Impact of Point-of-care (POC) Viral Load (VL) Testing During Pregnancy in Zimbabwe

Impact of Point-of-Care (POC) Viral Load (VL) Testing on Ensuring Appropriate Management of Viremia During Pregnancy to Prevent Vertical Transmission: an Observational Difference-in-difference Cohort Study

The Ministry of Health and Child Care (MOHCC) in collaboration with Clinton Health Access Initiative (CHAI) will conduct an observational cohort study to determine the impact and cost-effectiveness of POC VL testing for pregnant women. It is hypothesized that POC VL testing will enable an increased proportion of pregnant women to be virally suppressed at delivery, which will avert vertical transmission.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Device: Point-of-care (POC) viral load (VL) testing plus refresher training; Other: Standard of care central laboratory VL testing plus refresher training

Detailed Description

Twenty public health facilities that offer HIV care to pregnant women and maternity services will be included in the study with half offering VL testing at the first antenatal care visit using the centralized VL system (standard of care cluster) and the other half offering onsite POC VL (POC cluster). The primary end-point will be the proportion of enrolled pregnant women who are virally suppressed at the time of delivery. Positivity rate will be measured as a secondary outcome. Primary and secondary outcomes will be compared between study arms. As well, a baseline assessment in each facility will be included to enable a difference in difference analysis within clusters, in which viral suppression rates at delivery and other outcomes are compared before and after the intervention.

The primary research question to be addressed by this study is: Does the availability of POC VL testing during ANC increase the proportion of women who are virally suppressed at the time of delivery?

The primary objective is to demonstrate the impact of POC VL on ensuring viral suppression at the time of delivery (defined as a viral load < 1,000 cpm within 2 weeks of delivery) for pregnant women living with HIV (PWLHIV) who are on ART in order to avert vertical transmission.

In addition, this study will:

• document the at-birth and 4-6 week EID positivity rate
• document proportion of women who have undetectable VL at the time of delivery (defined as below the limit of detection (LOD) of the VL test)
• document the baseline coverage of VL monitoring during the first ANC visit for WLHIV on ART ≥ 6 months
• compare the timeliness of VL result receipt by clinics (HCW) and clients between facilities with POC VL and those using centralized testing
• calculate the cost-effectiveness of POC VL for increasing the proportion of women who are virally suppressed at delivery

• Study Type: Interventional
• Enrollment (Actual): 1715
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Zimbabwe
  • Bulawayo, Zimbabwe
    • Luveve Clinic
  • Bulawayo, Zimbabwe
    • Mpilo Central Hospital
  • Bulawayo, Zimbabwe
    • Nkulumane Clinic
  • Bulawayo, Zimbabwe
    • Pelandaba Clinic
  • Bulawayo, Zimbabwe
    • United Bulawayo Hospital
  • Harare, Zimbabwe
    • Budiriro PolyClinic
  • Harare, Zimbabwe
    • Chitungwiza Central Hospital
  • Harare, Zimbabwe
    • Gleview
  • Harare, Zimbabwe
    • Hatcliffe PolyClinic
  • Harare, Zimbabwe
    • Highfield PolyClinic
  • Harare, Zimbabwe
    • Kambuzuma
  • Harare, Zimbabwe
    • Kuwadzana PolyClinic
  • Harare, Zimbabwe
    • Mabvuku PolyClinic
  • Harare, Zimbabwe
    • Mbare polyclinic
  • Harare, Zimbabwe
    • Rujeko
  • Harare, Zimbabwe
    • Rutsanana PolyClinic
  • Harare, Zimbabwe
    • Seke South Clinic
  • Harare, Zimbabwe
    • St. Mary's Clinic
  • Harare, Zimbabwe
    • Warren Park PolyClinic
  • Harare, Zimbabwe
    • Zengeza Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Sites will be selected for inclusion in the study based on following criteria:

• Offer HIV testing and antiretroviral therapy (ART) services
• Offer prevention of mother-to-child transmission (PMTCT) and maternity services
• Offer Viral load monitoring either using POC or through referral
• Availability of Second line ART
• Located in 2 provinces in which VL testing labs are located
• Have historic monthly ANC cohorts of ≥ 6 pregnant women living with HIV (PWLHIV) already on ART

Patient Inclusion Criteria:

Baseline Cohort:

All women living with HIV on ART ≥7 months who deliver at the study facilities during the enrollment period, who do not meet the study criteria for the intervention cohort, were on ART at ANC1 and are of the age of consent (≥ 18 years old) will be offered participation. Informed consent will be obtained to collect a study-specific blood sample to perform a VL test in the central lab at the time of delivery. 7 months has been selected to be comparable to women in the intervention cohort who may present for ANC1 at 4 weeks prior to delivery who are on ART ≥ 6 months.

