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We examined changes in the proportion of people with human immunodeficiency virus (PWH) with virologic suppression (VS) in a multisite US cohort before and since the coronavirus disease 2019 (COVID-19) pandemic. Overall, prior gains in VS slowed during COVID-19, with disproportionate impacts on Black PWH and PWH who inject drugs.

BackgroundAfter coronavirus disease 2019 (COVID-19) shelter-in-place (SIP) orders, viral suppression (VS) rates initially decreased within a safety-net human immunodeficiency virus (HIV) clinic in San Francisco, particularly among people living with HIV (PLWH) who are experiencing homelessness. We sought to determine if proactive outreach to provide social services, scaling up of in-person visits, and expansion of housing programs could reverse this decline.MethodsWe assessed VS 24 months before and 13 months after SIP using mixed-effects logistic regression followed by interrupted time series (ITS) analysis to examine changes in the rate of VS per month. Loss to follow-up (LTFU) was assessed via active clinic tracing.ResultsData from 1816 patients were included; the median age was 51 years, 12% were female, and 14% were experiencing unstable housing/homelessness. The adjusted odds of VS increased 1.34 fold following institution of the multicomponent strategies (95% confidence interval [CI], 1.21-1.46). In the ITS analysis, the odds of VS continuously increased 1.05 fold per month over the post-intervention period (95% CI, 1.01-1.08). Among PLWH who previously experienced homelessness and successfully received housing support, the odds of VS were 1.94-fold higher (95% CI, 1.05-3.59). The 1-year LTFU rate was 2.8 per 100 person-years (95% CI, 2.2-3.5).ConclusionsThe VS rate increased following institution of the multicomponent strategies, with a lower LFTU rate compared with prior years. Maintaining in-person care for underserved patients, with flexible telemedicine options, along with provision of social services and permanent expansion of housing programs, will be needed to support VS among underserved populations during the COVID-19 pandemic.

Background We compared proportions of participants with target detected, target not detected (TND), and elevated viral load (VL) and assessed baseline variables associated with week 144 inflammatory biomarker levels between dolutegravir-lamivudine (DTG/3TC) and tenofovir alafenamide–based regimens (TBRs) in the TANGO study (post hoc). Methods TANGO is an open-label, multicenter, phase 3 study that randomized adults with VL <50 copies/mL to switch to once-daily fixed-dose DTG/3TC or continue TBR. At baseline and each study visit, the VL was measured. Elevated VL event frequencies were assessed, including "blips." Interleukin 6, D-dimer, high-sensitivity C-reactive protein, soluble CD14, and soluble CD163 were measured at baseline and at week 144. Loge-transformed week 144 biomarker levels were compared between treatment groups using an analysis of covariance model adjusting for baseline variables. Results High, comparable proportions of participants had VL <40 copies/mL and TND at week 144 (DTG/3TC, 279 of 369 [76%]; TBR, 267 of 372 [72%], intention-to-treat exposed Snapshot analysis; adjusted difference, 3.9% [95% confidence interval, −2.5% to 10.2%]), with similar TND proportions at all postbaseline visits (123 of 369 [33%] vs 101 of 372 [27%], respectively). Similar proportions of DTG/3TC participants had ≥1 postbaseline VL ≥50 copies/mL (28 of 369 [8%] vs 42 of 372 [11%] for TBR), primarily blips (18 of 369 [5%] and 26 of 372 [7%], respectively). Week 144 inflammatory biomarker levels were low and comparable between groups and associated with multiple demographic and baseline characteristics, including baseline biomarker levels, indicating a multifactorial inflammatory response. Conclusions Week 144 biomarker levels were low and generally comparable between treatment groups, reflecting similar, robust, and durable viral suppression observed using the stringent TND end point. Trial registration: ClinicalTrials.gov , NCT03446573. [ABSTRACT FROM AUTHOR]

Introduction: The first complete long-acting antiretroviral therapy (ART) regimen, cabotegravir + rilpivirine long-acting (CAB + RPV LA) injectable, was approved in the US for HIV-1 treatment in individuals on a stable antiretroviral regimen with a viral load < 50 copies/mL, no treatment failure history, and no resistance to either cabotegravir or rilpivirine. We describe injection schedule adherence and virologic effectiveness of CAB + RPV LA in routine clinical care in the US. Methods: From the OPERA® cohort, all adults with HIV who received their first CAB + RPV LA injection and ≥ 1 continuation injections between 21 January 2021 and 15 March 2022 were included. The injection target date was updated monthly and set to the same date of the month as the previous injection. Continuation injections administered within 7 days before or after the target date were considered on time, as per the label. Virologic undetectability (viral load < 50 copies/mL), suppression (viral load < 200 copies/mL), and confirmed virologic failure (2 consecutive viral loads ≥ 200 copies/mL or 1 viral load ≥ 200 copies/mL followed by discontinuation) were described among individuals with a viral load < 50 copies/mL at initiation and ≥ 1 follow-up viral load. Results: Among 321 individuals on CAB + RPV LA, 90% of the continuation injections were administered on time (within ± 7 days of the target date). Of the 237 individuals with a viral load < 50 copies/mL at initiation and ≥ 1 follow-up viral load, nearly all were undetectable (95%) or suppressed (99%) at their last viral load measurement, 96% maintained virologic suppression with all measured viral loads < 200 copies/mL, and four confirmed virologic failures were observed. Injection delays were infrequent, and did not affect virologic outcomes over the short term. Conclusion: In this large US cohort, most monthly CAB + RPV LA injections were administered on time and high levels of virologic control were achieved. These results suggest that CAB + RPB LA injectable can be administered effectively during routine clinical care. [ABSTRACT FROM AUTHOR]

Integrase inhibitor-based (INSTI) antiretroviral therapy (ART) regimens are preferred for most people with HIV (PWH). We examined factors associated with INSTI use among PWH in San Francisco who started ART in 2009-2016. PWH who experienced homelessness were less likely, and older PWH were more likely, to use an INSTI.

Background: Meeting the challenge of antiretroviral therapy (ART) whose efficacy can last a lifetime requires continuous updating of the virological, pharmacological, and quality of life outcomes to be pursued and a continuous review of literature data on the efficacy and tolerability of new drugs and therapeutic strategies. Methods: With the aim of identifying open questions and answers about the current controversies in modern ART, we adapted the Design Thinking methodology to the needs of the design phase of a scientific article, involving a team of experts in HIV care. Results: Five main pillars of treatment success were discussed: sustained virologic suppression over time; immunological recovery; pharmacological attributes; long-term tolerability and safety of ART; and people’s satisfaction and quality of life. The definition of the outcomes to be achieved in each thematic area and the tools to achieve them were reviewed and discussed. Conclusions: Long-term treatment success should be intended as a combination of HIV-RNA suppression, immune recovery, and high quality of life. To achieve this, the regimen should be well-tolerated, with high potency, genetic barrier, and forgiveness, and should be tailored by a person-centered perspective, based on individual needs, preferences, and therapeutic history.

