Adherence to antiretroviral therapy, virologic failure and workload at the Rustenburg Provincial Hospital

Background: Adherence to antiretroviral therapy (ART) is a strong predictor of progression to AIDS and death. It remains the most important potentially alterable factor that determines treatment outcomes.Methods: The study is a cross-sectional survey of self-reported adherence to ART and associated factors. It included a randomly selected sample of 100 adult patients who began ART between June 2006 and December 2007. A modified Adult AIDS Clinical Trials Group questionnaire was used. The analysis compared self-reported adherence levels by factor and viral load test results.Results: Only 71% of patients had an adherence > 95%. Poor adherence was related to changes in daily routines (being away from home [21%] and busy with other things [17%]). All patients with symptoms suggestive of clinical depression had virologic failure. More unemployed patients (50.7%) had virologic failure than did employed patients (40%) (p = < 0.05). The clinic had a tenfold increase in patient enrolment and a ninefold decline in staff-to-patient ratio, and the proportion of patients lost to follow-up doubled in the preceding four years.Conclusion: Adherence to ART was poor. The capacity of the clinic to manage patients adequately has declined significantly. Decentralisation of ART services to primary health care facilities should be considered.Keywords: adherence; ART; HIV; human resource; South Afric

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

Directly observed antiretroviral therapy: a systematic review and meta-analysis of randomised clinical trials.

BACKGROUND: Directly observed therapy has been recommended to improve adherence for patients with HIV infection who are on highly active antiretroviral therapy, but the benefit and cost-effectiveness of this approach has not been established conclusively. We did a systematic review and meta-analysis of randomised trials of directly observed versus self-administered antiretroviral treatment. METHODS: We did duplicate searches of databases (from inception to July 27, 2009), searchable websites of major HIV conferences (up to July, 2009), and lay publications and websites (March-July, 2009) to identify randomised trials assessing directly observed therapy to promote adherence to antiretroviral therapy in adults. Our primary outcome was virological suppression at study completion. We calculated relative risks (95% CIs), and pooled estimates using a random-effects method. FINDINGS: 12 studies met our inclusion criteria; four of these were done in groups that were judged to be at high risk of poor adherence (drug users and homeless people). Ten studies reported on the primary outcome (n=1862 participants); we calculated a pooled relative risk of 1.04 (95% CI 0.91-1.20, p=0.55), and noted moderate heterogeneity between the studies (I(2)= 53.8%, 95% CI 0-75.7, p=0.0247) for directly observed versus self-administered treatment. INTERPRETATION: Directly observed antiretroviral therapy seems to offer no benefit over self-administered treatment, which calls into question the use of such an approach to support adherence in the general patient population. FUNDING: None

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

Bacille Calmette-Guérin (BCG) vaccine and potential cross-protection against SARS-CoV-2 infection - Assumptions, knowns, unknowns and need for developing an accurate scientific evidence base

After a century of controversies on its usefulness in protection against TB, underlying mechanisms of action, and benefits in various groups and geographical areas, the BCG vaccine is yet again a focus of global attention- this time due to the global COVID-19 pandemic caused by the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Recent studies have shown that human CD4+ and CD8+ T-cells primed with a BCG-derived peptide developed high reactivity to its corresponding SARS-CoV-2-derived peptide. Furthermore, BCG vaccine has been shown to substantially increase interferon-gamma (IFN-g) production and its effects on CD4+ T-cells and these non-specific immune responses through adjuvant effect could be harnessed as cross protection against severe forms of COVID-19.The completion of ongoing BGG trials is important as they may shed light on the mechanisms underlying BCG-mediated immunity and could lead to improved efficacy, increased tolerance of treatment, and identification of other ways of combining BCG with other immunotherapies

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

Timing of antiretroviral therapy and adverse pregnancy outcomes : a systematic review and meta-analysis

BACKGROUND: Although life-long combination antiretroviral therapy (ART) is recommended for all HIV-infected individuals, there are limited data on pregnancy outcome with ART initiation pre-conception. We assessed the safety of ART initiated pre-conception versus post-conception on adverse pregnancy outcome. METHODS: We conducted a systematic review of studies from low-, middle-, and high-income countries. We searched Cochrane Central Register of Controlled Trials, EMBASE, LILACS, MEDLINE for randomized trials, quasi-randomized trials and prospective cohort studies conducted between 01 January 1980 to 01 June 2016). Risk ratios were pooled using a random-effects model. FINDINGS: Eleven studies were included (N=19,189 mother-infant pairs). Women initiating ART pre-conception compared to post-conception were significantly more likely to deliver preterm (pooled risk ratio[RR]=1·20, 95% confidence interval[CI] 1·01-1·14, 10 studies), very preterm (RR=1·53, 95%CI 1·22-1·92, two studies), or have low birth weight (LBW) infants (RR=1·30, 95%CI 1·04-1·62, two studies). Data on neonatal mortality was limited. We found no increase in very LBW (RR=0.18, 95% CI 0.02-1.51, one study), small for gestational age (SGA) (RR = 1·13, 95% CI 0·94-1·35, two studies), severe SGA (RR=1·09, 95%CI 0·82-1·45, one study), stillbirth (RR= RR=1·30, 95% CI 0·99-1·69, two studies) or congenital anomalies (RR= RR=1·24, 95% CI 0·61-2·49, one study). INTERPRETATION: The benefits of ART for maternal health and prevention of perinatal transmission outweigh risks, but there remain limited, poor quality data on the extent/severity of these risks. We found elevated preterm delivery and low birth weight rates associated with pre-conception ART. As pre-conception ART rapidly increases globally, it will be critical to monitor for potential adverse pregnancy outcomes

Lower Pill Burden and Once-Daily Antiretroviral Treatment Regimens for HIV Infection: A Meta-Analysis of Randomized Controlled Trials

Background. Contemporary antiretroviral treatment regimens are simpler than in the past, with lower pill burden and once-daily dosing frequency common. We performed a meta-analysis of randomized controlled trials (RCTs) to investigate the impact of pill burden and once-daily vs twice-daily dosing on ART adherence and virological outcomes. Methods. A literature search of 4 electronic databases through 31 March 2013 was used. RCTs comparing once-daily vs twice-daily ART regimens that also reported on adherence and virological suppression were included. Study design, study population characteristics, intervention, outcome measures, and study quality were extracted. Study quality was rated using the Cochrane risk-of-bias tool. Results. Nineteen studies met our inclusion criteria (N = 6312 adult patients). Higher pill burden was associated with both lower adherence rates (P = .004) and worse virological suppression (P < .0001) in both once-daily and twice-daily subgroups, although the association with adherence in the once-daily subgroup was not statistically significant. The average adherence was modestly higher in once-daily regimens than twice-daily regimens (weighted mean difference = 2.55%; 95% confidence interval [CI], 1.23 to 3.87; P = .0002). Patients on once-daily regimens did not achieve virological suppression more frequently than patients on twice-daily regimens (relative risk [RR] = 1.01; 95% CI, 0.99 to 1.03; P = .50). Both adherence and viral load suppression decreased over time, but adherence decreased less with once-daily dosing than with twice-daily dosing. Conclusions. Lower pill burden was associated with both better adherence and virological suppression. Adherence, but not virological suppression, was slightly better with once- vs twice-daily regimens