Enhanced metabolic health and immune response with bictegravir/emtricitabine/TAF: Insights from a 96­week retrospective study.

Bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF), as a fixed dosed combination, is effective in people living with human immunodeficiency virus (PLWH) previously treated with other therapeutic regimens. The aim of the present retrospective observational real-life study was to analyze virological suppression and immunological, metabolic and safety profile of B/F/TAF. Data were collected from 127 PLHW who switched from any regimen to B/F/TAF. Viral load and virological suppression (viral load <50 copies/ml) were assessed by using real-time PCR methodologies; CD4 and CD8 T cell count as well as CD4/CD8 ratio were determined by cytofluorimetric analyses; other metabolic parameters such as total cholesterol, triglycerides, High- and Low-Density Lipoproteins were assessed by using immunoenzymatic assay. All of the aforementioned parameters were assessed at different timepoints (Baseline, 48 and 96 weeks) for the patients switching to B/F/TAF. Of 127 PLHW [96 (75.6%) male and 31 (24.4%) female, with a mean age of 46.8±10.7 years], 107 PLHW were included in the analysis. The percentage of virologically suppressed PLWH increased from 66.4 to 74.8% at 96 weeks. A statistically significant increase in absolute CD4 (P<0.0001) and CD8 T cell count (P=0.002) was observed. Of importance, there was a significant increase in CD4/CD8 ratio from 0.95 (0.52-1.31) to 1.16 (0.75-1.39) (P=0.003) after 96 weeks. There was a significant decrease in the median values of triglycerides (P<0.0001) and total cholesterol (P<0.0001). Serum creatinine showed a significant increase (P=0.0001). In real life, switching to B/F/T was safe and highly effective both virologically and immunologically. Decrease in cholesterol and triglyceride levels suggested a favorable metabolic profile, which may decrease inflammation, leading to a healthier state and less organ damage.

Patient-Reported Outcomes After Switching to a 2-Drug Regimen of Fixed-Dose Combination Dolutegravir/Lamivudine: 48-Week Results from the SALSA Study.

Patient-reported outcomes (PROs) facilitate communication between patients and providers, enhancing patient-centered care. We report PROs for virologically suppressed people living with HIV-1 who switched to dolutegravir/lamivudine (DTG/3TC) or continued their 3- or 4-drug current antiretroviral regimen (CAR) in the phase 3 SALSA study. Secondary endpoints included change from baseline in HIV Treatment Satisfaction Questionnaire (status version; HIVTSQs) and HIV Symptom Distress Module (HIV-SDM) at Weeks 4, 24, and 48. A post hoc analysis assessed change in HIVTSQs and HIV-SDM by age (≥ 50 and < 50 years). Higher HIVTSQs scores represent greater treatment satisfaction (range, 0-60); lower HIV-SDM scores indicate less symptom bother (range, 0-80). Participants in the DTG/3TC (n = 246) and CAR (n = 247) groups reported comparable baseline HIVTSQs total scores (mean [SD], 55.2 [6.5] and 55.8 [5.5], respectively). Beginning at Week 4, mean HIVTSQs scores in the DTG/3TC group further increased vs. CAR and were sustained through Week 48. Baseline mean (SD) HIV-SDM symptom bother scores were comparable between the DTG/3TC (9.0 [9.9]) and CAR (7.9 [9.3]) groups. Small improvements in HIV-SDM scores favoring DTG/3TC were observed at Weeks 4 and 24 and sustained through Week 48 (though not significant between groups). Participants aged ≥ 50 and < 50 years who switched to DTG/3TC reported higher satisfaction and less symptom distress vs. CAR; these results were generally comparable between age groups. Participants who switched to DTG/3TC reported rapid and sustained improvements in treatment satisfaction compared with those who continued CAR, reinforcing the benefits of DTG/3TC beyond virologic suppression (NCT04021290; registration date, 7/11/2019).

Incidence and predictors of attrition from HIV treatment among adults living with HIV in high-caseload facilities following implementation of universal test and treat strategy in Ethiopia: A prospective cohort study.

