COVID-19 impact on newly initiated and restarted antiretroviral treatment patients in the Eastern Cape, South Africa.

BACKGROUND: Initiating newly diagnosed people living with human immunodeficiency virus (HIV) onto antiretroviral treatment (ART) and retaining patients on treatment are vital to South Africa's ART programme. In 2020, coronavirus disease 2019 (COVID-19) and its accompanying containment (lockdown) measures presented unprecedented challenges to achieving these objectives. AIM: This study describes the impact of COVID-19 and related restrictions on district-level numbers of newly diagnosed people living with HIV and defaulting ART patients. SETTING: Buffalo City Metropolitan Municipality (BCMM) in the Eastern Cape of South Africa. METHODS: Mixed-methods approach: Monthly aggregated electronic patient data (newly initiated and restarted on ART) from 113 public healthcare (PHC) facilities were analysed (December 2019 to November 2020) across varying levels of COVID-19 lockdown regulation periods; telephonic in-depth interviews at 10 rural BCMM PHC facilities were conducted with facility staff, community health workers (CHWs) and intervention personnel. RESULTS: The number of newly initiated ART patients decreased dramatically compared with pre-COVID-19 levels. The overall number of restarted ART patients increased in response to fears of co-infection with COVID-19. Facility-level communications and community outreach promoting HIV testing and treatment were disrupted. Novel approaches to providing services to ART patients were developed. CONCLUSION: Programmes for identifying undiagnosed people living with HIV and services aimed at retaining ART patients in care were profoundly impacted by COVID-19. The value of CHWs was highlighted, as were communication innovations.Contribution: This study describes the impact of COVID-19 and related regulations on HIV testing, ART initiation and adherence to treatment in a District of the Eastern Cape of South Africa.

The effect of supervision on community health workers' effectiveness with households in rural South Africa: A cluster randomized controlled trial.

BACKGROUND: Community health workers (CHWs) can supplement professional medical providers, especially in rural settings where resources are particularly scarce. Yet, outcomes of studies evaluating CHWs effectiveness have been highly variable and lack impact when scaled nationally. This study examines if child and maternal outcomes are better when existing government CHWs, who are perinatal home visitors, receive ongoing enhanced supervision and monitoring, compared to standard care. METHODS AND FINDINGS: A cluster randomized controlled effectiveness trial was conducted comparing outcomes over 2 years when different supervision and support are provided. Primary health clinics were randomized by clinic to receive monitoring and supervision from either (1) existing supervisors (Standard Care (SC); n = 4 clinics, 23 CHWs, 392 mothers); or (2) supervisors from a nongovernmental organization that provided enhanced monitoring and supervision (Accountable Care [AC]; n = 4 clinic areas, 20 CHWs, 423 mothers). Assessments were conducted during pregnancy and at 3, 6, 15, and 24 months post-birth with high retention rates (76% to 86%). The primary outcome was the number of statistically significant intervention effects among 13 outcomes of interest; this approach allowed us to evaluate the intervention holistically while accounting for correlation among the 13 outcomes and considering multiple comparisons. The observed benefits were not statistically significant and did not show the AC's efficacy over the SC. Only the antiretroviral (ARV) adherence effect met the significance threshold established a priori (SC mean 2.3, AC mean 2.9, p < 0.025; 95% CI = [0.157, 1.576]). However, for 11 of the 13 outcomes, we observed an improvement in the AC compared to the SC. While the observed outcomes were not statistically significant, benefits were observed for 4 outcomes: increasing breastfeeding for 6 months, reducing malnutrition, increasing ARV adherence, and improving developmental milestones. The major study limitation was utilizing existing CHWs and being limited to a sample of 8 clinics. There were no major study-related adverse events. CONCLUSIONS: Supervision and monitoring were insufficient to improve CHWs' impact on maternal and child outcomes. Alternative strategies for staff recruitment and narrowing the intervention outcomes to the specific local community problems are needed for consistently high impact. TRIAL REGISTRATION: Clinicaltrials.gov, NCT02957799.

Hepatocellular carcinoma presentation and prognosis among Nigerian adults with and without HIV.

