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We propose to use Twitter data as social-spatial sensors. This study deals with the question whether research papers on certain diseases are perceived by people in regions (worldwide) that are especially concerned by these diseases. Since (some) Twitter data contain location information, it is possible to spatially map the activity of Twitter users referring to certain papers (e.g., dealing with tuberculosis). The resulting maps reveal whether heavy activity on Twitter is correlated with large numbers of people having certain diseases. In this study, we focus on tuberculosis, human immunodeficiency virus (HIV), and malaria, since the World Health Organization ranks these diseases as the top three causes of death worldwide by a single infectious agent. The results of the social-spatial Twitter maps (and additionally performed regression models) reveal the usefulness of the proposed sensor approach. One receives an impression of how research papers on the diseases have been perceived by people in regions that are especially concerned by these diseases. Our study demonstrates a promising approach for using Twitter data for research evaluation purposes beyond simple counting of tweets. [ABSTRACT FROM AUTHOR]

Objective: To end the AIDS epidemic by 2030, despite the increasing poverty and inequalities, policies should be designed to deal with population heterogeneity and environmental changes. Bottom-up designs, such as the Agent-Based Model (ABM), can model these features, dealing with such complexity. HIV/AIDS has a complex dynamic of structural factors, risk behaviors, biomedical characteristics and interventions. All embedded in unequal, stigmatized and heterogeneous social structure. To understand how ABMs can model this complexity, we performed a scoping review of HIV applications, highlighting their potentialities. Methods: We searched on PubMed, Web of Science, and Scopus repositories following the PRISMA extension for scoping reviews. Our inclusion criteria were HIV/AIDS studies with an ABM application. We identified the main articles using a local co-citation analysis and categorized the overall literature aims, (sub)populations, regions, and if the papers declared the use of ODD protocol and limitations. Results: We found 154 articles. We identified eleven main papers, and discussed them using the overall category results. Most studies model Transmission Dynamics (37/154), about Men who have sex with Men (MSM) (41/154), or individuals living in the US or South Africa (84/154). Recent studies applied ABM to model PrEP interventions (17/154) and Racial Disparities (12/154). Only six papers declared the use of ODD Protocol (6/154), and 34/154 didn't mention the study limitations. Conclusions: While ABM is among the most sophisticated techniques available to model HIV/AIDS complexity. Their applications are still restricted to some realities. However, researchers are challenged to think about social structure due model characteristics, the inclusion of these features is still restricted to case-specific. Data and computational power availability can enhance this feature providing insightful results. [ABSTRACT FROM AUTHOR]

There is a growing population of adults aged 50 years or older living with HIV, facing unique challenges in care due to age, minority status, and stigma. Co-design methodologies, aligning with patient-centered care, have potential for informing interventions addressing the complex needs of older adults with HIV. Despite challenges, co-design has shown promise in empowering older individuals to actively participate in shaping their care experiences. The scoping review outlined here aims to identify gaps in existing co-design work with this population, emphasizing the importance of inclusivity based on PROGRESS-Plus characteristics for future patient-oriented research. This scoping review protocol is informed by the Joanna Briggs Institute Manual to explore co-design methods in geriatric HIV care literature. The methodology encompasses six stages: 1) developing research questions, 2) creating a search strategy, 3) screening and selecting evidence, 4) data extraction, 5) data analysis using content analysis, and 6) consultation with key stakeholders, including community partners and individuals with lived experience. The review will involve a comprehensive literature search, including peer-reviewed databases and gray literature, to identify relevant studies conducted in the past 20 years. The inclusive criteria focus on empirical data related to co-design methods in HIV care for individuals aged 50 or older, aiming to inform future research and co-design studies in geriatric HIV care. The study will be limited by the exclusion of papers not published or translated to English. Additionally, the varied terminology used to describe co-design across different research may result in the exclusion of articles using alternative terms. The consultation with key stakeholders will be crucial for translating insights into meaningful co-design solutions for virtual HIV care, aiming to provide a comprehensive synthesis that informs evidence-based strategies and addresses disparities in geriatric HIV care. [ABSTRACT FROM AUTHOR]

In this paper, we have identified and analyzed the emergence, structure and dynamics of the paradigmatic research fronts that established the fundamentals of the biomedical knowledge on HIV/AIDS. A search of papers with the identifiers "HIV/AIDS", "Human Immunodeficiency Virus", “HIV-1” and "Acquired Immunodeficiency Syndrome" in the Web of Science (Thomson Reuters), was carried out. A citation network of those papers was constructed. Then, a sub-network of the papers with the highest number of inter-citations (with a minimal in-degree of 28) was selected to perform a combination of network clustering and text mining to identify the paradigmatic research fronts and analyze their dynamics. Thirteen research fronts were identified in this sub-network. The biggest and oldest front is related to the clinical knowledge on the disease in the patient. Nine of the fronts are related to the study of specific molecular structures and mechanisms and two of these fronts are related to the development of drugs. The rest of the fronts are related to the study of the disease at the cellular level. Interestingly, the emergence of these fronts occurred in successive "waves" over the time which suggest a transition in the paradigmatic focus. The emergence and evolution of the biomedical fronts in HIV/AIDS research is explained not just by the partition of the problem in elements and interactions leading to increasingly specialized communities, but also by changes in the technological context of this health problem and the dramatic changes in the epidemiological reality of HIV/AIDS that occurred between 1993 and 1995. [ABSTRACT FROM AUTHOR]

The battle against viral drug resistance highlights the need for innovative approaches to replace time-consuming and costly traditional methods. Deep generative models offer automation potential, especially in the fight against Human immunodeficiency virus (HIV), as they can synthesize diverse molecules effectively. In this paper, an application of an LSTM-based deep generative model named "LSTM-ProGen" is proposed to be tailored explicitly for the de novo design of drug candidate molecules that interact with a specific target protein (HIV-1 protease). LSTM-ProGen distinguishes itself by employing a long-short-term memory (LSTM) architecture, to generate novel molecules target specificity against the HIV-1 protease. Following a thorough training process involves fine-tuning LSTM-ProGen on a diverse range of compounds sourced from the ChEMBL database. The model was optimized to meet specific requirements, with multiple iterations to enhance its predictive capabilities and ensure it generates molecules that exhibit favorable target interactions. The training process encompasses an array of performance evaluation metrics, such as drug-likeness properties. Our evaluation includes extensive silico analysis using molecular docking and PCA-based visualization to explore the chemical space that the new molecules cover compared to those in the training set. These evaluations reveal that a subset of 12 de novo molecules generated by LSTM-ProGen exhibit a striking ability to interact with the target protein, rivaling or even surpassing the efficacy of native ligands. Extended versions with further refinement of LSTM-ProGen hold promise as versatile tools for designing efficacious and customized drug candidates tailored to specific targets, thus accelerating drug development and facilitating the discovery of new therapies for various diseases. [ABSTRACT FROM AUTHOR]

Background: Depression is a very common psychiatric disorder in worldwide. Globally, Human Immunodeficiency Virus (HIV) is highly prevalent among women, and are disproportionately affected by depression. Antiretroviral Therapy (ART) adherence which could highly be affected by depression is yet to be explored effectively. Depression affects overall poor HIV clinical outcomes, socioeconomic and social interactions. However, it is not well understood specifically how depression affects ART adherence in women living with HIV (WLWHIV). Investigating the effects of depression on ART adherence is critical in order to develop nuanced new evidence to address non-adherence in WLWHIV. Objective: To conduct a meta-analysis on the correlation between depression and adherence to antiretroviral therapy among women living with HIV in the globe. Method: Using population, exposed and outcome approach, we searched Scopus, PubMed, EMBASE, Cochrane Library, Psych info, Web of science and google scholar for cohort and cross-sectional studies globally. The search strategy was structured comprising terms associated with antiretroviral therapy and adherence, women living with HIV and depression. We evaluated the paper quality, using the Newcastle-Ottawa Scales (NOS). The fixed effect model was used to analysis the effect of depression on ART adherence. Result: A total of 8 articles comprise 6474 participants were included in this study. There were controversial findings related to the effect of depression to ART adherence. Among three cross-sectional study, one article demonstrating, depression was associated with ART adherence. Of the five cohort studies, four cohort studies reported association. The overall pooled estimated effect of depression on ART adherence was 1.02 [RR = 1.015 with 95% CI (1.004, 1.026)] with a p-value of 0.005. Conclusion and recommendation: Depression was the risk factor for ART adherence among women living with HIV. It is therefore, necessary for clinician to note this and perform screening for ART adherence. Trial registration: The review protocol was developed with prospero registration:CRD42023415935. [ABSTRACT FROM AUTHOR]

Background: In economic analyses of HIV interventions, South Africa is often used as a case in point, due to the availability of good epidemiological and programme data and the global relevance of its epidemic. Few analyses however use locally relevant cost data. We reviewed available cost data as part of the South African HIV Investment Case, a modelling exercise to inform the optimal use of financial resources for the country’s HIV programme. Methods: We systematically reviewed publication databases for published cost data covering a large range of HIV interventions and summarised relevant unit costs (cost per person receiving a service) for each. Where no data was found in the literature, we constructed unit costs either based on available information regarding ingredients and relevant public-sector prices, or based on expenditure records. Results: Only 42 (5%) of 1,047 records included in our full-text review reported primary cost data on HIV interventions in South Africa, with 71% of included papers covering ART. Other papers detailed the costs of HCT, MMC, palliative and inpatient care; no papers were found on the costs of PrEP, social and behaviour change communication, and PMTCT. The results informed unit costs for 5 of 11 intervention categories included in the Investment Case, with the remainder costed based on ingredients (35%) and expenditure data (10%). Conclusions: A large number of modelled economic analyses of HIV interventions in South Africa use as inputs the same, often outdated, cost analyses, without reference to additional literature review. More primary cost analyses of non-ART interventions are needed. [ABSTRACT FROM AUTHOR]

Background: Prevention of mother-to-child transmission (PMTCT) of HIV service is conceptualized as a series of cascades that begins with all pregnant women and ends with the detection of a final HIV status in HIV-exposed infants (HEIs). A low rate of cascade completion by mothers' results in an increased risk of HIV transmission to their infants. Therefore, this review aimed to understand the uptake and determinants of key PMTCT services cascades in East Africa. Methods: We searched CINAHL, EMBASE, MEDLINE, Scopus, and AIM databases using a predetermined search strategy to identify studies published from January 2012 through to March 2022 on the uptake and determinants of PMTCT of HIV services. The quality of the included studies was assessed using the Mixed Methods Appraisal Tool. A random-effects model was used to obtain pooled estimates of (i) maternal HIV testing (ii) maternal ART initiation, (iii) infant ARV prophylaxis and (iv) early infant diagnosis (EID). Factors from quantitative studies were reviewed using a coding template based on the domains of the Andersen model (i.e., environmental, predisposing, enabling and need factors) and qualitative studies were reviewed using a thematic synthesis approach. Results: The searches yielded 2231 articles and we systematically reduced to 52 included studies. Forty quantitative, eight qualitative, and four mixed methods papers were located containing evidence on the uptake and determinants of PMTCT services. The pooled proportions of maternal HIV test and ART uptake in East Africa were 82.6% (95% CI: 75.6–88.0%) and 88.3% (95% CI: 78.5–93.9%). Similarly, the pooled estimates of infant ARV prophylaxis and EID uptake were 84.9% (95% CI: 80.7–88.3%) and 68.7% (95% CI: 57.6–78.0) respectively. Key factors identified were the place of residence, stigma, the age of women, the educational status of both parents, marital status, socioeconomic status, Knowledge about HIV/PMTCT, access to healthcare facilities, attitudes/perceived benefits towards PMTCT services, prior use of maternal and child health (MCH) services, and healthcare-related factors like resource scarcity and insufficient follow-up supervision. Conclusion: Most of the identified factors were modifiable and should be considered when formulating policies and planning interventions. Hence, promoting women's education and economic empowerment, strengthening staff supervision, improving access to and integration with MCH services, and actively involving the community to reduce stigma are suggested. Engaging community health workers and expert mothers can also help to share the workload of healthcare providers because of the human resource shortage. [ABSTRACT FROM AUTHOR]