BACKGROUND: The introduction of universal test and treat (UTT) strategy has demonstrated a reduction in attrition in some low-resource settings. UTT was introduced in Ethiopia in 2016. However, there is a paucity of information regarding the magnitude and predictors of attrition from HIV treatment in Ethiopia. This study aims to assess the incidence and predictors of attrition from HIV treatment among adults living with HIV (PLHIV) in high-caseload facilities following the implementation of universal test and treat strategy in Ethiopia from March 2019 to June 2020. METHODS: A prospective cohort of individuals in HIV care from 39 high-caseload facilities in Oromia, Amhara, Tigray, Addis Ababa and Dire Dawa regions of Ethiopia was conducted for 12 months. Participants were adults aged 15 year and older who were first testers recruited for 3 months from March to June 2019. Subsequent follow-up was for 12 months, with data collected on sociodemographic and clinical conditions at baseline, 6 and 12 months and attrition at 6 and 12 months. We defined attrition as discontinuation from follow-up care due to loss to follow-up, dropout or death. Data were collected using Open Data Kit at field level and aggregated centrally. Kaplan-Meier survival analysis was employed to assess survival probability to the time of attrition from treatment. The Cox proportional hazards regression model was used to measure association of baseline predictor variables with the proportion of antiretroviral therapy (ART) patients retained in ART during the follow up period. RESULTS: The overall incidence rate for attrition from HIV treatment among the study participants during 12 months of follow-up was 5.02 cases per 1000 person-weeks [95% confidence interval (CI): 4.44-5.68 per 1000 person-weeks]. Study participants from health facilities in Oromia and Addis Ababa/Dire Dawa had 68% and 51% higher risk of attrition from HIV treatment compared with participants from the Amhara region, respectively [adjusted hazard ratio (AHR) = 1.68, 95% CI: 1.22-2.32 and AHR = 1.51, 95% CI: 1.05-2.17, respectively]. Participants who did not have a child had a 44% higher risk of attrition compared with those who had a child (AHR = 1.44, 95% CI: 1.12-1.85). Individuals who did not own mobile phone had a 37% higher risk of attrition than those who owned a mobile phone (AHR = 1.37, 95% CI: 1.02-1.83). Ambulatory/bedridden functional status at the time of diagnosis had a 44% higher risk of attrition compared with participants with a working functional status (AHR = 1.44, 95% CI: 1.08-1.92) at any time during the follow-up period. CONCLUSION: The overall incidence of attrition among people living with HIV enrolled into HIV treatment was not as high as what was reported by other studies. Independent predictors of attrition were administrative regions in Ethiopia where health facilities are located, not having a child, not owning a mobile phone and being ambulatory/bedridden functional status at the time of diagnosis. Concerted efforts should be taken to reduce the magnitude of attrition from HIV treatment and address its drivers.

Long-acting injectable antiretroviral treatment: experiences of people with HIV and their healthcare providers in Uganda.

INTRODUCTION: Long-acting injectable antiretroviral treatment (LAI-ART) has emerged as a novel alternative to the burden of daily oral pills. The bi-monthly intramuscular injectable containing cabotegravir and rilpivirine holds the promise of improving adherence to ART. The perspectives of potential users of LAI-ART, the majority of whom reside in Eastern and Southern Africa, are still largely unexplored. We set out to understand the experiences of people with HIV (PWH) who received LAI-ART at Fort Portal Regional Referral Hospital in mid-Western Uganda for at least 12 months. METHODS: This qualitative study, conducted between July and August 2023, was nested within a larger study. We conducted four focus groups with 32 (out of 69) PWH who received intramuscular injections of cabotegravir and rilpivirine. In-depth interviews were held with six health workers who delivered LAI-ART to PWH. Data were analyzed by thematic approach broadly modeled on the five domains of the Consolidated Framework for Implementation Research (CFIR). RESULTS: There was high acceptability of LAI-ART (30 /32 or 94%) participants requested to remain on LAI-ART even after the end of the 12-month trial. Adherence to ART was reportedly improved when compared to daily oral treatment. Participants credited LAI-ART with; superior viral load suppression, redemption from the daily psychological reminder of living with HIV, enhanced privacy in HIV care and treatment, reduced HIV-related stigma associated with taking oral pills and that it absolved them from carrying bulky medication packages. Conversely, nine participants reported pain around the injection site and a transient fever soon after administering the injection as side effects of LAI-ART. Missed appointments for receiving the bi-monthly injection were common. Providers identified health system barriers to the prospective scale-up of LAI-ART which include the perceived high cost of LAI-ART, stringent cold chain requirements, physical space limitations, and workforce skills gaps in LAI-ART delivery as potential drawbacks. CONCLUSION: Overall, PWH strongly preferred LAI-ART and expressed a comparatively higher satisfaction with this treatment alternative. Health system barriers to potential scale-up are essential to consider if a broader population of PWH will benefit from this novel HIV treatment option in Uganda and other resource-limited settings. TRIAL REGISTRATION: Trial Registry Number PACTR ID PACTR202104874490818 (registered on 16/04/2021).

