Parallel analysis of transcription, integration, and sequence of single HIV-1 proviruses.

HIV-1-infected cells that persist despite antiretroviral therapy (ART) are frequently considered "transcriptionally silent," but active viral gene expression may occur in some cells, challenging the concept of viral latency. Applying an assay for profiling the transcriptional activity and the chromosomal locations of individual proviruses, we describe a global genomic and epigenetic map of transcriptionally active and silent proviral species and evaluate their longitudinal evolution in persons receiving suppressive ART. Using genome-wide epigenetic reference data, we show that proviral transcriptional activity is associated with activating epigenetic chromatin features in linear proximity of integration sites and in their inter- and intrachromosomal contact regions. Transcriptionally active proviruses were actively selected against during prolonged ART; however, this pattern was violated by large clones of virally infected cells that may outcompete negative selection forces through elevated intrinsic proliferative activity. Our results suggest that transcriptionally active proviruses are dynamically evolving under selection pressure by host factors.

Testing and Treatment Interventions in Community Settings Key to Controlling a Recent Human Immunodeficiency Virus Outbreak Among People Who Inject Drugs in Glasgow: A Modeling Study.

BACKGROUND: A human immunodeficiency virus (HIV) outbreak was identified among people who inject drugs (PWID) in Glasgow in 2015, with >150 diagnoses by the end of 2019. The outbreak response involved scaling up HIV testing and improving HIV treatment initiation and retention. METHODS: We parameterized and calibrated a dynamic, deterministic model of HIV transmission among PWID in Glasgow to epidemiological data. We use this model to evaluate HIV testing and treatment interventions. We present results in terms of relative changes in HIV prevalence, incidence, and cases averted. RESULTS: If the improvements in both testing and treatment had not occurred, we predict that HIV prevalence would have reached 17.8% (95% credible interval [CrI], 14.1%-22.6%) by the beginning of 2020, compared to 5.9% (95% CrI, 4.7%-7.4%) with the improvements. If the improvements had been made on detection of the outbreak in 2015, we predict that peak incidence would have been 26.2% (95% CrI, 8.8%-49.3%) lower and 62.7% (95% CrI, 43.6%-76.6%) of the outbreak cases could have been averted. The outbreak could have been avoided if the improvements had already been in place. CONCLUSIONS: Our modeling suggests that the HIV testing and treatment interventions successfully brought the HIV outbreak in Glasgow under control by the beginning of 2020.

Effectiveness of double-dose dolutegravir in people receiving rifampin-based tuberculosis treatment: an observational, cohort study of people with HIV from six countries.

BACKGROUND: Tenofovir-lamivudine-dolutegravir (TLD) is the preferred first-line antiretroviral therapy (ART) regimen. An additional 50 mg dose of dolutegravir (TLD + 50) is required with rifampin-containing tuberculosis (TB) co-treatment. There are limited data on the effectiveness of TLD + 50 in individuals with TB/HIV. METHODS: Prospective, observational cohort study at 12 sites in Haiti, Kenya, Malawi, South Africa, Uganda, Zimbabwe. Participants starting TLD and rifampin-containing TB treatment were eligible. Primary outcome was HIV-1 RNA ≤1000 copies/mL at end of TB treatment. FINDINGS: We enrolled 91 participants with TB/HIV: 75 (82%) ART-naïve participants starting TLD after a median 15 days on TB treatment, 10 (11%) ART-naïve participants starting TLD and TB treatment, 5 (5%) starting TB treatment after a median 3.3 years on TLD, and 1 (1%) starting TB treatment and TLD after changing from efavirenz/lamivudine/tenofovir. Median age was 37 years, 35% female, median CD4 count 120 cells/mm3 (IQR 50-295), 87% had HIV-1 RNA >1000 copies/mL. Two participants died during TB treatment. Among 89 surviving participants, 80 were followed to TB treatment completion, including 7 who had no HIV-1 RNA result due to missed visits. Primary virologic outcome was assessed in 73 participants, of whom 69 (95%, 95% CI 89-100%) had HIV-1 RNA ≤1000 copies/mL. No dolutegravir resistance mutations were detected among four participants with HIV-1 RNA >1000 copies/mL. INTERPRETATION: In routine programmatic settings, concurrent rifampin-containing TB treatment and TLD + 50 was feasible, well-tolerated, and achieved high rates of viral suppression in a cohort of predominantly ART-naïve people with TB/HIV.