Background: Observational data suggest lower HIV risk with norethisterone enanthate (NET-EN) than with depo-medroxyprogesterone acetate intramuscular (DMPA-IM) injectable contraceptives. If confirmed, a switch between these similar injectable methods would be programmatically feasible and could impact the trajectory of the HIV epidemic. We aimed in this paper to investigate the effects of DMPA-IM and NET-EN on estradiol levels, measures of depression and sexual activity and menstrual effects, relevant to HIV risk; and to ascertain whether these measures are associated with estradiol levels. Methods: This open-label trial conducted at two sites in South Africa from 5 November 2018 to 30 November 2019, randomized HIV-negative women aged 18–40 to DMPA-IM 150 mg intramuscular 12-weekly (n = 262) or NET-EN 200 mg intramuscular 8-weekly (n = 259). Data were collected on hormonal, behavioral and menstrual effects at baseline and at 25 weeks (25W). Results: At 25W, median 17β estradiol levels were substantially lower than at baseline (p<0.001) for both methods: 76.5 pmol/L (interquartile range (IQR) 54.1 to 104.2) in the DMPA-IM group (n = 222), and 69.8 pmol/L (IQR: 55.1 to 89.3) in the NET-EN group (n = 225), with no statistical difference between the two methods (p = 0.450). Compared with DMPA-IM, NET-EN users reported significantly less amenorrhoea, fewer sexual acts, fewer users reporting at least one act of unprotected sex, more condom use with steady partner, more days with urge for sexual intercourse, more days feeling partner does not love her, and more days feeling sad for no reason. We did not find a clear association between estradiol levels and sexual behavior, depression and menstrual effects. Behavioral outcomes suggest less sexual exposure with NET-EN than DMPA-IM. The strength of this evidence is high due to the randomized study design and the consistency of results across the outcomes measured. Conclusions: Estradiol levels were reduced to postmenopausal levels by both methods. Secondary outcomes suggesting less sexual exposure with NET-EN are consistent with reported observational evidence of less HIV risk with NET-EN. A randomized trial powered for HIV acquisition is feasible and needed to answer this important question. Trial registration: PACTR 202009758229976. [ABSTRACT FROM AUTHOR]

Introduction: Adolescents with HIV in sub-Saharan Africa face challenges transitioning to adult HIV care, which can affect long-term HIV care adherence and retention. An adolescent transition package (ATP) focused on transition tools can improve post-transition clinical outcomes, but its implementation costs are unknown. Methods: We estimated the average cost per patient of an HIV care visit and ATP provision to adolescents. Data was collected from 13 HIV clinics involved in a randomized clinical trial evaluating ATP in western Kenya. We conducted a micro-costing and activity-driven time estimation to assess costs from the provider perspective. We developed a flow-map, conducted staff interviews, and completed time and motion observation. ATP costs were estimated as the difference in average cost for an HIV care transition visit in the intervention compared to control facilities. We assessed uncertainty in costing estimates via Monte Carlo simulations. Results: The average cost of an adolescent HIV care visit was 29.8USD (95%CI 27.5, 33.4) in the standard of care arm and 32.9USD (95%CI 30.5, 36.8) in the ATP intervention arm, yielding an incremental cost of 3.1USD (95%CI 3.0, 3.4) for the ATP intervention. The majority of the intervention cost (2.8USD) was due ATP booklet discussion with the adolescent. Conclusion: The ATP can be feasibly implemented in HIV care clinics at a modest increase in overall clinic visit cost. Our cost estimates can be used to inform economic evaluations or budgetary planning of adolescent HIV care interventions in Kenya. [ABSTRACT FROM AUTHOR]

Introduction: HIV transmission continues among gay and bisexual men who have sex with men (GBMSM), with those who are younger, or recent migrants, or of minority ethnicity or who are gender diverse remaining at increased risk. We aimed to identify and describe recent studies evaluating the effectiveness of HIV prevention interventions for GBMSM in high income countries. Methods: We searched ten electronic databases for randomized controlled trials (RCTs), conducted in high income settings, and published since 2013 to update a previous systematic review (Stromdahl et al, 2015). We predefined four outcome measures of interest: 1) HIV incidence 2) STI incidence 3) condomless anal intercourse (CLAI) (or measure of CLAI) and 4) number of sexual partners. We used the National Institute for Health and Care Excellence (UK) Quality Appraisal of Intervention Studies tool to assess the quality of papers included in the review. As the trials contained a range of effect measures (e.g. odds ratio, risk difference) comparing the arms in the RCTs, we converted them into standardized effect sizes (SES) with 95% confidence intervals (CI). Results: We identified 39 original papers reporting 37 studies. Five intervention types were identified: one-to-one counselling (15 papers), group interventions (7 papers), online interventions (9 papers), Contingency Management for substance use (2 papers) and Pre-exposure Prophylaxis (PrEP) (6 papers). The quality of the studies was mixed with over a third of studies rated as high quality and 11% rated as poor quality. There was some evidence that one-to-one counselling, group interventions (4–10 participants per group) and online (individual) interventions could be effective for reducing HIV transmission risk behaviours such as condomless anal intercourse. PrEP was the only intervention that was consistently effective at reducing HIV incidence. Conclusions: Our systematic review of the recent evidence that we were able to analyse indicates that PrEP is the most effective intervention for reducing HIV acquisition among GBMSM. Targeted and culturally tailored behavioural interventions for sub-populations of GBMSM vulnerable to HIV infection and other STIs should also be considered, particularly for GBMSM who cannot access or decline to use PrEP. [ABSTRACT FROM AUTHOR]

T his article studied a mathematical model for the diffusive human immunodeficiency virus-type 1 (HIV-1) infection combining with stem cell therapy. The HIV-1 infection is a chronic disease and the viral replication continues if the patient stopes use the antiretroviral therapy (cART). Therefore, it is important to seek the cure of HIV-1 infection and some medical trials showed the cure by stem cell therapy and there are others failure to achieve the cure of HIV-1 with same treatments. The novelty of this paper is constructing a mathematical model with adding diffusion terms to study the effect of spread of virus and other cells in the body. Theoretical analysis such as boundedness, positivity, stability (local/global) of the HIV-1 model is presented. The model is solved analytically by the tanh expansion method. The results show that the tanh expansion method is a very useful technique, that can give a good prediction of the effect of stem cell therapy on infected cells on the spread of the virus. The results further demonstrated that the best way to control the disease is by limiting the spread of the virus; more so than the spread of other components. [ABSTRACT FROM AUTHOR]

Background: The number of elderly people living with HIV (EPLHIV) has increased significantly as a result of antiretroviral treatment (ART) and this has brought about a variety of psychosocial challenges that have an impact on their quality of life (QoL). Various psychosocial interventions have been tried or implemented in Sub-Saharan Africa (SSA) to improve QoL of EPLHIV. However, there is paucity of data on the types and effectiveness of these interventions. This systematic review, therefore, aims to explore available psychosocial interventions in SSA and their effectiveness in improving the QoL of EPLHIV. Methods: We will search PubMed, PsycINFO, LILACS, Cochrane Library, Google Scholar, HINARI, Africa Journals Online, Scopus and Web of Science to retrieve publications on psychosocial interventions implemented to improve QoL of EPLHIV from inception of the identified databases to 31st December 2023 without language restrictions. Also, supplementary sources such as conference proceedings, preprint repositories, databases of dissertations, as well as WHO and governmental databases can be explored for additional studies. For unpublished studies, trial registries and experts would be contacted, and reference lists of retrieved papers will be manually searched. Retrieved studies will be deduplicated using Mendeley and exported to Rayyan. At least two reviewers will independently select studies, extract data and assess the quality of the included studies using validated tools. Dichotomous outcomes data will be assessed and reported as odds ratio (OR) or risk ratio (RR) and for continuous outcomes, mean difference (MD) will be used; all reported with their 95% confidence interval (CI). Heterogeneity will be explored graphically by inspecting the overlapping of CIs and assessed quantitatively using the I2 statistic. Expected outcomes: This systematic review will be the first to rigorously identify psychosocial intervention on QoL of EPLHIV in SSA and assess their effectiveness with the aim to provide regional and country- specific data that will inform the selection and implementation of appropriate and socially acceptable policies across countries in SSA. Key findings of the review are expected to contribute critical evidence on availability, types and effectiveness of psychosocial interventions for improving quality of life of vulnerable elderly persons in SSA living with HIV. Furthermore, the review will explore any variation and possible correlates of psychosocial interventions by age, sex, CD4 count (if available), setting and geographic location within SSA that will provide healthcare professionals with reliable evidence, with the ultimate goal of inspiring countries in SSA to adopt innovative interventions to improve HIV care. Trial registration: Systematic review registration: The systematic review protocol has been registered in the International Prospective Register for Systematic Reviews (PROSPERO), with registration ID CRD42021278218. [ABSTRACT FROM AUTHOR]

Background: Cambodia is widely credited for its successful HIV epidemic control. However, in recent years there have been signs of increasing HIV prevalence among men who have sex with men (MSM) and transgender women (TGW). This paper reviews HIV epidemiological, social science and HIV program implementation studies conducted over the past 20 years to explore possible reasons for the rising HIV prevalence among these groups and to formulate recommendations for improved policies, HIV programmatic interventions and further research. Methods: For this scoping review, we searched the PubMed and Google Scholar databases for scientific publications related to HIV and MSM and TGW in Cambodia published since 1999. From each of the returned citations we subsequently studied reference lists to find additional data sources. We also searched websites for reports commissioned by national and international governmental and non-governmental organizations. Results: Twenty-seven relevant studies and papers were found and reviewed; most were epidemiological in nature. Recent epidemiological studies and reports show an increase in HIV prevalence among Cambodian MSM and TGW. The epidemiology of HIV infection in these groups has been relatively well-described and analyzed. While initially MSM and TGW were grouped together, in more recent years they have been studied in their own right, recognizing their specific HIV and other prevention needs. Few studies were found investigating Cambodian same-sex cultures and social and cultural contexts in which HIV transmission among MSM and TGW occurs. A few evaluation studies were found, but it remains unknown how effective current HIV service implementation modalities are, or how successful strategies to increase access to essential HIV prevention, testing and treatment services have been employed for MSM and TGW in Cambodia. Conclusions: Research about Cambodian MSM and TGW in the context of HIV primarily concerns bio-behavioral knowledge generation. Cambodia is unlikely to achieve control of the HIV epidemic among MSM and TGW without doing better in-depth social science research on its multiple sexual- and gender minority cultures, and without understanding what differentiated implementation modalities, strategies and approaches are most effective to address HIV among its increasingly diverse MSM and TGW populations. [ABSTRACT FROM AUTHOR]

