Emerging priorities for HIV service delivery

Nathan Ford and co-authors discuss global priorities in the provision of HIV prevention and treatment services

Persistent methicillin-susceptible bacteremia rapidly cleared with cefazolin and ertapenem combination therapy in a patient with COVID-19

Methicillin-susceptibl

Early antiretroviral therapy not associated with higher cryptococcal meningitis mortality in people with human immunodeficiency virus in high-income countries: An international collaborative cohort study

BACKGROUND: Randomized controlled trials (RCTs) from low- and middle-income settings suggested that early initiation of antiretroviral therapy (ART) leads to higher mortality rates among people with HIV (PWH) who present with cryptococcal meningitis (CM). There is limited information about the impact of ART timing on mortality rates in similar people in high-income settings. METHODS: Data on ART-naive PWH with CM diagnosed from 1994 to 2012 from Europe/North America were pooled from the COHERE, NA-ACCORD, and CNICS HIV cohort collaborations. Follow-up was considered to span from the date of CM diagnosis to earliest of the following: death, last follow-up, or 6 months. We used marginal structural models to mimic an RCT comparing the effects of early (within 14 days of CM) and late (14-56 days after CM) ART on all-cause mortality, adjusting for potential confounders. RESULTS: Of 190 participants identified, 33 (17%) died within 6 months. At CM diagnosis, their median age (interquartile range) was 38 (33-44) years; the median CD4+ T-cell count, 19/μL (10-56/μL); and median HIV viral load, 5.3 (4.9-5.6) log10 copies/mL. Most participants (n = 157 [83%]) were male, and 145 (76%) started ART. Mimicking an RCT, with 190 people in each group, there were 13 deaths among participants with an early ART regimen and 20 deaths among those with a late ART regimen. The crude and adjusted hazard ratios comparing late with early ART were 1.28 (95% confidence interval, .64-2.56) and 1.40 (.66-2.95), respectively. CONCLUSIONS: We found little evidence that early ART was associated with higher mortality rates among PWH presenting with CM in high-income settings, although confidence intervals were wide

A mid-level health manager intervention to promote uptake of isoniazid preventive therapy among people with HIV in Uganda: A cluster randomised trial

BACKGROUND: Despite longstanding guidelines endorsing isoniazid preventive therapy (IPT) for people with HIV, uptake is low across sub-Saharan Africa. Mid-level health managers oversee IPT programmes nationally; interventions aimed at this group have not been tested. We aimed to establish whether providing structured leadership and management training and facilitating subregional collaboration and routine data feedback to mid-level managers could increase IPT initiation among people with HIV compared with standard practice. METHODS: We conducted a cluster randomised trial in Uganda among district-level health managers. We randomly assigned clusters of between four and seven managers in a 1:1 ratio to intervention or control groups. Our intervention convened managers into mini-collaboratives facilitated by Ugandan experts in tuberculosis and HIV, and provided business leadership and management training, SMS platform access, and data feedback. The control was standard practice. Participants were not masked to trial group, but study statisticians were masked until trial completion. The primary outcome was IPT initiation rates among adults with HIV in facilities overseen by participants over a period of 2 years (2019-21). We conducted prespecified analyses that excluded the third quarter of 2019 (Q3-2019) to understand intervention effects independent of a national 100-day IPT push tied to a financial contingency during Q3-2019. This trial is registered with ClinicalTrials.gov (NCT03315962), and is ongoing. FINDINGS: Between Nov 15, 2017, and March 14, 2018, managers from 82 of 82 eligible districts (61% of Uganda\u27s 135 districts) were enrolled and randomised: 43 districts to intervention, 39 to control. Intervention delivery took place between Dec 6, 2017, and Feb 2, 2022. Over 2 years, IPT initiation rates were 0·74 versus 0·65 starts per person-year in intervention versus control groups (incidence rate ratio [IRR] 1·14, 95% CI 0·88-1·46; p=0·16). Excluding Q3-2019, IPT initiation was higher in the intervention group versus the control group: 0·32 versus 0·25 starts per person-year (IRR 1·27, 95% CI 1·00-1·61; p=0·026). INTERPRETATION: Following an intervention targeting managers in more than 60% of Uganda\u27s districts, IPT initiation rates were not significantly higher in intervention than control groups. After accounting for large increases in IPT from a 100-day push in both groups, the intervention led to significantly increased IPT rates, sustained after the push and during the COVID-19 pandemic. Our findings suggest that interventions centred on mid-level health managers can improve IPT implementation on a large, subnational scale, and merit further exploration to address key public health challenges for which strong evidence exists but implementation remains suboptimal. FUNDING: National Institute of Allergy and Infectious Diseases