Definition of Virological Endpoints Improving the Design of Human Immunodeficiency Virus (HIV) Cure Strategies Using Analytical Antiretroviral Treatment Interruption.

BACKGROUND: Analytical treatment interruption (ATI) is the gold standard in HIV research for assessing the capability of new therapeutic strategies to control viremia without antiretroviral treatment (ART). The viral setpoint is commonly used as endpoint to evaluate their efficacy. However, in line with recommendations from a consensus meeting, to minimize the risk of increased viremia without ART, trials often implement short ATI phases and stringent virological ART restart criteria. This approach can limit the accurate observation of the setpoint. METHODS: We analyzed viral dynamics in 235 people with HIV from 3 trials, examining virological criteria during ATI phases. Time-related (eg time to rebound, peak, and setpoint) and viral load magnitude-related criteria (peak, setpoint, and time-averaged AUC [nAUC]) were described. Spearman correlations were analyzed to identify (1) surrogate endpoints for setpoint and (2) optimal virological ART restart criteria mitigating the risks of ART interruption and the evaluation of viral control. RESULTS: Comparison of virological criteria between trials showed strong dependencies on ATI design. Similar correlations were found across trials, with nAUC the most strongly correlated with the setpoint, with correlations >0.70. A threshold >100 000 copies/mL for 2 consecutive measures is requested as a virological ART restart criterion. CONCLUSIONS: Our results are in line with recommendations and emphasize the benefits of an ATI phase >12 weeks, with regular monitoring, and a virological ART restart criterion of 10 000 copies/mL to limit the risk for patients while capturing enough information to keep nAUC as an optimal proxy to the setpoint.

"HIV has taught us that you can survive anything": findings from auto-ethnographic video diaries exploring resilience among people living with HIV during the Covid pandemic in five countries.

This study aimed to elucidate the intrinsic and extrinsic resilience resources among people living with HIV (PLWH) during the Covid pandemic. Autoethnographic video diaries from 29 PLWH from Argentina, UK, Philippines, Zimbabwe, and Trinidad and Tobago were included. Data were thematically analysed and validated with community partners and a video was co-produced. PLWH displayed a readiness to adopt healthy behaviours and engage in optimistic and constructive thinking about the future. Hobbies and daily activities, supportive relationships with peers living with HIV, family and friends, opportunities to mobilise and contribute to their communities in meaningful ways, supportive healthcare providers and reliable access to antiretroviral treatment helped foster psychological resilience among PLWH. The extrinsic resilience resources also supported positive physical health outcomes among PLWH through improved medication adherence.

Difficult-to-treat HIV in Sweden: a cross-sectional study.

BACKGROUND: Our aim was to examine the prevalence and characteristics of difficult-to-treat HIV in the current Swedish HIV cohort and to compare treatment outcomes between people with difficult and non-difficult-to-treat HIV. METHODS: In this cross-sectional analysis of the Swedish HIV cohort, we identified all people with HIV currently in active care in 2023 from the national register InfCareHIV. We defined five categories of difficult-to-treat HIV: 1) advanced resistance, 2) four-drug regimen, 3) salvage therapy, 4) virologic failure within the past 12 months, and 5) ≥ 2 regimen switches following virologic failure since 2008. People classified as having difficult-to-treat HIV were compared with non-difficult for background characteristics as well as treatment outcomes (viral suppression and self-reported physical and psychological health). RESULTS: Nine percent of the Swedish HIV cohort in 2023 (n = 8531) met at least one criterion for difficult-to-treat HIV. Most of them had ≥ 2 regimen switches (6%), and the other categories of difficult-to-treat HIV were rare (1-2% of the entire cohort). Compared with non-difficult, people with difficult-to-treat HIV were older, had an earlier first year of positive HIV test and lower CD4 counts, and were more often female. The viral suppression rate among people with difficult-to-treat HIV was 84% compared with 95% for non-difficult (p = 0.001). People with difficult-to-treat HIV reported worse physical (but not psychological) health, and this remained statistically significant after adjustment for age, sex, and transmission group. CONCLUSIONS: Although 9% of the HIV cohort in Sweden in 2023 were classified as having difficult-to-treat HIV, a large proportion of these were virally suppressed, and challenges such as advanced resistance and need for salvage therapy are rare in the current Swedish cohort.