Background Antiretroviral therapy (ART) expansion and viral load as a treatment monitoring approach have increased the demand for viral load testing. Many hurdles affect the coverage, quality, and use of viral load results. Estimates of viral load monitoring and viral suppression rates are needed to assess the performance of ART programs and improve human immunodeficiency virus (HIV) management outcomes. Methods People with HIV (PWH) viral load monitoring data were routinely collected in 84 health facilities in Kinshasa, Democratic Republic of the Congo (DRC), between 2013 and 2020. The number of PWH under ART, the number of participants with at least 1 viral load test result, the rate of viral suppression (defined as ≤1000 HIV ribonucleic acid copies per mL), and the mean turnaround time from sample collection to release of viral load test results were collected together with clinical data. Results A total of 14 057 PWH were included in the analysis. People with HIV were mainly enrolled after the "test and treat" implementation. The patients were followed for a median period of 27 months. The proportion of PWH with at least 1 available viral load largely increased in recent years. The delay from sample collection to release of viral load test results decreased overtime, from 35 days in 2018 to 16 days in 2020. Pregnancy and advanced HIV disease were associated with a lower chance of viral suppression. Conclusions There has been considerable success in increasing viral load access for all PWH under therapy in DRC. Nevertheless, viral load testing should be intensified with a particular effort to be made in groups at higher risk of viral failure. [ABSTRACT FROM AUTHOR]

BackgroundThe relationship of internalized HIV stigma to key care cascade metrics in the United States is not well established using large-scale, geographically diverse data.SettingCenter for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort study.MethodsBeginning in February 2016, we administered a yearly, validated 4-item internalized HIV stigma scale (response scale 1 = strongly disagree to 5 = strongly agree, Cronbach's alpha 0.91) at 7 CNICS sites and obtained cohort data through November 2017. We compared mean stigma levels by sociodemographic characteristics and used multivariable logistic regression, controlling for the same sociodemographic covariates, to evaluate the association between mean stigma and (1) concurrent viremia; (2) missed visits; and (3) poor visit constancy. We used inverse probability weighting (IPW) to account for differences between patients who did and did not undergo stigma assessment.ResultsOf 13,183 CNICS patients, 6448 (49%) underwent stigma assessment. Mean stigma was 1.99 (SD 1.07), and 28.6% agreed/strongly agreed with at least 1 stigma question. Patients younger than 50 years, racial/ethnic minorities, cis-women, and heterosexuals had higher mean stigma. Mean stigma score was associated with concurrent viremia [adjusted odds ratio (AOR) 1.13, 95% confidence interval (CI): 1.02 to 1.25, P 0.02], missed visits (AOR 1.10, 95% CI: 1.02 to 1.19, P 0.01), and poor visit constancy, although the effect on visit constancy was attenuated in the IPW model (AOR 1.05, 95% CI: 0.98 to 1.13, P 0.17).ConclusionsHigher internalized HIV stigma had a modest but statistically significant association with concurrent viremia and poor retention in care. Further inquiry with prospective analyses is warranted.

Yan Wu,1– 3,&ast; Shuaifeng Liu,4,&ast; Liuxi Chu,1– 3 Quan Zhang,5,6 Jin Yang,3,7 Shan Qiao,5 Xiaoming Li,5 Yuejiao Zhou,4 Huihua Deng,1– 3 Zhiyong Shen4 1Department of Brain and Learning Science, School of Biological Science & Medical Engineering, Southeast University, Nanjing, People’s Republic of China; 2Key Laboratory of Child Development and Learning Science (Southeast University), Ministry of Education, Nanjing, People’s Republic of China; 3Institute of Child Development and Education, Research Center for Learning Science, Southeast University, Nanjing, People’s Republic of China; 4Unit of AIDS Prevention and Control, Guangxi Zhuang Autonomous Region Center for Disease Prevention and Control, Nanning, People’s Republic of China; 5Department of Health Promotion, Education and Behavior, South Carolina SmartState Center for Healthcare Quality (CHQ), Arnold School of Public Health, University of South Carolina, Columbia, SC, USA; 6College of Graduate Health Sciences, The University of Tennessee Health Science Center, Memphis, TN, USA; 7Department of Preventive Medicine, School of Public Health, Southeast University, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huihua Deng, Department of Brain and Learning Science, School of Biological Science & Medical Engineering, Southeast University, No. 2 Sipailou, Nanjing, 210096, People’s Republic of China, Tel +86 25 8379 5664, Fax +86 25 8379 3779, Email dengrcls@seu.edu.cn Zhiyong Shen, Unit of AIDS Prevention and Control, Guangxi Zhuang Autonomous Region Center for Disease Prevention and Control, No. 18 Jinzhou Road, Nanning, 530028, People’s Republic of China, Tel +86 771 251 8838, Email shenzhiyong99999@sina.comBackground: Hair antiretroviral concentrations are an objective and non-invasive measure of adherence to long-term antiretroviral therapy (ART) and can further predict virologic outcomes among people living with HIV/AIDS (PLWH). Zidovudine, one of the mainstream antiretrovirals in China, has been verified to have high reliability in adherence assessment, especially for its hair concentrations. However, data are limited in its predicting virologic outcomes. Therefore, this study aimed to characterize whether hair zidovudine concentrations can predict virologic suppression among Chinese PLWH compared with hair lamivudine concentrations and two self-reported measures, the overall frequency of adherence behaviors and percentage adherence.Methods: This cross-sectional study randomly recruited 564 PLWH currently treated with zidovudine, lamivudine, and other ART agents (efavirenz, nevirapine, or lopinavir/ritonavir) in Guangxi, China. Hair antiretroviral concentrations were determined using the LC-ESI+-MS/MS method. Receiver operating characteristic (ROC) curves were used to estimate the optimal classification thresholds of hair concentrations of zidovudine and lamivudine, and the two self-reported measures. Based on those optimal classification thresholds, logistic regression was used to examine whether those four adherence measures can predict virologic suppression (HIV-1 RNA < 200 copies/mL).Results: ROC curves demonstrated good classification performance for association with virologic suppression of zidovudine with the optimal threshold at 58 pg/mg and lamivudine at 255 pg/mg but no self-reported measures. PLWH with hair zidovudine concentrations > 58 pg/mg had an adjusted odds ratio (aOR) of 43.191 (95% confidence interval (CI) = 10.171‒183.418, p < 0.001) for virologic suppression. Hair lamivudine concentrations were also associated with virologic suppression (aOR = 10.656, 95% CI = 3.670‒30.943, p < 0.001). However, two self-reported measures did not predict virologic suppression (aORs = 1.157 and 2.488, ps > 0.149).Conclusion: Hair zidovudine concentrations can be served as an alternative tool for clinically predicting virologic suppression among PLWH in China.Keywords: hair antiretroviral concentrations, zidovudine, virologic suppression, PLWH, LC-MS/MS