Introduction: Depression is one of the most common psychiatric disorders, affecting approximately 60% of people infected with the human immunodeficiency virus (HIV). Low and middle-income countries (LMICs), including Ethiopia, bear a disproportionate burden of depression among HIV/AIDS patients. Several factors, including perceived stigma, have been linked to increased depression among HIV/AIDS patients. Therefore, we aimed to estimate the pooled effect of perceived stigma on depression among HIV/AIDS patients in Ethiopia. Methods: For this systematic review and meta-analysis, we systematically retrieved all relevant studies starting from January 1, 2000 to June 1, 2022 from PubMed, HINARI, and Google Scholar. This review included observational studies that reported the effect of perceived stigma on the prevalence of depression among HIV-positive adults in Ethiopia. The effect estimate of the pooled effect of perceived stigma on depression was conducted using DerSimonian-Laird's random effect model using STATA/MP version 16. An adjusted odds ratio (AOR), along with a 95% confidence interval (CI), was conducted to estimate the strength of the association between perceived stigma and depression. Results: Eleven studies with a total of 4,153 HIV-positive adults were included for meta-analysis. The results of the meta-analysis revealed that the odds of depression were higher among patients with perceived stigma (AOR: 3.78, 95% CI: 2.73, 5.24). The pooled prevalence of depression among HIV/AIDS patients in Ethiopia was 39% (95% CI: 32%, 46%) (I2 = 98%, p ≤ 0.0001). The subgroup analysis revealed that the primary studies conducted in the Oromia region had the highest pooled prevalence of depression at 48% (95% CI: 32%, 63%). Conclusion: The pooled estimates of the meta-analysis revealed that perceived stigma and depression were strongly associated. Stigma and depression screenings should be carried out for additional treatments and prevention, and programs supporting Ethiopia's PLWHA population should be strengthened. [ABSTRACT FROM AUTHOR]

Co-diagnosis of HIV and tuberculosis presents a treatment dilemma. Starting both treatments at the same time can cause a flood of immune response called immune reconstitution inflammatory syndrome (IRIS) which can be lethal. But, how long to delay HIV treatment is less understood. In 2011, based on the conclusions of three separate studies, WHO recommended starting HIV treatment earlier for those with later HIV disease progression. This paper conducts a replication study of one of the three studies, by Havlir and colleagues. Using their publicly available data, we were able to replicate most of the results presented in the original paper. In our measurement and estimation analyses we use different estimation techniques to assess the robustness of the results. We find that adjusting for loss to follow-up does not affect the main results of the paper. However, an ANCOVA estimation and an instrumental variable model weaken the main result of the paper of better outcomes with early HIV treatment only for those who are sicker, reducing significance from the 5% to the 10% level. A change-point analysis also detects no changes in effect by timing of HIV treatment initiation or different thresholds of CD4 count for the primary outcome. This result suggests that the choice of start time for HIV treatment initiation should be based on other factors including potential drug interactions, overlapping side effects, a high pill burden and severity of illness rather than CD4 threshold and preset timeframes. While we caution against overgeneralizing, the result of this replication is aligned with more recent studies that show no evidence that early initiation of HIV treatment reduces mortality for any patients. [ABSTRACT FROM AUTHOR]

Human Immunodeficiency Virus (HIV) is a major global public health issue that affects the quality of life (QoL) of people living with HIV (PLHIV) globally and in Indonesia. As a part of a large-scale qualitative study investigating HIV risk factors and impacts on PLHIV and facilitators of and barriers to their access to HIV care services in Yogyakarta and Belu, Indonesia, this paper describes their in-depth views and experiences of the influence of HIV on their QoL. Ninety-two participants were recruited using the snowball sampling technique. Data were collected using in-depth interviews. In addition, the World Health Organisation Quality of Life questionnaire (WHOQOL–HIV BREF) was also distributed to each of them to fill out prior to the interviews. Chi-Square analysis was used to analyse data from the survey and a framework analysis was applied to guide qualitative data analysis. The findings reported several factors affecting the QoL of the participants. These included (i) environmental factors, such as living in rural areas, the unavailability of HIV care services and public transport, and long-distance travel to healthcare facilities; (ii) personal beliefs associated with HIV; (iii) sexual and social relationships and their influence of the QoL of participants; and (iv) level of independence and physical health condition following HIV diagnosis. The findings indicate the need for intervention programs that address the availability and accessibility of HIV care services to PLHIV within rural communities and support various physical, psychological, and financial needs of PLHIV. These can be implemented by providing supplements and nutritious food, HIV counselling and door-to-door/community-based ART service delivery to PLHIV, which may increase their engagement in and adherence to the treatment and improve their physical and psychological condition and QoL. [ABSTRACT FROM AUTHOR]

Background: Nigeria is one of six countries with half the global burden of youth living with HIV. Interventions to date have been inadequate as AIDS-related deaths in Nigeria's youth have remained unchanged in recent years. The iCARE Nigeria HIV treatment support intervention, a combination of peer navigation and SMS text message medication reminders to promote viral suppression, demonstrated initial efficacy and feasibility in a pilot trial among youth living with HIV in Nigeria. This paper describes the study protocol for the large-scale trial of the intervention. Methods: The iCARE Nigeria-Treatment study is a randomized stepped wedge trial of a combination (peer navigation and text message reminder) intervention, delivered to youth over a period of 48 weeks to promote viral suppression. Youth receiving HIV treatment at six clinical sites in the North Central and South Western regions of Nigeria were recruited for participation. Eligibility criteria included registration as a patient at participating clinics, aged 15–24 years, on antiretroviral therapy for at least three months, ability to understand and read English, Hausa, Pidgin English, or Yoruba, and intent to remain a patient at the study site during the study period. The six clinic sites were divided into three clusters and randomized to a sequence of control and intervention periods for comparison. The primary outcome is plasma HIV-1 viral load suppression, defined as viral load ≤ 200 copies/mL, in the intervention period versus the control period at 48 weeks of intervention. Discussion: Evidence-based interventions to promote viral load suppression among youth in Nigeria are needed. This study will determine efficacy of a combination intervention (peer navigation and text message reminder) and collect data on potential implementation barriers and facilitators to inform scale-up if efficacy is confirmed. Trial registration: ClinicalTrials.gov number, NCT 04950153, retrospectively registered July 6, 2021, https://clinicaltrials.gov/. [ABSTRACT FROM AUTHOR]

Background: Routine Data Quality Assessments (RDQAs) were developed to measure and improve facility-level electronic medical record (EMR) data quality. We assessed if RDQAs were associated with improvements in data quality in KenyaEMR, an HIV care and treatment EMR used at 341 facilities in Kenya. Methods: RDQAs assess data quality by comparing information recorded in paper records to KenyaEMR. RDQAs are conducted during a one-day site visit, where approximately 100 records are randomly selected and 24 data elements are reviewed to assess data completeness and concordance. Results are immediately provided to facility staff and action plans are developed for data quality improvement. For facilities that had received more than one RDQA (baseline and follow-up), we used generalized estimating equation models to determine if data completeness or concordance improved from the baseline to the follow-up RDQAs. Results: 27 facilities received two RDQAs and were included in the analysis, with 2369 and 2355 records reviewed from baseline and follow-up RDQAs, respectively. The frequency of missing data in KenyaEMR declined from the baseline (31% missing) to the follow-up (13% missing) RDQAs. After adjusting for facility characteristics, records from follow-up RDQAs had 0.43-times the risk (95% CI: 0.32–0.58) of having at least one missing value among nine required data elements compared to records from baseline RDQAs. Using a scale with one point awarded for each of 20 data elements with concordant values in paper records and KenyaEMR, we found that data concordance improved from baseline (11.9/20) to follow-up (13.6/20) RDQAs, with the mean concordance score increasing by 1.79 (95% CI: 0.25–3.33). Conclusions: This manuscript demonstrates that RDQAs can be implemented on a large scale and used to identify EMR data quality problems. RDQAs were associated with meaningful improvements in data quality and could be adapted for implementation in other settings. [ABSTRACT FROM AUTHOR]

Background: While national adoption of universal HIV treatment guidelines has led to improved, timely uptake of antiretroviral therapy (ART), longer-term care outcomes are understudied. There is little data from real-world service delivery settings on patient attrition, viral load (VL) monitoring, and viral suppression (VS) at 24 and 36 months after HIV treatment initiation. Methods and findings: For this retrospective cohort analysis, we used observational data from 25 countries in the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium's Asia-Pacific, Central Africa, East Africa, Central/South America, and North America regions for patients who were ART naïve and aged ≥15 years at care enrollment between 24 months before and 12 months after national adoption of universal treatment guidelines, occurring 2012 to 2018. We estimated crude cumulative incidence of loss-to-clinic (CI-LTC) at 12, 24, and 36 months after enrollment among patients enrolling in care before and after guideline adoption using competing risks regression. Guideline change–associated hazard ratios of LTC at each time point after enrollment were estimated via cause-specific Cox proportional hazards regression models. Modified Poisson regression was used to estimate relative risks of retention, VL monitoring, and VS at 12, 24, and 36 months after ART initiation. There were 66,963 patients enrolling in HIV care at 109 clinics with ≥12 months of follow-up time after enrollment (46,484 [69.4%] enrolling before guideline adoption and 20,479 [30.6%] enrolling afterwards). More than half (54.9%) were females, and median age was 34 years (interquartile range [IQR]: 27 to 43). Mean follow-up time was 51 months (standard deviation: 17 months; range: 12, 110 months). Among patients enrolling before guideline adoption, crude CI-LTC was 23.8% (95% confidence interval [95% CI] 23.4, 24.2) at 12 months, 31.0% (95% CI [30.6, 31.5]) at 24 months, and 37.2% (95% [CI 36.8, 37.7]) at 36 months after enrollment. Adjusting for sex, age group, enrollment CD4, clinic location and type, and country income level, enrolling in care and initiating ART after guideline adoption was associated with increased hazard of LTC at 12 months (adjusted hazard ratio [aHR] 1.25 [95% CI 1.08, 1.44]; p = 0.003); 24 months (aHR 1.38 [95% CI 1.19, 1.59]; p <.001); and 36 months (aHR 1.34 [95% CI 1.18, 1.53], p <.001) compared with enrollment before guideline adoption, with no before–after differences among patients with no record of ART initiation by end of follow-up. Among patients retained after ART initiation, VL monitoring was low, with marginal improvements associated with guideline adoption only at 12 months after ART initiation. Among those with VL monitoring, VS was high at each time point among patients enrolling before guideline adoption (86.0% to 88.8%) and afterwards (86.2% to 90.3%), with no substantive difference associated with guideline adoption. Study limitations include lags in and potential underascertainment of care outcomes in real-world service delivery data and potential lack of generalizability beyond IeDEA sites and regions included in this analysis. Conclusions: In this study, adoption of universal HIV treatment guidelines was associated with lower retention after ART initiation out to 36 months of follow-up, with little change in VL monitoring or VS among retained patients. Monitoring long-term HIV care outcomes remains critical to identify and address causes of attrition and gaps in HIV care quality. Using real-world service delivery data, Ellen Brazier and team examine long-term HIV care outcomes under universal HIV treatment guidelines across 25 countries. Author summary: Why was this study done?: Although universal HIV treatment recommendations have been adopted in national HIV treatment guidelines, longer-term HIV care outcomes under such guidelines are poorly documented and largely limited to single-country studies with short follow-up times. No multicountry studies using real-world service delivery data have examined long-term HIV care outcomes associated under universal HIV treatment guidelines. What did the researchers do and find?: With data on 66,963 patients enrolling in HIV care at 109 clinics participating in the International epidemiology Databases to Evaluate AIDS (IeDEA) research consortium across 25 countries where universal HIV treatment guidelines were adopted, we estimated the hazard ratios of loss-to-clinic (LTC) at 12, 24, and 36 months after enrollment, comparing those enrolling in HIV care after guideline adoption to those enrolling before guideline adoption. Among 57,615 patients with documented initiation of antiretroviral therapy (ART), we also estimated the relative risks of clinic retention, viral load (VL) monitoring, and viral suppression (VS) at 12, 24, and 36 months after ART initiation, comparing those enrolling after versus before national adoption of universal treatment guidelines. Compared with patients enrolling in HIV care and initiating HIV treatment before national adoption of universal treatment guidelines, those enrolling and initiating treatment after guideline adoption had higher risk of being LTC at 12 months, 24 months, and 36 months after enrollment. Among patients retained in care after ART initiation, those enrolling in HIV care after the adoption of universal HIV treatment guidelines were more likely to have VL monitoring at 12 months after ART initiation and less likely at 36 months, with no difference at 24 months. VS was high at each time point among patients enrolling before and after the adoption of universal HIV treatment guidelines, with no substantive change associated with guideline adoption. What do these findings mean?: Our results raise concerns about long-term retention of patients after ART initiation, as well as the capacity of HIV programs to provide essential aspects of HIV care, including annual VL monitoring for timely identification of adherence problems and treatment failure. Our findings that patient retention in care at the clinic where ART was initiated decreased after the adoption of universal HIV treatment guidelines and that there has been no improvement in annual VL monitoring among patients retained in care should motivate efforts to identify and address factors associated with attrition among patients enrolling in HIV care, as well as barriers to routine VL testing in the era of universal treatment of all people living with HIV. Study limitations include potential underascertainment of patient outcomes in real-world service delivery data, lags in the availability of real-world service delivery data, and the nonrepresentativeness of the clinics and countries reflected in IeDEA datasets available for analysis. [ABSTRACT FROM AUTHOR]