Impact of differentiated service delivery models on retention in HIV care and viral suppression among people living with HIV in sub-Saharan Africa: A systematic review and meta-analysis of randomised controlled trials.

Differentiated service delivery (DSD) models, such as adherence clubs (ACs), are client-centred approaches where clinically stable people living with HIV (PLHIV) meet to receive various services, including psychosocial support, brief symptoms screening, and refills of antiretroviral medications, among others. We conducted a review to assess the impact of DSD models, including ACs, on sustaining retention in care (RC) and achieving viral suppression (VS) among PLHIV in sub-Saharan Africa. The review protocol was registered in PROSPERO (CRD42023418988). We searched the literature from PubMed, Scopus, Web of Science, Embase and Google Scholar from their inception through May 2023. Eligible randomised controlled trials of adherence clubs were reviewed to assess impact on retention and viral suppression. Random effect models were used to estimate the risk ratios (RR) and 95% confidence intervals (CI). The literature search yielded a total of 1596 records of which 16 randomised clinical trials were determined to be eligible. The trials were conducted in diverse populations among adults and children with a total of 13,886 participants. The RR between any DSD models and standard of care (SoC) was 1.09 (95% CI: 1.08-1.11, I2 : 0%, p: <0.96) and 1.01 (95% CI: 1.00-1.02, I2 : 0%, p: <0.85) for RC and VS, respectively. The RR between ACs and SoC was 1.01 (95% CI: 0.96-1.07, I2 : 84%, p: <0.01) and 1.02 (95% CI: 0.98-1.07, I2 : 77%, p: <0.01) for RC and VS, respectively. DSD models, including ACs, show comparable effectiveness to SoC in maintaining care and achieving viral suppression for stable PLHIV. To maximise adoption, an implementation science approach is crucial for designing effective strategies and overcoming challenges.

Factors associated with antiretroviral treatment adherence among people living with HIV in Guangdong Province, China: a cross sectional analysis.

BACKGROUND: Understanding factors associated with antiretroviral treatment (ART) adherence is crucial for ART success among people living with HIV (PLHIV) in the "test and treat" era. Multiple psychosocial factors tend to coexist and have a syndemic effect on ART adherence. We aimed to explore factors associated with ART adherence and the syndemic effect of multiple psychosocial factors on ART adherence among PLHIV newly starting ART in Guangdong Province, China. METHODS: Newly diagnosed PLHIV from six cities in Guangdong Province were recruited between May 2018 and June 2019, and then followed up from May 2019 to August 2020. Baseline and follow-up data were collected from a questionnaire and the national HIV surveillance system, the follow-up data of which were analyzed in this study. A Center for Adherence Support Evaluation (CASE) index > 10 points was defined as optimal ART adherence, which was measured via participants' self-reported adherence during follow-up survey. Multivariable logistic regression was used to identify factors associated with ART adherence. Exploratory factor analysis (EFA) and multi-order latent variable structural equation modeling (SEM) were performed to explore the syndemic effect of multiple psychosocial factors on ART adherence. RESULTS: A total of 734 (68.53%) follow-up participants were finally included in this study among the 1071 baseline participants, of whom 91.28% (670/734) had self-reported optimal ART adherence. Unemployment (aOR = 1.75, 95%CI: 1.01-3.02), no medication reminder (aOR = 2.28, 95%CI: 1.09-4.74), low medication self-efficacy (aOR = 2.28, 95%CI: 1.27-4.10), low social cohesion (aOR = 1.82, 95%CI: 1.03-3.19), no social participation (aOR = 5.65, 95%CI: 1.71-18.63), and ART side effects (aOR = 0.46, 95%CI: 0.26-0.81) were barriers to optimal ART adherence. The EFA and second-order latent variable SEM showed a linear relationship (standardized coefficient = 0.43, P < 0.001) between ART adherence and the latent psychosocial (syndemic) factor, which consisted of the three latent factors of medication beliefs and self-efficacy (standardized coefficient = 0.65, P < 0.001), supportive environment (standardized coefficient = 0.50, P < 0.001), and negative emotions (standardized coefficient=-0.38, P < 0.01). The latent factors of medication beliefs and self-efficacy, supportive environment, and negative emotions explained 42.3%, 25.3%, and 14.1% of the variance in the latent psychosocial factor, respectively. CONCLUSIONS: About nine out of ten PLHIV on ART in Guangdong Province self-reported optimal ART adherence. However, more efforts should be made to address barriers to optimal ART adherence.