Background We assessed the efficacy and safety of dolutegravir/lamivudine (DTG/3TC) in a US test-and-treat setting at a secondary 48-week time point of the multicenter, single-arm, phase IIIb STAT study. Methods Participants were eligible adults newly diagnosed with human immunodeficiency virus (HIV)-1 and had started once-daily DTG/3TC within 14 days of diagnosis, before laboratory results were available. Antiretroviral therapy (ART) was modified if baseline testing indicated DTG or 3TC resistance, hepatitis B virus (HBV) coinfection, or creatinine clearance <30 mL/min per 1.73 m2, and these participants remained in the study. A proportion with HIV-1 ribonucleic acid (RNA) <50 copies/mL at Week 48 was calculated among all participants (intention-to-treat-exposed [ITT-E] missing = failure analysis) and those with available data (observed analysis). Results At Week 48, 82% of all participants regardless of ART (107 of 131; ITT-E missing = failure) and 97% with available data (107 of 110; observed analysis) achieved HIV-1 RNA <50 copies/mL. High proportions of virologic response were seen overall, including in participants with high viral load (≥500 000 copies/mL; 89%) or low CD4+ cell count (<200 cells/mm3; 78%) at baseline. Ten participants had treatment modification (baseline HBV coinfection, n = 5; participant/proxy decision, n = 2; baseline M184V resistance mutation, adverse event [AE; rash], and pregnancy, n = 1 each) before Week 48. Two participants met confirmed virologic failure criteria. No treatment-emergent resistance was observed. Ten participants reported drug-related AEs (all grade 1–2); no serious drug-related AEs occurred. Conclusions Results demonstrated high proportions of participants with sustained virologic suppression, no treatment-emergent resistance, and good safety over 48 weeks, supporting first-line use of DTG/3TC in a test-and-treat setting. [ABSTRACT FROM AUTHOR]

Abstract Introduction In 2010, the Canadian province of British Columbia (BC) initiated the Seek and Treat for Optimal Prevention of HIV/AIDS (STOP HIV/AIDS) program to improve HIV testing, linkage to care, and treatment uptake, thereby operationalizing the HIV Treatment as Prevention (TasP) framework at the population-level. In this analysis, we evaluated self-reported HIV care experiences and therapeutic outcomes among people diagnosed with HIV prior to and after implementation of this provincial program. Methods A cross-sectional analysis was performed on the baseline data of a cohort of people living with HIV (PLWH) (19 years and older) in the province of BC sampled from July 2016 to September 2018. All participants consented to linking their survey data to the provincial HIV treatment registry. Individuals diagnosed with HIV from January 1 2000—December 31 2009 were classified as pre-intervention and those diagnosed January 1 2010—December 31 2018 as post-intervention cohorts. Bivariate analyses were run using Chi-square and Wilcoxon Rank Sum tests. Cox proportional hazards regression model demonstrates time to antiretroviral therapy (ART) initiation (from HIV baseline) and virological suppression (2 consecutive plasma viral load measurements

Housing instability negatively impacts outcomes in people [living] with human immunodeficiency virus (PLHIV), yet the effect of diverse living arrangements has not previously been evaluated. Using 6 dwelling types to measure housing status, we found a strong inverse association between housing instability and viral suppression across a spectrum of unstable housing arrangements.

Background: GEMINI-1 and GEMINI-2 (ClinicalTrials.gov, NCT02831673 and NCT02831764, respectively) are double-blind, multicenter, phase III studies that demonstrated the non-inferiority of once-daily dolutegravir + lamivudine to dolutegravir + tenofovir disoproxil fumarate/emtricitabine in achieving HIV-1 RNA <50 copies/mL at 48, 96, and 144 weeks in treatment-naive adults with HIV-1 infection. Objective: We present a post hoc analysis of the impact of treatment adherence on Week 48 virologic response. Methods: Adherence was estimated using pill counts and categorized as ≥90% vs <90%. Unadjusted treatment differences with exact 95% CIs were derived for the proportion of participants with HIV-1 RNA <50 copies/mL within each adherence category, using Snapshot algorithm and last available on-treatment viral load through Week 48. Results: In each treatment group, 5% of participants had <90% adherence (dolutegravir + lamivudine group, 35/716; dolutegravir + tenofovir disoproxil fumarate/emtricitabine group, 34/717). The proportion of participants with HIV-1 RNA <50 copies/mL (Snapshot) at Week 48 in the <90% adherence group was 69% in the dolutegravir + lamivudine group and 65% in the dolutegravir + tenofovir disoproxil fumarate/emtricitabine group (analysis by last on-treatment viral load: 91% and 85%, respectively). Corresponding proportions in the ≥90% adherence group were 93% and 96% (analysis by last on-treatment viral load: 97% and 99%, respectively). Conclusions: Decreased adherence resulted in lower Week 48 virologic efficacy outcomes that were comparable between treatment groups. These results indicate that the robust antiviral activity and regimen forgiveness of dolutegravir + lamivudine is similar to dolutegravir-containing 3-drug regimens (see graphical abstract). [ABSTRACT FROM AUTHOR]

Objectives: To examine if point-of-care urine tenofovir testing-informed counseling could be used to improve virologic suppression (VS) among participants with virologic failure (VF) after ≥1 prior round of enhanced adherence counseling (EAC)., Methods: Participants were enrolled from 42 clinics across Namibia. At each monthly medication pick-up, participants completed the point-of-care urine test and received EAC informed by this testing (EAC+). If VS was not achieved after 3 months of EAC+, up to 3 additional rounds of EAC+ were provided, with resistance testing at month (M)9., Results: Of 310 potentially-eligible participants across 42 clinics in Namibia, we enrolled 211 participants with VF (median age 33 years, 61% female); 195 reached M3 defined as receiving EAC+ and follow-up viral load testing; 169 achieved VS within M3 (87%, p<0 . 001) and 97% by M9 (181/186) compared to 40% (22/55) prior to the intervention (p<0.001). Resistance testing was performed in five remaining participants with VF at M9, of whom 1/5 (20%) developed dolutegravir resistance., Conclusions: The urine tenofovir assay when incorporated into adherence counseling has potential to be a cost-effective intervention among participants failing tenofovir-based regimens, increasing VS to 97% in those failing TLD. Encouraging results of this pre-post intervention will be rigorously tested in a randomized trial., Competing Interests: Declaration of competing interest The authors report no conflicts of interest, (Copyright © 2024. Published by Elsevier Ltd.)