INTRODUCTION: Hepatocellular carcinoma (HCC) is an increasing cause of mortality in Nigeria among persons with HIV (PLH), as access to antiretroviral therapy (ART) improves. In this study we describe clinical, radiological, and laboratory characteristics in Nigerian adults with HCC, with and without HIV, and examine how HIV impacts survival. METHODS: This prospective observational study was conducted between August 2018 and November 2021 at two Nigerian hospitals [Jos University Teaching Hospital (JUTH) and Lagos University Teaching Hospital (LUTH)]. Subjects ≥18 years with HCC diagnosed according to American Association for the Study of Liver Diseases (AASLD) criteria were included. Baseline characteristics were compared, and Kaplan-Meier curves were generated to estimate survival. RESULTS: 213 subjects [177 (83%) without HIV and 36 (17%) with HIV (PLH)] were enrolled. Median age was 52 years (IQR 42,60) and most subjects were male (71%). 83% PLH were on antiretroviral therapy (ART). Hepatitis B surface antigen (HBsAg) positivity was similar between the two groups [91/177 (51%) without HIV vs. 18/36 (50%) with HIV; p = 0.86]. 46/213 (22%) subjects had active hepatitis C (anti-HCV+/HCV RNA>10 IU/mL). Cirrhosis was more common in PLH but there were no other significant differences in clinical and tumor characteristics between the groups. Overall, 99% subjects were symptomatic and 78% in late-stage HCC. Median overall survival was significantly shorter in PLH vs. without HIV (0.98 months vs 3.02 months, HR = 1.55, 95%CI 1.02, 2.37, p = 0.04). This association was not significant after adjusting for known risk factors including gender, current alcohol use, alpha-fetoprotein (AFP), albumin, and total bilirubin (HR = 1.38, 95%CI 0.84, 2.29, p = 0.21). CONCLUSION: HCC presented late with an extremely poor overall prognosis, highlighting the urgent need for more intensive surveillance in Nigeria to diagnose HCC at earlier stages. Early diagnosis and management of viral hepatitis, and access to HCC therapies, could prevent early mortality among persons with HCC, especially among PLH.

Antimicrobial resistance from a One Health perspective in Zambia: a systematic review.

BACKGROUND: Antimicrobial resistance (AMR) is widely acknowledged as a global health problem, yet its extent is not well evaluated, especially in low-middle income countries. It is challenging to promote policies without focusing on healthcare systems at a local level, therefore a baseline assessment of the AMR occurrence is a priority. This study aimed to look at published papers relating to the availability of AMR data in Zambia as a means of establishing an overview of the situation, to help inform future decisions. METHODS: PubMed, Cochrane Libraries, Medical Journal of Zambia and African Journals Online databases were searched from inception to April 2021 for articles published in English in accordance with the PRISMA guidelines. Retrieval and screening of article was done using a structured search protocol with strict inclusion/exclusion criteria. RESULTS: A total of 716 articles were retrieved, of which 25 articles met inclusion criteria for final analysis. AMR data was not available for six of the ten provinces of Zambia. Twenty-one different isolates from the human health, animal health and environmental health sectors were tested against 36 antimicrobial agents, across 13 classes of antibiotics. All the studies showed a degree of resistance to more than one class of antimicrobials. Majority of the studies focused on antibiotics, with only three studies (12%) highlighting antiretroviral resistance. Antitubercular drugs were addressed in only five studies (20%). No studies focused on antifungals. The most common organisms tested, across all three sectors, were Staphylococcus aureus, with a diverse range of resistance patterns found; followed by Escherichia coli with a high resistance rate found to cephalosporins (24-100%) and fluoroquinolones (20-100%). CONCLUSIONS: This review highlights three important findings. Firstly, AMR is understudied in Zambia. Secondly, the level of resistance to commonly prescribed antibiotics is significant across the human, animal, and environmental sectors. Thirdly, this review suggests that improved standardization of antimicrobial susceptibility testing in Zambia could help to better delineate AMR patterns, allow comparisons across different locations and tracking of AMR evolution over time.

The impact of the COVID-19 pandemic on mental health, associated factors and coping strategies in people living with HIV: a scoping review.