HIV-associated rectovaginal fistulae in children: a single-centre retrospective study in the antiretroviral era.

PURPOSE: Acquired rectovaginal fistulae (RVF) are a complication of paediatric HIV infection. We report our experience with the surgical management of this condition. METHODS: We retrospectively reviewed the records of paediatric patients with HIV-associated RVF managed at Chris Hani Baragwanath Academic Hospital (2011-2023). Information about HIV management, surgical history, and long-term outcomes was collected. RESULTS: Ten patients with HIV-associated RVF were identified. Median age of presentation was 2 years (IQR: 1-3 years). Nine patients (9/10) underwent diverting colostomy, while one demised before the stoma was fashioned. Fistula repair was performed a median of 17 months (IQR: 7.5-55 months) after colostomy. An ischiorectal fat pad was interposed in 5/9 patients. Four (4/9) patients had fistula recurrence, 2/9 patients developed anal stenosis, and 3/9 perineal sepsis. Stoma reversal was performed a median of 16 months (IQR: 3-25 months) after repair. Seven patients (7/9) have good outcomes without soiling, while 2/9 have long-term stomas. Failure to maintain viral suppression after repair was significantly associated with fistula recurrence and complications (φ = 0.8, p < 0.05). CONCLUSION: While HIV-associated RVFs remain a challenging condition, successful surgical treatment is possible. Viral suppression is a necessary condition for good outcomes.

Metabolic, Mitochondrial, and Inflammatory Effects of Efavirenz, Emtricitabine, and Tenofovir Disoproxil Fumarate in Asymptomatic Antiretroviral-Naïve People with HIV.

This study aimed to comprehensively assess the metabolic, mitochondrial, and inflammatory effects of first-line efavirenz, emtricitabine, and tenofovir disoproxil fumarate (EFV/FTC/TDF) single-tablet regimen (STR) relative to untreated asymptomatic HIV infection. To this end, we analyzed 29 people with HIV (PWH) treated for at least one year with this regimen vs. 33 antiretroviral-naïve PWH. Excellent therapeutic activity was accompanied by significant alterations in metabolic parameters. The treatment group showed increased plasmatic levels of glucose, total cholesterol and its fractions (LDL and HDL), triglycerides, and hepatic enzymes (GGT, ALP); conversely, bilirubin levels (total and indirect fraction) decreased in the treated cohort. Mitochondrial performance was preserved overall and treatment administration even promoted the recovery of mitochondrial DNA (mtDNA) content depleted by the virus, although this was not accompanied by the recovery in some of their encoded proteins (since cytochrome c oxidase II was significantly decreased). Inflammatory profile (TNFα, IL-6), ameliorated after treatment in accordance with viral reduction and the recovery of TNFα levels correlated to mtDNA cell restoration. Thus, although this regimen causes subclinical metabolic alterations, its antiviral and anti-inflammatory properties may be associated with partial improvement in mitochondrial function.

Safety and Efficacy of Triple Therapy With Dolutegravir Plus 2 Nucleoside Reverse Transcriptase Inhibitors in Treatment-Naive Human Immunodeficiency Virus Type 2 Patients: Results From a 48-Week Phase 2 Study.

BACKGROUND: Integrase strand transfer inhibitor-based regimens are recommended for first-line therapy in human immunodeficiency virus type 2 (HIV-2). Nonetheless, dolutegravir (DTG) clinical trial data are lacking. METHODS: We conducted a phase 2, single-arm, open-label trial to evaluate the safety and efficacy of a triple therapy regimen that included DTG in persons with HIV-2 (PWHIV-2) in Portugal. Treatment-naive adults receive DTG in combination with 2 nucleoside reverse transcriptase inhibitors (NRTIs). Treatment efficacy was evaluated by the proportion of patients who achieved a plasma viral load (pVL) <40 copies/mL and/or by the change from baseline in CD4+ T-cell count and in CD4/CD8 ratio at week 48. RESULTS: A total of 30 patients were enrolled (22 women; median age, 55 years). At baseline, 17 (56.7%) individuals were viremic (median, pVL 190 copies/mL; interquartile range [IQR], 99-445). The median CD4 count was 438 cells/µL (IQR, 335-605), and the CD4/CD8 ratio was 0.8. Three patients discontinued the study. At week 48, all participants (27) had pVL <40 copies/mL. No virological failures were observed. Mean changes in CD4 count and CD4/CD8 ratio at week 48 were 95.59 cells/µL (95% confidence interval [CI], 28-163) and 0.32 (95% CI, .19 to .46). The most common drug-related adverse events were headache and nausea. One participant discontinued due to central nervous system symptoms. No serious adverse events were reported. CONCLUSIONS: DTG plus 2 NRTIs is safe and effective as first-line treatment for PWHIV-2 with a tolerability profile previously known. No virological failures were observed that suggest a high potency of DTG in HIV-2 as occurs in HIV-1. CLINICAL TRIALS REGISTRATION: M NCT03224338.