Long-acting HIV Treatments: Study Design, Logistics, and Access.

New long-acting HIV treatment products have the potential to change the HIV epidemic in the United States and globally. Phase 3 clinical trials of HIV treatments tend to underrepresent populations bearing a disproportionate burden of the HIV epidemic-including women, racial minorities, trans and gender-diverse people, older adults, the unhoused, people who inject drugs, those in rural areas, individuals with mental illness, and other marginalized groups. These populations commonly face significant challenges in adhering to daily HIV treatment regimens. Conducting clinical trials of long-acting treatment targeting specific unmet medical needs of these populations can improve understanding of optimal care approaches, broaden the indication for use of long-acting products, and inform treatment guidelines, all of which can influence reimbursement and access policies. Innovative trial designs and programmatic implementation can improve inclusivity for long-acting therapy. This article summarizes discussions of a multistakeholder workshop on study designs for long-acting HIV treatments.

Long-acting injectable ART to advance health equity: a descriptive analysis of US clinic perspectives on barriers, needed support and programme goals for implementation from applications to the ALAI UP Project.

INTRODUCTION: Approval of the first long-acting injectable antiretroviral therapy (LAI ART) medication heralded a new era of HIV treatment. However, the years since approval have been marked by implementation challenges. The "Accelerating Implementation of Multilevel Strategies to Advance Long-Acting Injectable for Underserved Populations (ALAI UP Project)" aims to accelerate the systematic and equitable delivery of LAI ART. METHODS: We coded and analysed implementation barriers according to the Consolidated Framework for Implementation Research (CFIR) domains, desired resources and programme goals from questionnaire short-answer responses by clinics across the United States responding to ALAI UP's solicitation to participate in the project between November 2022 and January 2023. RESULTS: Thirty-eight clinics responded to ALAI UP's solicitation. The characteristics of LAI ART as an innovation (cost, complexity of procurement, dosing interval, limited eligibility) precipitated and interacted with barriers in other CFIR domains. Barriers included obtaining coverage for the cost of medication (27/38 clinics) (outer setting); need for new workflows and staffing (12/38) and/or systems to support injection scheduling/coordination (16/38), transportation and expanded clinic hours (13/38) (inner setting); and patient (10/38) and provider (7/38) education (individuals). To support implementation, applicants sought: technical assistance to develop protocols and workflows (18/38), specifically strategies to address payor challenges (8/38); additional staff for care coordination and benefits navigation (17/38); opportunities to share experiences with other implementing clinics (12/38); patient-facing materials to educate and increase demand (7/38); and support engaging communities (6/38). Clinics' LAI ART programme goals varied. Most prioritized delivering LAI ART to their most marginalized patients struggling to achieve viral suppression on oral therapy, despite awareness that current US Food and Drug Administration approval is only for virally suppressed patients. The goal for LAI ART reach after 1 year of implementation ranged from ≤10% of patients with HIV on LAI ART (17/38) to ≥50% of patients (2/38). CONCLUSIONS: Diverse clinic types are interested in offering LAI ART and most aspire to use LAI ART to support their most vulnerable patients sustain viral suppression. Dedicated resources centred on equity and relevant to context and population are needed to support implementation. Otherwise, the introduction of LAI ART risks exacerbating, not ameliorating, health disparities.

Ensuring People Living with HIV Inform the Future of HIV Treatment in Low- and Middle-Income Countries: A Scoping Review and Recommendations for a Community-Led Research Agenda.

The HIV treatment landscape in low- and middle-income countries (LMICs) is rapidly evolving, exemplified by the expansion of differentiated service delivery (DSD) during the coronavirus disease (COVID-19) pandemic. Long-acting products represent a new frontier that will require a significant redesign of health systems. It is critical to understand service delivery and product preferences of people living with HIV (PLHIV) and ensure evidence generation is guided by community priorities. We conducted a scoping review to identify gaps among preference studies and inform future research. Peer-reviewed articles published from January 2014-May 2022 reporting acceptability or preference data from PLHIV or caregivers for one or more service delivery or product attribute were eligible. Service delivery studies were restricted to LMIC populations while product studies had no geographical restrictions. Based on gaps identified, we consulted advocates to develop community-led research agenda recommendations. Of 6,493 studies identified, 225 studies on service delivery attributes and 47 studies on product preferences were eligible. The most frequently studied delivery models were integration (n = 59) and technology-based interventions (n = 55). Among product literature, only 15 studies included LMIC populations. Consultation with advocates highlighted the need for research on long-acting products, including among pediatric, pregnant, and breastfeeding PLHIV, PLHIV on second-line regimens, and key populations. Consultation also emphasized the need to understand preferences on clinic visit frequency, side effects, and choice. While the preference literature has expanded, gaps remain around long-acting regimens and their delivery. To fill these gaps, the research agenda must be guided by the priorities of communities of PLHIV.

