Enablers and barriers to vaccine uptake and handwashing practices to prevent and control COVID-19 in Kenya, Uganda, and Tanzania: a systematic review

The global emergence of coronavirus disease 2019 (COVID-19) posed unprecedented challenges, jeopardizing decades of progress in healthcare systems, education, and poverty eradication. While proven interventions such as handwashing and mass vaccination offer effective means of curbing COVID-19 spread, their uptake remains low, potentially undermining future pandemic control efforts. This systematic review synthesized available evidence of the factors influencing vaccine uptake and handwashing practices in Kenya, Uganda, and Tanzania in the context of COVID-19 prevention and control. We conducted an extensive literature search across PubMed, Science Direct, and Google Scholar databases following Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. Out of 391 reviewed articles, 18 were eligible for inclusion. Some of the common barriers to handwashing in Kenya, Uganda, and Tanzania included lack of trust in the government’s recommendations or messaging on the benefits of hand hygiene and lack of access to water, while some of the barriers to vaccine uptake included vaccine safety and efficacy concerns and inadequate awareness of vaccination sites and vaccine types. Enablers of handwashing practices encompassed hand hygiene programs and access to soap and water while those of COVID-19 vaccine uptake included improved access to vaccine knowledge and, socio-economic factors like a higher level of education. This review underscores the pivotal role of addressing these barriers while capitalizing on enablers to promote vaccination and handwashing practices. Stakeholders should employ awareness campaigns and community engagement, ensure vaccine and hygiene resources’ accessibility, and leverage socio-economic incentives for effective COVID-19 prevention and control.Clinical trial registration: [https://clinicaltrials.gov/], identifier [CRD42023396303]

Dynamic MAIT cell response with progressively enhanced innateness during acute HIV-1 infection.

Mucosa-associated invariant T (MAIT) cell loss in chronic HIV-1 infection is a significant insult to antimicrobial immune defenses. Here we investigate the response of MAIT cells during acute HIV-1 infection utilizing the RV217 cohort with paired longitudinal pre- and post-infection samples. MAIT cells are activated and expand in blood and mucosa coincident with peak HIV-1 viremia, in a manner associated with emerging microbial translocation. This is followed by a phase with elevated function as viral replication is controlled to a set-point level, and later by their functional decline at the onset of chronic infection. Interestingly, enhanced innate-like pathways and characteristics develop progressively in MAIT cells during infection, in parallel with TCR repertoire alterations. These findings delineate the dynamic MAIT cell response to acute HIV-1 infection, and show how the MAIT compartment initially responds and expands with enhanced function, followed by progressive reprogramming away from TCR-dependent antibacterial responses towards innate-like functionality

Switch to long-acting cabotegravir and rilpivirine in virologically suppressed adults with HIV in Africa (CARES): week 48 results from a randomised, multicentre, open-label, non-inferiority trial

Background Long-acting injectable cabotegravir and rilpivirine is licensed for individualised treatment of HIV-1 infection in resource-rich settings. Additional evidence is required to support use in African treatment programmes where demographic factors, viral subtypes, previous treatment, and delivery and monitoring approaches differ. The aim of this study was to determine whether switching to long-acting therapy with injections every 8 weeks is non-inferior to daily oral therapy in Africa. Methods CARES is a randomised, open-label, non-inferiority trial being conducted at eight sites in Uganda, Kenya, and South Africa. Participants with HIV viral load below 50 copies per mL on oral antiretroviral therapy and no history of virological failure were randomly assigned (1:1; web-based, permuted blocks) to receive cabotegravir (600 mg) and rilpivirine (900 mg) by intramuscular injection every 8 weeks, or to continue oral therapy. Viral load was monitored every 24 weeks. The primary outcome was week 48 viral load below 50 copies per mL, assessed with the Food and Drug Administration snapshot algorithm (non-inferiority margin 10 percentage points) in the intention-to-treat exposed population. This trial is registered with the Pan African Clinical Trials Registry (202104874490818) and is ongoing up to 96 weeks. Findings Between Sept 1, 2021, and Aug 31, 2022, we enrolled 512 participants (295 [58%] female; 380 [74%] previous non-nucleoside reverse transcriptase inhibitor exposure). Week 48 viral load was below 50 copies per mL in 246 (96%) of 255 participants in the long-acting therapy group and 250 (97%) of 257 in the oral therapy group (difference –0·8 percentage points; 95% CI –3·7 to 2·3), demonstrating non-inferiority (confirmed in per-protocol analysis). Two participants had virological failure in the long-acting therapy group, both with drug resistance; none had virological failure in the oral therapy group. Adverse events of grade 3 or greater severity occurred in 24 (9%) participants on long-acting therapy and ten (4%) on oral therapy; one participant discontinued long-acting therapy (for injection-site reaction). Interpretation Long-acting therapy had non-inferior efficacy compared with oral therapy, with a good safety profile, and can be considered for African treatment programmes

Infants Receiving Very Early Antiretroviral Therapy Have High CD4 Counts in the First Year of Life.

UNLABELLED: We followed 54 infants with in utero HIV after initiating very early antiretroviral treatment. At weeks 24 and 48, ≥80% had CD4 ≥1500 cells/mm3 and CD4% ≥25%. Routine Pneumocystis jirovecii pneumonia prophylaxis in the first year of life may not be necessary for all very early treated infants. CLINICAL TRIALS REGISTRATION: NCT02140255

Prospective International Study of Incidence and Predictors of Immune Reconstitution Inflammatory Syndrome and Death in People Living With Human Immunodeficiency Virus and Severe Lymphopenia

Background. Patients living with human immunodeficiency virus (PLWH) with low CD4 counts are at high risk for immune reconstitution inflammatory syndrome (IRIS) and death at antiretroviral therapy (ART) initiation. Methods. We investigated the clinical impact of IRIS in PLWH and CD4 counts 106 μg/mL and BMI <15.6 kg/m2 as predictive of death. Conclusions. For PLWH with severe immunosuppression initiating ART, baseline low BMI and hemoglobin and high CRP and D-dimer levels may be clinically useful predictors of IRIS and death risk

Dynamic MAIT cell response with progressively enhanced innateness during acute HIV-1 infection.

Mucosa-associated invariant T (MAIT) cell loss in chronic HIV-1 infection is a significant insult to antimicrobial immune defenses. Here we investigate the response of MAIT cells during acute HIV-1 infection utilizing the RV217 cohort with paired longitudinal pre- and post-infection samples. MAIT cells are activated and expand in blood and mucosa coincident with peak HIV-1 viremia, in a manner associated with emerging microbial translocation. This is followed by a phase with elevated function as viral replication is controlled to a set-point level, and later by their functional decline at the onset of chronic infection. Interestingly, enhanced innate-like pathways and characteristics develop progressively in MAIT cells during infection, in parallel with TCR repertoire alterations. These findings delineate the dynamic MAIT cell response to acute HIV-1 infection, and show how the MAIT compartment initially responds and expands with enhanced function, followed by progressive reprogramming away from TCR-dependent antibacterial responses towards innate-like functionality