Impact of Point-of-Care Birth Test-and-Treat on Clinical Outcomes Among Infants With HIV: A Cluster-Randomized Trial in Mozambique and Tanzania

Abstract

Background: We assessed the impact of point-of-care (PoC) test-and-treat at birth on clinical outcomes and viral suppression among human immunodeficiency virus (HIV)-positive infants in Mozambique and Tanzania.

Methods: This cluster-randomized trial allocated health facilities to intervention, providing PoC testing and antiretroviral treatment (ART) at birth and week 4-8, or control, starting these at week 4-8. The primary outcome was proportions of clinical events (mortality, morbidity, retention, virological failure, toxicity) among HIV-positive infants at month 18. We estimated incidence rate ratios adjusted for timing of HIV detection (aIRR) and reported viral suppression <1000 copies/mL.

Results: Among 6602 neonates enrolled during October 2019-September 2021, 125 were diagnosed with HIV by week 12. In the intervention arm, 38 of 69 (55.1%) were diagnosed at birth. In the control arm, 27 of 56 (48.2%) were retrospectively detected to be HIV-positive at birth, of whom 6 of 56 (10.7%) died or were lost to follow-up before testing. Median age at ART initiation was 6 (intervention) versus 33 days (control). Birth test-and-treat was not associated with a significant reduction in clinical outcomes up to month 18 (53 [76.8%] vs 48 [85.7%]; aIRR, 0.857 [95% confidence interval, .505-1.492]), but showed a 68% relative reduction in 6-month mortality. Viral suppression was poor overall.

Conclusions: PoC test-and-treat at birth is feasible in resource-poor settings and resulted in clinically relevant reduction of early mortality, though improved clinical outcomes were not sustained to month 18. Poor viral suppression may undermine early benefits, calling for better pediatric treatments and adherence interventions. Clinical Trials Registration. NCT04032522.

Keywords: HIV; birth testing; neonatal treatment; point-of-care testing; test-and-treat.

Graphical Abstract

This graphical abstract is also available at Tidbit: https://tidbitapp.io/institutional-portal/clinical-infectious-diseases/tidbits/impact-of-point-of-care-birth-test-and-treat-on-clinical-outcomes-among-infants-with-hiv-a-cluster-randomized-trial-in-mozambique-and-tanzania-b24b5824-f7c1-4058-aba0-d1aaeb7c4117/update

Figure 1.

Enrollment and follow-up attendance at birth and months 3–18 with newly HIV-positive infants shown for birth, week 4–8, and month 3. ^aBased on average HIV-positive deliveries per site. ^bReasons for withdrawing consent listed as mother/family not accepting the HIV diagnosis of the child (n = 3) or not available (n = 1). ^cReason for withdrawing consent not available (n = 1). All other instances of consent withdrawn due to mother/family not accepting the child’s HIV diagnosis. Abbreviations: DBS, dried blood spot; HIV, human immunodeficiency virus; M3, month 3; M6, month 6; M12, month 12; M18, month 18; W4-8, week 4–8.

Figure 2.

Event-free probability of (A) death, (B) medical event (hospitalization or severe medical condition), and (C) loss to retention between study groups in 125 infants with HIV up to month 18. Censored values (+) indicate last known follow-up time for infants still at risk.

Figure 3.

A, Sankey diagram showing the proportions of infants in each viral load (VL) category by timepoint (rectangular blocks) and the size and directions of transfers between categories and timepoints (flow lines). The category “Unknown” (gray) includes infants not on antiretroviral therapy, infants who have died or were lost to retention, and infants without VL results. Proportions are calculated without including “Unknown” values in the denominator. B, Violin plots showing the distribution of log₁₀ VL by timepoint between intervention (red) and control groups (blue). Colored lines show the change in medians. The horizontal dashed line at log₁₀ 3.0 represents the cutoff value for viral suppression. C, Frequency and proportion of infants in each VL category by timepoint. Abbreviations: HIV-1, human immunodeficiency virus type 1; M3, month 3; M6, month 6; M12, month 12; M18, month 18; Med., medium; Supp., suppressed; VL, viral load; W4-8, week 4–8.

Figure 4.

Most recent viral load by occurrence of (A) combined event (death, medical event, grade III/IV laboratory event, HIV viral load >1000 copies/mL at month 18 or the last study visit, or loss to retention) (B, death, C, medical event, and D, loss to retention) cumulatively up to month 6, 12, and 18. Bonferroni-corrected P values calculated using the Mann-Whitney U test. Abbreviations: HIV-1, human immunodeficiency virus type 1; M6, month 6; M12, month 12; M18, month 18.