Background: GEMINI-1 and GEMINI-2 (ClinicalTrials.gov, NCT02831673 and NCT02831764, respectively) are double-blind, multicenter, phase III studies that demonstrated the non-inferiority of once-daily dolutegravir + lamivudine to dolutegravir + tenofovir disoproxil fumarate/emtricitabine in achieving HIV-1 RNA

Background: Older adults living with HIV (OALWH) are a growing population facing unique challenges to successful antiretroviral therapy. Objective: To assess efficacy and safety profiles of antiretroviral regimens, including those containing dolutegravir, in OALWH. Methods: Combined data from 6 phase III/IIIb trials in treatment-naive (ARIA, FLAMINGO, SINGLE, SPRING-2; N = 2634) and treatment-experienced (DAWNING, SAILING; N = 1339) participants receiving dolutegravir- or non–dolutegravir-based regimens were analyzed by age (

BackgroundRequirements for frequent dispensing of antiretroviral therapy (ART) place demands on health systems and can lead to suboptimal adherence and disengagement in care for patients due to the time and cost of frequent clinic visits. Rigorous data are needed to define optimal ART dispensing strategies and to evaluate the impact of a longer medication supply on retention and virologic suppression and determine whether this strategy lowers costs for both the patient and the health system. To date, no randomized studies have tested the benefits of 6-month dispensing of ART compared to 3-month and standard of care approaches.MethodsThis study will be an unblinded cluster-randomized, matched controlled trial conducted among 8200 stable, HIV-infected individuals age 18 years and older on ART in Malawi and Zambia, to compare three ART dispensing intervals on the outcomes of retention in care (primary outcome), virologic suppression, and cost-effectiveness. Thirty clusters will be matched according to country, facility type, and ART cohort size and randomized to one of three study arms: standard of care, 3-month dispensing, and 6-month dispensing. Study participants will be followed, and outcomes will be measured at 12, 24, and 36 months. A subset of participants (n = 240) and providers (n = 180) will also participate in qualitative interviews to evaluate feasibility and acceptability of different ART dispensing intervals.DiscussionThis study will be the first to compare 6-month and 3-month ART dispensing intervals for stable, HIV-infected individuals in Malawi and Zambia. We focus on outcomes relevant to country programs, including retention, virologic suppression, and cost-effectiveness. Results from the study will help resource-limited health systems better understand the full scope of outcomes resulting from various ART dispensing intervals and help to inform health policy decisions.Trial registrationClinicalTrials.gov, NCT03101592 . Registered on 18 March 2017. Pan African Clinical Trials, PACTR201706002336105 . Registered on 2 June 2017.

Introduction: In 2010, the Canadian province of British Columbia (BC) initiated the Seek and Treat for Optimal Prevention of HIV/AIDS (STOP HIV/AIDS) program to improve HIV testing, linkage to care, and treatment uptake, thereby operationalizing the HIV Treatment as Prevention (TasP) framework at the population-level. In this analysis, we evaluated self-reported HIV care experiences and therapeutic outcomes among people diagnosed with HIV prior to and after implementation of this provincial program.Methods: A cross-sectional analysis was performed on the baseline data of a cohort of people living with HIV (PLWH) (19 years and older) in the province of BC sampled from July 2016 to September 2018. All participants consented to linking their survey data to the provincial HIV treatment registry. Individuals diagnosed with HIV from January 1 2000-December 31 2009 were classified as pre-intervention and those diagnosed January 1 2010-December 31 2018 as post-intervention cohorts. Bivariate analyses were run using Chi-square and Wilcoxon Rank Sum tests. Cox proportional hazards regression model demonstrates time to antiretroviral therapy (ART) initiation (from HIV baseline) and virological suppression (2 consecutive plasma viral load measurements < 200 copies/ml).Results: Of the 325 participants included in this analysis, 198 (61%) were diagnosed with HIV in the pre-intervention era and 127 (39%) in the post-intervention era. A higher proportion of participants in post-intervention era were diagnosed at walk-in clinics (45% vs. 39%) and hospitals (21% vs. 11%) (vs pre-intervention) (p = 0.042). Post-intervention participants had initiated ART with less advanced HIV disease (CD4 count 410 vs. 270 cells/ul; p = 0.001) and were less likely to experience treatment interruptions at any point in the 5 years after HIV diagnosis (17% vs. 48%; p < 0.001). The post-intervention cohort had significantly more timely ART initiation (aHR: 5.97, 95%CI 4.47, 7.97) and virologic suppression (aHR: 2.03, 95%CI 1.58, 2.60) following diagnosis, after controlling for confounders.Conclusions: We found favourable treatment experiences and more timely ART initiation and virologic suppression after a targeted TasP provincial program. Our results illustrate the importance of accessible low-barrier HIV testing and treatment in tackling the HIV epidemic. [ABSTRACT FROM AUTHOR]

Background: Preexisting drug resistance limits the utility of HIV antiretroviral therapy. Studies have demonstrated safety and efficacy of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF), including in patients with M184V/I substitutions. Setting: We investigated virologic outcomes through 48 weeks of B/F/TAF treatment in individuals with preexisting primary integrase strand transfer inhibitor resistance (INSTI-R). Methods: Preexisting INSTI-R was retrospectively evaluated from 7 B/F/TAF studies. INSTI-R was assessed by historical genotypes and/or baseline RNA or DNA sequencing. Viral loads were measured at all visits. Results: Preexisting primary INSTI-R substitutions were detected in 20 of the 1907 participants (1.0%). The 20 participants were predominantly male (75%), were Black (65%), had HIV-1 subtype B (85%), and had baseline median CD4 counts of 594 cells/mm3 and median age of 52 years. Most of the participants (n = 19) were virologically suppressed at baseline and had one primary INSTI-R substitution, E92G, Y143C/H, S147G, Q148H/K/R, N155S, or R263K, +/-secondary substitutions. All suppressed participants maintained virologic suppression throughout 48 weeks without any viral blips. One treatment-naive participant had virus with Q148H+G140S that was fully sensitive to bictegravir but only partially to dolutegravir (phenotype <2.5-fold change and >4-fold change, respectively). With a baseline viral load of 30,000 copies/mL, this participant was virologically suppressed by week 4 and maintained <50 copies/mL through week 48. Conclusions: This small cohort with primary INSTI-R achieved and/or maintained virologic suppression through 48 weeks of B/F/TAF treatment. Consistent with the potent in vitro activity of bictegravir against most INSTI-R patterns, B/F/TAF may be a potential treatment option for patients with select preexisting INSTI-R, if confirmed by further studies. [ABSTRACT FROM AUTHOR]

Background: The cascade of human immunodeficiency virus (HIV) care in patients with psychiatric disorders is poorly understood. Aim: This study determined the prevalence of HIV and described its cascade of care among patients with psychiatric disorders in the Eastern Cape province, South Africa. The study also examined the correlates of HIV comorbidity with psychiatric disorders in the cohort. Methods: In this cross-sectional study, a total of 368 individuals attending the Psychiatric Outpatients' Department of Cecilia Makiwane Hospital in Eastern Cape were interviewed with a structured questionnaire. Relevant items on demographics and clinical information were extracted from the medical records. Virologic suppression was defined as viral load < 1000 RNA copies/mL. Results: The HIV prevalence after the intervention was 18.8% and a significant proportion of participants already knew their status (n = 320; 87.0%). Linkage to care and antiretroviral therapy initiation occurred in 61 participants, of those diagnosed with HIV (88.4%), with 84.1% being eligible for viral load monitoring (n = 58) and 53.4% having achieved virologic suppression. Being female (AOR = 5.48; 95% CI 2.61-11.51) and black (adjusted odds ratio [AOR] = 3.85; 95% confidence interval [CI] 1.06-14.03) were independent predictors of HIV comorbidity in individuals living with psychiatric disorders. Conclusion: This study found a moderately high prevalence (close to 19%) of HIV in individuals with psychiatric disorders, with a significant correlation with being female and being black people. This study also found a significant gap in the linkage to antiretroviral therapy (ART) initiation and a low rate of virologic suppression of 53.4%. Clinicians, therefore, should monitor and provide interventions for patients with concomitant HIV infection along this cascade of care. [ABSTRACT FROM AUTHOR]