Human Immunodeficiency Virus type 1 protease (HIV-1 PR) is one of the most challenging targets of antiretroviral therapy used in the treatment of AIDS-infected people. The performance of protease inhibitors (PIs) is limited by the development of protease mutations that can promote resistance to the treatment. The current study was carried out using statistics and bioinformatics tools. A series of thirty-three compounds with known enzymatic inhibitory activities against HIV-1 protease was used in this paper to build a mathematical model relating the structure to the biological activity. These compounds were designed by software; their descriptors were computed using various tools, such as Gaussian, Chem3D, ChemSketch and MarvinSketch. Computational methods generated the best model based on its statistical parameters. The model's applicability domain (AD) was elaborated. Furthermore, one compound has been proposed as efficient against HIV-1 protease with comparable biological activity to the existing ones; this drug candidate was evaluated using ADMET properties and Lipinski's rule. Molecular Docking performed on Wild Type, and Mutant Type HIV-1 proteases allowed the investigation of the interaction types displayed between the proteases and the ligands, Darunavir (DRV) and the new drug (ND). Molecular dynamics simulation was also used in order to investigate the complexes' stability allowing a comparative study on the performance of both ligands (DRV & ND). Our study suggested that the new molecule showed comparable results to that of darunavir and maybe used for further experimental studies. Our study may also be used as pipeline to search and design new potential inhibitors of HIV-1 proteases. [ABSTRACT FROM AUTHOR]

Mathematical models are powerful tools in HIV epidemiology, producing quantitative projections of key indicators such as HIV incidence and prevalence. In order to improve the accuracy of predictions, such models need to incorporate a number of behavioural and biological heterogeneities, especially those related to the sexual network within which HIV transmission occurs. An individual-based model, which explicitly models sexual partnerships, is thus often the most natural type of model to choose. In this paper we present PopART-IBM, a computationally efficient individual-based model capable of simulating 50 years of an HIV epidemic in a large, high-prevalence community in under a minute. We show how the model calibrates within a Bayesian inference framework to detailed age- and sex-stratified data from multiple sources on HIV prevalence, awareness of HIV status, ART status, and viral suppression for an HPTN 071 (PopART) study community in Zambia, and present future projections of HIV prevalence and incidence for this community in the absence of trial intervention. Author summary: In this paper we present PopART-IBM, an individual-based model used to simulate HIV transmission in communities in high prevalence settings. We show that PopART-IBM can simulate transmission over a span of decades in a large community in less than a minute. This computational efficiency allows us to calibrate the model within an inference framework, and we show an illustrative example of calibration using an adaptive population Monte Carlo Approximate Bayesian Computation algorithm for a community in Zambia that was part of the HPTN-071 (PopART) trial. We compare the detailed model output to real-world data collected during the trial from this community. Finally, we project how the HIV epidemic would have changed over time in this community if no intervention from the trial had occurred. [ABSTRACT FROM AUTHOR]

Background: The objectives of this scoping review are to investigate the characteristics assessed by existing vulnerability indices and the health outcomes achieved by applying them to people experiencing homelessness. This review forms part of the development and implementation of a novel tool to prioritise people experiencing homelessness for healthcare based on their need and capacity to access healthcare. Methods: Included papers were primary research, published in the English language, participants were experiencing homelessness and aged over 18 years at the time of the study, a vulnerability index was used in the study, sample size was greater than 30, and the study had a health focus. Databases searched were MEDLINE, Embase, CINAHL, Scopus, PubMed and Web of Science, between January-April 2020. The Joanna Briggs Appraisal criteria were used to quality appraise the included studies. Results were synthesised narratively. Results: Six papers were included, a total of 27,509 participants. The reported use of the indices varied; they included screening and profiling homeless populations, comparing homeless populations, and two studies evaluated the predictive capacity, reliability and validity of the indices. One vulnerability index focused on screening for human immunodeficiency virus, one used a 50-item index and four used a nine-item index. No direct health outcomes were reported from applying the vulnerability indices. The studies identified limitations of using vulnerability indices, including the potential bias of relying on self-reported data and two studies highlighted the need for further psychometric testing to ensure validity and reliability of the indices. Discussion: The sample of included studies was small. Vulnerability indices are reportedly a useful and easily accessible method of gaining valuable data on the health status and health needs of people experiencing homelessness. The variety of characteristics included in the vulnerability indices suggests the importance of tailoring vulnerability indices to the needs of the population to which it is to be applied. Conducting appropriate psychometric testing is critical so that an index can be used to accurately inform decision making and accurately prioritise people experiencing homelessness who are most at risk of mortality and morbidity. A specific tool that prioritises people experiencing homelessness for access to health care is not yet available. The review was funded by a St Vincent's Network Inclusive Health grant. [ABSTRACT FROM AUTHOR]

Background: Mental health is a critical and neglected public health problem for adolescents in sub-Saharan Africa. In this paper we aim to determine the prevalence of depressive symptoms and the association with HIV risk behaviours in adolescents aged 15–19 years in Zambia and SA. Methods: We conducted a cross-sectional survey from August-November 2017 in seven control communities of HPTN 071 (PopART) trial (a community-randomised trial of universal HIV testing and treatment), enrolling approximately 1400 eligible adolescents. HIV-status was self-reported. Depressive symptoms were measured with the Short Mood and Feelings Questionnaire (SMFQ), with a positive screen if adolescents scored ≥12. We fitted a logistic regression model to identify correlates of depressive symptoms with subgroup analyses among those who self-reported ever having had sex, by gender and country. Results: Out of 6997 households approached, 6057 (86.6%) were enumerated. 2546 adolescents were enumerated of whom 2120 (83.3%) consented to participate and were administered the SMFQ. The prevalence of depressive symptoms was 584/2120 (27.6%) [95%CI: 25.7%-29.5%]. Adolescents in SA were less likely to experience depressive symptoms (Adjusted Odds Ratio [AOR] = 0.63 (95% CI: 0.50, 0.79), p-value<0.0001). Female adolescents (AOR = 1.46 (95% CI: 1.19, 1.81), p-value<0.0001); those who reported ever having sex and being forced into sex (AOR = 1.80 (95% CI: 1.45, 2.23), p-value<0.001) and AOR = 1.67 (95% CI: 0.99, 2.84); p-value = 0.057 respectively) were more likely to experience depressive symptoms. Among 850 (40.1%) adolescents who self-reported to ever having had sex; those who used alcohol/drugs during their last sexual encounter were more likely to experience depressive symptoms (AOR = 2.18 (95% CI: 1.37, 3.47); p-value = 0.001), whereas those who reported using a condom were less likely to experience depressive symptoms (AOR = 0.74 (95% CI: 0.55, 1.00); p-value = 0.053). Conclusion: The prevalence of depressive symptoms among adolescents ranged from 25–30% and was associated with increased HIV-risk behaviour. [ABSTRACT FROM AUTHOR]

This paper reports the results of a public engagement study on heritable human genome editing (HHGE) carried out in South Africa, which was conducted in accordance with a study protocol that was published in this journal in 2021. This study is novel as it is the first public engagement study on HHGE in Africa. It used a deliberative public engagement (DPE) methodology, entailing inter alia that measures were put in place to ensure that potential participants became informed about HHGE, and that deliberations between the participants were facilitated with the aim of seeking consensus. A diverse group of 30 persons was selected to participate in the DPE study, which took place via Zoom over three consecutive weekday evenings. The main results are: Provided that HHGE is safe and effective, an overwhelming majority of participants supported allowing the use of HHGE to prevent genetic health conditions and for immunity against TB and HIV/Aids, while significant majorities opposed allowing HHGE for enhancement. The dominant paradigm during the deliberations was balancing health benefits (and associated improvements in quality of life) with unforeseen health risks (such as loss of natural immunity). The seriousness of a health condition emerged as the determining factor for the policy choice of whether to allow an application of HHGE. More generally, equal access to HHGE qua healthcare service featured as an important value, and it was uncontested that the South African government should allocate resources to promote scientific research into HHGE. These results are aligned with the policy principles for regulating HHGE in South Africa suggested by Thaldar et al. They call for urgent revision of South African ethics guidelines that currently prohibit research on HHGE, and for dedicated HHGE legal regulations that provide a clear and comprehensive legal pathway for researchers who intend to conduct HHGE research and clinical trials. [ABSTRACT FROM AUTHOR]