INTRODUCTION: The COVID-19 pandemic and associated measures implemented by authorities have created additional stressors and increased the risk of psychological illnesses among people living with HIV (PLWH). Yet, there is no collective evidence on the mental health status of this population during the global pandemic and associated factors. This scoping review aimed to synthesize the evidence in the current literature related to the mental health outcomes and challenges faced by PLWH during the COVID-19 pandemic, identify the associated factors with psychological distress and summarize various coping strategies to ease these psychological distresses used by this population. METHODS: We conducted a scoping review following the PRISMA-ScR guideline and a literature search in four electronic databases in August 2022. Three reviewers independently screened all the search records and extracted the data from studies that met the inclusion criteria. Factors associated with worsened mental health outcomes were synthesized according to the socio-ecological framework. RESULTS: Among 1100 research records, 45 articles met the eligibility criteria and were included in the final review and data extraction, most of which were quantitative analyses. PLWH reported high rates of mental health problems during the pandemic. Multi-level factors were associated with increased psychological distress, including substance use, antiretroviral adherence, social support, financial hardship and economic vulnerability during the pandemic. PLWH used social media as a coping strategy to foster social support to deal with growing mental distress. Increased mental health illnesses were associated with increased substance use, it was also found associated with suboptimal medication adherence and antiretroviral therapy (ART) care engagement. DISCUSSION: PLWH experienced high rates of mental health illnesses, such as depression during the global COVID-19 pandemic. There is an urgent need to provide comprehensive HIV treatment and mental health services as the pandemic continues to evolve. CONCLUSIONS: The review summarized how the mental health of PLWH was affected during the COVID-19 pandemic. Future work in the implementation of effective interventions to promote mental health in this population is needed, not only to ensure their quality of life but also to help them maintain ART adherence and healthcare during more unprecedented times.

Sexual Behaviour and Attitudes towards Safe Sex of Youth Receiving Antiretroviral Care at Public Health Facilities in Palapye District, Botswana.

BACKGROUND: Sexual behaviour of HIV-infected youths is very important in determining the direction of the HIV epidemic, as these youths are reservoirs of HIV and can propagate its transmission if they engage in risky sexual behaviours. However, support structures for secondary prevention are weak even in healthcare settings. There is a need to understand the sexual behaviour of these youths and, in turn, tailor appropriate secondary prevention strategies, hence the current study was designed to assess sexual behaviour and attitudes towards safe sex of youth receiving antiretroviral care at public health facilities in Palapye district, Botswana. METHOD: This quantitative, descriptive cross-sectional survey was used to describe the sexual behaviour and attitudes towards safe sex and identify factors associated with risky sexual behaviours among HIV-infected youths aged between 15 and 19 years receiving antiretroviral therapy (ART) care from public healthcare facilities in Palapye District, Botswana. RESULTS: A total of 188 youths participated in this study, 56% being females while 44% were males. We reported that 15.4% had ever had sex. At their last sexual encounter, more than half of the youths (51.7%) had not used condoms. More than a third of the participants were under the influence of alcohol during their last sexual experience. Generally, the youths had good attitudes towards safe sex, as most youths said they would prioritise protecting their sexual partners and themselves from HIV and STIs. Alcohol use, substance use and not considering religion as important were strongly associated with having ever had sex. CONCLUSIONS: A significant proportion of HIV-infected youths are sexually active, whereas their preventive practices such as condom use are poor despite good attitudes towards safe sex. Alcohol use, substance use and not perceiving religion as important were associated with risky sexual behaviours.

The quality of antiretroviral medicines: an uncertain problem.