Abstract Background The KwaZulu-Natal (KZN) province of South Africa has the highest prevalence of HIV infection in the world. Viral load (VL) testing is a crucial tool for clinical and programmatic monitoring. Within uMkhanyakude district, VL suppression rates were 91% among patients with VL data; however, VL performance rates averaged only 38·7%. The objective of this study was to determine if enhanced clinic processes and community outreach could improve VL monitoring within this district. Methods A packaged intervention was implemented at three rural clinics in the setting of the KZN HIV AIDS Drug Resistance Surveillance Study. This included file hygiene, outreach, a VL register and documentation revisions. Chart audits were used to assess fidelity. Outcome measures included percentage VL performed and suppressed. Each rural clinic was matched with a peri-urban clinic for comparison before and after the start of each phase of the intervention. Monthly sample proportions were modelled using quasi-likelihood regression methods for over-dispersed binomial data. Results Mkuze and Jozini clinics increased VL performance overall from 33·9% and 35·3% to 75·8% and 72·4%, respectively which was significantly greater than the increases in the comparison clinics (RR 1·86 and 1·68, p

Kamban Hirasen, 1 Matthew P Fox, 1–3 Cheryl J Hendrickson, 1 Tembeka Sineke, 1 Dorina Onoya 1 1Health Economics and Epidemiology Research Office, Department of Internal Medicine, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; 2Department of Global Health, Boston University School of Public Health, Boston, MA, USA; 3Department of Epidemiology, Boston University School of Public Health, Boston, MA, USACorrespondence: Dorina OnoyaHealth Economics and Epidemiology Research Office, 39 Empire Road, Empire Park, Parktown, Johannesburg 2193, South AfricaTel +27 010 001 7936Email donoya@heroza.orgIntroduction: Officially rolled out on 01 September 2016, South Africa’s Universal Test and Treat (UTT) policy calls for first-line antiretroviral treatment (ART) initiation among all known HIV-positive patients, irrespective of CD4 cell count. We evaluate treatment outcomes of patients initiated on first-line ART directly before and after the implementation of UTT.Methods: We analysed prospectively collected clinical cohort data among ART-naïve adult patients within two HIV clinics in Johannesburg, South Africa. We compare two groups: 1) an unexposed pre-UTT group initiating treatment from 01 December 2014 to 31 May 2015; and 2) an exposed UTT group initiating treatment from 01 December 2016 to 31 May 2017. Primary treatment outcomes included lost to follow-up (LTFU) (> 90 days late for the last scheduled visit with no subsequent clinical visit). Cox proportional hazards models were used to estimate the association between pre-UTT vs UTT initiation on LTFU by 12 months.Results: We included 2410 patients. A total of 1267 (52.6%) patients initiated ART before UTT implementation and 1143 (47.4%) after the change in policy. LTFU (adjusted Hazard Ratio (aHR): 1.51; 95% Confidence Interval (CI): 1.16– 1.98) between groups and specifically among those initiating with a CD4 cell count ≤ 500 cells/mm 3 (aHR: 1.59; 95% CI: 1.21– 2.10) was higher among patients initiating ART under UTT.Conclusion: LTFU under UTT proved higher than that of previous periods. Patients initiating first-line therapy under the treat-all policy may often start treatment in better health, subsequently not perceiving a direct benefit to treatment which may deter patients from consistent engagement in HIV treatment programmes.Keywords: universal access, antiretroviral therapy, lost to follow-up, virologic suppression, resource-limited settings, South Africa

Kamban Hirasen,1,* Denise Evans,1,* Nelly Jinga,1 Rita Grabe,2 Julia Turner,2 Sello Mashamaite,2 Lawrence C Long,1,3 Matthew P Fox1,3,4 1Health Economics and Epidemiology Research Office, Department of Internal Medicine, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; 2Right to Care, Johannesburg, South Africa; 3Department of Global Health, Boston University School of Public Health, Boston, MA, USA; 4Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA*These authors contributed equally to this workCorrespondence: Denise Evans Tel +27 10 001 0637Email devans@heroza.orgIntroduction: The best method to measure adherence to antiretroviral therapy (ART) in resource-limited settings has not yet been established, particularly among adolescents and young adults (AYAs). The use of mobile technology may address the need for standardized tools in measuring adherence in this often marginalized population.Methods: We conducted a cross-sectional validation study among AYAs (18– 35 years) attending a South African HIV clinic between 07/2015-09/2017. We determine the diagnostic accuracy of two modes of delivering an adherence questionnaire (self-administered electronic vs interviewer-administered paper-adherence questionnaire) comprising two self-reported adherence tools (South African National Department of Health (NDoH) adherence questionnaire and the Simplified Medication Adherence Questionnaire (SMAQ)) to identify poor adherence compared to; 1) a detectable viral load (≥ 1000 copies/mL) and 2) a sub-optimal concentration of efavirenz (EFV) (EFV ≤ 1.00 μg/mL) measured by therapeutic drug monitoring (TDM).Results: Of 278 included participants, 7.1% and 7.3% completing the electronic- and paper-questionnaires had a detectable viral load, while 14.7% and 16.5% had a sub-optimal concentration of EFV, respectively. According to viral load monitoring, the electronic-adherence questionnaire had a higher sensitivity (Se) in detecting poor adherence than the paper-based version across the NDoH adherence questionnaire (Se: 63.6% vs 33.3%) and SMAQ (Se: 90.9% vs 66.7%). In contrast, when using blood drug concentration (EFV ≤ 1.00 μg/mL), the paper-adherence questionnaire produced a higher sensitivity across both adherence tools; namely the NDoH adherence questionnaire (Se: 50.0% vs 38.1%) and SMAQ (Se: 75.0% vs 57.1%).Conclusion: When using more accurate real-time measures of poor adherence such as TDM in this young adult population, we observe a higher sensitivity of an interviewer-administered paper-adherence questionnaire than an identical set of self-administered adherence questions on an electronic tablet. An interviewer-administered questionnaire may elicit more accurate responses from participants through a sense of increased accountability when engaging with health care workers.Keywords: antiretroviral therapy, adherence, adolescents, virologic suppression, therapeutic drug monitoring, South Africa

Background: The cascade of human immunodeficiency virus (HIV) care in patients with psychiatric disorders is poorly understood. Aim: This study determined the prevalence of HIV and described its cascade of care among patients with psychiatric disorders in the Eastern Cape province, South Africa. The study also examined the correlates of HIV comorbidity with psychiatric disorders in the cohort. Methods: In this cross-sectional study, a total of 368 individuals attending the Psychiatric Outpatients’ Department of Cecilia Makiwane Hospital in Eastern Cape were interviewed with a structured questionnaire. Relevant items on demographics and clinical information were extracted from the medical records. Virologic suppression was defined as viral load 1000 RNA copies/mL. Results: The HIV prevalence after the intervention was 18.8% and a significant proportion of participants already knew their status (n = 320; 87.0%). Linkage to care and antiretroviral therapy initiation occurred in 61 participants, of those diagnosed with HIV (88.4%), with 84.1% being eligible for viral load monitoring (n = 58) and 53.4% having achieved virologic suppression. Being female (AOR = 5.48; 95% CI 2.61–11.51) and black (adjusted odds ratio [AOR] = 3.85; 95% confidence interval [CI] 1.06–14.03) were independent predictors of HIV comorbidity in individuals living with psychiatric disorders. Conclusion: This study found a moderately high prevalence (close to 19%) of HIV in individuals with psychiatric disorders, with a significant correlation with being female and being black people. This study also found a significant gap in the linkage to antiretroviral therapy (ART) initiation and a low rate of virologic suppression of 53.4%. Clinicians, therefore, should monitor and provide interventions for patients with concomitant HIV infection along this cascade of care.

