"The effect of 48-weeks azithromycin therapy on levels of soluble biomarkers associated with HIV-associated chronic lung disease".

OBJECTIVES: HIV-associated immune activation contributes to chronic lung disease (CLD) in children and adolescents living with HIV. Azithromycin has immunomodulatory and anti-microbial properties that may be useful for treating HIV-associated CLD (HCLD). This study describes the effect of azithromycin on expression of plasma soluble biomarkers in children and adolescents with HCLD. METHODS: This study was nested within a multi-site double-blind, placebo controlled, randomised controlled trial (RCT) of azithromycin in individuals aged 6-19 years with HCLD (defined as FEV1 z-score < -1) in Malawi and Zimbabwe (BREATHE (NCT02426112)). Participants were randomized 1:1 to once-weekly oral azithromycin with weight-based dosing, for 48 weeks, or placebo. Twenty-six plasma soluble biomarkers were measured on a MagPix Luminex instrument at enrolment, after 48-weeks of treatment and 24-weeks after treatment cessation. Mixed effects models were constructed to compare biomarker expression across treatment and placebo groups. RESULTS: Weekly azithromycin was associated with reduced levels of C-Reactive Protein (CRP), E-Selectin, Matrix metalloproteinase 10 (MMP-10). Treatment effects for all soluble biomarkers were not sustained 24-weeks after treatment cessation with biomarker expression returning to pre-treatment levels. CONCLUSIONS: We observed real-world effects of azithromycin on acute inflammation, neutrophil accumulation, and extracellular matrix degradation, that were not sustained after treatment cessation. These results are pertinent when using azithromycin for its immunomodulatory properties, or targeting pathways represented by the soluble biomarkers in this study.

Interrupted Access to and Use of Family Planning Among Youth in a Community-Based Service in Zimbabwe During the First Year of the COVID-19 Pandemic.

The COVID-19 pandemic has had serious impacts on economic, social, and health systems, and fragile public health systems have become overburdened in many countries, exacerbating existing service delivery challenges. This study describes the impact of the COVID-19 pandemic on family planning services within a community-based integrated HIV and sexual and reproductive health intervention for youth aged 16-24 years being trialled in Zimbabwe (CHIEDZA). It examines the experiences of health providers and clients in relation to how the first year of the pandemic affected access to and use of contraceptives.

Brief Report: Improving Early Infant Diagnosis Observations: Estimates of Timely HIV Testing and Mortality Among HIV-Exposed Infants.

BACKGROUND: Improving efforts toward elimination of mother-to-child transmission of HIV requires timely early infant diagnosis (EID) among all HIV-exposed infants, but the occurrence of timely EID and infant survival may be underascertained in routine, facility-bound program data. METHODS: From March 2015 to May 2015, we traced a random sample of HIV-positive mother and HIV-exposed infant pairs lost to follow-up for EID in facility registers in Zimbabwe. We incorporated updated information into weighted survival analyses to estimate incidence of EID and death. Reasons for no EID were surveyed from caregivers. RESULTS: Among 2651 HIV-positive women attending antenatal care, 1823 (68.8%) infants had no documented EID by 3 months of age. Among a random sample of 643 (35.3%) HIV-exposed infants lost to follow-up for EID, vital status was ascertained among 371 (57.7%) and updated care status obtained from 256 (39.8%) mothers traced. Among all HIV-infected mother-HIV-exposed infant pairs, weighted estimates found cumulative incidence of infant death by 90 days of 3.9% (95% confidence interval: 3.4% to 4.4%). Cumulative incidence of timely EID with death as a competing risk was 60%. The most frequently cited reasons for failure to uptake EID were "my child died" and "I didn't know I should have my child tested." CONCLUSIONS: Our findings indicate uptake of timely EID among HIV-exposed infants is underestimated in routine health information systems. High, early mortality among HIV-exposed infants underscores the need to more effectively identify HIV-positive mother-HIV exposed infant pairs at high risk of adverse outcomes and loss to follow-up for enhanced interventions.