OBJECTIVES: Substandard and falsified (SF) antiretrovirals (ARVs) risk poor outcomes and drug resistance, potentially affecting millions of people in need of treatment and prevention. We assessed the available evidence on SF ARV and related medical devices to discuss their potential public health impact. METHODS: Searches were conducted in Embase, PubMed, Google, Google Scholar, Web of Science and websites with interest in ARV quality in English and French up to 30 November 2021. Publications reporting on the prevalence of SF ARV were assessed in a quantitative analysis using the Medicine Quality Assessment Reporting Guidelines (MEDQUARG). RESULTS: We included 205 publications on SF ARV and 11 on SF medical devices. Nineteen prevalence surveys of SF ARV, published between 2003 and 2021, were included, with no surveys relevant to SF medical devices. The prevalence survey sample size ranged from 3 to 2630 samples (median (Q1-Q3): 16.0 (10.5-44.5); 3 (15.8%) used random outlet sampling methods. Of the 3713 samples included in the prevalence surveys, 1.4% (n=51) failed at least one test. Efavirenz, nevirapine and lamivudine-nevirapine-stavudine combination were the most surveyed ARV with failure frequencies of 3.6% (7/193), 2.6% (5/192) and 2.8% (5/177), respectively. The median (Q1%-Q3%) concordance with the MEDQUARG criteria was 42.3% (34.6%-55.8%). CONCLUSION: These results suggest that there are few data in the public domain of the quality of ARV in supply chains; the proportion of SF ARV is relatively low in comparison to other classes of essential medicines. Even a low proportion of the ARV supply chain being poor quality could make a large difference in the HIV/AIDS international landscape. The 95-95-95 target for 2026 and other international targets could be greatly hampered if even 1% of the millions of people taking ARV (for both prevention and prophylaxis) receive medicines that do not meet quality standards. More surveillance of SF ARV is needed to ensure issues are detected.

Factors influencing adherence to anti-retroviral therapy in amazonian indigenous people living with HIV/AIDS.

BACKGROUND: Indigenous communities in Peru has been historically affected by high mortality rates attributable to HIV-AIDS infection, associated with a low access to health services, and socio-cultural barriers. In this context, the study aimed to describe factors associated with antiretroviral treatment adherence in people from Awajun and Wampis indigenous communities, living with HIV-AIDS in a Peruvian Amazonian region. METHODS: A cross-sectional study was completed with a consecutive sample of people from indigenous communities (Awajun or Wampis) living with HIV, who were receiving antiretroviral treatment for at least the last three months. Participants were recruited between October 1 and December 30, 2021, from four districts of Bagua and Condorcanqui provinces in the Amazonian region. An ad-hoc questionnaire was used to collect information about demographic, economic, and socio-cultural factors and access to health services. The Simplified Medication Adherence Questionnaire (SMAQ) was used to evaluate adherence to antiretroviral therapy. Multivariate logistic regression analysis with backward stepwise was performed to explore factors that might influence adherence. RESULTS: Of the 208 participants, 28.8% reported complete adherence to antiretroviral treatment. The multivariate logistic regression showed that occupation (aPR: 1.86; 95%CI 1.15-3.02), economic income (aPR: 0.64; 95%CI 0.41-0.99), and adverse reactions to antiretroviral therapy (aPR: 0.36; 95%CI 0.18-0.70) were related to complete adherence to medication. CONCLUSION: Only a third of participants reported complete adherence to antiretroviral therapy. Factors associated with adherence to antiretroviral medication were related to socioeconomic conditions and adverse reactions to the therapeutic scheme. Interventions to improve adherence in indigenous people living with HIV should consider these factors in order to develop effective implementation strategies.

Changing attitudes towards HIV testing and treatment among three generations of men in Cameroon: a qualitative analysis using the Fogg Behavior Model.

INTRODUCTION: Men are less likely than women to test for HIV and promptly initiate antiretroviral treatment, resulting in advanced HIV disease and increased mortality rates among them. METHODS: In-depth interviews were conducted with men and leaders in the west and central regions of Cameroon. Men were recruited from existing community groups and stratified by age: 21-30 years, 31-40 years, and 41 years and older. Community leaders were recommended by the community dialogue structure chairman. Interviews were conducted using a semi-structured guide in English or French, depending on the participant's preference. Transcripts were coded in the MAXQDA v.12 software and analyzed using thematic analysis and by age group. The Fogg Behavior Model was used to gain a deeper understanding of the different perceptions across all age groups. RESULTS: Younger men (21-30 years) were generally more accepting of HIV testing, as it had become normative behavior. Although financial barriers could limit access, free testing was mentioned as a prompt to initiate HIV testing. The middle age men (31-40 years) had the most concerns about HIV testing interrupting their work day and recommended increasing testing locations and hours. The older men (41 + years) were the least motivated to get tested, citing worries about the impact on their social standing within the community. All age groups reported being motivated to begin treatment if they were found to be HIV-positive. Participants also provided insights regarding community HIV testing and treatment messaging. Younger and older men preferred to hear directly from qualified health professionals, but younger men noted that social media, radio, and TV could be utilized. Middle age men also identified TV and radio as effective mediums, if door-to-door messaging was not an option. CONCLUSIONS: The study highlights important considerations when planning future information-sharing activities for HIV testing and treatment. Since lived experiences differ across generations and societal roles continue to change, not only should the content of messages differ among the generations, but the means of communication must also be considered to ensure the messages are conveyed through a trusted source.

