Twice-daily versus once-daily antiretroviral therapy and coformulation strategies in HIV-infected adults: benefits, risks, or burden?

The recent development of once-daily antiretroviral agents and fixed-dose combination formulations has been an important development in antiretroviral regimen simplification. Recent studies indicate that once-daily antiretroviral regimens improve adherence, especially in antiretroviral-naïve patients and in difficult-to-treat populations, such as the homeless or marginally housed. However, there are potential risks with the higher peak and lower trough plasma drug concentrations that may result from certain once-daily formulations. Due to the multifactorial and complex nature of adherence behavior, clinicians’ efforts to improve patient adherence should not be limited to prescribing once-daily regimens, but should also consider social support, side effect management, and adherence support tools, such as pillbox organizers and other targeted interventions. Additional research will clarify the benefits of once-daily and fixed-dose combination regimens on clinical and virologic outcomes. Comprehensive cost-benefit analysis of regimen simplification could help facilitate evidence-based decisions regarding antiretroviral regimen choices

Predictors associated with critical care need and in-hospital mortality among children with laboratory-confirmed COVID-19 infection in a high HIV infection burden region

IntroductionDespite the extra mortality associated with COVID-19 death globally, there is scant data on COVID-19-related paediatric mortality in Sub-Saharan Africa. We assessed predictors of critical care needs and hospital mortality in South African children with laboratory-confirmed SARS-CoV-2 infection in region with high HIV infection burden.MethodsWe conducted a secondary multicentre analysis of the AFREhealth cohort (a multinational, multicentre cohort of paediatric COVID-19 clinical outcomes across six African countries) of children admitted to the Inkosi Albert Luthuli, a quaternary hospital in KwaZulu-Natal, South Africa, with confirmed RT-PCR between March 2020 and December 2020. We constructed multivariable logistic regression to explore factors associated with the need for critical care (high care/ intensive care hospitalisation or oxygen requirement) and cox-proportional hazards models to further assess factors independently associated with in-hospital death.ResultsOf the 82 children with PCR-confirmed SARS-CoV-2 infection (mean ± SD age: 4.2 ± 4.4 years), 35(42.7%) were younger than one year, 52(63%) were female and 59(71%) had a pre-existing medical condition. Thirty-seven (45.2%) children required critical care (median (IQR) duration: 7.5 (0.5–13.5) days) and 14(17%) died. Independent factors associated with need for critical care were being younger than 1 year (aPR: 3.02, 95%CI: 1.05–8.66; p = 0.04), having more than one comorbidity (aPR: 2.47, 95%CI: 1.32–4.61; p = 0.004), seizure (aPR: 2.39, 95%CI: 1.56–3.68; p < 0.001) and impaired renal function. Additionally, independent predictors of in-hospital mortality were exposure to HIV infection (aHR: 6.8, 95%CI:1.54–31.71; p = 0.01), requiring invasive ventilation (aHR: 3.59, 95%CI: 1.01–12.16, p = 0.048) and increase blood urea nitrogen (aHR: 1.06, 95%CI: 1.01–1.11; p = 0.017). However, children were less likely to die from COVID-19 if they were primarily admitted to quaternary unit (aHR: 0.23, 95%CI: 0.1–0.86, p = 0.029).ConclusionWe found a relatively high hospital death rate among children with confirmed COVID-19. During COVID-19 waves, a timely referral system and rapid identification of children at risk for critical care needs and death, such as those less than one year and those with comorbidities, could minimize excess mortality, particularly in high HIV-infection burden countries

Treatment simplification in HIV-infected adults as a strategy to prevent toxicity, improve adherence, quality of life and decrease healthcare costs

