Swaziland Safe Generations

Study Overview
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Brief Summary
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The purpose of this study is to understand how best to provide care and treatment services to human immunodeficiency virus (HIV) positive pregnant women and their babies in Swaziland. The study is designed to evaluate a new approach for Preventing Mother-to-Child Transmission (PMTCT)where all HIV positive pregnant women initiate lifelong triple antiretroviral (ARV) therapy regardless of their disease stage. The goal is to prevent delays in women accessing treatment for their own health and ensure that women and their children remain in care. This study will compare this new approach to PMTCT, known as Option B+, to Option A, which is the current standard of care for PMTCT in Swaziland. The study will be conducted at 10 health facilities in the Manzini and Lubombo regions in Swaziland. The study has three components: the main component is a PMTCT Options Evaluation where data from medical records will be abstracted on all HIV positive pregnant women attending antenatal services at the 10 selected study facilities; data will be abstracted on their HIV exposed infants as well. Other components of the study include a PMTCT Options Acceptability Evaluation using semi-structured questionnaires with PMTCT clients and health care workers (HCWs) as well as a cost effectiveness evaluation comparing costs under conditions of Option A and Option B+.

Detailed Description
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Purpose: Situkulwane Lesiphephile-Safe Generations is an implementation science research study designed to evaluate an innovative PMTCT strategy that includes a modified Option B approach, where all HIV positive pregnant women initiate lifelong triple antiretroviral (ARV) therapy independent of CD4+ count (Option B+) and all HIV positive pregnant and postpartum women and their infants are engaged in the same structured appointment and follow-up protocols currently available only to women receiving antiretroviral therapy (ART). The study hypothesizes that this single, uniform and streamlined treatment and retention approach for all HIV positive pregnant women will eliminate delays, prevent losses and will: (1) result in a higher proportion of mothers and infants successfully completing the PMTCT cascade and fewer new pediatric infections; (2) lead to a higher proportion of ART-eligible women initiating triple ART earlier in pregnancy; (3) will be more feasible to implement; 4) have greater acceptability among staff and patients; and 5) will be more cost-effective compared to Option A. Design: Stepped wedge design at 10 health facilities with one facility transitioning from Option A to the Option B+ approach every month over 12 months. Outcome measures will be compared under Option A and Option B+ conditions for all sites as well as before and after the transition at each site. Routinely collected data from facility registers and medical records will be abstracted to determine study outcomes. In addition, two purposely selected cohorts of (1)120 PMTCT clients and; (2) approximately 50 health care workers will complete questionnaires at repeated time points to assess acceptability of Option A and Option B+ approaches. Study Population: All HIV positive pregnant women not on ART engaging in PMTCT services at the study sites will be part of the PMTCT Options Evaluation. This will include HIV+ women not on ART enrolling in PMTCT services and pregnant women newly testing HIV+ in the absolute neutrophil count (ANC). A subset of HIV+ pregnant women not on ART engaging in PMTCT services and health care workers providing PMTCT services at the study sites will be enrolled in an acceptability evaluation. Study Size: A total of approximately 2,600 HIV positive pregnant women enrolled in PMTCT services at ten Ministry of Health (MOH) facilities. Primary Objective: To compare the impact of implementing Option A and Option B+ on the composite endpoint of infant HIV-positive polymerase chain reaction (PCR) at 6 months postpartum or maternal loss to follow-up at 6 months postpartum. Secondary Objectives: To compare Option A and Option B+ on proportion of pregnant women with CD4+<350 cells/mm3 initiating ART during pregnancy and on duration of ART received prior to delivery for ART-eligible pregnant women To compare Option A and Option B+ on the proportion of women and children retained in HIV care at 12, and 18 months postpartum To examine patient and provider level acceptability of Option A and Option B+ To compare the cost-effectiveness of Option A and Option B+ Tertiary Objectives: To determine pregnancy and infant outcomes (including fetal losses, neonatal death, birth weight and gestational age) among HIV+ pregnant women receiving PMTCT and compare outcomes by maternal ARV regimens. To compare Option A and Option B+ on maternal and child adherence as measured by prescriptions dispensed for maternal and infant antiretroviral medications.

Official Title
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Situkulwane Lesiphephile-Safe Generations: Improving Approaches to Antiretroviral Therapy for HIV-Positive Pregnant Women

Conditions
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HIV/AIDS

Intervention / Treatment
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* Other: Option B+


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women at least 18 years of age Documented pregnancy (per routine ANC protocol in this setting) Documented HIV-infection (per routine ANC protocol in this setting) Infants born to eligible and enrolled women Exclusion Criteria: • Women already on ART when entering ANC

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| PMTCT Options Evaluation<br>All HIV positive pregnant women not on ART engaging in PMTCT services at the study sites will be included. This will include HIV+ women not on ART enrolling in PMTCT services and pregnant women newly testing HIV+ in the ANC. All women will eventually receive the intervention of Option B+ as each clinic transitions from Option A to B+. | Other: Option B+<br>* Using one low toxicity triple ARV regimen [(tenofovir (TDF) + lamivudine/emtricitabine (3TC/FTC) + efavirenz (EFV)] for all women, rather than adapting regimens by CD4+ Engaging all pregnant and postpartum women and their infants in the structured appointment and follow-up system currently only available to women receiving ART Providing a simplified standardized public health approach both antenatally and postnatally, with adherence and retention support tailored to the particular health and social needs of peripartum women<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of (1) infant HIV positive PCR at six months postpartum OR (2) mother lost to follow-up from at six months postpartum | Combined maternal-child endpoint: The primary outcome will be measured on all HIV+ pregnant women not on ART at their first ANC visit at a participating study site, approximately 2600 women(becoming mother-infant pairs postpartum). This includes women entering PMTCT with known HIV+ status, not on ART, and women testing HIV+ on entry into ANC. | Up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of pregnant women with CD4+<350 cells/mm3 initiating ART during pregnancy | ART Initiation During Pregnancy: Proportion of pregnant women with CD4+<350 cells/mm3 initiating ART during pregnancy | Up to 24 months | 
| Proportion of women and children retained in HIV care at 12 and 18 months postpartum | Maternal/Infant Retention in Care: Proportion of women and children retained in HIV care at 12 and 18 months postpartum | Up to 24 months | 
| Duration of ART/ARV received prior to delivery | ART/ARV Duration: Duration of ART/ARV received prior to delivery | Up to 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PMTCT, HIV/AIDS, Option B+, Swaziland