Background: Older adults living with HIV (OALWH) are a growing population facing unique challenges to successful antiretroviral therapy. Objective: To assess efficacy and safety profiles of antiretroviral regimens, including those containing dolutegravir, in OALWH. Methods: Combined data from 6 phase III/IIIb trials in treatment-naive (ARIA, FLAMINGO, SINGLE, SPRING-2; N = 2634) and treatment-experienced (DAWNING, SAILING; N = 1339) participants receiving dolutegravir- or non–dolutegravir-based regimens were analyzed by age (<50, ≥50 to <65, and ≥65 years). Baseline data included comorbidities and numbers of concomitant medications. Week 48 efficacy outcomes included virologic response (HIV-1 RNA <50 copies/mL) and CD4+ cell count change from baseline. Safety outcomes included incidence of adverse events (AEs), serious AEs, and AE-related withdrawals. Results: Use of ≥5 concomitant medications was more frequently reported among treatment-naive and treatment-experienced participants aged ≥50 to <65 (30% [90/296] and 25% [57/227], respectively) and ≥65 years (43% [10/23] and 29% [4/14]) than among those aged <50 years (13% [310/2315] and 11% [118/1098]). Comorbidities were more prevalent in the older age groups. For dolutegravir-based regimens, Week 48 rates of virologic response and change in CD4+ cell count were similar across age groups (treatment naive, 80–87% and 234–251 cells/mm3; treatment experienced, 70–100% and 105–156 cells/mm3, respectively). There were no major differences in safety outcomes in each age group. Conclusions: In these analyses of combined phase III/IIIb trial data, efficacy and safety of dolutegravir-based regimens were generally similar across age groups in treatment-naive or treatment-experienced participants. Polypharmacy and comorbidities were more common among OALWH than those aged <50 years. [ABSTRACT FROM AUTHOR]

ObjectiveTo assess whether CD8 T-cell activation predicts risk of AIDS and non-AIDS morbidity during suppressive antiretroviral treatment (ART).DesignPost-hoc analyses of ART-naive participants in prospective ART studies. Participants with HIV-RNA levels 200 copies/ml or less and CD8 T-cell activation data (%CD38HLA-DR) at year-1 of ART were selected to determine years 2-5 incidence of AIDS and non-AIDS events.MethodsWe censored data at time of ART interruption or virologic failure. Inverse probability of censoring-weighted logistic regression was used to correct for informative censoring.ResultsWe included 1025 participants; 82% were men, median age 38 years, pre-ART CD4 cell count 255 cells/μl, and year-1-activated CD8 T cells 24%. Of these, 752 had 5 years of follow-up; 379 remained on ART and had no confirmed plasma HIV-RNA more than 200 copies/ml. The overall probability of an AIDS or non-AIDS event in years 2-5 was estimated at 13% [95% confidence interval (CI) 10-15%] had everyone remained on suppressive ART. Higher year-1-activated CD8 T-cell percentage increased the probability of subsequent events [odds ratio 1.22 per 10% higher (95% CI 1.04-1.44)]; this effect was not significant after adjusting for age. Among those age 50 years at least (n=108 at year 1), the probability of an event in years 2-5 was 37% and the effect of CD8 T-cell activation was more apparent (odds ratio=1.42, P=0.02 unadjusted and adjusted for age).ConclusionCD8 T-cell activation is prognostic of clinical events during suppressive ART, although this association is confounded by age. The consequences of HIV-associated immune activation may be more important in patients 50 years and older.

Abstract Cardiovascular diseases and thrombotic events became major clinical problems in the combined antiretroviral therapy (cART) era. Although the precise mechanisms behind these clinical problems have not been fully elucidated, a persistent pro-inflammatory state plays a central role. As platelets play important roles on both, thrombus formation and inflammatory/immune response, we aimed at investigating platelet function in HIV-infected subjects virologically controlled through cART. We evaluate parameters of activation, mitochondrial function and activation of apoptosis pathways in platelets from 30 HIV-infected individuals under stable cART and 36 healthy volunteers. Despite viral control achieved through cART, HIV-infected individuals exhibited increased platelet activation as indicated by P-selectin expression and platelet spreading when adhered on fibrinogen-coated surfaces. Platelets from HIV-infected subjects also exhibited mitochondrial dysfunction and activation of apoptosis pathways. Finally, thrombin stimuli induced lower levels of P-selectin translocation and RANTES secretion, but not TXA2 synthesis, in platelets from HIV-infected individuals compared to control; and labeling of platelet alpha granules showed reduced granule content in platelets from HIV-infected individuals when compared to healthy subjects. In summary, platelets derived from HIV-infected individuals under stable cART exhibit a phenotype of increased activation, activation of the intrinsic pathway of apoptosis and undermined granule secretion in response to thrombin.

Abstract Background Current World Health Organization (WHO) guidelines recommend early initiation of HIV positive patients on antiretroviral therapy (ART) irrespective of their clinical or immunological status known as the test and start approach. Lesotho, like many other countries introduced this approach in 2016 as a strategy to reach epidemic control. There will be rapidly growing number of HIV-infected individuals initiating treatment leading to practical challenges on health systems such as congestion, long waiting time for patients and limited time to provide quality services to patients. Differentiated models of ART delivery is an innovative solution that helps to increase access to care, while reducing the burden on existing health systems. Ultimately this model will help to achieve retention and viral suppression. We describe a demonstration study designed to evaluate a community-based differentiated model of multi-month dispensing (MMD) approaches of ART among stable HIV patients in Lesotho. Methods This study will be a three-arm cluster randomised trial, which will enrol approximately 5760 HIV-infected individuals who are stable on ART in 30 selected clusters. The clusters, which are health facilities, will be randomly assigned into the following differentiated model of care arms: (i) 3 monthly ART supply at facilities (Control), (ii) 3 monthly ART supply through community ART groups (CAGs) and (iii) 6 monthly ART supply through community ART distribution points (CAD). Primary outcomes are retention in care and virologic suppression, and secondary outcomes include feasibility and cost effectiveness. Discussion Important lessons will be learnt to allow for improved implementation of such demonstration projects, including various needs for reliable supply of medication, access to quality clinical data including access to viral loads (VLs) results, frameworks to support lay worker cadre, involvement of community stakeholders, and reliable data systems including records of key indicators. MMD will have positive implications including improved retention, virologic suppression, convenience and access to medication. Trial registration ClinicalTrials.gov Identifier: NCT03438370. Accepted on 16 February 2018.