Evaluating the Preliminary Effectiveness of the Person-Centered Care Assessment Tool (PCC-AT) in Zambian Health Facilities: Protocol for a Mixed Methods Cross-Sectional Study.

BACKGROUND: Person-centered care (PCC) within HIV treatment services has demonstrated potential to overcome inequities in HIV service access while improving treatment outcomes. Despite PCC being widely considered a best practice, no consensus exists on its assessment and measurement. This study in Zambia builds upon previous research that informed development of a framework for PCC and a PCC assessment tool (PCC-AT). OBJECTIVE: This mixed methods study aims to examine the preliminary effectiveness of the PCC-AT through assessing the association between client HIV service delivery indicators and facility PCC-AT scores. We hypothesize that facilities with higher PCC-AT scores will demonstrate more favorable HIV treatment continuity, viral load (VL) coverage, and viral suppression in comparison to those of facilities with lower PCC-AT scores. METHODS: We will implement the PCC-AT at 30 randomly selected health facilities in the Copperbelt and Central provinces of Zambia. For each study facility, data will be gathered from 3 sources: (1) PCC-AT scores, (2) PCC-AT action plans, and (3) facility characteristics, along with service delivery data. Quantitative analysis, using STATA, will include descriptive statistics on the PCC-AT results stratified by facility characteristics. Cross-tabulations and/or regression analysis will be used to determine associations between scores and treatment continuity, VL coverage, and/or viral suppression. Qualitative data will be collected via action planning, with detailed notes collected and recorded into an action plan template. Descriptive coding and emerging themes will be analyzed with NVivo software. RESULTS: As of May 2024, we enrolled 29 facilities in the study and data analysis from the key informant interviews is currently underway. Results are expected to be published by September 2024. CONCLUSIONS: Assessment and measurement of PCC within HIV treatment settings is a novel approach that offers HIV treatment practitioners the opportunity to examine their services and identify actions to improve PCC performance. Study results and the PCC-AT will be broadly disseminated for use among all project sites in Zambia as well as other HIV treatment programs, in addition to making the PCC-AT publicly available to global HIV practitioners. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/54129.

Costs of home-delivered antiretroviral therapy refills for persons living with HIV: evidence from a pilot randomized controlled trial in KwaZulu-Natal, South Africa.

Antiretroviral therapy (ART) is needed across the lifetime to maintain viral suppression for people living with HIV. In South Africa, obstacles to reliable access to ART persist and are magnified in rural areas, where HIV services are also typically costlier to deliver. A recent pilot randomized study (the Deliver Health Study) found that home-delivered ART refills, provided at a low user fee, effectively overcame logistical barriers to access and improved clinical outcomes in rural South Africa. In the present costing study using the payer perspective, we conducted retrospective activity-based micro-costing of home-delivered ART within the Deliver Health Study and when provided at-scale (in a rural setting), and compared to facility-based costs using provincial expenditure data (covering both rural and urban settings). Within the context of the pilot Deliver Health Study which had an average of three deliveries per day for three days a week, home-delivered ART cost (in 2022 USD) $794 in the first year and $714 for subsequent years per client after subtracting client fees, compared with $167 per client in provincial clinic-based care. We estimated that home-delivered ART can reasonably be scaled up to 12 home deliveries per day for five days per week in the rural setting. When delivered at scale, home-delivered ART cost $267 in the first year and $183 for subsequent years per client. Average costs of home delivery further decreased when increasing the duration of refills from three-months to six- and 12-month scripts (from $183 to $177 and $135 per client, respectively). Personnel costs were the largest cost for home-delivered refills while ART drug costs were the largest cost of clinic-based refills. When provided at scale, home-delivered ART in a rural setting not only offers clinical benefits for a hard-to-reach population but is also comparable in cost to the provincial standard of care.

Long-acting prescriptions and therapy for HIV-1 from market launch to the present in Germany (May 2021 to December 2023).

