnant. Nearly all (3/4) of the mothers whose infants seroconverted were married or cohabiting, among whom seven of 3 knew their partner s HIV status upon enrollment in the study. Couples HIV counseling and testing before and during pregnancy is needed to encourage disclosure, prevent transmission to a seronegative partner, avoid super-infection, and prevent MTCT. The women who participated in this study exhibited high levels of PMTCT service utilization and preventive behaviors, but the low EBF rates in Kabwe and Nchelenge were an exception to this general finding. Women from Kabwe exhibited especially low rates, with less than one-third of mothers reporting exclusive breastfeeding. At 6 weeks and 4 weeks of age, among infants who seronconverted, EBF rates were comparably low. Among the 3 mothers of HIV-positive infants who reported on infant feeding at 6 weeks, just 6 reported EBF. Likewise, just 4 of mothers of HIV-positive infants reported EBF at 4 weeks. It is unclear why the reported EBF levels were so much lower than that of the general population in Zambia, in which 85 percent of infants ages to 3 months are exclusively breastfed (Central Statistical Office et al. 04). PMTCT providers and CHWs should continue to promote EBF in their interactions with pregnant women living with HIV. Evaluation of the PMTCT program in Zambia 3

26 Nevertheless, any generalizations of these findings to the broader population must be made with caution. Our study population was drawn from women who were seeking ANC in a facility, and who already knew their HIV status. The observed facility-based delivery rates in our study were substantially higher than those reported in the general population. Since facility delivery rates typically are regarded as a proxy for overall maternal healthcare access and utilization, it is a safe assumption that the women in our study sample had better access and service uptake compared to pregnant women in the general population. This is particularly noteworthy in Kabwe district, where study participants facility delivery rate (9 percent) was nearly twice as high as the provincial facility delivery rate (50 percent). (Central Statistical Office et al. 04) Furthermore, among HIV-positive pregnant women who undergo first-time HIV testing during ANC, only half receive their test result. (Chi et al. 05) Our study population did not include pregnant women who either never seek facility-based ANC, or who do not know their HIV status. tably, all 4 women whose infants seroconverted had delivered in a facility. Therefore, we expect that our estimated MTCT rates are an underestimate compared to the broader population of HIV-positive pregnant women. 4 Evaluation of the PMTCT program in Zambia