Principal Investigator: Gbolahan Ajibola, MB, BS, MPH

Study Objectives:

Primary Aim 1: POC HIV testing of infants at birth

Aim 1a: To describe the feasibility and evaluate the effectiveness of implementing facility-based targeted point-of-care (POC) HIV testing of high-risk neonates at birth.

Aim 1b: To determine the percentage of high-risk neonates with in utero HIV infection in the current era, and the times to HIV diagnosis and to ART initiation with birth POC testing, with descriptive comparisons to existing national data for 6-week infant PCR HIV testing.

Primary Aim 2: Early DTG-based ART for Infants

Aim 2a: To compare time to HIV-1 RNA suppression, and proportion with suppression at 12 weeks, with early DTG-based ART compared with early LPV/r-based ART (EIT cohort comparison).

Aim 2b: To compare clinical and virologic outcomes of infants on early DTG-based ART compared with early LPV/r-based ART through 96 weeks (EIT cohort comparison).

Aim 2c: To evaluate the longitudinal evolution of viral reservoirs in HIV-1 infected infants treated with DTG-containing ART, relative to the EIT cohort.

Aim 2d: To analyze signs of immune selection in proviral reservoir sequences from infants undergoing early treatment with DTG-containing ART.

Secondary Aims:

1. To describe caregiver perspective (acceptability and ease of administration) of the dispersible

DTG tablets and its subsequent impact on adherence, including when dispersed in breast milk or formula.

2. To describe the proportion of children tested negative by POC at birth who later receive HIV DNA PCR testing at 6-10 weeks.

3. To describe drug resistance mutations in plasma and cells from mothers and infants, and the proportion of infants with transmitted drug resistance mutations.

4. To explore the cost effectiveness of de-centralized birth testing for HIV in Botswana

Study Design:

This is a longitudinal observational cohort study that will evaluate the potential benefits of near-POC birth testing and the use of very early DTG-based ART in HIV-infected infants in Botswana. The study is implementing an optimal standard-of-care (early testing and rapid start of the recommended ART regimen for children), and therefore it is not considered a clinical trial.

Study population:

HIV-exposed neonates at high risk of HIV acquisition for screening and HIV-infected neonates who are study eligible and their HIV-infected mothers (age 18 or older) will represent the population enrolled in the treatment cohort.

Sample size:

We plan to enroll 10-30 neonates who test HIV-positive and are able to initiate ART within 7 days after birth in Botswana.

Sample size for targeted Birth Screening and Infant POC HIV Testing: Our experience in EIT provides evidence that we will have a high acceptability for immediate POC Cepheid Xpert® HIV-1 testing. Based on this we anticipate that of a total of ~1200 possible screens that will be available at selected centers over the 30 months accrual period, 900 actual screens will occur (accounting for 25% missed screens for refusals, weekends and holidays, and imperfect risk factor assessment).

Sample size for the DTG Treatment Cohort: sample size calculations are based on the percentage of children fully suppressed at 12 weeks. Based on our EIT numbers, 22/40 (55%) achieved viral suppression within 12 weeks of treatment initiation to <40 copies/ml. Hence, in the event that 20 children participate in this study, we will have 80% power to detect a 25% difference in 12-week suppression from treatment initiation.

Study Duration: Enrolled children will be followed for at least 96 weeks.

Sponsor: Eunice Kennedy Shriver National Institute of Child Health & Human Development