https://doi.org/10.5061/dryad.3bk3j9kwr

Description of the data and file structure

Study setting and design

We conducted a quasi-experimental pre-post study examining the effects of the community POC model at six health facilities and their surrounding communities (i.e., “sites”) in Lusaka, Zambia. The study sites were selected based on their comparable urban demography, catchment areas, and patient populations. All sites had similarly high annual volumes of pregnant and breastfeeding women (PBFW) living with HIV and infants who are HIV-exposed accessing prevention of vertical transmission of HIV services and infants living with HIV accessing ART. Each site is staffed by government healthcare workers, including nurses, clinicians, and laboratory technicians, and provides antenatal care (ANC), labor and delivery, dried blood spot (DBS)-based EID testing, ART, and other services for the prevention of vertical transmission of HIV. We delivered the community POC model during the “post-intervention period” from June 1, 2019—May 31, 2020 during which time MIPs were actively enrolled, followed, and received the intervention. For a comparison group, we defined an analogous pre-intervention period from June 1, 2017—May 31, 2018, and reviewed existing routine medical records at the same study sites for all PBFW living with HIV with an infant born during this period and followed their records through November 30, 2019 to ascertain a testing outcome.  

The study was approved by the U.S. Centers for Disease Control and Prevention Institutional Review Board (IRB, #6877), the University of Zambia Biomedical Research Ethics Committee (#014-09-16), the National Health Research Authority (#MH/101/23/10/1), the Zambia Medicines Regulatory Authority (#DMS/7/9/22/CT/070), the University of Alabama at Birmingham IRB (#17033000), and the University of North Carolina Chapel Hill IRB (#17-1798).

Participants

For the pre- and post-intervention periods, we reviewed routine MOH paper and electronic records at the 6 study sites to identify “potential high-risk” MIPs. In this paper, we defined MIPs as potentially high-risk for an adverse HIV outcome if they included a PBFW ≥18 years and an infant or young child who was: 0 days to 17 months old during the pre- or post-periods, had probable or known HIV exposure based on history of a missing or positive maternal or positive infant rapid antibody test, and/or missing or late (by > 4 weeks) latest age-appropriate EID testing milestone (i.e., from age 6 weeks, 6 months, and/or from 6 weeks post-cessation of breastfeeding per the standard of care [SOC] below). For the post-intervention period, we traced by phone or in person potential high-risk MIPs who also had one or more of the following: a. attended ≥1 ANC visits without receiving HIV testing; b. delivered at home and did not return for post-natal care at a health facility (i.e., child not tested for HIV); c. were documented as being HIV-positive but never initiated ART; or d. experienced treatment interruption or otherwise disengaged from HIV care. MIPs who met the aforementioned criteria, confirming them as high-risk, and who provided written informed consent to receive the intervention were enrolled in the post-intervention cohort. For the pre-intervention period, we were granted a waiver of informed consent for the review of existing, de-identified routine data. For this period, we included records for all potential high-risk MIPs with a non-missing EID testing record. MIPs in which the infant had evidence of receiving all EID testing milestones and the mother was documented to have been initiated and retained on ART were excluded from the study.

Standard of Care

Under the SOC during the pre-intervention period, infants exposed to HIV were followed at the clinic from birth until cessation of breastfeeding or age 18 months, whichever occurred first. Infants and young children received facility-based EID testing by DNA PCR (done off-site at a specialized referral laboratory) from age 6 weeks, 6 months, and at 9 months or from 6 weeks after breastfeeding cessation by rapid antibody testing (with DNA PCR confirmation). Nevirapine plus zidovudine (AZT) prophylaxis was prescribed to all infants who were HIV-exposed for 6 weeks after birth, with extension of prophylaxis to 12+ weeks for infants born to women with selected high-risk criteria per national guidelines (i.e., women with established HIV infection and not on ART or having received <12 weeks of ART at the time of delivery, or women with viral load [VL] >1,000 copies/mL within the 4 weeks before delivery when VL available).20 All PBFW and children living with HIV were eligible for immediate, lifelong ART regardless of CD4+ count or WHO stage. Prevention of vertical transmission of HIV and EID services largely involved passive ascertainment of maternal HIV exposure status and HIV testing of infants who are HIV-exposed and present for care in ANC, ART, Under 5, outpatient malnutrition, and post-natal care clinics.

Community-based active case-finding model

Our community POC model has been described previously.18 Briefly, it incorporated the following core components: 1) review of site-level routine MOH records to identify high-risk MIPs; 2) a dedicated team, fully integrated within the national prevention of vertical transmission of HIV and EID program (known as the “PMTCT program”), to conduct POC EID testing in the home, community, or nearest convenient location (including health facilities) based on maternal preference; and 3) mobile use of the m-PIMA platform. Six dedicated study teams, assigned to one study site each, partnered with MOH staff from the MNCH departments at the sites to deliver the model, and were comprised of a nurse study coordinator, one data coordinator, two data associates, six research assistants (RAs), and six peer educators.