Background: Despite the history of United States of America (USA)-based partners implementing global health programs in low- and middle-income countries (LMIC), future models for sustainable healthcare rely on local country ownership and leadership. Transition is the process of shifting programs towards country ownership, where local stakeholders plan, manage, and deliver health programs. Transition is not a singular event but a process which may include a phase where health programs are led and managed by local entities but still reliant on awards from international partners. This phase is scarcely described yet can impact long-term program sustainability if navigated poorly. This qualitative study examines the transition of Zimbabwe's voluntary medical male circumcision and HIV care and treatment services from management by a USA-based organization, the International Training and Education Center for Health (I-TECH), to management under a new Zimbabwean organization, the Zimbabwe Technical Assistance, Training and Education Centre for Health (Zim-TTECH). The primary objective of this paper is to explore challenges, successes, and lessons learned during this transition to inform other non-governmental organizations. Methods: We conducted sixteen virtual, key informant interviews using purposeful sampling, identifying potential participants based on their role in the transition team (leadership, administrative, financial, or human resources) and willingness to consent to the study. We aimed for equal representation from USA-based, I-TECH headquarters staff and Zimbabwe-based, Zim-TTECH staff involved in the transition team. Data were analyzed in Atlas.Ti using deductive and inductive methods, followed by a thematic analysis guided by several frameworks for program transition and organizational change. Results: Findings suggest five themes to guide transition: 1) Develop a vision and empower leadership for change by delegating clear roles and supporting local ownership; 2) Plan and strategize for transition in a manner that accounts for historical context; 3) Communicate with and inform stakeholders to understand transition perceptions, understand barriers to transition, and enable open communications related to risks and benefits; 4) Engage and mobilize staff by constructing necessary infrastructure and providing technical assistance as needed; and 5) Define short-term and long-term success. Conclusion: Transition processes were challenged by the local country context, compressed transition timelines, and all-or-nothing measures of transition success. Facilitators included strong staff capacity and a synergistic partnership model between Zim-TTECH and I-TECH. Global funders and international organizations should support local LMIC partners in their pathway to independence by removing restrictions on funding awards, including transitioning ownership mid-stream, and positioning leadership of international awards for in-country entities. [ABSTRACT FROM AUTHOR]

Introduction: In this paper we perform a replication analysis of “Effect of a cash transfer programme for schooling on prevalence of HIV and herpes simplex type 2 in Malawi: a cluster randomised trial” by Sarah Baird and others published in “The Lancet” in 2012. The original study was a two-year cluster randomized intervention trial of never married girls aged 13–22 in Malawi. Enumeration areas were randomized to either an intervention involving cash transfer (conditional or unconditional of school enrollment) or control. The study included 1708 Malawian girls, who were enrolled at baseline and had biological testing for HIV and herpes simplex virus type 2 (HSV-2) at 18 months. The original findings showed that in the cohort of girls enrolled in school at baseline, the intervention had an effect on school enrollment, sexual outcomes, and HIV and HSV-2 prevalence. However, in the baseline school dropout cohort, the original study showed no intervention effect on HIV and HSV-2 prevalence. Methods: We performed a replication of the study to investigate the consistency and robustness of key results reported. A pre-specified replication plan was approved and published online. Cleaned data was obtained from the original authors. A pure replication was conducted by reading the methods section and reproducing the results and tables found in the original paper. Robustness of the results were examined with alternative analysis methods in a measurement and estimation analysis (MEA) approach. A theory of change analysis was performed testing a causal pathway, the effect of intervention on HIV awareness, and whether the intervention effect depended on the wealth of the individual. Results: The pure replication found that other than a few minor discrepancies, the original study was well replicated. However, the randomization and sampling weights could not be verified due to the lack of access to raw data and a detailed sample selection plan. Therefore, we are unable to determine how sampling influenced the results, which could be highly dependent on the sample. In MEA it was found that the intervention effect on HIV prevalence in the baseline schoolgirls cohort was somewhat sensitive to model choice, with a non-significant intervention effect for HIV depending on the statistical model used. The intervention effect on HSV-2 prevalence was more robust in terms of statistical significance, however, the odds ratios and confidence intervals differed from the original result by more than 10%. A theory of change analysis showed no effect of intervention on HIV awareness. In a causal pathway analysis, several variables were partial mediators, or potential mediators, indicating that the intervention could be working through its effect on school enrollment or selected sexual behaviors. Conclusions: The effect of intervention on HIV prevalence in the baseline schoolgirls was sensitive to the model choice; however, HSV-2 prevalence results were confirmed. We recommend that the results from the original published analysis indicating the impact of cash transfers on HIV prevalence be treated with caution. [ABSTRACT FROM AUTHOR]

Background: The burden of HIV, HBV, and HCV infections remains disproportionately high in sub-Saharan Africa, with high rates of co-infections. Multiplex rapid diagnostic tests for HIV, HBV and HCV serological testing with high analytical performances may improve the "cascade of screening" and quite possibly the linkage-to-care with reduced cost. Based on our previous field experience of HIV self-testing, we herein aimed at evaluating the practicability and acceptability of a prototype finger-stick whole-blood Triplex HIV/HCV/HBsAg self-test as a simultaneous serological screening tool for HIV, HBV, and HCV in the Democratic Republic of the Congo (DRC). Methods: A cross-sectional multicentric study consisting of face-to-face, paper-based, and semi-structured questionnaires with a home-based and facility-based recruitment of untrained adult volunteers at risk of HIV, HBV, and HCV infections recruited from the general public was conducted in 2020 in urban and rural areas in the DRC. The practicability of the Triplex self-test was assessed by 3 substudies on the observation of self-test manipulation including the understanding of the instructions for use (IFU), on the interpretation of Triplex self-test results and on its acceptability. Results: A total of 251 volunteers (mean age, 28 years; range, 18–49; 154 males) were included, from urban [160 (63.7%)] and rural [91 (36.3%)] areas. Overall, 242 (96.4%) participants performed the Triplex self-test and succeeded in obtaining a valid test result with an overall usability index of 89.2%. The correct use of the Triplex self-test was higher in urban areas than rural areas (51.2% versus 16.5%; aOR: 6.9). The use of video IFU in addition to paper-based IFU increased the correct manipulation and interpretation of the Triplex self-test. A total of 197 (78.5%) participants correctly interpreted the Triplex self-test results, whereas 54 (21.5%) misinterpreted their results, mainly the positive test results harboring low-intensity band (30/251; 12.0%), and preferentially the HBsAg band (12/44; 27.3%). The rates of acceptability of reuse, distribution of the Triplex self-test to third parties (partner, friend, or family member), linkage to the health care facility for confirmation of results and treatment, and confidence in the self-test results were very high, especially among participants from urban areas. Conclusions: This pilot study shows evidence for the first time in sub-Saharan Africa on good practicability and high acceptability of a prototype Triplex HIV/HCV/HBsAg self-test for simultaneous diagnosis of three highly prevalent chronic viral infections, providing the rational basis of using self-test harboring four bands of interest, i.e. the control, HIV, HCV, and HBsAg bands. The relatively frequent misinterpretation of the Triplex self-test points however the necessity to improve the delivery of this prototype Triplex self-test probably in a supervised setting. Finally, these observations lay the foundations for the potential large-scale use of the Triplex self-test in populations living in sub-Saharan Africa at high risk for HIV, HBV, and HCV infections. [ABSTRACT FROM AUTHOR]

Background: To establish successful strategies and increasing the utilization of preventive services, there is a need to explore the extent to which the general female population is aware and use the service for cervical cancer-screening among women infected with HIV in Africa. Available evidences in this regard are controversial and non-conclusive on this potential issue and therefore, we estimated the pooled effect of the proportion of knowledge, attitude and practice of HIV infected African women towards cervical cancer screening to generate evidence for improved prevention strategies. Methods: We applied a systematic review and meta-analysis of studies conducted in Africa and reported the proportion of knowledge, attitude and practice towards cervical cancer screening. We searched electronic databases: PubMed/Medline, SCOPUS, ScienceDirect, Web of science, Cumulative Index of Nursing and allied Health Sciences (CINAHL) and Google scholar databases to retrieve papers published in English language till August 2020. We used random-effects model to estimate the pooled effect, and funnel plot to assess publication bias. The registration number of this review study protocol is CRD42020210879. Results: In this review, we included eight published papers comprising 2,186 participants. The estimated pooled proportion of knowledge of the participants was 43.0% (95%CI:23.0–64.0) while the pooled estimates of attitudes and practices were 38.0% (95%CI: 1.0–77.0) and 41.0% (95%CI: 4.0–77.0), respectively. The proportion of the outcome variables were extremely heterogeneous across the studies with I2> 98%). Conclusion: The pooled estimates of knowledge, attitude and practice were lower than other middle income countries calls for further activities to enhance the uptake of the services and establish successful strategies. [ABSTRACT FROM AUTHOR]

The United States President's Emergency Plan for AIDS Relief (PEPFAR) has been credited with saving millions lives and helping to change the trajectory of the global human immunodeficiency virus (HIV) epidemic. This study assesses whether PEPFAR has had impacts beyond health by examining changes in five economic and educational outcomes in PEPFAR countries: the gross domestic product (GDP) per capita growth rate; the share of girls and share of boys, respectively, who are out of school; and female and male employment rates. We constructed a panel data set for 157 low- and middle-income countries between 1990 and 2018 to estimate the macroeconomic impacts of PEPFAR. Our PEPFAR group included 90 countries that had received PEPFAR support over the period. Our comparison group included 67 low- and middle-income countries that had not received any PEPFAR support or had received minimal PEPFAR support (<$1M or <$.05 per capita) between 2004 and 2018. We used differences in differences (DID) methods to estimate the program impacts on the five economic and educational outcome measures. This study finds that PEPFAR is associated with increases in the GDP per capita growth rate and educational outcomes. In some models, we find that PEPFAR is associated with reductions in male and female employment. However, these effects appear to be due to trends in the comparison group countries rather than programmatic impacts of PEPFAR. We show that these impacts are most pronounced in COP countries receiving the highest levels of PEPFAR investment. [ABSTRACT FROM AUTHOR]

Background: Premarital HIV testing offers an opportunity where prospective couples can know their HIV status before marriage to prevent both heterosexual and vertical transmission of HIV. Therefore, this study aimed to determine whether there is any significant difference in the prevalence of premarital HIV testing among women who had autonomous versus non-autonomous marriage, and to investigate the factors associated with premarital HIV testing among women who had autonomous versus non-autonomous marriage in Ethiopia. Methods: Data were extracted from 2016 Ethiopia Demographic and Health Survey dataset and analyzed by using SPSS version 20. Frequencies and weighted percentage of the variables, and second-order Rao-Scott statistic were computed. Multivariable logistic regression analysis was used to identify factors between the two groups. An adjusted odds ratio with 95% confidence interval was considered to state statistically significant associations. Result: From 9602 included sample, 4,043 (42.1%) of the women had autonomous marriage, and 5,559(57.9%) of the women had non-autonomous marriage. The prevalence of premarital HIV testing in Ethiopia among women who had autonomous marriage was 30.5% (95% CI: 27.7–33.4%) compared to 20.6% (95% CI: 18.5–22.8) among women who had a non-autonomous marriage. No differences in associated factors were found between women who had autonomous versus non autonomous marriage to uptake HIV testing. In both groups, residence in rural area, education attainment (primary, secondary, higher), media access, being rich and richest, knowing the places for HIV testing, chewing chat, and drinking alcohol were significantly predicts premarital HIV testing. Conclusion: The study indicated that 10% more women in autonomous marriage tested for HIV relative to non-autonomous women whilst being an urban resident, educated, having access to media, household wealth and knowledge of testing facilities significantly predict HIV testing among women in Ethiopia. The paper recommends the Ethiopian government shall expand access to education among women while improving their access to media to enhance their socioeconomic wellbeing and health. Furthermore, it is better to inspire women to undergo autonomous marriage by fostering education in the community to enhance premarital HIV testing. [ABSTRACT FROM AUTHOR]