Background: In Europe, the combination of cabotegravir (CAB) with rilpivirine (RPV) has been approved as a dual injection long-acting (LA) therapy for the treatment of human immunodeficiency virus type 1 (HIV-1) infections in adults since December 2020. Studies have shown that between 36 and 61% of people living with HIV (PLWHIV) prefer LA therapy. However, there are no real-world data on the number of people receiving LA therapy, in Germany or internationally. The aim of this study was to assess the current situation and trends in usage of LA therapy for the treatment of HIV-1 in Germany. Methods: Based on pharmacy prescription data derived from Insight Health, the monthly number of prescriptions for oral CAB, CAB-LA, and RPV-LA over the entire period of availability in Germany was analyzed and evaluated (May 2021 to December 2023). The number of 1st and 2nd initiation injections and subsequent maintenance injections was calculated on the basis of the prescriptions for oral CAB initiation. Results: The bimonthly schedule resulted in two growing cohorts from September 2021 with an estimated 14,523 CAB-LA prescriptions over the entire period. Accordingly, in December 2023, there were approximately 1,364 PLWHIV receiving LA therapy, of whom 1,318 were receiving maintenance therapy. Only treatments with bimonthly regimens were carried out. Accounting for people not covered by statutory health insurance (~13%), a total of ~1,600 PLWHIV were receiving LA therapy in Germany in December 2023. The average rounded annual cost of therapy in 2023 was €11,940 (maintenance therapy with initiation) and €10,950 (maintenance therapy without initiation). Conclusion: To our knowledge, this is the first study of real-world use and number of people receiving LA therapy. A strength of our study is the nearly complete coverage of people with statutory health insurance in Germany. The predicted demand for LA therapy does not match the actual number of people receiving LA therapy. Although the number of PLWHIV receiving LA therapy increased steadily, they accounted for just under 2% of the estimated total number of people receiving HIV therapy in Germany in 2023, almost 2 years after the market launch. No significant increase in prescriptions is expected; on the contrary, the trend is leveling off and is unlikely to change drastically in the near future. Hence, the need for this mode of therapy in Germany appears to be limited. Follow-up studies at regular intervals on the further course would be useful and are recommended, as well as investigations into the possible reasons for the slow uptake to inform public health experts and possibly broaden treatment options.

Parenteral platforms for tunable, long-acting administration of a highly hydrophobic antiretroviral drug.

GSK2838232 (GSK8232) is a second-generation maturation inhibitor (MI) developed for the treatment of HIV with excellent broad-spectrum virological profiles. The compound has demonstrated promising clinical results as an orally administered agent. Additionally, the compound's physical and pharmacological properties present opportunities for exploitation as long-acting parenteral formulations. Despite unique design constraints including solubility and dose of GSK8232, we report on three effective tunable drug delivery strategies: active pharmaceutical ingredient (API) suspensions, ionic liquids, and subdermal implants. Promising sustained drug release profiles were achieved in rats with each approach. Additionally, we were able to tune drug release rates through a combination of passive and active strategies, broadening applicability of these formulation approaches beyond GSK8232. Taken together, this report is an important first step to advance long-acting formulation development for critical HIV medicines that do not fit the traditional profile of suitable long-acting candidates.

LAI-ART Awareness, Willingness, Barriers and Facilitators among Black Sexual Minority Men Living with HIV in the US South.

Black sexual minority men (BSMM) continue to bear a disproportionate burden of HIV in the United States, with the highest incidence and prevalence in the southern region of the country. In Texas, BSMM living with HIV (BSMM+) have the lowest rates of viral suppression of all SMM and have lower antiretroviral treatment (ART) adherence than white and Hispanic SMM. Long-acting injectable ART (LAI-ART) can potentially overcome several barriers to daily oral ART adherence (e.g., stigma, forgetfulness, pill fatigue). However, little is known about the knowledge, willingness, barriers, and facilitators regarding LAI-ART among BSMM+. From July 2022 to September 2023, we conducted in-depth, semi-structured interviews with 27 BSMM+ from the Houston and Dallas Metropolitan Areas, Texas. Data were analyzed using a thematic analysis approach. Most men knew about LAI-ART, but their understanding varied based on their existing sources of information. Some men were enthusiastic, some were cautious, and some reported no interest in LAI-ART. Barriers to LAI-ART included a lack of public insurance coverage of LAI-ART; fear of needles and side effects; the frequency of injection visits; the requirement of viral suppression before switching from oral ART to LAI-ART; and satisfaction with oral daily ART. Motivators of LAI-ART uptake included the eliminated burden of daily pills and reduced anxiety about possibly missing doses. BSMM+ may be among those who could most benefit from LAI-ART, though more research is needed to understand which factors influence their willingness and how the barriers to LAI-ART might be addressed, particularly among diverse communities of SMM of color.

