Protocol for a prospective evaluation of postpartum engagement in HIV care among women living with HIV in South Africa

Introduction KwaZulu-Natal (KZN), South Africa (SA) has the highest prevalence of pregnant women living with HIV in the world. Pregnancy and the postpartum period offer opportunities to engage women in HIV care, to prevent perinatal transmission and to optimise maternal and infant well-being. However, research suggests that remaining engaged in HIV care during this time can be challenging. Methods and analysis We are conducting a 5-year prospective cohort study among pregnant women living with HIV in KZN to estimate the rates and factors associated with attrition from HIV care during this critical period. To determine who is most likely to fall out of care, we are examining a range of relevant variables informed by a socioecological model of HIV care, including individual, relational, community and healthcare system variables. We are enrolling 18-45-year-old women, at 28 weeks or more of pregnancy, who are living with HIV and currently taking antiretroviral therapies. Participants complete quantitative assessments at baseline (pregnancy) and at 6, 12, 18 and 24 months postpartum. A subset of women and their partners are invited to complete qualitative interviews to further explore their experiences in HIV care. The main study outcomes are suppressed HIV RNA and retention in care at each study assessment. Our understanding of the factors that drive postpartum attrition from HIV care will ultimately inform the development of interventions to facilitate continued engagement in postpartum HIV care. Ethics and dissemination This protocol has been approved by the Human Research Ethics Committee (Medical) at The University of the Witwatersrand (Johannesburg, SA) and the Partners Human Research Committee at Partners HealthCare (Boston, Massachusetts, USA). Site support and approval were obtained from the District Hospital and the KZN Provincial Department of Health. Results will be disseminated through peer-reviewed manuscripts, reports and both local and international presentations (Ethics Registration #170 212). This is a prospective cohort study of women enrolled in a PMTCT programme, planned to be conducted between 9 June 2017 and 31 May 2022. Up to 500 HIV-positive women between the ages of 18 and 45 will be recruited. The study includes five assessment points: baseline (pregnancy) and 6, 12, 18 and 24 months postpartum. At each assessment, participants complete a quantitative interview and blood draws to measure HIV RNA, which is stored for HIV genotyping, if appropriate. Stored blood samples will be discarded at the end of the study. The baseline assessment occurs on the same day that a participant consents to study participation, unless she prefers that the visit occur on another day (eg, to give her the chance to discuss participation with her partner and/or family). Data collected during this assessment include individual (eg, health beliefs, depression, substance use), relational (eg, social support, relationships with intimate partners, intimate partner violence, HIV disclosure), community (eg, poverty, stigma, work commitment) and healthcare system (eg, knowledge of service integration, HIV clinic distance, time waiting, time travelling to clinic) constructs. Medical details are also assessed related to HIV (eg, CD4 count, current medications) as well as pregnancy (eg, antenatal visits attended) and postpartum (eg, infant weight, gestational age, HIV status) periods. Please see table 1 for details. Measures included at each major assessment HIV RNA levels are retained at each assessment. Genotype results are retained at 6 months, 12 months, 18 months and 24 months postpartum. *HIV RNA is entered after study visit. †Genotyping only done if participants’ VL>1000. ASI, Addiction Severity Index; BL, baseline; CES-D, Center for Epidemiological Studies Depression; PACTG, Pediatric AIDS Clinical Trials Group – Pediatric International Adherence Questionnaire Behavior/Identification; PRAMS, Pregnancy Risk Assessment Monitoring System; VL, viral load. Optional qualitative interviews are planned to occur during the follow-up period among a subsample of female participants (n~50). These interviews will be conducted among three groups of women: those who achieved suppressed HIV RNA for at least two consecutive assessments (ie, sustained suppression; n=12–15, depending on thematic saturation), those who did not achieve suppressed HIV RNA for at least two consecutive assessments (ie, sustained non-suppression; n=12–15) and those who moved from suppressed HIV RNA to unsuppressed HIV RNA or the reverse (n=14–20). To obtain a diversity of experiences, a proportion of participants meeting these criteria will be offered the qualitative interview after their major assessment visit (ie, 6, 12 and 18 month visits). We will also interview male partners for a subsample of these women (up to 25); women must invite their male partners to participate to avoid inadvertent disclosure of HIV status. To estimate true attrition from care, it is important to determine if a participant who is seemingly lost to