Point-of-Care Tenofovir Urine Testing for the Prediction of Treatment Failure and Drug Resistance During Initial Treatment for Human Immunodeficiency Virus Type 1 (HIV-1) Infection.

BACKGROUND: Viral rebound during antiretroviral treatment (ART) is most often driven by suboptimal adherence in the absence of drug resistance. We assessed the diagnostic performance of point-of-care (POC) tenofovir (TFV) detection in urine for the prediction of viral rebound and drug resistance during ART. METHODS: We performed a nested case-control study within the ADVANCE randomized clinical trial (NCT03122262) in Johannesburg, South Africa. Adults with human immunodeficiency virus (HIV) and newly initiating ART were randomized to receive either dolutegravir or efavirenz, tenofovir disoproxil fumarate or alafenamide, and emtricitabine. All participants with rebound ≥200 copies/mL between 24 and 96 weeks of follow-up were selected as cases and matched to controls with virological suppression <50 copies/mL. Rapid POC urine-TFV detection was performed retrospectively. RESULTS: We included 281 samples from 198 participants. Urine-TFV was detectable in 30.7% (70/228) of cases and in 100% (53/53) of controls. Undetectable urine-TFV predicted rebound with a sensitivity of 69% [95% confidence interval {CI}: 63-75] and specificity of 100% [93-100]. In cases with virological failure and sequencing data (n = 42), NRTI drug resistance was detected in 50% (10/20) of cases with detectable urine-TFV versus in 8.3% (2/24) of cases with undetectable urine-TFV. Detectable urine-TFV predicted NRTI resistance (odds ratio [OR] 10.4 [1.8-114.4] P = .005) with a sensitivity of 83% [52-98] and specificity of 69% [50-84]. CONCLUSIONS: POC objective adherence testing using a urine-TFV test predicted viral rebound with high specificity. In participants with rebound, urine-TFV testing predicted the selection of drug resistance. Objective adherence testing may be used to rapidly provide insight into adherence, suppression, and drug resistance during ART.

Clinical Perspective on Human Immunodeficiency Virus Care of Ukrainian War Refugees in Poland.

BACKGROUND: The Russian invasion of Ukraine forced migration for safety, protection, and assistance. Poland is the primary sheltering country for Ukrainian refugees, providing support including medical care, which resulted in the rapid ∼15% increase in the number of followed-up people with human immunodeficiency virus (HIV) (PWH) in the country. Here, we present the national experience on HIV care provided for refugees from Ukraine. METHODS: Clinical, antiretroviral, immunological, and virologic data from 955 Ukrainian PWH entering care in Poland since February 2022 were analyzed. The dataset included both antiretroviral-treated (n = 851) and newly diagnosed (n = 104) patients. In 76 cases, protease/reverse transcriptase/integrase sequencing was performed to identify drug resistance and subtype. RESULTS: Most (70.05%) of the patients were female, with a predominance of heterosexual (70.3%) transmissions. Anti-hepatitis C antibody and hepatitis B antigen were present in 28.7% and 2.9% of the patients, respectively. A history of tuberculosis was reported in 10.1% of cases. Among previously treated patients, the viral suppression rate was 89.6%; 77.3% of newly HIV diagnosed cases were diagnosed late (with lymphocyte CD4 count <350 cells/µL or AIDS). The A6 variant was observed in 89.0% of sequences. Transmitted mutations in the reverse transcriptase were found in 15.4% treatment-naive cases. Two patients with treatment failure exhibited multiclass drug resistance. CONCLUSIONS: Migration from Ukraine influences the characteristics of HIV epidemics in Europe, with an increase in the proportion of women and hepatitis C coinfected patients. Antiretroviral treatment efficacy among previously treated refugees was high, with new HIV cases frequently diagnosed late. The A6 subtype was the most common variant.