Person-centred interventions to improve patient-provider relationships for HIV services in low- and middle-income countries: a systematic review.

INTRODUCTION: Person-centred care (PCC) has been recognized as a critical element in delivering quality and responsive health services. The patient-provider relationship, conceptualized at the core of PCC in multiple models, remains largely unexamined in HIV care. We conducted a systematic review to better understand the types of PCC interventions implemented to improve patient-provider interactions and how these interventions have improved HIV care continuum outcomes and person-reported outcomes (PROs) among people living with HIV in low- and middle-income countries. METHODS: We searched databases, conference proceedings and conducted manual targeted searches to identify randomized trials and observational studies published up to January 2023. The PCC search terms were guided by the Integrative Model of Patient-Centeredness by Scholl. We included person-centred interventions aiming to enhance the patient-provider interactions. We included HIV care continuum outcomes and PROs. RESULTS: We included 28 unique studies: 18 (64.3%) were quantitative, eight (28.6.%) were mixed methods and two (7.1%) were qualitative. Within PCC patient-provider interventions, we inductively identified five categories of PCC interventions: (1) providing friendly and welcoming services; (2) patient empowerment and improved communication skills (e.g. supporting patient-led skills such as health literacy and approaches when communicating with a provider); (3) improved individualized counselling and patient-centred communication (e.g. supporting provider skills such as training on motivational interviewing); (4) audit and feedback; and (5) provider sensitisation to patient experiences and identities. Among the included studies with a comparison arm and effect size reported, 62.5% reported a significant positive effect of the intervention on at least one HIV care continuum outcome, and 100% reported a positive effect of the intervention on at least one of the included PROs. DISCUSSION: Among published HIV PCC interventions, there is heterogeneity in the components of PCC addressed, the actors involved and the expected outcomes. While results are also heterogeneous across clinical and PROs, there is more evidence for significant improvement in PROs. Further research is necessary to better understand the clinical implications of PCC, with fewer studies measuring linkage or long-term retention or viral suppression. CONCLUSIONS: Improved understanding of PCC domains, mechanisms and consistency of measurement will advance PCC research and implementation.

Pharmacokinetics of tenofovir alafenamide, emtricitabine, and dolutegravir in a patient on peritoneal dialysis.

INTRODUCTION: Peritoneal dialysis (PD) is an effective renal replacement modality in people with HIV (PWH) with end-stage kidney disease (ESKD), particularly those with residual kidney function. Data on pharmacokinetics (PK) of antiretrovirals in patients on peritoneal dialysis are limited. METHODS: A single-participant study was performed on a 49-year-old gentleman with ESKD on PD and controlled HIV on once daily dolutegravir (DTG) 50 mg + tenofovir alafenamide (TAF) 25 mg / emtricitabine (FTC) 200 mg. He underwent serial blood plasma, peripheral blood mononuclear cell, and urine PK measurements over 24 h after an observed DTG + FTC/TAF dose. RESULTS: Plasma trough (Cmin) concentrations of TAF, tenofovir (TFV), FTC, and DTG were 0.05, 164, 1,006, and 718 ng/mL, respectively. Intracellular trough concentrations of TFV-DP and FTC-TP were 1142 and 11,201 fmol/million cells, respectively. Compared to published mean trough concentrations in PWH with normal kidney function, observed TFV and FTC trough concentrations were 15.5- and 20-fold higher, while intracellular trough concentrations of TFV-DP and FTC-TP were 2.2-fold and 5.4-fold higher, respectively. TFV and FTC urine levels were 20 times lower than in people with normal GFR. CONCLUSIONS: In a single ESKD PWH on PD, daily TAF was associated with plasma TFV and intracellular TFV-DP trough concentrations 15-fold and 2-fold higher than those of people with uncompromised kidney function, potentially contributing to nephrotoxicity. This suggests that TFV accumulates on PD; thus, daily TAF in PD patients may require dose adjustment or regimen change to optimize treatment, minimize toxicity, and preserve residual kidney function.

The Impact of Human Immunodeficiency Virus on Women in the United States.