The Kanyakla study: Randomized controlled trial of a microclinic social network intervention for promoting engagement and retention in HIV care in rural western Kenya

BACKGROUND: Existing social relationships are a potential source of social capital that can enhance support for sustained retention in HIV care. A previous pilot study of a social network-based \u27microclinic\u27 intervention, including group health education and facilitated HIV status disclosure, reduced disengagement from HIV care. We conducted a pragmatic randomized trial to evaluate microclinic effectiveness. METHODS: In nine rural health facilities in western Kenya, we randomized HIV-positive adults with a recent missed clinic visit to either participation in a microclinic or usual care (NCT02474992). We collected visit data at all clinics where participants accessed care and evaluated intervention effect on disengagement from care (≥90-day absence from care after a missed visit) and the proportion of time patients were adherent to clinic visits (\u27time-in-care\u27). We also evaluated changes in social support, HIV status disclosure, and HIV-associated stigma. RESULTS: Of 350 eligible patients, 304 (87%) enrolled, with 154 randomized to intervention and 150 to control. Over one year of follow-up, disengagement from care was similar in intervention and control (18% vs 17%, hazard ratio 1.03, 95% CI 0.61-1.75), as was time-in-care (risk difference -2.8%, 95% CI -10.0% to +4.5%). The intervention improved social support for attending clinic appointments (+0.4 units on 5-point scale, 95% CI 0.08-0.63), HIV status disclosure to close social supports (+0.3 persons, 95% CI 0.2-0.5), and reduced stigma (-0.3 units on 5-point scale, 95% CI -0.40 to -0.17). CONCLUSIONS: The data from our pragmatic randomized trial in rural western Kenya are compatible with the null hypothesis of no difference in HIV care engagement between those who participated in a microclinic intervention and those who did not, despite improvements in proposed intervention mechanisms of action. However, some benefit or harm cannot be ruled out because the confidence intervals were wide. Results differ from a prior quasi-experimental pilot study, highlighting important implementation considerations when evaluating complex social interventions for HIV care. TRIAL REGISTRATION: Clinical trial number: NCT02474992

Examining the effects of HIV self-testing compared to standard HIV testing services in the general population: A systematic review and meta-analysis

BACKGROUND: We updated a 2017 systematic review and compared the effects of HIV self-testing (HIVST) to standard HIV testing services to understand effective service delivery models among the general population. METHODS: We included randomized controlled trials (RCTs) comparing testing outcomes with HIVST to standard testing in the general population and published between January 1, 2006 and June 4, 2019. Random effects meta-analysis was conducted and pooled risk ratios (RRs) were reported. The certainty of evidence was determined using the GRADE methodology. FINDINGS: We identified 14 eligible RCTs, 13 of which were conducted in sub-Saharan Africa. Support provided to self-testers ranged from no/basic support to one-on-one in-person support. HIVST increased testing uptake overall (RR:2.09; 95% confidence interval: 1.69-2.58; INTERPRETATION: HIVST appears to be safe and effective among the general population in sub-Saharan Africa with a range of delivery models. It identified and linked additional people with HIV to care. These findings support the wider availability of HIVST to reach those who may not otherwise access testing