Kamban Hirasen,1 Denise Evans,1 Mhairi Maskew,1 Ian M Sanne,1–3 Kate Shearer,1 Caroline Govathson,1 Given Malete,1 Sheryl A Kluberg,4 Matthew P Fox1,4,51Health Economics and Epidemiology Research Office, Department of Internal Medicine, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; 2Right to Care, Johannesburg, South Africa; 3Clinical HIV Research Unit, Department of Internal Medicine, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; 4Department of Global Health, Boston University School of Public Health, Boston, MA, USA; 5Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA Background: Long-term antiretroviral therapy (ART) adherence is critical for achieving optimal HIV treatment outcomes. Fixed-dose combination (FDC) single-pill regimens, introduced in South Africa in April 2013, has simplified pill taking. We evaluated treatment outcomes among patients initiated on a FDC compared to a similar multi-pill ART regimen in Johannesburg, South Africa.Methods: We conducted a retrospective cohort study of ART-naïve HIV-positive non-pregnant adult (≥18 years) patients without tuberculosis who initiated first-line ART on tenofovir and emtricitabine or lamivudine with efavirenz at Themba Lethu Clinic in Johannesburg, South Africa. We compared those initiated on a multi-pill ART regimen (3–5 pills/day; September 1, 2011–August 31, 2012) to those initiated on a FDC ART regimen (one pill/day; September 1, 2013–August 31, 2014). Treatment outcomes included attrition (combination of lost to follow-up and mortality), missed medical visits, and virologic suppression (viral load

Abstract Background Requirements for frequent dispensing of antiretroviral therapy (ART) place demands on health systems and can lead to suboptimal adherence and disengagement in care for patients due to the time and cost of frequent clinic visits. Rigorous data are needed to define optimal ART dispensing strategies and to evaluate the impact of a longer medication supply on retention and virologic suppression and determine whether this strategy lowers costs for both the patient and the health system. To date, no randomized studies have tested the benefits of 6-month dispensing of ART compared to 3-month and standard of care approaches. Methods This study will be an unblinded cluster-randomized, matched controlled trial conducted among 8200 stable, HIV-infected individuals age 18 years and older on ART in Malawi and Zambia, to compare three ART dispensing intervals on the outcomes of retention in care (primary outcome), virologic suppression, and cost-effectiveness. Thirty clusters will be matched according to country, facility type, and ART cohort size and randomized to one of three study arms: standard of care, 3-month dispensing, and 6-month dispensing. Study participants will be followed, and outcomes will be measured at 12, 24, and 36 months. A subset of participants (n = 240) and providers (n = 180) will also participate in qualitative interviews to evaluate feasibility and acceptability of different ART dispensing intervals. Discussion This study will be the first to compare 6-month and 3-month ART dispensing intervals for stable, HIV-infected individuals in Malawi and Zambia. We focus on outcomes relevant to country programs, including retention, virologic suppression, and cost-effectiveness. Results from the study will help resource-limited health systems better understand the full scope of outcomes resulting from various ART dispensing intervals and help to inform health policy decisions. Trial Registration ClinicalTrials.gov, NCT03101592 . Registered on 18 March 2017. Pan African Clinical Trials, PACTR201706002336105 . Registered on 2 June 2017.

There is a need to establish consensus for harmonization in antiretroviral (ARV) therapy (ART) switch treatment strategy and address the dilemma that exists in terms of subpar immune response to therapy or an immunologic deterioration while on therapy. The purpose of this review is to identify the factors that contribute to ARV treatment failure, such as insufficient dosage, drug interactions, poor adherence, drug resistance, and poor medication absorption. It is crucial to adopt a more efficient strategy to address this challenging dilemma. After ARV treatment failure, the aim of therapy is virologic suppression, which targets plasma viral load below the limits of detection as assessed by very sensitive tests with lower limits of quantification of 20 to 75 RNA copies/ml. The therapeutic objectives when complete virologic suppression is not possible, should be to maintain or restore immunologic function, stop the progression of the clinical illness, and minimize the emergence of new drug resistance that could further restrict the options for ARV drugs. Treatment history and drug-resistance testing, including the findings of previous and ongoing resistance tests, should be considered while selecting ARV regimens. Hence, the treatment approach post-ARV failure can be personalized based on clinical, immunologic, virologic, or as a mix of the three domains on a case-to-case basis. The evaluation of projected ARV activity should be based on treatment history and previous resistance test findings., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Sharma et al.)

Supplemental Digital Content is Available in the Text. Background: Tenofovir-diphosphate (TFV-DP) in dried blood spots (DBS) is an objective long-term adherence measure, but data are limited on its ability to predict virologic suppression (VS) in people on antiretroviral (ARV) treatment. There are also no data comparing DBS TFV-DP with plasma ARV concentrations as predictors of VS. Methods: Women who were on a first-line regimen of tenofovir, emtricitabine, and efavirenz (EFV) were enrolled in a cross-sectional study. Plasma EFV and tenofovir (TFV), DBS TFV-DP assays, and 30-day self-reported adherence were evaluated as predictors of VS (<50 copies/mL) with the area under the curve of receiver operating characteristics and logistic regression. Results: We enrolled 137 women; mean age of 33 years; median 4 years on antiretroviral therapy; 88 (64%) had VS. In receiver operating characteristics analyses: DBS TFV-DP [0.926 (95% CI: 0.876 to 0.976)] had a higher area under the curve than plasma TFV [0.864 (0.797 to 0.932); P = 0.006], whereas plasma EFV [0.903 (0.839–0.967)] was not significantly different from DBS TFV-DP (P = 0.138) or plasma TFV (P = 0.140); all ARV assays performed better than self-report. The association of TFV-DP in DBS with VS strengthened with increasing concentrations [reference <350 fmol/punch: 350–699 fmol/punch aOR 37 (8–178); 700–1249 fmol/punch aOR 47 (13–175); ≥1250 fmol/punch aOR 175 (20–1539)]. "White coat adherence" (defined as DBS TFV-DP <350 fmol/punch with detectable plasma TFV) was only detected in 4 women. Conclusions: Plasma EFV, TFV, and DBS TFV-DP were all strong predictors of VS. EFV or TFV assays have potential for development as point-of-care assays for use as objective adherence measures in resource-limited settings. [ABSTRACT FROM AUTHOR]

