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Abstract Background The physiological effects of renin-angiotensin system modulation in acute respiratory distress syndrome (ARDS) remain controversial and have not been investigated in randomized trials. We sought to determine whether angiotensin-II treatment is associated with improved oxygenation in shock-associated ARDS. Methods Post-hoc subgroup analysis of the Angiotensin Therapy for High Output Shock (ATHOS-3) trial. We studied patients who met modified Berlin ARDS criteria at enrollment. The primary outcome was PaO2/FiO2-ratio (P:F) at 48-h adjusted for baseline P:F. Secondary outcomes included oxygenation index, ventilatory ratio, PEEP, minute-ventilation, hemodynamic measures, patients alive and ventilator-free by day-7, and mortality. Results Of 81 ARDS patients, 34 (42%) and 47 (58%) were randomized to angiotensin-II or placebo, respectively. In angiotensin-II patients, mean P:F increased from 155 mmHg (SD: 69) at baseline to 265 mmHg (SD: 160) at hour-48 compared with no change with placebo (148 mmHg (SD: 63) at baseline versus 164 mmHg (SD: 74) at hour-48)(baseline-adjusted difference: + 98.4 mmHg [95%CI 35.2–161.5], p = 0.0028). Similarly, oxygenation index decreased by − 6.0 cmH2O/mmHg at hour-48 with angiotensin-II versus − 0.4 cmH2O/mmHg with placebo (baseline-adjusted difference: -4.8 cmH2O/mmHg, [95%CI − 8.6 to − 1.1], p = 0.0273). There was no difference in PEEP, minute ventilation, or ventilatory ratio. Twenty-two (64.7%) angiotensin-II patients had sustained hemodynamic response to treatment at hour-3 versus 17 (36.2%) placebo patients (absolute risk-difference: 28.5% [95%CI 6.5–47.0%], p = 0.0120). At day-7, 7/34 (20.6%) angiotensin-II patients were alive and ventilator-free versus 5/47(10.6%) placebo patients. Day-28 mortality was 55.9% in the angiotensin-II group versus 68.1% in the placebo group. Conclusions In post-hoc analysis of the ATHOS-3 trial, angiotensin-II was associated with improved oxygenation versus placebo among patients with ARDS and catecholamine-refractory vasodilatory shock. These findings provide a physiologic rationale for trials of angiotensin-II as treatment for ARDS with vasodilatory shock. Trial Registration: ClinicalTrials.Gov Identifier: NCT02338843 (Registered January 14th 2015).

ObjectivesTo eliminate vertical transmission of HIV, global institutions recommend using a risk-guided approach for HIV prevention services in antenatal and postnatal settings. Identifying predictors of maternal HIV acquisition can inform the development of risk-guided approaches, but individual studies of predictors can have limited power and generalizability.MethodsWe conducted a systematic review and narrative synthesis to identify common predictors of maternal HIV acquisition in sub-Saharan Africa (SSA). We searched four databases for full-text articles that estimated associations between at least one predictor and risk of HIV acquisition among pregnant and/or lactating women (PLW) in SSA. We restricted our synthesis to predictors assessed in at least four study populations. For these predictors, we summarized how each predictor was defined and used vote counting and descriptive statistics to characterize overall trends.ResultsWe identified 26 eligible publications that summarized results from 24 unique studies. Studies were implemented in 12 countries between 1988 and 2021 and enrolled a total of 164,480 PLW at risk of acquiring HIV. Of the 66 predictors evaluated, 16 met our inclusion criteria. Estimated associations tended to be imprecise and variability in how predictors were measured precluded meta-analyses. We observed trends towards a higher risk of maternal HIV acquisition among young women and women who reported early coital debut, multiple partnerships, sexually transmitted infections, being unaware of partner HIV status, or having a partner living with HIV. In most studies, PLW in stable, monogamous relationships experienced a lower risk of acquiring HIV than those who were single, separated, or in a polygynous marriage. HIV risk perception, condom use, and vaginal drying were also commonly associated with HIV acquisition risk.ConclusionsIn our systematic review and narrative synthesis, we identified several easily measured characteristics that were associated with HIV acquisition among PLW in multiple study populations across SSA. Such findings can support the development and refinement of risk-guided approaches for HIV prevention in the region.