Effectiveness of Dolutegravir in People on Rifampin-Based Tuberculosis Treatment

Background: Tenofovir-lamivudine-dolutegravir (TLD) is the WHO-preferred first-line regimen for people with HIV, but drug-drug interactions between dolutegravir (DTG) and rifampin (RIF) require an additional 50mg DTG (TLD+50) in people receiving tuberculosis (TB)/HIV co-treatment. RIF is a key drug in TB treatment, but is a potent inducer of metabolizing enzymes and efflux transporters, which can markedly lower drug concentrations. There are limited data on the effectiveness of TLD+50 in people with TB/HIV from program settings. Method(s): We conducted a prospective, observational study at 12 sites in 6 countries (Haiti, Kenya, Malawi, South Africa, Uganda, Zimbabwe). Participants received concomitant TLD+50 and RIF-based TB treatment provided as standard of care by HIV and TB treatment programs. Primary outcome was HIV-1 RNA <1000 copies/mL (cpm) at end of TB treatment. New DTG resistance mutations were defined as those present at end of TB treatment but not present at start. Result(s): From 11/2019-6/2021, we enrolled 91 participants with TB/HIV, including 75 ART-naive participants (82%) starting TLD+50 after a median of 15 days on TB treatment, 10 ART-naive participants (11%) starting TLD+50 and RIF together, 5 (5%) starting TB treatment and changing to TLD+50 after a median of 3.3y on TLD, and 1 (1%) starting RIF and TLD+50 after changing from EFV/3TC/TDF. Median age was 37y (IQR 32-43), 35% were female, 100% cis-gender, median CD4 count was 120 cells/mm3 (IQR 50-295), 87% had HIV-1 RNA >1000 copies/mL. Two participants died during TB treatment (week 4 disseminated TB, week 12 suspected COVID-19), 1 interrupted TLD+50 due to jaundice;and 1 discontinued TB treatment due to drug-induced liver injury. Among 89 surviving participants, 6 were lost to follow-up and a further 10 had no HIV-1 RNA result due to missed or remote visits. Primary virologic outcome was therefore assessed in 73 (80%), of whom 69 (95%, Wald 95% CI 89-100%) had HIV-1 RNA <=1000 cpm;68 (93%) had HIV-1 RNA <200 cpm. No sex specific differences in viral suppression were observed. No DTG resistance mutations were detected among 4 participants with HIV-1 RNA >1000 cpm. Conclusion(s): Concomitant RIF-containing TB treatment and TLD+50 was welltolerated and achieved excellent viral suppression in a cohort of predominantly ART-naive people with TB/HIV. These multi-country data from program settings support feasibility and effectiveness of current treatment approaches for TB/ HIV co-infection.

EFFECTS of the COVID-19 LOCKDOWN on MENTAL HEALTH CARE USE in PEOPLE LIVING with HIV

Background: Mental health complications are highly prevalent among people living with HIV. Left untreated mental health complications can negatively affect HIV treatment outcomes. In March 2020, South Africa introduced a lockdown in response to the COVID-19 pandemic. Lockdowns might induce or exacerbate mental health conditions and limit access to treatment. We studied the effect of the lockdown on mental health care use among HIV-positive beneficiaries of a South African private sector medical aid scheme. Methods: We performed an interrupted time series analysis using insurance claims from January 1, 2017, to June 1, 2020 of HIV-positive beneficiaries aged 18 years or older from a large private sector medical aid scheme. Weekly outpatient consultation and hospital admission rates were calculated for substance use disorders (ICD10 F10-F19), serious mental disorders (F20-F29, F31), depression (F32, F34.1, F54), anxiety (F40-F48), and any mental disorder (F00-F99). We estimated adjusted odds ratios (OR) for the effect of the lockdown on weekly hospital admission and outpatient consultation rates. Results: 61,873 adults living with HIV were followed up for a median of 151 weeks. Hospital admission rates (OR 0.38;95% CI 0.27-0.54) and outpatient consultation rates (OR 0.72;95% CI 0.64-0.82) for any mental disorder decreased substantially after the implementation of the lockdown in March 2020 and did not recover to pre-lockdown levels until June 1, 2020 (Figure). Substantial decreases were observed in hospital admissions rates for substance use disorders (OR 0.13;95% CI 0.02-0.73), depression (OR 0.30;95% CI 0.16-0.54), and serious mental disorders (OR 0.58;95%CI 0.17-2.02). Decreases in outpatient consultation rates were observed for substance use disorders (OR 0.21;95% CI 0.08-0.55), anxiety disorders (OR 0.64;95% CI 0.54-0.76), depression (OR 0.71;95% CI 0.62-0.82), and serious mental disorders (OR 0.85;95% CI 0.72-1.00). Conclusion: Reduced mental health care contact rates during the COVID-19 lockdown likely reflect a substantial unmet need for mental health services with potential long-term consequences for people living with HIV and comorbid mental health complications. Steps to ensure access and continuity of mental health services during future lockdowns should be considered.

Essential medicine selection during the COVID-19 pandemic: Enabling access in uncharted territory

The COVID-19 pandemic requires urgent decisions regarding treatment policy in the face of rapidly evolving evidence. In response, the South African Essential Medicines List Committee established a subcommittee to systematically review and appraise emerging evidence, within very short timelines, in order to inform the National Department of Health COVID-19 treatment guidelines. To date, the subcommittee has reviewed 14 potential treatments, and made recommendations based on local context, feasibility, resource requirements and equity. Here we describe the rapid review and evidence-to-decision process, using remdesivir and dexamethasone as examples. Our experience is that conducting rapid reviews is a practical and efficient way to address medicine policy questions under pandemic conditions.