Managers' and providers' perspectives on barriers and facilitators for the implementation of differentiated service delivery models for HIV treatment in Mozambique: a qualitative study.

INTRODUCTION: In 2018, Mozambique's Ministry of Health launched a guideline for a nationwide implementation of eight differentiated service delivery models to optimize HIV service delivery and achieve universal coverage of HIV care and treatment. The models were (1) Fast-track, (2) Three-month Antiretrovirals Dispensing, (3) Community Antiretroviral Therapy Groups, (4) Adherence Clubs, (5) Family-approach, and three one-stop shop models for (6) Tuberculosis, (7) Maternal and Child Health, and (8) Adolescent-friendly Health Services. This study identified drivers of implementation success and failure across these differentiated service delivery models. METHODS: Twenty in-depth individual interviews were conducted with managers and providers from the Ministry of Health and implementing partners from all levels of the health system between July and September 2021. National-level participants were based in the capital city of Maputo, and participants at provincial, district and health facility levels were from Sofala province, a purposively selected setting. The Consolidated Framework for Implementation Research (CFIR) guided data collection and thematic analysis. Deductively selected constructs were assessed while allowing for additional themes to emerge inductively. RESULTS: The CFIR constructs of Relative Advantage, Complexity, Patient Needs and Resources, and Reflecting and Evaluating were identified as drivers of implementation, whereas Available Resources and Access to Knowledge and Information were identified as barriers. Fast-track and Three-month Antiretrovirals Dispensing models were deemed easier to implement and more effective in reducing workload. Adherence Clubs and Community Antiretroviral Therapy Groups were believed to be less preferred by clients in urban settings. COVID-19 (an inductive theme) improved acceptance and uptake of individual differentiated service delivery models that reduced client visits, but it temporarily interrupted the implementation of group models. CONCLUSIONS: This study described important determinants to be addressed or leveraged for the successful implementation of differentiated service delivery models in Mozambique. The models were considered advantageous overall for the health system and clients when compared with the standard of care. However, successful implementation requires resources and ongoing training for frontline providers. COVID-19 expedited individual models by loosening the inclusion criteria; this experience can be leveraged to optimize the design and implementation of differentiated service delivery models in Mozambique and other countries.

Attrition from HIV treatment after enrollment in a differentiated service delivery model: A cohort analysis of routine care in Zambia.

BACKGROUND: Many sub-Saharan Africa countries are scaling up differentiated service delivery (DSD) models for HIV treatment to increase access and remove barriers to care. We assessed factors associated with attrition after DSD model enrollment in Zambia, focusing on patient-level characteristics. METHODS: We conducted a retrospective record review using electronic medical records (EMR) of adults (≥15 years) initiated on antiretroviral (ART) between 01 January 2018 and 30 November 2021. Attrition was defined as lost to follow-up (LTFU) or died by November 30, 2021. We categorized DSD models into eight groups: fast-track, adherence groups, community pick-up points, home ART delivery, extended facility hours, facility multi-month dispensing (MMD, 4-6-month ART dispensing), frequent refill care (facility 1-2 month dispensing), and conventional care (facility 3 month dispensing, reference group). We used Fine and Gray competing risk regression to assess patient-level factors associated with attrition, stratified by sex and rural/urban setting. RESULTS: Of 547,281 eligible patients, 68% (n = 372,409) enrolled in DSD models, most commonly facility MMD (n = 306,430, 82%), frequent refill care (n = 47,142, 13%), and fast track (n = 14,433, 4%), with <2% enrolled in the other DSD groups. Retention was higher in nearly all DSD models for all dispensing intervals, compared to the reference group, except fast track for the ≤2 month dispensing group. Retention benefits were greatest for patients in the extended clinic hours group and least for fast track dispensing. CONCLUSION: Although retention in HIV treatment differed by DSD type, dispensing interval, and patient characteristics, nearly all DSD models out-performed conventional care. Understanding the factors that influence the retention of patients in DSD models could provide an important step towards improving DSD implementation.