HIV can evolve remarkably quickly in response to antiretroviral therapies and the immune system. This evolution stymies treatment effectiveness and prevents the development of an HIV vaccine. Consequently, there has been a great interest in using population genetics to disentangle the forces that govern the HIV adaptive landscape (selection, drift, mutation, and recombination). Traditional population genetics approaches look at the current state of genetic variation and infer the processes that can generate it. However, because HIV evolves rapidly, we can also sample populations repeatedly over time and watch evolution in action. In this paper, we demonstrate how time series data can bound evolutionary parameters in a way that complements and informs traditional population genetic approaches. Specifically, we focus on our recent paper (Feder et al., 2016, eLife), in which we show that, as improved HIV drugs have led to fewer patients failing therapy due to resistance evolution, less genetic diversity has been maintained following the fixation of drug resistance mutations. Because soft sweeps of multiple drug resistance mutations spreading simultaneously have been previously documented in response to the less effective HIV therapies used early in the epidemic, we interpret the maintenance of post-sweep diversity in response to poor therapies as further evidence of soft sweeps and therefore a high population mutation rate (θ) in these intra-patient HIV populations. Because improved drugs resulted in rarer resistance evolution accompanied by lower post-sweep diversity, we suggest that both observations can be explained by decreased population mutation rates and a resultant transition to hard selective sweeps. A recent paper (Harris et al., 2018, PLOS Genetics) proposed an alternative interpretation: Diversity maintenance following drug resistance evolution in response to poor therapies may have been driven by recombination during slow, hard selective sweeps of single mutations. Then, if better drugs have led to faster hard selective sweeps of resistance, recombination will have less time to rescue diversity during the sweep, recapitulating the decrease in post-sweep diversity as drugs have improved. In this paper, we use time series data to show that drug resistance evolution during ineffective treatment is very fast, providing new evidence that soft sweeps drove early HIV treatment failure. [ABSTRACT FROM AUTHOR]

Background: Access to healthcare services, from diagnosis through end of life (EOL), is important among persons living with Human Immunodeficiency Syndrome (HIV) and Acquired Immunodeficiency Syndrome (AIDS) (PLWHA). However, little is known about the availability of hospice services in Appalachian areas. Therefore, the objective of this study is to describe the geographic distribution of hospice, homecare and nursing home facilities in order to demonstrate current existence of and access to resources for EOL care among PLWHA in the Appalachian regions of Tennessee and Alabama. Methods: This paper reports on the second aim of a larger sequential, mixed methods qualitative-quantitative (qual→quan) study. Data from advance care planning (ACP) surveys were collected by both electronic (n = 28) and paper copies (n = 201) and, among other things, obtained information on zip codes of residence of PLWHA. This enabled assessment of the geographic distribution of residences of PLWHA in relation to the distribution of healthcare services such as hospice and home healthcare services. Hospice and Home Healthcare data were obtained from the Tennessee and Alabama Departments of Health. The street addresses of these facilities were used to geocode and map the geographic distributions of the facilities using Street Map USA. Travel times to Hospice and Home Healthcare facilities were computed and mapped using ArcGIS 10.3. Results: We identified a total of 32 hospice and 69 home healthcare facilities in the Tennessee Appalachian region, while the Alabama Appalachian region had a total of 110 hospice and 86 home healthcare facilities. Most care facilities were located in urban centers. The distribution of care facilities was worse in Tennessee with many counties having no facilities, requiring up to an hour drive time to reach patients. A total of 86% of the PLWHA indicated preference to die at home. Conclusions: Persons living with HIV/AIDS in Appalachia face a number of challenges at the end of life that make access to EOL services difficult. Although respondents indicated a preference to die at home, the hospice/homecare infrastructure and resources are overwhelmingly inadequate to meet this need. There is need to improve access to EOL care in the Appalachian regions of both Tennessee and Alabama although the need is greater in Tennessee. [ABSTRACT FROM AUTHOR]

Background: Risk perception has been found to be a crucial factor explaining inconsistent or non-use of HIV prevention interventions. Considerations of risk need to expand beyond risk of infection to also include the personal, social, emotional, and economic risks associated with prevention intervention use. Objectives: This systematic review of qualitative peer-reviewed literature from sub-Saharan Africa examines perceptions of risk associated with HIV infection and HIV prevention intervention use. Data sources: We searched Medline, Embase, PsychInfo, Africa Wide Info, CINAHL, and Global Health for publications and screened them for relevance. Study eligibility criteria: Peer-reviewed qualitative studies published since 2003 were eligible for inclusion if they examined risk perception or uncertainty in the context of a medically regulated intervention. Only studies focusing on adults were included. Study appraisal and synthesis methods: Included publications were quality assessed using the Hawker method and coded thematically. Results: 10318 unique papers were identified, of which 29 are included. Among the themes identified, a particularly salient one was the potential of HIV prevention interventions to threaten the stability of a relationship and impact on how and when people may—or may not—choose to use prevention interventions. Limitations: This literature review excludes grey-literature, which may have distinct valuable insights. We also excluded quantitative studies that may have challenged or triangulated our findings. Conclusions and implications: When considering the risk of HIV acquisition, it is insufficient to examine biological risk in isolation from the personal, relational and economic costs associated with intervention use. This loss of emotional, physical, or material support may be perceived as more consequential than the prevention of a potential infection. [ABSTRACT FROM AUTHOR]

Background: In Australia, pre-exposure prophylaxis (PrEP) is targeted to individuals at high risk for HIV infection. We describe the HIV risk profile and characteristics of PRELUDE participants, and evaluate the population validity of the sample in representing high-risk gay and bisexual men (GBM) eligible for PrEP. Methods: PRELUDE is an on-going, open-label, single-arm observational study. Participants were identified in clinics and screened for eligibility using a paper-based risk assessment tool which followed the New South Wales (NSW) PrEP guidelines. Selection was validated using an independent online behavioural survey, completed by study participants upon enrolment. Demographic information was analysed using descriptive statistics, and kappa tests were used to determine agreement between reporting of high-risk practices in the risk assessment and behavioural survey. Results: During 2014–15, 471 individuals were targeted for enrolment; 341 were assessed for PrEP eligibility and 313 were enrolled. Of these, 303 (97%) identified as GBM. Overall, 85% of GBM met at least one high-risk criterion; 68% reported receptive intercourse with an HIV-positive or unknown status casual male partner, and 37% reported methamphetamine use in the three months preceding enrolment. The remaining 15% were enrolled based on medium-risk behaviours, or at the clinicians’ discretion. We found an 82% total agreement between self-reported high-risk behaviour and clinicians’ categorisation of GBM as being at high risk for HIV based on PrEP eligibility criteria. Conclusions: Behavioural eligibility criteria used by clinicians successfully identified individuals at high risk for HIV infection. This targeted approach ensures that the greatest public health and HIV prevention benefits can be derived in a setting without universal access to PrEP. [ABSTRACT FROM AUTHOR]

Access to HIV care services, including antiretroviral therapy (ART), is essential for improving health outcomes of people living with HIV (PLHIV) and reducing HIV transmission and AIDS-related deaths. As a part of a qualitative study in Belu, this paper describes the use of traditional medicines for HIV treatment and family and social influence as barriers to access to HIV care services among PLHIV. One-on-one in-depth interviews were employed to collect data from 46 PLHIV (26 women and 20 men) and 10 healthcare professionals. They were recruited using the snowball sampling technique. The study information sheets were initially posted on information boards in healthcare facilities. Potential participants who contacted to confirm their participation were recruited for an interview and then asked for help to distribute the information sheets to their eligible colleagues who might be willing to participate. Data analysis was performed using NVivo 12 software and guided by a qualitative data analysis framework. The findings showed that the use of traditional medicines, a well-known cultural practice in Belu, was a barrier to access to HIV care services among PLHIV. The influence of family in determining the use of traditional medicines for HIV treatment, supported by the lack of knowledge of ART, effectiveness of traditional medicines in treating other health issues, and social influence of relatives, neighbours, and friends, were also significant barriers to PLHIV's access to HIV care services. The findings indicate the need for dissemination of HIV care-related information for PLHIV, family, and community members to increase their knowledge of the service, ART and its function, and to support and improve access to HIV care services especially ART by PLHIV. [ABSTRACT FROM AUTHOR]

To control the HIV/AIDS epidemics in Guangxi Zhuang Autonomous Region in China, Guangxi government launched the 5-year Guangxi AIDS Conquering Project (GACP, Phase I: 2010-2014, Phase II: 2015-2020). In the project, three measures are implemented, such as great improvements of the coverage of HIV/AIDS education, promotion of HIV voluntary counseling and testing, and enhancement of antiretroviral treatment. In this paper, we explore the effects of the three measures of GACP by construction of a Susceptible-Infected-Diagnosed-Treated population compartments model and via evaluation of the basic reproduction number derived from the model. A computational framework is developed for estimating the model parameters based on the HIV surveillance data, with application of the Markov-Chain Monte-Carlo method and Nonlinear Least Squares method. By estimating the new infections and evaluating the basic reproduction number, we find that the implementation of the three measures of GACP has a significant effect on controlling the rise of HIV/AIDS cases and the epidemic trend. Compared with HIV voluntary counseling and testing, strengthening HIV/AIDS education and expanding the coverage of antiretroviral treatment show a greater impact on HIV/AIDS epidemic control, which provides a reference project for other provinces with a similar epidemic situation in Guangxi Zhuang Autonomous Region. At the same time, our research fills the current research gap for the evaluation of large-scale AIDS prevention and control projects in developing areas. [ABSTRACT FROM AUTHOR]

Achievement of viral load suppression among people living with HIV is one of the most important goals for effective HIV epidemic response. In Ukraine, people who inject drugs (PWID) experience the largest HIV burden. At the same time, this group disproportionally missed out in HIV treatment services. We performed a secondary data analysis of the national-wide cross-sectional bio-behavioral surveillance survey among PWID to assess the population-level prevalence of detectable HIV viremia and identify key characteristics that explain the outcome. Overall, 11.4% of PWID or 52.6% of HIV-positive PWID had a viral load level that exceeded the 1,000 copies/mL threshold. In the group of HIV-positive PWID, the detectable viremia was attributed to younger age, monthly income greater than minimum wage, lower education level, and non-usage of antiretroviral therapy (ART) and opioid agonistic therapy. Compared with HIV-negative PWID, the HIV-positive group with detectable viremia was more likely to be female, represented the middle age group (35–49 years old), had low education and monthly income levels, used opioid drugs, practiced risky injection behavior, and had previous incarceration history. Implementing the HIV case identification and ART linkage interventions focused on the most vulnerable PWID sub-groups might help closing the gaps in ART service coverage and increasing the proportion of HIV-positive PWID with viral load suppression. [ABSTRACT FROM AUTHOR]