The declining trend in HIV prevalence from population-based surveys in Cameroon between 2004 and 2018: myth or reality in the universal test and treat era?

BACKGROUND: HIV remains an epidemic of major public health importance in Cameroon but a decline in HIV prevalence has been observed according to population-based surveys conducted in 2004, 2011 and 2018. We sought to review current evidence for declining HIV prevalence despite increasing survival owing to 'universal test and treat' and to explore the reason for the decrease, particularly the role of behavioural change. METHODS: We conducted a secondary analysis using HIV prevalence, behavioural and social determinants data of the Demographic and Health Survey Program databases. Trend lines were fitted to data that were available for a minimum of three points in time during the 1991-2018 period. Regression coefficients associated p-values and 95% confidence intervals were obtained using Microsoft Excel software. RESULTS: Overall adult HIV prevalence decreased significantly from 5.4% (95%CI: 4.8-6.0) in 2004 to 4.3% (95%CI: 3.8-4.8) in 2011 and further down to 2.7% (95%CI: 2.3-3.1) in 2018 at a rate of about 1.4% every septennium (ß = -1.4, R² = 0.98, p = 0.03). Yet, the number of persons surviving with HIV increased from about 0.05 million in 1991 to 0.5 million in 2018 corresponding to an increase in access to antiretroviral therapy from less than 10% to universal coverage of 80% respectively. Concurrent reductions in risky sexual behaviours were observed: a delayed sexual debut by one year, decreased sexual violence by 7%, decreased polygamous unions by 16%, decreased multiple sexual partners by 15.3% and increased condom use by 26.3%. CONCLUSION: The observed decline in HIV prevalence is statistically valid and reflects the observed decline in risky sexual behaviour that need to be sustained by the National HIV programme. Though universal access to ART has increased the number of persons surviving with HIV, this has not led to an increased prevalence of HIV in a setting with a rising population.

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

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

Determinants of comprehensive knowledge on mother-to-child transmission of HIV and its prevention among childbearing women in Rwanda: insights from the 2020 Rwandan Demographic and Health Survey.

BACKGROUND: Maternal knowledge on mother-to-child transmission (MTCT) and its prevention has been identified to enhance maternal testing and adherence to antiretroviral therapy (ART) regimen. Examining prevalence and associated factors on MTCT and its prevention among women provides empirical evidence for design and implementation of health strategies aimed at increasing MTCT knowledge and its elimination. This study therefore examined women's comprehensive knowledge and associated factors on MTCT and its prevention among childbearing women in Rwanda. METHODS: Analysis was conducted on a weighted sample of 14,634 women from the 2020 Rwanda Demographic and Health Survey (RDHS). Dataset cleaning and missing value analysis was conducted. Chi square, bivariate and multivariable regression was then conducted in complex samples in SPSS. Alpha level set at p < 0.05 and at 95% Confidence Interval (95% CI). All analysis were adjusted for unequal probability sampling using survey weights. Bivariate and multivariable results were reported with crude and adjusted odds ratios. RESULTS: The mean age was 29.2 years, SD-9.1. Prevalence of HIV testing and comprehensive knowledge on MTCT and its prevention among women in Rwanda was 79.6% and 65.1% respectively. Findings from this study showed that married women have higher odds (aOR = 1.18, 95% CI = 1.04-1.35) of comprehensive knowledge on MTCT and its prevention compared to those unmarried. Women who were living in southern (aOR = 1.23, 95%CI = 1.02-1.48) and eastern (aOR = 1.37, 95% CI = 1.13-1.66) parts of Rwanda were more likely to have adequate knowledge on MTCT of HIV and its prevention than those in Kigali. Also, women who received post-test counselling (aOR = 1.26, 95% CI = 1.01-2.11) have increased knowledge on MTCT than those who did not. Women with access to radio (aOR = 1.18, 95% CI = 1.06-1.32) and television (aOR = 1.25, 95% CI = 1.07-1.45) at least once a week were more likely to have adequate knowledge on MTCT and its prevention compared to those who do not in Rwanda. CONCLUSION: There is inadequate knowledge on MTCT and its elimination among women of reproductive age in Rwanda. Strategies to enhance knowledge on MTCT and its prevention among childbearing women should be adopted through rigorous educational sensitization campaigns using local media such as radio and television. Health services that focus on prevention of MTCT must emphasize post-test counselling.