Impact of interventions for tuberculosis prevention and care in South Africa - a systematic review of mathematical modelling studies.

BACKGROUND: Substantial additional efforts are needed to prevent, find and successfully treat tuberculosis (TB) in South Africa (SA). In thepast decade, an increasing body of mathematical modelling research has investigated the population-level impact of TB prevention and careinterventions. To date, this evidence has not been assessed in the SA context. OBJECTIVE: To systematically review mathematical modelling studies that estimated the impact of interventions towards the World HealthOrganization's End TB Strategy targets for TB incidence, TB deaths and catastrophic costs due to TB in SA. METHODS: We searched the PubMed, Web of Science and Scopus databases for studies that used transmission-dynamic models of TB in SAand reported on at least one of the End TB Strategy targets at population level. We described study populations, type of interventions andtheir target groups, and estimates of impact and other key findings. For studies of country-level interventions, we estimated average annualpercentage declines (AAPDs) in TB incidence and mortality attributable to the intervention. RESULTS: We identified 29 studies that met our inclusion criteria, of which 7 modelled TB preventive interventions (vaccination,antiretroviral treatment (ART) for HIV, TB preventive treatment (TPT)), 12 considered interventions along the care cascade for TB(screening/case finding, reducing initial loss to follow-up, diagnostic and treatment interventions), and 10 modelled combinationsof preventive and care-cascade interventions. Only one study focused on reducing catastrophic costs due to TB. The highest impactof a single intervention was estimated in studies of TB vaccination, TPT among people living with HIV, and scale-up of ART. Forpreventive interventions, AAPDs for TB incidence varied between 0.06% and 7.07%, and for care-cascade interventions between 0.05%and 3.27%. CONCLUSION: We describe a body of mathematical modelling research with a focus on TB prevention and care in SA. We found higherestimates of impact reported in studies of preventive interventions, highlighting the need to invest in TB prevention in SA. However, studyheterogeneity and inconsistent baseline scenarios limit the ability to compare impact estimates between studies. Combinations, rather thansingle interventions, are likely needed to reach the End TB Strategy targets in SA.

SARS-CoV-2 Omicron subvariants exhibit distinct fusogenicity, but similar sensitivity, to pan-CoV fusion inhibitors.

Continuous emergence of the Omicron variant, along with its subvariants, has caused an increasing number of infections, reinfections, and vaccine-breakthrough infections, seriously threatening human health. Recently, several new Omicron subvariants, such as BA.5, BA.2.75, BA.4.6, and BF.7, bearing distinct mutation profiles in their spike (S) proteins, have significantly increased their capacity to evade vaccine-induced immunity and have shown enhanced infectivity and transmissibility, quickly becoming dominant sublineages. In this study, we found the S proteins of these Omicron subvariants to have 2- to 4-fold more efficient membrane fusion kinetics than that of the original Omicron variant (BA.1), indicating that these novel Omicron subvariants might possess increased pathogenicity. We also identified that peptide-based pan-CoV fusion inhibitors, EK1 and EK1C4, showed equal efficacy against membrane fusion mediated by S proteins of the noted Omicron subvariants and infection by their pseudoviruses. Additionally, either immune sera induced by wild-type (WT) SARS-CoV-2 RBD-based vaccine or BA.2 convalescent sera showed potent synergism with EK1 against both WT SARS-CoV-2 and various Omicron subvariants, further suggesting that EK1-based fusion inhibitors are promising candidates for development as clinical antiviral agents against the currently circulating Omicron subvariants.

Evolution of Antiretroviral Drug Rilpivirine and Approach to Oncology.