We trained study and site MOH staff on the community POC model and mobile use of the m-PIMA. RAs were trained to review routine medical records to identify potential high-risk MIPs who met the study inclusion criteria as outlined above. Upon identifying a potential high-risk MIP, RAs would use routinely available locator information to contact the mother or caregiver by phone or, failing that, by home visit to ask if they might be interested in study participation. If interested, RAs verified participants’ study eligibility, consented them for the study, confirmed their high risk criteria, and offered them the community POC model. Consenting parents or guardians were asked for their preferred site for HIV testing in the community (e.g., their home, a friend or relative’s home, community health post, etc.) or the nearest health facility. If the parent/guardian chose to test their child outside the home, the study team accompanied them to their preferred site in the community or at the facility. RAs had experience as lay HIV counselors and were trained on DBS sample collection and EID testing using the m-PIMA. Study peer educators, who had backgrounds as community health workers from study communities, supported MIP home visits and community follow ups. MOH nurse midwives were available at each study site to perform confirmatory EID testing using the m-PIMA in cases of a first positive test in the community.

Study Procedures

Pre-post cohort construction

For the post-intervention period, we constructed a cohort of high-risk MIPs whose infants were born June 1, 2019—May 31, 2020 and who met study eligibility criteria using a two-step process. In the first step, trained RAs reviewed thefollowing routine records to identify potential high-risk MIPs: the national SmartCare HIV electronic medical record (EMR), CIDRZ Central Laboratory Information Management System (LIMS), and routine MOH registers from the ANC, prevention of vertical transmission of HIV, Under 5, and HIV Testing Services (HTS) departments. MIPs potentially at high risk based on review of these routine records had their data entered into a secure, electronic study log. For mothers with documented HIV infection, we reviewed the SmartCare EMR and ART clinic records for any evidence of missed ART initiation, ART treatment interruption, or other disengagement from HIV care to further define their risk status. In the second step, we contacted MIPs in the study log by phone or in person in the community, confirmed their high risk status in person, and offered them study participation and the community POC model as described above.

For the pre-intervention period, we reviewed all available medical records at the study sites and constructed a cohort of all MIPs who met study eligibility criteria and received the SOC between June 1, 2017—May 31, 2018. Individual-level clinical and demographic data were abstracted from available records through November 30, 2019, to allow at least 18 months of observation time.

EID Testing and Linkage to Care Procedures

RAs collected ~400 μl of blood by heel or finger prick from infants. Approximately 350 μl (70 μl x 5 spots) was collected onto a DBS card while 25 μl was collected directly into a capillary tube and tested on location using the m-PIMA. m-PIMA results were made available to the parent/guardian within one hour, while DBS samples were sent to the central laboratory for confirmatory DNA PCR testing. If the m-PIMA test result returned positive, the study team escorted the parent/guardian to the nearest health facility for repeat testing using the same m-PIMA platform and to immediately initiate ART. If the m-PIMA test result returned negative, the parent/guardian was asked to return to the clinic within 4 weeks to receive the results of confirmatory DBS DNA PCR testing, at which time the infant exited the study if this was negative. Parents/guardians of infants testing positive on m-PIMA also were required to return to the health facility to collect results of confirmatory DBS DNA PCR testing. Infants confirmed to have HIV-infection remained on ART. Concordant and discordant results were managed per national guidelines.

Data Collection

All MIPs had the following routine data abstracted from their medical records: demographic information, maternal HIV status, infant HIV testing history, maternal ART history, infant ART history (if relevant), and follow up visit dates. MIPs in the post-intervention cohort underwent study specific data collection at enrolment and follow up on HIV, obstetric, and infant clinical histories, EID testing history, and maternal and infant medication histories. All data were entered into a study database in Microsoft Excel (Redmond, WA, USA) for the pre-intervention period and OpenClinica for all data collected during the post-intervention period.

Study follow up

Infants who tested as being HIV-positive through the study were followed for 12 weeks past enrollment to observe 3-month retention on ART and to complete a one-time study follow up visit.

Outcomes

The primary outcome was HIV positivity, a metric of the efficiency of EID testing and overall risk status of the mother-infant pair, defined as the percent of exposed infants with a documented positive EID test result. The numerator was the number of eligible exposed infants with a documented positive EID test result from age 6 weeks and the denominator as the number of infants with a documented EID test result. For IYCs living with HIV, the primary outcome was** **ART uptake, and 3-month survival and retention in care. Secondary outcomes included median infant age at time of first documented EID test result, time from sample collection to return of results to the caregiver (i.e., total turnaround time),time from specimen collection to ART initiation, and median age at ART initiation.

Files and variables

File: detect_dryad-17feb2025.csv

Description: De-identified, raw data used to conduct analysis associated with manuscript entitled: “Differentiated community-­ based point-of-­care early infant diagnosis to improve HIV diagnosis and ART initiation among infants and young children in Zambia: a quasi-­ experimental cohort study” accepted to BMJ Global Health.

Variables

• ever_pos: infant HIV test result
• age_cat: maternal age category
• setting: setting of birth/delivery
• anc_visit: count of antenatal care visits
• risk_cat: risk category qualifying the mother infant pair for study participation
• facilitycode: study facility
• dob_mon: month of birth/delivery
• group: binary variable representing intervention or control group

Note: Missing values represented as “.” or “Not recorded”.

Access information

Other publicly accessible locations of the data:

• NA

Data was derived from the following sources:

• Paper registers from study clinics and electronic sources in maternal care units, where applicable