follow-up is simply receiving care elsewhere. We employ a number of tracing techniques to keep track of participants throughout the course of the study if a participant cannot be contacted by phone or does not attend a scheduled visit; participants have the option of consenting to each of these strategies. First, we seek permission to contact participants via social media (eg, Facebook, WhatsApp). We also collect the names of up to 10 individuals who might know how to connect with the participant and reach out to these individuals if the participant cannot be contacted. During these calls, study staff protect participants’ confidentiality by identifying their affiliation with a ‘maternal health study’ (or some other programme prespecified by the participant). Finally, we have the option to visit the participant’s home to conduct the assessment and complete the blood draw. For each missed appointment, study staff can attempt up to three home visits. If a participant cannot be located to complete an assessment, a review of the participant’s medical record is conducted. All data drawn from the National Health Laboratory Service medical record (eg, CD4, HIV RNA) are recorded on a record review form. Participants in this study are pregnant women living with HIV who are currently enrolled in a programme to PMTCT of HIV at an antenatal clinic. Women are recruited from a district hospital in a large urban centre in eThekwini District, KZN over a period of 2 years. Although adherence to PMTCT programmes is suboptimal,39–44 97% of women in South Africa receive at least some antenatal care.45 Participants are recruited during the third trimester of pregnancy (as women in South Africa often present late for antenatal care).46 Study inclusion criteria are presented in box 1 and consist of living with HIV; age between 18 and 45 years; at 28 weeks of pregnancy or greater (ie, in the third trimester); currently on ARV therapy; fluent in English or isiZulu; access to a phone and willing to give researchers permission to contact them for repeated assessments and able to give informed consent. After initial consent for screening is obtained, participants are assessed for eligibility using a screening script. Participants who meet all criteria and would like to participate sign a second informed consent document to enrol and then complete a full baseline assessment. There are no exclusion criteria with respect to parity or gravity; all participants are eligible for lifetime ARVs per South African HIV treatment guidelines.10 47 48 The ARV treatment guidelines also indicate that participants who experience a pregnancy loss are still eligible for lifetime treatment; thus, pregnancy loss will not be exclusionary once enrolled in the study. Women with active or untreated major mental illness that would interfere with participation (eg, untreated psychosis, bipolar disorder, dementia or active suicidality) are excluded and referred for mental health treatment via counsellors at the recruitment site. Participants who are acutely distressed or suicidal will be escorted to on-site mental health services immediately. Potential participants may be excluded if, in the opinion of the Principal Investigator, participation in the study would be unsafe, would complicate interpretation of study findings or otherwise interfere with achieving study objectives. A range of individual, relational, community and healthcare system variables are measured at each assessment informed by a socioecological model42 (figure 1). Some of the individual-level variables include substance use, health beliefs and depression. Substance use is assessed with the Addiction Severity Index-Lite,49 which probes lifetime and recent substance use, including severity. Health beliefs are measured with the 8-item Perceived HIV Self-Management Scale,50 and depression is assessed with the Center for Epidemiologic Studies Depression scale,51 52 which is widely used in South Africa53 and has been validated among pregnant women living with HIV.54 Examples of relational variables measured throughout the study include social support, intimate partner violence and HIV disclosure. Social support is measured via the Modified Duke-UNC Functional Social Support Questionnaire,55 56 which assesses the availability of emotional, informational and tangible support as well as the number of individuals providing support. The presence of intimate partner violence within the last year is documented with the Abuse Assessment Screen.57 58 If the participant answers ‘yes’ to one or more questions, a clinical assessment is conducted. To assess HIV disclosure, participants are asked to whom they have disclosed their HIV status and if their pregnancy partner is aware of their HIV status. Community-level variables include stigma and employment policies. Stigma is measured with the HIV Stigma Scale,59 which assesses several domains, such as personalised stigma, disclosure concerns, negative self-image and concerns with public attitudes towards HIV. For participants who report employment, we assess maternity leave and sick time policies. Healthcare system variables include knowledge of service