Substantial improvements have been made in reducing HIV incidence rates among women in the United States. However, numerous disparities affect women's risk of HIV acquisition, in addition to affecting treatment outcomes for women living with HIV. As people with HIV continue to live longer due to antiretroviral therapy, clinicians must be cognizant of various health, financial, and social implications that can affect HIV self-management. Successfully ending the HIV epidemic will require more targeted approaches on prevention, linkage to care, and treatment while also addressing underlying factors that affect women's engagement in HIV-related services across the HIV care continuum.

A 5-Year Review of the Impact of Lottery Incentives on HIV-Related Services.

PURPOSE OF REVIEW: Lottery incentives are an innovative approach to encouraging HIV prevention, treatment initiation, and adherence behaviours. This paper reviews the latest research on lottery incentives' impact on HIV-related services, and their effectiveness for motivating behaviours to improve HIV service engagement and HIV health outcomes. RECENT FINDINGS: Our review of ten articles, related to lottery incentives, published between 2018 and 2023 (inclusive) shows that lottery incentives have promise for promoting HIV-related target behaviours. The review highlights that lottery incentives may be better for affecting simpler behaviours, rather than more complex ones, such as voluntary medical male circumcision. This review recommends tailoring lottery incentives, ensuring contextual-relevance, to improve the impact on HIV-related services. Lottery incentives offer tools for improving uptake of HIV-related services. The success of lottery incentives appears to be mediated by context, the value and nature of the incentives, and the complexity of the target behaviour.

Long-Acting Injectable ART in Practice: A Mixed Methods Implementation Study Assessing the Feasibility of Using LAI ART in High Risk Populations and At Alternative Low Barrier Care Sites.

Long-acting injectable (LAI) antiretroviral therapy (ART) has the potential to change the lives of people living with HIV (PLWH). To ensure equitable access to new treatment modalities, we examined the feasibility and acceptability of administering Cabotegravir Rilpivirine Long Acting (CAB/RPV LA) to individuals who experience challenging social determinants of health (SDoH) and struggle with adherence to traditional oral ART. Quantitative and qualitative data were used to assess feasibility of utilizing ART at alternative clinic. Data were collected on individuals eligible to receive CAB/RPV LA at an alternative street-based clinic and on individuals receiving CAB/RPV LA at a traditional HIV clinic. After 6 months, participants were interviewed about their experience. Providers involved in the implementation were also interviewed about their experiences. Only one participant (out of 5) who received CAB/RPV LA at the alternative clinic received consistent treatment, whereas 17 out of 18 participants receiving CAB/RPV LA at the traditional clinic site were adherent. Participants and providers believed that LAI had potential for making treatment adherence easier, but identified several barriers, including discrepancies between patients' desires and their lifestyles, impact of LAI on interactions with the medical system, risk of resistance accompanying sub-optimal adherence, and need for a very high level of resources. While LAI has major potential benefits for high-risk patients, these benefits must be balanced with the complexities of implementation. Despite challenges that impacted study outcomes, improving treatment outcomes for PLWH requires addressing SDoH and substance use.

Linkage to HIV care and early retention in HIV care among men in the 'universal test-and-treat' era in a high HIV-burdened district, KwaZulu-Natal, South Africa.

INTRODUCTION: Despite the numerous efforts and initiatives, males with HIV are still less likely than women to receive HIV treatment. Across Sub-Saharan Africa, men are tested, linked, and retained in HIV care at lower rates than women, and South Africa is no exception. This is despite the introduction of the universal test-and-treat (UTT) prevention strategy anticipated to improve the uptake of HIV services. The aim of this study was to investigate linkage to and retention in care rates of an HIV-positive cohort of men in a high HIV prevalence rural district in KwaZulu-Natal province, South Africa. METHODS: From January 2018 to July 2019, we conducted an observational cohort study in 18 primary health care institutions in the uThukela district. Patient-level survey and clinical data were collected at baseline, 4-months and 12-months, using isiZulu and English REDCap-based questionnaires. We verified data through TIER.Net, Rapid mortality survey (RMS), and the National Health Laboratory Service (NHLS) databases. Data were analyzed using STATA version 15.1, with confidence intervals and p-value of ≤0.05 considered statistically significant. RESULTS: The study sample consisted of 343 male participants diagnosed with HIV and who reside in uThukela District. The median age was 33 years (interquartile range (IQR): 29-40), and more than half (56%; n = 193) were aged 18-34 years. Almost all participants (99.7%; n = 342) were Black African, with 84.5% (n = 290) being in a romantic relationship. The majority of participants (85%; n = 292) were linked to care within three months of follow-up. Short-term retention in care (≤ 12 months) was 46% (n = 132) among men who were linked to care within three months. CONCLUSION: While the implementation of the UTT strategy has had positive influence on improving linkage to care, men's access of HIV treatment remains inconsistent and may require additional innovative strategies.