Introduction: Human Immunodeficiency Virus (HIV) is continued to be a major public health problem in low-income countries and more importantly in Africa. For the last decade, access to Antiretroviral Therapy (ART) and its impact in improving quality of life and reducing HIV-related morbidity and mortality has significantly been improved in Africa. Nevertheless, the emergency of HIV drug resistance (HIVDR) has posed challenges in achieving optimal ART treatment outcomes and is alarmingly increasing globally in general and in Africa in particular. Comprehensive epidemiological data on the magnitude of HIVDR and HIVDR mutations, and predictors of HIVDR are, however, limited in Africa. Objective: The main objective of this systematic review will be to estimate the pooled proportion of HIVDR and HIVDR mutations, and identify factors associated with HIVDR among people living with HIV/AIDS (PLWH) in Africa. Method: Published Literature from 2000 until 30 October 2021 will be searched in PubMed/Medline Ovid, HINARI, SCOPUS, EMBASE, CINAHL, Web of Sciences, and Cochrane electronic databases. Initially, the literature will be screened based on title/abstract and followed by full-text appraisal for methodological quality using JBI critical appraisal tools. Data will be extracted from eligible articles after the full-text appraisal. Heterogeneity will be qualitatively assessed by a visual Funnel plot and quantitatively measured by an index of heterogeneity (I2 statistics). Random-effects model will be fitted to estimate the proportion of HIVDR and each HIVDR mutations. Sub-group and sensitivity analyses will be conducted to reduce heterogeneity. Meta-regression will be done by median year of sampling per study to observe the pattern of changes over time. Publication bias will be assessed by egger's statistics. In case of publication bias, Trim and Fill analysis will be conducted to overcome small-study effect. Data analysis will be performed using Stata version 14. Ethics and dissemination: As the data sources are published papers, the protocol will not require an ethical approval letter. The final report of the review will be published in a peer-reviewed journal. [ABSTRACT FROM AUTHOR]

Background: Optimizing services to facilitate engagement and retention in care of people living with HIV (PLWH) on antiretroviral therapies (ARTs) is critical to decrease HIV-related morbidity and mortality and HIV transmission. We systematically reviewed the literature for the effectiveness of implementation strategies to reestablish and subsequently retain clinical contact, improve viral load suppression, and reduce mortality among patients who had been lost to follow-up (LTFU) from HIV services.Methods and Findings: We searched 7 databases (PubMed, Cochrane, ERIC, PsycINFO, EMBASE, Web of Science, and the WHO regional databases) and 3 conference abstract archives (CROI, IAC, and IAS) to find randomized trials and observational studies published through 13 April 2020. Eligible studies included those involving children and adults who were diagnosed with HIV, had initiated ART, and were subsequently lost to care and that reported at least one review outcome (return to care, retention, viral suppression, or mortality). Data were extracted by 2 reviewers, with discrepancies resolved by a third. We characterized reengagement strategies according to how, where, and by whom tracing was conducted. We explored effects, first, among all categorized as LTFU from the HIV program (reengagement program effect) and second among those found to be alive and out of care (reengagement contact outcome). We used random-effect models for meta-analysis and conducted subgroup analyses to explore heterogeneity. Searches yielded 4,244 titles, resulting in 37 included studies (6 randomized trials and 31 observational studies). In low- and middle-income countries (LMICs) (N = 16), tracing most frequently involved identification of LTFU from the electronic medical record (EMR) and paper records followed by a combination of telephone calls and field tracing (including home visits), by a team of outreach workers within 3 months of becoming LTFU (N = 7), with few incorporating additional strategies to support reengagement beyond contact (N = 2). In high-income countries (HICs) (N = 21 studies), LTFU were similarly identified through EMR systems, at times matched with other public health records (N = 4), followed by telephone calls and letters sent by mail or email and conducted by outreach specialist teams. Home visits were less common (N = 7) than in LMICs, and additional reengagement support was similarly infrequent (N = 5). Overall, reengagement programs were able to return 39% (95% CI: 31% to 47%) of all patients who were characterized as LTFU (n = 29). Reengagement contact resulted in 58% (95% CI: 51% to 65%) return among those found to be alive and out of care (N = 17). In 9 studies that had a control condition, the return was higher among those in the reengagement intervention group than the standard of care group (RR: 1.20 (95% CI: 1.08 to 1.32, P < 0.001). There were insufficient data to generate pooled estimates of retention, viral suppression, or mortality after the return.Conclusions: While the types of interventions are markedly heterogeneity, reengagement interventions increase return to care. HIV programs should consider investing in systems to better characterize LTFU to identify those who are alive and out of care, and further research on the optimum time to initiate reengagement efforts after missed visits and how to best support sustained reengagement could improve efficiency and effectiveness. [ABSTRACT FROM AUTHOR]

Background: Cotrimoxazole and isoniazid preventive therapy (CPT, IPT) have been shown to be efficacious therapies for the prevention of opportunistic infections and tuberculosis (TB) among people living with human immunodeficiency virus (HIV). Despite governments' efforts to translate World Health Organization recommendations into practice, implementation remains challenging. This review aimed to explore and compare CPT and IPT with respect to similarities and differences of barriers identified across high TB/HIV burden countries. A secondary objective was to identify facilitators for implementing both preventive therapies. Methods: We searched MEDLINE, Web of Science and SCOPUS databases for peer-reviewed literature published before September 2020. We extracted and synthesized our findings using Maxqda software. We applied framework synthesis in conjunction with metasummary to compare both therapies with respect to similarities and differences of barriers identified across seven health system components (in line with the modified WHO's Framework for action). Protocol registration: PROSPERO (CRD42019137778). Findings: We identified four hundred and eighty-two papers, of which we included forty for review. Although most barrier themes were identical for both preventive therapies, we identified seven intervention-specific themes. Like for CPT, barriers identified for IPT were most frequently classified as 'service delivery-related barriers' and 'patient & community-related barriers'. 'Health provider-related barriers' played an important role for implementing IPT. Most facilitators identified referred to health system strengthening activities. Conclusions: For researchers with limited working experience in high TB/HIV burden countries, this review can provide valuable insights about barriers that may arise at different levels of the health system. For policymakers in high TB/HIV burden countries, this review offers strategies for improving the delivery of IPT (or any newer therapy regimen) for the prevention of TB. Based on our findings, we suggest initial and continuous stakeholder involvement, focusing on the efficient use and reinforcement of existing resources for health. [ABSTRACT FROM AUTHOR]

TB is rated as one of the world’s deadliest diseases and South Africa ranks 9th out of the 22 countries with hardest hit of TB. Although many pieces of research have been carried out on this subject, this paper steps further by inculcating past knowledge into the model, using Bayesian approach with informative prior. Bayesian statistics approach is getting popular in data analyses. But, most applications of Bayesian inference technique are limited to situations of non-informative prior, where there is no solid external information about the distribution of the parameter of interest. The main aim of this study is to profile people living with TB in South Africa. In this paper, identical regression models are fitted for classical and Bayesian approach both with non-informative and informative prior, using South Africa General Household Survey (GHS) data for the year 2014. For the Bayesian model with informative prior, South Africa General Household Survey dataset for the year 2011 to 2013 are used to set up priors for the model 2014. [ABSTRACT FROM AUTHOR]

Background: The report of the Joint United Nations Programme on HIV/AIDS (UNAIDS) for World AIDS Day 2014 highlighted a Fast-Track Strategy that sets ambitious treatment and prevention targets to reduce global HIV incidence to manageable levels by 2020 and end the AIDS epidemic by 2030. The 90-90-90 treatment targets for 2020 call for 90% of people living with HIV to know their HIV status, 90% of people who know their status to receive treatment, and 90% of people on HIV treatment to be virally suppressed. This paper examines how scale-up of voluntary medical male circumcision (VMMC) services in four priority countries in sub-Saharan Africa could contribute to ending the AIDS epidemic by 2030 in the context of concerted efforts to close the treatment gap, and what the impact of VMMC scale-up would be if the 90-90-90 treatment targets were not completely met. Methods: Using the Goals module of the Spectrum suite of models, this analysis modified ART (antiretroviral treatment) scale-up coverage from base scenarios to reflect the 90-90-90 treatment targets in four countries (Lesotho, Malawi, South Africa, and Uganda). In addition, a second scenario was created to reflect viral suppression levels of 75% instead of 90%, and a third scenario was created in which the 90-90-90 treatment targets are reached in women, with men reaching more moderate coverage levels. Regarding male circumcision (MC) coverage, the analysis examined both a scenario in which VMMCs were assumed to stop after 2015, and one in which MC coverage was scaled up to 90% by 2020 and maintained at 90% thereafter. Results: Across all four countries, scaling up VMMC is projected to provide further HIV incidence reductions in addition to those achieved by reaching the 90-90-90 treatment targets. If viral suppression levels only reach 75%, scaling up VMMC leads to HIV incidence reduction to nearly the same levels as those achieved with 90-90-90 without VMMC scale-up. If only women reach the 90-90-90 targets, scaling up VMMC brings HIV incidence down to near the levels projected with 90-90-90 without VMMC scale-up. Regarding cost, scaling up VMMC increases the annual costs during the scale-up phase, but leads to lower annual costs after the MC coverage target is achieved. Conclusions: The scenarios modeled in this paper show that the highly durable and effective male circumcision intervention increases epidemic impact levels over those of treatment-only strategies, including the case if universal levels of viral suppression in men and women are not achieved by 2020. In the context of 90-90-90, prioritizing continued successful scale-up of VMMC increases the possibility that future generations will be free not only of AIDS but also of HIV. [ABSTRACT FROM AUTHOR]

HIV-1 establishes a persistent proviral reservoir by integrating into the genome of infected host cells. Current antiretroviral treatments do not target this persistent population of proviruses which include latently infected cells that upon treatment interruption can be reactivated to contribute to HIV-1 rebound. Deep sequencing of persistent HIV proviruses has revealed that greater than 90% of integrated HIV genomes are defective and unable to produce infectious virions. We hypothesized that intragenic elements in the HIV genome support transcription of aberrant HIV-1 RNAs from defective proviruses that lack long terminal repeats (LTRs). Using an intact provirus detection assay, we observed that resting CD4+ T cells and monocyte-derived macrophages (MDMs) are biased towards generating defective HIV-1 proviruses. Multiplex reverse transcription droplet digital PCR identified env and nef transcripts which lacked 5' untranslated regions (UTR) in acutely infected CD4+ T cells and MDMs indicating transcripts are generated that do not utilize the promoter within the LTR. 5'UTR-deficient env transcripts were also identified in a cohort of people living with HIV (PLWH) on ART, suggesting that these aberrant RNAs are produced in vivo. Using 5' rapid amplification of cDNA ends (RACE), we mapped the start site of these transcripts within the Env gene. This region bound several cellular transcription factors and functioned as a transcriptional regulatory element that could support transcription and translation of downstream HIV-1 RNAs. These studies provide mechanistic insights into how defective HIV-1 proviruses are persistently expressed to potentially drive inflammation in PLWH. Author summary: People living with HIV establish a persistent reservoir which includes latently infected cells that fuel viral rebound upon treatment interruption. However, the majority of HIV-1 genomes in these persistently infected cells are defective. Whether these defective HIV genomes are expressed and whether they contribute to HIV associated diseases including accelerated aging, neurodegenerative symptoms, and cardiovascular diseases are still outstanding questions. In this paper, we demonstrate that acute infection of macrophages and resting T cells is biased towards generating defective viruses which are expressed by DNA regulatory elements in the HIV genome. These studies describe an alternative mechanism for chronic expression of HIV genomes. [ABSTRACT FROM AUTHOR]