Since the advent of highly active antiretroviral therapy (HAART), the treatment of human immunodeficiency virus (HIV) infection has become more potent and better tolerated. While the current treatment regimens still have limitations, they are more effective, more convenient, and less toxic than regimens used in the early HAART era, and new agents, formulations and strategies continue to be developed. Simplification of therapy is an option for many patients currently being treated with antiretroviral therapy (ART). The main goals are to reduce pill burden, improve quality of life and enhance medication adherence, while minimizing short- and long-term toxicities, reducing the risk of virologic failure and maximizing cost-effectiveness. ART simplification strategies that are currently used or are under study include the use of once-daily regimens, less toxic drugs, fixed-dose coformulations and induction-maintenance approaches. Improved adherence and persistence have been observed with the adoption of some of these strategies. The role of regimen simplification has implications not only for individual patients, but also for health care policy. With increased interest in ART regimen simplification, it is critical to study not only implications for individual tolerability, toxicity, adherence, persistence and virologic efficacy, but also cost, scalability, and potential for dissemination and implementation, such that limited human and financial resources are optimally allocated for maximal efficiency, coverage and sustainability of global HIV/AIDS treatment

Life expectancy of persons receiving combination antiretroviral therapy in low-income countries: a cohort analysis from Uganda

Little is known about the effect of combination antiretroviral therapy (cART) on life expectancy in sub-Saharan Africa

Comparison of Antiretroviral Therapy Adherence Among HIV-Infected Older Adults with Younger Adults in Africa: Systematic Review and Meta-analysis.

As access to antiretroviral treatment in low- and middle-income countries improves, the number of older adults (aged ≥ 50 years) living with HIV is increasing. This study compares the adherence to antiretroviral treatment among older adults to that of younger adults living in Africa. We searched PubMed, Medline, Cochrane CENTRAL, CINAHL, Google Scholar and EMBASE for keywords (HIV, ART, compliance, adherence, age, Africa) on publications from 1st Jan 2000 to 1st March 2016. Eligible studies were pooled for meta-analysis using a random-effects model, with the odds ratio as the primary outcome. Twenty studies were included, among them were five randomised trials and five cohort studies. Overall, we pooled data for 148,819 individuals in two groups (older and younger adults) and found no significant difference in adherence between them [odds ratio (OR) 1.01; 95% CI 0.94-1.09]. Subgroup analyses of studies using medication possession ratio and clinician counts to measure adherence revealed higher proportions of older adults were adherent to medication regimens compared with younger adults (OR 1.06; 95% CI 1.02-1.11). Antiretroviral treatment adherence levels among older and younger adults in Africa are comparable. Further research is required to identify specific barriers to adherence in the aging HIV affected population in Africa which will help in development of interventions to improve their clinical outcomes and quality of life

Mobile Health Technology for Enhancing the COVID-19 Response in Africa: A Potential Game Changer?

Disclosure: J. B. N. is also a coprincipal investigator of TOGETHER, an adaptive randomized clinical trial of novel agents for treatment of high-risk outpatient COVID-19 patients in South Africa; supported by the Bill & Melinda Gates Foundation; and a member of COVID-19 Scientific Committee of the Democratic Republic of the Congo. R. T. L. is an infectious disease specialist and global health researcher with support from the Canadian Institutes of Health Research, Michael Smith Foundation, for Health Research and Grand Challenges Canada, and is cofounder of the WelTel (www.weltelhealth.com), as well as a member of the roster of experts for the WHO Task Force for Digital Health. He served on the front lines of the 2003 SARS epidemic and led a consortium on the Ebola outbreak response in 2014. Sir Zumla is co-PI of the Pan-African Network on Emerging and Re-Emerging Infections (PANDORA-ID-NET: https://www.pandora-id.net/) funded by the European and Developing Countries Clinical Trials Partnership the EU Horizon 2020 Framework Programme for Research and Innovation. Sir Zumla is recipient of a National Institutes of Health Research senior investigator award

Advancing global health through cardiovascular research, mentorship, and capacity building: in memoriam, professor Bongani Mayosi (1967–2018)