Viral load suppression in HIV-infected adolescents in cameroon: towards achieving the UNAIDS 95% viral suppression target.

BACKGROUND: Achieving the UNAIDS 95% sustained viral suppression (VS) rate requires considerable global efforts, particularly among adolescents living with HIV (ALHIV) who are often associated with high rates of virological failure (VF). In this study, we prospectively assessed the rate of VS, and the factors associated with VF in a cohort of adolescents followed up according to the WHO guidelines in Cameroon. METHODS: A cross-sectional study was carried out in 2021 among adolescents (aged 10-19 years) receiving ART in the national program in Cameroon. Socio-demographic and clinical data were collected using patients' medical files and a brief interview with the participant and/or his guardian. Thereafter, a first viral load test (VL1) was performed using the ABBOTT Platform. For adolescents with VL1 > 1000 copies/ml, adherence-enhancing interventions were routinely performed each month for 3 consecutive months, after which a second viral load (VL2) was measured. Adolescents with VL2 > 1000 copies/ml were considered in VF. RESULTS: Overall, 280 adolescents were enrolled, of whom 89.3% (250/280) acquired HIV infection via mother-to-child transmission. The median age was 16.0 (IQR: 13.0-18.0) years and the median duration on ART was 9.8 (IQR: 5.1-12.8) years. Females and males were almost equally represented, as 52.1% (146/280) were female, while 47.9% (134/280) were males (p = 0.47). The VS rate was 88.2% (CI: 83.8-91.7%) overall; 89.0% (CI: 82.0-93.1%) and 88.7% (CI: 81.2-93.0%) in females and males, respectively. Being on second or third-line ART, self-declared suboptimal adherence, and a history of past VF were independently associated with VF. CONCLUSION: The high rate of VS we report in this study is welcome in the era of the 95/95/95 UNAIDS goals, and indicates that improving treatment outcomes in this specific and fragile population that represent adolescents in Sub-Saharan Africa is achievable. TRIAL REGISTRATION: 20/10/2020 NCT04593979 ( https://clinicaltrials.gov/ct2/show/NCT04593979 ).

Immediate initiation of antiretroviral treatment: knowledge, attitudes, and practices among clinic staff in New York City.

BACKGROUND: Immediate initiation of antiretroviral treatment (iART) is a proven intervention that significantly decreases time to viral suppression and increases patient retention. iART involves starting medication as early as possible, often after a reactive rapid HIV test or re-engagement in care, although it does not have a universal definition. We aimed to understand iART from an implementation science perspective in a wide range of New York City (NYC) clinics providing HIV primary care, including staff knowledge, attitudes, and practices, as well as clinic barriers and facilitators to iART. METHODS: We used a mixed-methods, convergent study design, with a quantitative survey and in-depth interview (IDI), to understand individual-level knowledge, attitudes, and practices, as well as clinic-level barriers and facilitators to iART. We recruited at least one medical and non-medical staff member from a diverse purposive sample of 30 NYC clinics. In quantitative analyses, we used separate binomial logistic regression models to estimate odds ratios (OR) and 95% confidence intervals (95% CI). In qualitative analyses, we used codebooks created by thematic analyses structured using a Framework Model to develop descriptive analytic memos. RESULTS: Recruited staff completed 46 surveys and 17 IDIs. We found high levels of awareness of the viral suppression and retention in care benefits of iART. Survey respondents more commonly reported medication starts within three to four days of a reactive rapid HIV test rather than same-day initiation. Among survey respondents, compared to medical staff, non-medical staff were more likely to agree that medication should only be initiated after receiving confirmatory HIV test results (OR: 0.2, 95% CI: 0.06-0.8). Additionally, survey respondents from clinics serving a majority people of color were less likely to report iART on the same day as a reactive rapid HIV test (OR: 0.2, 95% CI: 0.02-1.0, p-value < 0.5). IDI results elucidated barriers to implementation, including perceived patient readiness, which potentially leads to added disparities in iART access. CONCLUSION: iART has proven benefits and support for its implementation among HIV clinic staff. Our findings indicate that barriers to expanding iART access may be overcome if implementation resources are allocated strategically, which can further progress towards health equity.

Uptake of an App-Based Case Management Service for HIV-Positive Men Who Have Sex With Men in China: Process Evaluation Study.