Rilpivirine is an antiretroviral drug used to treat AIDS worldwide. The drug is a non-nucleoside reverse transcriptase inhibitor that halts the cDNA elongation process and, thus, the capacity of the HIV-1 virus to replicate. With the new wave of drug repurposing in recent years, rilpivirine has been studied in this regard. This drug is useful in Zika virus treatment, with in vivo results indicating regression in neuronal effects often associated with this infection. Several cancer types have also been researched, from breast to leukemia and pancreatic cancer, and rilpivirine has proved to have inhibitory effects in various cell lines with low concentrations, causing cellular death, apoptosis, and cell cycle arrest. The pathways are not yet established, but some works have hypothesized and demonstrated that rilpivirine causes inhibition of Aurora A kinase and has effects on the Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway and the vascular endothelial growth factors-receptors (VEGFs-VEGFRs) pathway, which are known to be altered in cancer and tumors and can be targeted for cancer treatment. Further testing and clinical trials are needed, but this review demonstrates the potential of rilpivirine's repurposing for cancer treatment.

Should we expect weight changes in people with HIV and a reported weight gain only by switching antiretroviral therapy?

Weight gain following the initiation or the switch of antiretroviral therapy (ART) is well documented and mainly associated with some of the most recent drugs, such as integrase strand transfer inhibitors and tenofovir alafenamide. However, limited data have been published on weight trends in ART-experienced people living with HIV (PLWH) with a long exposure to HIV infection and antiretroviral drugs. In our study, we assessed changes in weight after switching ART among PLWH who reported weight gain under a previous regimen.

Prediction of Coreceptor Tropism in HIV-1 Subtype C in Botswana.

It remains unknown whether the C-C motif chemokine receptor type 5 (CCR5) coreceptor is still the predominant coreceptor used by Human Immunodeficiency Virus-1 (HIV-1) in Botswana, where the HIV-1 subtype C predominates. We sought to determine HIV-1C tropism in Botswana using genotypic tools, taking into account the effect of antiretroviral treatment (ART) and virologic suppression. HIV-1 gp120 V3 loop sequences from 5602 participants were analyzed for viral tropism using three coreceptor use predicting algorithms/tools: Geno2pheno, HIV-1C Web Position-Specific Score Matrices (WebPSSM) and the 11/25 charge rule. We then compared the demographic and clinical characteristics of people living with HIV (PLWH) harboring R5- versus X4-tropic viruses using χ2 and Wilcoxon rank sum tests for categorical and continuous data analysis, respectively. The three tools congruently predicted 64% of viruses as either R5-tropic or X4-tropic. Geno2pheno and the 11/25 charge rule had the highest concordance at 89%. We observed a significant difference in ART status between participants harboring X4- versus R5-tropic viruses. X4-tropic viruses were more frequent among PLWH receiving ART (χ2 test, p = 0.03). CCR5 is the predominant coreceptor used by HIV-1C strains circulating in Botswana, underlining the strong potential for CCR5 inhibitor use, even in PLWH with drug resistance. We suggest that the tools for coreceptor prediction should be used in combination.

HIV Drug Resistance in Adults Initiating or Reinitiating Antiretroviral Therapy in Uruguay-Results of a Nationally Representative Survey, 2018-2019.

The first nationally representative cross-sectional HIV drug resistance (HIVDR) survey was conducted in Uruguay in 2018-2019 among adults diagnosed with HIV and initiating or reinitiating antiretroviral therapy (ART). Protease, reverse transcriptase, and integrase genes of HIV-1 were sequenced. A total of 206 participants were enrolled in the survey; 63.2% were men, 85.7% were >25 years of age, and 35.6% reported previous exposure to antiretroviral (ARV) drugs. The prevalence of HIVDR to efavirenz or nevirapine was significantly higher (OR: 1.82, p < 0.001) in adults with previous ARV drug exposure (20.3%, 95% CI: 18.7-22.0%) compared to adults without previous ARV drug exposure (12.3%, 11.0-13.8%). HIVDR to any nucleoside reverse transcriptase inhibitors was 10.3% (9.4-11.2%). HIVDR to ritonavir-boosted protease inhibitors was 1.5% (1.1-2.1%); resistance to ritonavir-boosted darunavir was 0.9% (0.4-2.1%) among adults without previous ARV drug exposure and it was not observed among adults with previous ARV drug exposure. Resistance to integrase inhibitors was 12.7% (11.7-13.8%), yet HIVDR to dolutegravir, bictegravir, and cabotegravir was not observed. The high level (>10%) of HIVDR to efavirenz highlights the need to accelerate the transition to the WHO-recommended dolutegravir-based ART. Access to dolutegravir-based ART should be prioritised for people reporting previous ARV drug exposure.

