Results from the LIFE study conducted in Mozambique and Tanzania demonstrated that identifying HIV-infection in neonates and starting HIV treatment as early as birth reduces early infant mortality. However, this study also demonstrated that it is difficult to administer infant HIV treatments due to poor palatability of the infant drug formulation, socio-behavioural constrains for mothers, and care linkage challenges. This resulted in poor treatment adherence and efficacy as measured by viral load suppression rates in the blood.

The LIFE2Scale, funded by EDCTP and DZIF, targets to expand and optimize treatment and prevention interventions for 6000 mothers living with HIV and their newborns, and translate our previous research findings into policy and practice. We focus on primary healthcare and decentralized procedures to reduce access inequities in rural areas, applied in a hub & spoke model. Within a step-wedged cluster randomized design, 12 clusters gradually implement interventions, supporting identification of high-risk for vertical HIV transmission (maternal PoC VL screening at delivery, socio-behavioural constrains), linked with immediate birth test & treat procedures for neonates. A cluster is defined as one hub offering PoC HIV diagnostic services and several affiliated spoke health facilities. Procedures are supported by eHealth based linkage for HIV diagnostics and result dissemination, high risk targeted enhanced counselling, and institutionalized cases management support beyond routine services. The main objective of this study is to assess a more individual approach of closing the gap towards paediatric HIV elimination by optimized risk assessment and affiliated management procedures within one week post-delivery. The study further contains socio-behavioural and implementation science components focused on mothers and health care providers, as well as health economics analysis to assess sustainability within health systems. For HIV-infected infants immediately starting ART, we aim to confirm our previously observed impact on early infant mortality, hypothesising greater infant viral suppression rates with improved dolutegravir based paediatric regimens. Viral isolated are further characterized for drug resistance and against a broad range of broadly neutralizing antibodies (bnAbs), supporting current preventing and therapeutic bnAb strategies in this population.

Study recruitment started in April 2024, and study procedures are expected to be completed by December 2025.

In this cluster-randomized trial, funded by EDCTP, UNAIDS and DZIF, we allocated 28 primary public health facilities in Mozambique and Tanzania to interventions, providing PoC-early infant diagnosis and antiretroviral treatment from birth, or control, starting these at 4-8 weeks according to standard procedures. The primary outcome was to assess the clinical impact of birth test & treat procedures by the proportions of combined clinical events (mortality, morbidity, retention, viral treatment failure, treatment toxicities) between arms among HIV-positive infants at 18 months. We further evaluated if PoC load testing in mothers at delivery identifies high-risk scenarios for HIV transmission from the mother to her child, resulting into improved enhanced prophylactic infant treatments (IPT) in HIV-exposed infants and subsequently vertical transmission rates. Procedures were associated with a cost-effectiveness analysis and focused on feasibility and acceptability aspects for nurses and midwives to be conducted in a timely manner in order to guide national HIV programs. This study also included drug acquired and transmitted drug resistance analysis in the background of recommended IPT and lopinavir/ based infant ART regimens, as well as HIV reservoir analysis in HIV-infected infants receiving ART as early as birth

This study was conducted from 2019 to 2022. First results presented at the CROI 2023 Conference (Abstract 129 and 132) , final results are currently published.

The Baby Study (funded by DZIF) was conducted from 2015-2016 at several maternities in Tanzania. The study evaluated the accuracy and operational feasibility of the Cepheid Xpert® HIV-1 Qual assay for PoC-EID testing from fresh blood samples (Xpert-POC) and dried blood spots (DBS) samples (Xpert-DBS) against Roche TaqMan DBS HIV-DNA and/or plasma HIV-RNA testing at obstetric health facilities at birth, and weeks 1, 2, 3 and 6 postpartum in HIV-exposed infants. At week 6, 15 (2.5%) out of 614 infants were diagnosed with HIV; 10 (66.7%) of them at birth with a median HIV-RNA of 4570 copies/ml. At birth, the Xpert- PoC and Xpert-DBS were 100% sensitive (95%CI PoC: 69.2-100%, DBS: 66.4-100%) and 100% specific (PoC: 92.1-100%, DBS: 88.4-100%). Five infants with intra/postpartum HIV-infection were all correctly diagnosed by the Xpert® HIV-1 Qual assay at week three. In two cases, Xpert-PoC testing correctly identified HIV infection when DBS tests (Xpert and TaqMan) were negative suggesting a greater sensitivity. In two infants with confirmed HIV at birth, all HIV tests were negative at week six, possibly because of viral suppression under nevirapine prophylaxis. Problems were reported in 183/2736 (6.7%) of Xpert-PoC tests, mostly related to power cuts (57.9%). Nurses and midwives overall positively evaluated birth PoC EID procedures, especially appreciating real time test & treat procedures in response with mothers. However, procedures added to work-load and the wish for more focused responsibility tasking, more time and release from other routine work burden was reported.

The study also evaluated the accuracy and operational feasibility of the Cepheid Xpert® HIV-1 Viral Load (VL) in mothers against Roche TaqMan plasma HIV-RNA testing at delivery. Analysis was performed from 597 women, 21.8% of those revealed VL >1000 copies/mL, and using the Xpert VL system from 592 women with 22.2% of cases with VL >1000 copies/mL. The mean differences in HIV-RNA outcome between both assays was 0.188 log10 copies/mL (95%CI: 0.118 to 0.257), with a higher limit of 1.875 and a lower limit of -1.499 standard deviations of the mean. The sensitivity of the Xpert to detect HIV-RNA >1000 copies/mL as compared to the Roche TaqMan VL as gold standard was 95.3% (95%CI: 90.2 to 98.3), the specificity 97.6% (95.8 to 98.8), the positive predictive value 91.8% (85.8 to 95.8), and the negative predictive value 98.7% (97.2 to 99.5).

In Mozambique a series of studies were conducted since 2014 evaluating vertical transmission rates, the accuracy and operational feasibility of the Alere™ q HIV-1/2 Detect (Abbott HIV-1/2 Detect) against the Roche TaqMan, as well as the impact of PoC EID birth test & treat on the initiation of infant ART. The sensitivity and specificity of PoC EID testing were 98.5% (95% confidence interval (CI): 91.7 to 99.9, n = 65) and 99.9% (95% CI: 99.3 to 100, n = 762), respectively. PoC EID versus DBS referral standard of cate testing was affiliated with a significant increased proportion of infant initiating ART within the first 60 day postpartum (89.7% versus 12.8%; RR 7.34; P < 0.001). Furthermore, maternal VL screening at birth revealed a diagnostic performance of the Abbott m-PIMA HIV-1/2 VL assay against Roche TaqMan VL was evaluated. Using a threshold of 1000 copies/mL, the sensitivity and specificity of the POC VL assay were 95.0% (95% CI: 91.6% to 97.3%) and 96.5% (95% CI: 94.2% to 98.0%). The operational feasibility of on-site, nurse-performed PoC EID and VL procedures was overall demonstrated, supporting decentralization and task shifting of diagnostic procedures at primary health care facilities.