BACKGROUND: Men who have sex with men (MSM) in China are disproportionately affected by the HIV epidemic, and medication adherence to antiretroviral treatment in this vulnerable population is suboptimal. To address this issue, we developed an app-based case management service with multiple components, informed by the Information Motivation Behavioral skills model. OBJECTIVE: We aimed to conduct a process evaluation for the implementation of an innovative app-based intervention guided by the Linnan and Steckler framework. METHODS: Process evaluation was performed alongside a randomized controlled trial in the largest HIV clinic in Guangzhou, China. Eligible participants were HIV-positive MSM aged ≥18 years planning to initiate treatment on the day of recruitment. The app-based intervention had 4 components: web-based communication with case managers, educational articles, supportive service information (eg, information on mental health care and rehabilitation service), and hospital visit reminders. Process evaluation indicators of the intervention include dose delivered, dose received, fidelity, and satisfaction. The behavioral outcome was adherence to antiretroviral treatment at month 1, and Information Motivation Behavioral skills model scores were the intermediate outcome. Logistic and linear regression was used to investigate the association between intervention uptake and outcomes, controlling for potential confounders. RESULTS: A total of 344 MSM were recruited from March 19, 2019, to January 13, 2020, and 172 were randomized to the intervention group. At month 1 follow-up, there was no significant difference in the proportion of adherent participants between the intervention and control groups (66/144, 45.8% vs 57/134, 42.5%; P=.28). In the intervention group, 120 participants engaged in web-based communication with case managers and 158 accessed at least 1 of the delivered articles. The primary concern captured in the web-based conversation was the side effects of the medication (114/374, 30.5%), which was also one of the most popular educational articles topics. The majority (124/144, 86.1%) of participants that completed the month 1 survey rated the intervention as "very helpful" or "helpful." The number of educational articles accessed was associated with adequate adherence in the intervention group (odds ratio 1.08, 95% CI 1.02-1.15; P=.009). The intervention also improved the motivation score after adjusting for baseline values (ß=2.34, 95% CI 0.77-3.91; P=.004). However, the number of web-based conversations, regardless of conversation features, was associated with lower motivation scores in the intervention group. CONCLUSIONS: The intervention was well-received. Delivering educational resources of interest may enhance medication adherence. The uptake of the web-based communication component could serve as an indicator of real-life difficulties and could be used by case managers to identify potential inadequate adherence. TRIAL REGISTRATION: Clinicaltrial.gov NCT03860116; https://clinicaltrials.gov/ct2/show/NCT03860116. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/s12889-020-8171-5.

Machine learning to predict virological failure among HIV patients on antiretroviral therapy in the University of Gondar Comprehensive and Specialized Hospital, in Amhara Region, Ethiopia, 2022.

BACKGROUND: Treatment with effective antiretroviral therapy (ART) reduces viral load as well as HIV-related morbidity and mortality in HIV-positive patients. Despite the expanded availability of antiretroviral therapy around the world, virological failure remains a serious problem for HIV-positive patients. Thus, Machine learning predictive algorithms have the potential to improve the quality of care and predict the needs of HIV patients by analyzing huge amounts of data, and enhancing prediction capabilities. This study used different machine learning classification algorithms to predict the features that cause virological failure in HIV-positive patients. METHOD: An institution-based secondary data was used to conduct patients who were on antiretroviral therapy at the University of Gondar Comprehensive and Specialized Hospital from January 2020 to May 2022. Patients' data were extracted from the electronic database using a structured checklist and imported into Python version three software for data pre-processing and analysis. Then, seven supervised classification machine-learning algorithms for model development were trained. The performances of the predictive models were evaluated using accuracy, sensitivity, specificity, precision, f1-score, and AUC. Association rule mining was used to generate the best rule for the association between independent features and the target feature. RESULT: Out of 5264 study participants, 1893 (35.06%) males and 3371 (64.04%) females were included. The random forest classifier (sensitivity = 1.00, precision = 0.987, f1-score = 0.993, AUC = 0.9989) outperformed in predicting virological failure among all selected classifiers. Random forest feature importance and association rules identified the top eight predictors (Male, younger age, longer duration on ART, not taking CPT, not taking TPT, secondary educational status, TDF-3TC-EFV, and low CD4 counts) of virological failure based on the importance ranking, and the CD-4 count was recognized as the most important predictor feature. CONCLUSION: The random forest classifier outperformed in predicting and identifying the relevant predictors of virological failure. The results of this study could be very helpful to health professionals in determining the optimal virological outcome.