Future of Antiretroviral Drugs and Evolution of HIV-1 Drug Resistance.

Highly active antiretroviral (ARV) therapy has been used for many years, but the use in low- and middle-income countries of antiretroviral drugs with low genetic barrier to resistance, combined with limited availability of viral load testing, has led to higher rates of acquired drug resistance, sustaining the rate of transmitted drug resistance. Here, we describe the evolution of ARV drugs with the ongoing development of injectable long-acting forms and the requirements regarding all new ARV drugs (i.e., no transmitted drug resistance, no cross-resistance and high genetic barrier to resistance). Then, we report the evolution of both transmitted and acquired resistance regarding new ARV drugs. The WHO has set very ambitious but motivating goals for HIV testing, treatment and viral suppression, aiming to achieve rates of 95% for all three by 2025. Reaching these goals requires a wide implementation and use of close virological monitoring in LMICs.

The HIV Restriction Factor Profile in the Brain Is Associated with the Clinical Status and Viral Quantities.

HIV-encoded DNA, RNA and proteins persist in the brain despite effective antiretroviral therapy (ART), with undetectable plasma and cerebrospinal fluid viral RNA levels, often in association with neurocognitive impairments. Although the determinants of HIV persistence have garnered attention, the expression and regulation of antiretroviral host restriction factors (RFs) in the brain for HIV and SIV remain unknown. We investigated the transcriptomic profile of antiretroviral RF genes by RNA-sequencing with confirmation by qRT-PCR in the cerebral cortex of people who are uninfected (HIV[-]), those who are HIV-infected without pre-mortem brain disease (HIV[+]), those who are HIV-infected with neurocognitive disorders (HIV[+]/HAND) and those with neurocognitive disorders with encephalitis (HIV[+]/HIVE). We observed significant increases in RF expression in the brains of HIV[+]/HIVE in association with the brain viral load. Machine learning techniques identified MAN1B1 as a key gene that distinguished the HIV[+] group from the HIV[+] groups with HAND. Analyses of SIV-associated RFs in brains from SIV-infected Chinese rhesus macaques with different ART regimens revealed diminished RF expression among ART-exposed SIV-infected animals, although ART interruption resulted in an induced expression of several RF genes including OAS3, RNASEL, MX2 and MAN1B1. Thus, the brain displays a distinct expression profile of RFs that is associated with the neurological status as well as the brain viral burden. Moreover, ART interruption can influence the brain's RF profile, which might contribute to disease outcomes.

[News in HIV infection, long-acting injectable treatments]. / VIH : zoom sur les traitements injectables à longue durée d'action.

Long-acting injectable therapies have been added to the pharmacological arsenal available for the management of HIV infection, whether in the form of monotherapy (injectable cabotegravir) as part of pre-exposure prophylaxis (PrEP) or dual therapies (injectable cabotegravir/rilpivirine) for the treatment of HIV. These treatments are the subject of new international recommendations following the publication of pivotal trials, the results of which will be presented in this review. We will also discuss the practical modalities of their implementation as well as the challenges to be faced in the future.

Les traitements injectables à longue durée d'action complètent les options pharmacologiques disponibles dans la prise en charge de l'infection par le VIH, que ce soit sous la forme de monothérapie (cabotégravir injectable) en prophylaxie pré-exposition (PrEP) ou de bithérapie (cabotégravir/rilpivirine injectables) en traitement. Ces molécules font l'objet de nouvelles recommandations internationales suite à la publication d'essais déterminants dont les résultats sont détaillés dans cet article. Nous abordons également les modalités pratiques de leur implémentation ainsi que les défis auxquels nous devons nous préparer.