We are deeply saddened by the passing of Professor Bongani Mayosi. Bongani was one of the inaugural board members of Pilot and Feasibility Studies. He contributed greatly to the design and conduct of pilot and feasibility studies in cardiovascular research. Before his untimely death on Friday, July 27, 2018, he rose rapidly through the ranks to become a top cardiologist and one of the premier medical researchers in South Africa, Africa and the World Born in Mthatha, Eastern Cape Province on January 28, 1967, Bongani Mawethu Mayosi followed in his father’s footsteps to become a doctor. He trained at the now Nelson R. Mandela School of Medicine at University of KwaZulu-Natal, where he received his M.B., Ch.B. (Cum Laude) in 1989 and also met his wife, Professor and Head of Dermatology, Nonhlanhla Khumalo, in their first week of medical school. In 1990, the pair made their way to Port Elizabeth to work at the Livingstone Hospital as interns, before moving to Cape Town to establish long-term careers. After completing his specialist training in internal medicine and cardiology at the University of Cape Town (UCT), Professor Mayosi moved to Oxford University, UK, on a prestigious Nuffield Medical Fellowship where he completed a D.Phil. in cardiovascular genetics at the Wellcome Trust Centre for Human Genetics

Emerging antiretroviral drug resistance in sub-Saharan Africa: novel affordable technologies are needed to provide resistance testing for individual and public health benefits

In industrialized countries, viral load monitoring and genotypic antiretroviral drug resistance testing (GART) play an important role in the selection of initial and subsequent combination antiretroviral therapy (cART) regimens. In contrast, resource constraints in Africa limit access to assays that could detect virologic failure, transmitted drug resistance (TDR) and acquired drug resistance to cART. This has adverse consequences for both individual and public health. Although the further roll-out of antiretrovirals for prevention, including preexposure prophylaxis (PrEP) and universal test and treat (UTT) strategies, could reduce HIV-1 incidence, these strategies may increase TDR [1,2]. Here, we present arguments that the scale up of antiretrovirals use should be accompanied by cost-effective assays for early detection of virologic failure, surveillance of TDR and GART for individual patient management

Risk Factors for Suboptimal Antiretroviral Therapy Adherence in HIV-Infected Adolescents in Gaborone, Botswana: A Pilot Cross-Sectional Study

Objective: Little is known about factors associated with suboptimal antiretroviral treatment (ART) adherence among adolescents in Sub-Saharan Africa. Our objective was to determine the level of ART adherence and predictors of non-adherence among human immunodeficiency virus (HIV)-infected adolescents at the Botswana-Baylor Children\u27s Clinical Centre of Excellence in Gaborone, Botswana. Methods: In a cross-sectional study, 82 HIV-infected adolescents receiving ART and their caregivers were administered a structured questionnaire. The patient\u27s clinical information was retrieved from medical records. Outcome measures included excellent pill count ART adherence (\u3e95%) and virologic suppression (HIV viral load \u3c400 copies/mL). Multivariate logistic regression analysis was performed to identify independent predictors of ART non-adherence. Results: The overall median (interquartile range) ART adherence was 99% (96.5–100) (N = 82). Seventy-six percent of adolescents had excellent pill count ART adherence levels and 94% achieved virologic suppression. Male adolescents made up 65% of the non-adherent group (P = 0.02). Those who displayed suboptimal ART adherence were more likely to report having ever missed ART doses due to failure to pick up medication at the pharmacy (30.0% versus 9.7%, P = 0.03). In the multivariate logistic regression model, male sex (odds ratio [OR] 3.29, 95% confidence interval [CI] 1.13–9.54; P = 0.03) was the only factor which was independently associated with suboptimal ART adherence. Conclusions: A high proportion of HIV-infected adolescents studied had excellent ART adherence and virologic suppression, with male adolescents at higher risk of suboptimal adherence than females. Further research to investigate how gender relates to suboptimal adherence may aid in the design of targeted intervention strategies