Intervention Cohort:

Pregnant women who are known to be living with HIV and on ART for ≥ 6 months and attend the study facilities for ANC services and have an anticipated due date ≥ 4 weeks, will be offered participation in the study. It is expected that a woman who is on ART < 6 months may not yet have achieved viral suppression (using current NNRTI-containing regimens) and therefore conducting a VL at this time is not currently standard. According to Zimbabwe guidelines and consistent with normative guidance from the World Health Organization (WHO), any infant born to a woman living with HIV who is on ART for less than 4 weeks is considered at high risk of HIV transmission. Therefore, for this study the first ANC visit must be ≥ 4 weeks prior to delivery. Women must be at least the age of adult consent (≥ 18 years old) in Zimbabwe. If consent is obtained, a sample will be collected at ANC1 for VL testing.

Patient Exclusion Criteria:

Baseline Cohort

• PWLHIV not on ART at ANC1 or on ART < 7 months at time of delivery
• Women who have enrolled in or are eligible for the intervention cohort
• Women who are not HIV positive
• Pregnant women who are newly diagnosed as HIV positive during pregnancy
• Women who cannot or do not provide informed consent

Intervention Cohort

• Pregnant women who are newly diagnosed as HIV positive during pregnancy
• PWLHIV not on ART or on ART < 6 months at their first ANC visit
• Women who are not HIV positive
• Women who cannot or do not provide informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Point-of-care (POC); All facilities will receive a refresher training on Zimbabwe's 2018 Guidelines. At POC facilities, at the first antenatal visit (ANC1), all women enrolled in the intervention cohort will have a blood sample collected for VL which will be tested onsite using an existing POC device. If a woman is virally unsuppressed (VL ≥1000 cpm), she will be given adherence counseling and, if necessary, a treatment regimen switch/infant prophylaxis per national guidelines.	Device: Point-of-care (POC) viral load (VL) testing plus refresher training; VL testing at the first antenatal care visit will occur using POC VL testing in pregnant women, and a refresher training on Zimbabwe's guidelines will be provided at all facilities; Other Names: GeneXpert
Active Comparator: Standard of care (SOC); All facilities will receive a refresher training on Zimbabwe's 2018 Guidelines. At SOC facilities, at ANC1, all women enrolled in the intervention cohort will have a blood sample collected for VL which will be sent to centralized labs for testing. If a woman is virally unsuppressed (VL ≥1000 cpm), she will be given adherence counseling and, if necessary, a treatment regimen switch/infant prophylaxis per national guidelines.	Other: Standard of care central laboratory VL testing plus refresher training; VL testing at the first antenatal care visit will occur using central laboratory VL testing in pregnant women, and a refresher training on Zimbabwe's guidelines will be provided at all facilities

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Viral suppression at delivery	The proportion of enrolled PWLHIV on ART ≥ 6 months at their first ANC visit who are virally suppressed at delivery	Within 2 weeks after delivery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Viral suppression at delivery among those with an unsuppressed viral load at first antenatal care visit	The proportion of enrolled PWLHIV identified as having unsuppressed VL at first ANC who suppress at delivery	Within 2 weeks after delivery
Infant HIV infection	The proportion of infants who test HIV positive at birth and/or 4-6 weeks using an early infant diagnosis (EID) test	Within 6 weeks of birth
Turnaround time to VL results available at facility	The time between VL sample collection and result receipt by health care provider	Through end of the study, approximately 1 year
Turnaround time to VL results available to patient	The time between VL sample collection and result receipt by pregnant woman living with HIV	Through end of the study, approximately 1 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Costing of POC VL	The commodity costs of VL testing at ANC1 on the POC platform will be calculated ($USD per patient) and compared to the commodity costs of VL testing using the central laboratory given any differences in the primary and secondary endpoints by group	Through end of the study, approximately 1 year
Acceptability of POC VL	The acceptability to healthcare workers of offering POC VL testing at the first ANC visit, based on a survey	End of the study, approximately 1 year after study start

Collaborators and Investigators

• Sponsor: Clinton Health Access Initiative Inc.
• Collaborators: Ministry of Health and Child Welfare, Zimbabwe

Study record dates

Study Major Dates

• Study Start (Actual): August 5, 2019
• Primary Completion (Actual): August 31, 2020
• Study Completion (Actual): August 31, 2020

Study Registration Dates

• First Submitted: August 2, 2019
• First Submitted That Met QC Criteria: August 5, 2019
• First Posted (Actual): August 7, 2019

Study Record Updates

• Last Update Posted (Actual): January 27, 2021
• Last Update Submitted That Met QC Criteria: January 25, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: HIV; GeneXpert; Point-of-care; Viral load; Zimbabwe
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections
• Other Study ID Numbers: POC VL during pregnancy

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No