Heavy alcohol use and the HIV care continuum in Kenya: a population-based study.

Heavy alcohol use (HAU) can destabilize engagement along the HIV care continuum. Population-based studies assessing associations of HAU with HIV treatment outcomes are lacking, especially in sub-Saharan Africa. We leveraged data from the Kenya Population-based HIV Impact Assessment to identify associations of self-reported HAU, assessed using two items measuring the frequency and quantity of past-year alcohol consumption, with serum biomarkers for HIV serostatus unawareness, antiretroviral therapy (ART) non-use, and HIV viremia (≥1000 RNA copies/mL). Overall and sex-stratified survey-weighted logistic regression with jackknife variance estimation modeled adjusted odds ratios (adjOR) of HIV treatment indicators by HAU. Overall, 1491 persons living with HIV aged 15-64 years (68.4% female) were included. The prevalence of HAU was 8.9% (95% confidence interval [95%CI]: 6.8-11.0%) and was significantly more pronounced in males than females (19.6% vs. 4.0%, p < 0.001). In multivariable analysis, HAU was significantly (p < 0.001) associated with HIV serostatus unawareness (adjOR = 3.65, 95%CI: 2.14-6.23), ART non-use (adjOR = 3.81, 95%CI: 2.25-6.43), and HIV viremia (adjOR = 3.13, 95%CI: 1.85-5.32). Incorporating sex-specific alcohol use screening into HIV testing and treatment services in populations where HAU is prevalent could optimize clinical outcomes along the HIV care continuum.

Temporal dynamics and drivers of durable HIV viral load suppression and persistent high- and low-level viraemia during Universal Test and Treat scale-up in Uganda: a population-based study.

INTRODUCTION: Population-level data on durable HIV viral load suppression (VLS) following the implementation of Universal Test and Treat (UTT) in Africa are limited. We assessed trends in durable VLS and viraemia among persons living with HIV in 40 Ugandan communities during the UTT scale-up. METHODS: In 2015-2020, we measured VLS (<200 RNA copies/ml) among participants in the Rakai Community Cohort Study, a longitudinal population-based HIV surveillance cohort in southern Uganda. Persons with unsuppressed viral loads were characterized as having low-level (200-999 copies/ml) or high-level (≥1000 copies/ml) viraemia. Individual virologic outcomes were assessed over two consecutive RCCS survey visits (i.e. visit-pairs; ∼18-month visit intervals) and classified as durable VLS (<200 copies/ml at both visits), new/renewed VLS (<200 copies/ml at follow-up only), viral rebound (<200 copies/ml at initial visit only) or persistent viraemia (≥200 copies/ml at both visits). Population prevalence of each outcome was assessed over calendar time. Community-level prevalence and individual-level predictors of persistent high-level viraemia were also assessed using multivariable Poisson regression with generalized estimating equations. RESULTS: Overall, 3080 participants contributed 4604 visit-pairs over three survey rounds. Most visit-pairs (72.4%) exhibited durable VLS, with few (2.5%) experiencing viral rebound. Among those with any viraemia at the initial visit (23.5%, n = 1083), 46.9% remained viraemic through follow-up, 91.3% of which was high-level viraemia. One-fifth (20.8%) of visit-pairs exhibiting persistent high-level viraemia self-reported antiretroviral therapy (ART) use for ≥12 months. Prevalence of persistent high-level viraemia varied substantially across communities and was significantly elevated among young persons aged 15-29 years (vs. 40- to 49-year-olds; adjusted risk ratio [adjRR] = 2.96; 95% confidence interval [95% CI]: 2.21-3.96), males (vs. females; adjRR = 2.40, 95% CI: 1.87-3.07), persons reporting inconsistent condom use with non-marital/casual partners (vs. persons with marital/permanent partners only; adjRR = 1.38, 95% CI: 1.10-1.74) and persons reporting hazardous alcohol use (adjRR = 1.09, 95% CI: 1.03-1.16). The prevalence of persistent high-level viraemia was highest among males <30 years (32.0%). CONCLUSIONS: Following universal ART provision, most persons living with HIV in south-central Uganda are durably suppressed. Among persons exhibiting any viraemia, nearly half exhibited high-level viraemia for ≥12 months and reported higher-risk behaviours associated with onward HIV transmission. Intensified efforts linking individuals to HIV treatment services could accelerate momentum towards HIV epidemic control.