Introduction: The COVID-19 pandemic has caused widespread disruptions including to health services. In the early response to the pandemic many countries restricted population movements and some health services were suspended or limited. In late 2020 and early 2021 some countries re-imposed restrictions. Health authorities need to balance the potential harms of additional SARS-CoV-2 transmission due to contacts associated with health services against the benefits of those services, including fewer new HIV infections and deaths. This paper examines these trade-offs for select HIV services. Methods: We used four HIV simulation models (Goals, HIV Synthesis, Optima HIV and EMOD) to estimate the benefits of continuing HIV services in terms of fewer new HIV infections and deaths. We used three COVID-19 transmission models (Covasim, Cooper/Smith and a simple contact model) to estimate the additional deaths due to SARS-CoV-2 transmission among health workers and clients. We examined four HIV services: voluntary medical male circumcision, HIV diagnostic testing, viral load testing and programs to prevent mother-to-child transmission. We compared COVID-19 deaths in 2020 and 2021 with HIV deaths occurring now and over the next 50 years discounted to present value. The models were applied to countries with a range of HIV and COVID-19 epidemics. Results: Maintaining these HIV services could lead to additional COVID-19 deaths of 0.002 to 0.15 per 10,000 clients. HIV-related deaths averted are estimated to be much larger, 19–146 discounted deaths per 10,000 clients. Discussion: While there is some additional short-term risk of SARS-CoV-2 transmission associated with providing HIV services, the risk of additional COVID-19 deaths is at least 100 times less than the HIV deaths averted by those services. Ministries of Health need to take into account many factors in deciding when and how to offer essential health services during the COVID-19 pandemic. This work shows that the benefits of continuing key HIV services are far larger than the risks of additional SARS-CoV-2 transmission. [ABSTRACT FROM AUTHOR]

As a part of a larger qualitative study to understand HIV-risk factors and impacts on people living with HIV (PLHIV) (52 women and 40 men) in Belu and Yogyakarta, Indonesia, this paper reports the influences of cultural practices and religious beliefs on sexual relationships and behaviours of participants as contributors for HIV transmission. This study was conducted from June to December 2020. Data collection was conducted using one-one-one in-depth interviews. Participants were recruited using the snowball sampling technique. Data analysis was guided by a qualitative data analysis framework. The findings showed that cultural practices in Belu related to the use of bride wealth, managing spousal disputes, marriage, and condom use, influenced spousal relationships and sexual behaviours or practices which contributed to HIV transmission. Javanese cultural practices and expectation of an 'ideal wife', Islamic religious beliefs about expected husband-wife relationships, forbidden premarital sex, and the participants' individual interpretation of their religious beliefs about condom use spousal sexual relations, also influenced spousal sexual relations and behaviours, which supported HIV transmission among the participants. The findings indicate the need for HIV education programs that address cultural practices and religious beliefs for community members and population groups to enhance their understanding about HIV, condom use, and how cultural practices and religious beliefs play a role in HIV transmission. The findings also indicate the need for involvement of religious leaders in HIV education programs to bring insights to people and help them interpret their religious beliefs in health promoting ways. Future studies that explore different aspects of culture and religion which may contribute to HIV transmission are recommended. [ABSTRACT FROM AUTHOR]

Background: CD4 cell counts is widely used as a biomarker for treatment progression when studying the efficacy of drugs to treat HIV-infected patients. In the past, it had been also used in determining eligibility to initiate antiretroviral therapy. The main aim of this was to model the evolution of CD4 counts over time and use this model for an early prediction of subject-specific time to cross a pre-specified CD4 threshold. Methods: Hospital based retrospective cohort study of HIV-infected patients was conducted from January 2009 to December 2014 at University of Gondar hospital, Northwest Ethiopia. Fractional polynomial random effect model is used to model the evolution of CD4 counts over time in response to treatment and to estimate the individual probability to be above a pre-selected CD4 threshold. Human subject research approval for this study was received from University of Gondar Research Ethics Committee and the medical director of the hospital. Results: A total of 1347 patients were included in the analysis presented in this paper. The cohort contributed a total of 236.58 per 100 person-years of follow-up. Later the data were divided into two periods: the first is the estimation period in which the parameters of the model are estimated and the second is the prediction period. Based on the parameters from the estimation period, model based prediction for the time to cross a threshold was estimated. The correlations between observed and predicted values of CD4 levels in the estimation period were 0.977 and 0.982 for Neverapine and Efavirenz containing regimens, respectively; while the correlation between the observed and predicted CD4 counts in the prediction period are 0.742 and 0.805 for NVP and EFV, respectively. Conclusions: The model enables us to estimate a subject-specific expected time to cross a CD4 threshold and to estimate a subject-specific probability to have CD4 count above a pre-specified threshold at each time point. By predicting long-term outcomes of CD4 count of the patients one can advise patient about the potential ART benefits that accrue in the long-term. [ABSTRACT FROM AUTHOR]

Introduction: Stigma and discrimination (SAD) related to HIV compromise access and adherence to treatment and support programs among people living with HIV (PLHIV). The ambitious goal of ending the epidemic of HIV by 2030 set by the United Nations Joint Program of HIV/AIDS (UNAIDS) will thus only be achieved if HIV-related stigma and discrimination are reduced. The objective of this review was to locate, appraise and describe international literature reporting on interventions that addressed HIV-related SAD in healthcare settings. Methods: The databases searched were: Cumulative Index to Nursing and Allied Health (CINAHL), Excerpta Medica Database from Elsevier (EMBASE), PubMed and Psychological Information (PsycINFO) database. Two individuals independently appraised the quality of the papers using appraisal instruments from the Joanna Briggs Institute (JBI). Data were extracted from papers included in the review using the standardized data extraction tool from JBI. Quality of evidence for major outcomes was assessed using Grading of Recommendations, Assessment, Development and Evaluation (GRADE). Results: We retained 14 records reporting on eight studies. Five categories of SAD reduction (information-based, skills building, structural, contact-based and biomedical interventions) were identified. Training popular opinion leaders (POLs) resulted in significantly lower mean avoidance intent scores (MD = -1.87 [95% CI -2.05 to -1.69]), mean prejudicial attitude scores (MD = -3.77 [95% CI -5.4 to -2.09]) and significantly higher scores in mean compliance to universal precaution (MD = 1.65 [95% CI 1.41 to 1.89]) when compared to usual care (moderate quality evidence). The Summary of Findings table (SOF) is shown in . Conclusions: Evidence of moderate quality indicates that training popular opinion leaders is effective in reducing avoidance intent and prejudicial attitude and improving compliance to universal precaution. Very low quality evidence indicates that professionally-assisted peer group interventions, modular interactive training, participatory self-guided assessment and intervention, contact strategy combined with information giving and empowerment are effective in reducing HIV-related stigma.Further Randomized Controlled Trials (RCTs) are needed. Future trials need to use up-to-date and validated instruments to measure stigma and discrimination. [ABSTRACT FROM AUTHOR]

Background: Ineffective linkage to care (LTC) is a known challenge for community HIV testing. To overcome this challenge, a robust linkage to care strategy was adopted by the 2018 Nigeria HIV/AIDS Indicator and Impact Survey (NAIIS). The NAIIS linkage to care strategy was further adapted to improve Nigeria's programmatic efforts to achieve the 1st 90 as part of the Nigeria Antiretroviral Therapy (ART) Surge initiative, which also included targeted community testing. In this paper we provide an overview of the NAIIS LTC strategy and describe the impact of this strategy on both the NAIIS and the Surge initiatives. Methods: The NAIIS collaborated with community-based organizations (CBOs) and deployed mobile health (mHealth) technology with real-time dashboards to manage and optimize community LTC for people living with HIV (PLHIV) diagnosed during the survey. In NAIIS, CBOs' role was to facilitate linkage of identified PLHIV in community to facility of their choice. For the ART Surge, we modified the NAIIS LTC strategy by empowering both CBOs and mobile community teams as responsible for not only active LTC but also for community testing, ART initiation, and retention in care. Results: Of the 2,739 PLHIV 15 years and above identified in NAIIS, 1,975 (72.1%) were either unaware of their HIV-positive status (N = 1890) or were aware of their HIV-positive status but not receiving treatment (N = 85). Of these, 1,342 (67.9%) were linked to care, of which 952 (70.9%) were initiated on ART. Among 1,890 newly diagnosed PLHIV, 1,278 (67.6%) were linked to care, 33.7% self-linked and 66.3% were linked by CBOs. Among 85 known PLHIV not on treatment, 64 (75.3%) were linked; 32.8% self-linked and 67.2% were linked by a CBO. In the ART Surge, LTC and treatment initiation rates were 98% and 100%, respectively. Three-month retention for monthly treatment initiation cohorts improved from 76% to 90% over 6 months. Conclusions: Active LTC strategies by local CBOs and mobile community teams improved LTC and ART initiation in the ART Surge initiative. The use of mHealth technology resulted in timely and accurate documentation of results in NAIIS. By deploying mHealth in addition to active LTC, CBOs and mobile community teams could effectively scale up ART with real-time documentation of client-level outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Tuberculosis screening of people living with human immunodeficiency virus is an intervention recommended by the WHO to control the dual epidemic of TB and HIV. The extent to which the intervention is adhered to by the HIV healthcare providers (fidelity) determines the intervention's effectiveness as measured by patient outcomes, but literature on fidelity is scarce. This study assessed provider implementation fidelity to national guidelines on TB screening at HIV clinics in Ghana. Methods: It was a cross-sectional study that used structured questionnaires to gather data, involving 226 of 243 HIV healthcare providers in 27 HIV clinics across Ghana. The overall fidelity score comprised sixteen items with a maximum score of 48 grouped into three components of the screening intervention (TB diagnosis, TB awareness and TB symptoms questionnaire). Simple summation of item scores was done to determine fidelity score per provider. In this paper, we define the level of fidelity as low if the scores were below the median score and were otherwise categorized as high. Background factors potentially associated with implementation fidelity level were assessed using cluster-based logistic regression. Odds ratio with 95% confidence interval (CI) was used as the measure of association. Results: Of the 226 healthcare providers interviewed, 60% (135) were females with a mean age of 34.5 years (SD = 8.3). Most of them were clinicians [63% (142)] and had post-secondary non-tertiary education [62% (141)]. Overall, 53% (119) of the healthcare providers were categorized to have implemented the intervention with high fidelity. Also, 56% (126), 53% (120), and 59% (134) of the providers implemented the TB diagnosis, TB awareness and TB symptoms questionnaire components respectively with high fidelity. After adjusting for cluster effect, female providers (AOR = 2.36, 95%CI: 1.09–5.10, p = <0.029), those with tertiary education (AOR = 4.31, 95%CI: 2.12–9.10, p = 0.040), and clinicians (AOR = 1.78, 95%CI: 1.07–3.50, p = 0.045) were more likely to adhere to the guidelines compared to their counterparts. Conclusion: The number of providers with fidelity scores above the median was marginally greater (6%) than the number with fidelity score below the median. Similarly, for each of the components, the number of providers with fidelity scores higher than the median was marginally higher. This could explain the existing fluctuations in the intervention outcomes in Ghana. We found gender, profession and education were associated with provider implementation fidelity. To improve fidelity level among HIV healthcare providers, and realize the aims of the TB screening intervention among PLHIV in Ghana, further training on implementing all components of the intervention is critical. [ABSTRACT FROM AUTHOR]