integration (ie, participants’ knowledge of how to transfer care from PMTCT to mainstream HIV services after delivery) and specific clinic factors (eg, modes of transportation used to travel to clinic, travel time, amount of time spent at clinic and so on). Other measures that are assessed during the study are included in table 1. Social-ecological model of factors impacting HIV Care. The study is informed by a social-ecological framework42 that has been adapted to address factors potentially relevant to postpartum engagement in HIV care. Study assessments measure these factors at the individual, relational, community and healthcare system levels. PMTCT, prevent mother-to-child transmission. To maximise the integrity of self-report data, a racially and ethnically concordant female research assistant (whenever possible), fluent in both English and isiZulu, conducts the assessments. The baseline assessment is administered by a trained study staff member using an electronic tablet and takes place in a private room at the recruitment site. The data collected at baseline include basic sociodemographic information (eg, age, educational level and ethnicity) as well as the individual, relationship, community and healthcare system variables described above. Measures that are not readily available in isiZulu have been translated and back-translated and piloted before use. Please see table 1 for an outline of all measures that will be included at each assessment. At all assessment visits, nurses collect two 6 mL tubes of blood to measure HIV RNA levels, for possible HIV genotyping and/or sample storage. The HIV RNA testing is being conducted at each time point. Whole blood specimens are separated into plasma using standard centrifugation techniques, and HIV RNA is determined via RNA extraction and PCR amplification (this testing is being conducted by Global Clinical and Viral Laboratory (South Africa) using the Biomerieux assay). Participants with unsuppressed HIV RNA are given a letter referring them to their healthcare providers for further care. Although we use detectable HIV RNA as one indicator of attrition from HIV care, viraemia may also occur as a result of ARV resistance. Therefore, we are conducting HIV drug resistance testing for any participant with unsuppressed HIV RNA at the 6-month assessment. If drug resistance is detected, this information is shared with the participant and her identified provider to optimise clinical care. At all other assessments, plasma is stored if HIV RNA is >1000 copies/mL to enable more extensive resistance testing should our data warrant it. Only blood samples with HIV RNA >1000 copies/mL are retained in storage. Any stored blood samples will be appropriately discarded at the end of the study. The participants who are selected to complete the qualitative interview will be categorised according to the three viral suppression patterns described earlier. Participants who are selected for this phase complete up to two interviews between the 6 and 24 months postpartum visits. The male partners complete one interview during this time. All interview questions are open-ended to most effectively elicit information. For the female participants, the interview includes a free-list exercise to solicit unbiased accounts of experiences with postpartum engagement in HIV care. The participant is asked to list the top five barriers and facilitators of postpartum HIV care. The research assistant then probes to query the topic areas generated by the free-list activity to facilitate depth of discussion. Probes are designed to assess and understand how these factors specifically contributed to success or failure to stay engaged in HIV care, and how interventions may make use of facilitators to support continued engagement in care and/or to overcome barriers to retention in care. In addition to targeting topics generated by the free-list activity, the interviewer asks the participant about her current relationships (family, friends, community, pregnancy partner), perceptions of engagement in postpartum HIV care and how future interventions may support better engagement in postpartum HIV care. During the second interview, the participant is asked about changes in her level of engagement in care, facilitators and barriers experienced since her first interview. For the male pregnancy partners, the interview focuses on how partnership characteristics shape attrition from and retention in HIV care during the postpartum period. Interview themes include: his perception of his partner’s overall HIV care engagement since pregnancy, ways the romantic relationship impacts partner’s HIV care engagement, perceived barriers/facilitators to partner’s HIV care engagement and ways to better integrate male pregnancy partners in postpartum HIV care. Participants, community members and other relevant stakeholders will be involved in the reporting and dissemination of study findings as appropriate. The study team plans to provide regular (approximately quarterly) updates on the data collection process and study findings to the Community Advisory Board (CAB) as well as an annual update to KZN’s Department of Health.