Meeting the challenge of antiretroviral therapy (ART) whose efficacy can last a lifetime requires continuous updating of the virological, pharmacological, and quality of life outcomes to be pursued and a continuous review of literature data on the efficacy and tolerability of new drugs and therapeutic strategies. With the aim of identifying open questions and answers about the current controversies in modern ART, we adapted the Design Thinking methodology to the needs of the design phase of a scientific article, involving a team of experts in HIV care. Five main pillars of treatment success were discussed: sustained virologic suppression over time; immunological recovery; pharmacological attributes; long-term tolerability and safety of ART; and people's satisfaction and quality of life. The definition of the outcomes to be achieved in each thematic area and the tools to achieve them were reviewed and discussed. Long-term treatment success should be intended as a combination of HIV-RNA suppression, immune recovery, and high quality of life. To achieve this, the regimen should be well-tolerated, with high potency, genetic barrier, and forgiveness, and should be tailored by a person-centered perspective, based on individual needs, preferences, and therapeutic history. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: We compared proportions of participants with target detected, target not detected (TND), and elevated viral load (VL) and assessed baseline variables associated with week 144 inflammatory biomarker levels between dolutegravir-lamivudine (DTG/3TC) and tenofovir alafenamide-based regimens (TBRs) in the TANGO study (post hoc)., Methods: TANGO is an open-label, multicenter, phase 3 study that randomized adults with VL <50 copies/mL to switch to once-daily fixed-dose DTG/3TC or continue TBR. At baseline and each study visit, the VL was measured. Elevated VL event frequencies were assessed, including "blips." Interleukin 6, D-dimer, high-sensitivity C-reactive protein, soluble CD14, and soluble CD163 were measured at baseline and at week 144. Log e -transformed week 144 biomarker levels were compared between treatment groups using an analysis of covariance model adjusting for baseline variables., Results: High, comparable proportions of participants had VL <40 copies/mL and TND at week 144 (DTG/3TC, 279 of 369 [76%]; TBR, 267 of 372 [72%], intention-to-treat exposed Snapshot analysis; adjusted difference, 3.9% [95% confidence interval, -2.5% to 10.2%]), with similar TND proportions at all postbaseline visits (123 of 369 [33%] vs 101 of 372 [27%], respectively). Similar proportions of DTG/3TC participants had ≥1 postbaseline VL ≥50 copies/mL (28 of 369 [8%] vs 42 of 372 [11%] for TBR), primarily blips (18 of 369 [5%] and 26 of 372 [7%], respectively). Week 144 inflammatory biomarker levels were low and comparable between groups and associated with multiple demographic and baseline characteristics, including baseline biomarker levels, indicating a multifactorial inflammatory response., Conclusions: Week 144 biomarker levels were low and generally comparable between treatment groups, reflecting similar, robust, and durable viral suppression observed using the stringent TND end point. Trial registration:  ClinicalTrials.gov, NCT03446573., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Abstract: Introduction: HIV treatment guidelines now recommend antiretroviral therapy (ART) initiation regardless of CD4 count to maximize benefit both for the individual and society. It is unknown whether the initiation of ART at higher CD4 counts would affect adherence levels. We investigated whether initiating ART at higher CD4 counts was associated with sub‐optimal adherence (<95%) during the first 12 months of ART. Methods: A prospective cohort study nested within a two‐arm cluster‐randomized trial of universal test and treat was implemented from March 2012 to June 2016 to measure the impact of ART on HIV incidence in rural KwaZulu‐Natal. ART was initiated regardless of CD4 count in the intervention arm and according to national guidelines in the control arm. ART adherence was measured monthly using a visual analogue scale (VAS) and pill counts (PC). HIV viral load was measured at ART initiation, three and six months, and six‐monthly thereafter. We pooled data from participants in both arms and used random‐effects logistic regression models to examine the association between CD4 count at ART initiation and sub‐optimal adherence, and assessed if adherence levels were associated with virological suppression. Results: Among 900 individuals who initiated ART ≥12 months before study end, median (IQR) CD4 at ART initiation was 350 cells/mm3 (234, 503); median age was 34.6 years (IQR 27.4 to 46.4) and 71.7% were female. Adherence was sub‐optimal in 14.7% of visits as measured by VAS and 20.7% by PC. In both the crude analyses and after adjusting for potential confounders, adherence was not significantly associated with CD4 count at ART initiation (adjusted OR for linear trend in sub‐optimal adherence with every 100 cells/mm3 increase in CD4 count: 1.00, 95% CI 0.95 to 1.05, for VAS, and 1.03, 95% CI 0.99 to 1.07, for PC). Virological suppression at 12 months was 97%. Optimal adherence by both measures was significantly associated with virological suppression (p < 0.001 for VAS; p = 0.006 for PC). Conclusions: We found no evidence that higher CD4 counts at ART initiation were associated with sub‐optimal ART adherence in the first 12 months. Our findings should alleviate concerns about adherence in individuals initiating ART at higher CD4 counts, however long‐term outcomes are needed. ClinicalTrials.gov NCT01509508. [ABSTRACT FROM AUTHOR]

HIV-1 infection is characterized by loss of CD4 T cells, leading to immunodeficiency. Initiation of antiretroviral therapy (ART) results in suppression of the viral load and increased CD4 counts. Both viral and host factors determine CD4 cell responses to ART with approximately 15–30% of individuals having suboptimal increase of CD4 T cell count, most commonly due to lack of compliance to ART. A smaller fraction of patients will have immune reconstitution failure and suboptimal CD4 increase despite suppression of HIV replication, and these individuals are at risk for adverse health outcomes. We sought to characterize the factors associated with decreased immunological response among Manitoba’s HIV patient population. This retrospective case-control study included HIV patients with immune reconstitution failure despite suppression of HIV replication by ART. The immune reconstitution failure was defined by CD4 cell count increase from baseline of less than 100 CD4 cells/mm 3 or lack of increase to above 200 CD4 cells/mm 3 within one year of viral load suppression. Age and nadir CD4 cell counts are known risk factors associated with immune reconstitution failure. We chose controls (Patients with immune reconstitution success) of similar age and CD4 nadir cell with cases (Patients with immune reconstitution failure). We explored the potential effects of gender, HLA type, presence of co-infection, ethnicity, ART type, and rate of pre-treatment CD4 decline among cases and controls. Of more than 550 patients followed by our HIV clinic, 42 individuals met our definition of immune reconstitution failure and they were assigned to the cases group. 31 patients, comprising a range of ages and CD4 nadirs similar to those of the cases, were assigned to the control group. Our primary analysis was a regression model, predicting post-ART change in CD4 over time. After controlling for age and nadir CD4 cell counts, the only potential predictor that appears consistently associated with the rate of post-ART rise in CD4 over time in our cohort, regardless of the other variables that we have controlled for, is the rate of decline in CD4 pre-ART initiation. Several factors have been variably correlated with immune reconstitution failure of CD4 T cell count. Age and low CD4 nadir are factors previously shown to correlate with immune reconstitution failure; and we have controlled for them in our study. Another possible predictor is the rate of decline in CD4 pre-ART, which can serve as an additional marker of reconstitution failure and necessitate prioritizing individuals to ART initiation or identification of a subset of individuals that may be targeted for future adjunct strategies to improve immune recovery. [ABSTRACT FROM AUTHOR]

Introduction: Modern combined antiretroviral therapies (cART) allow to effectively suppress HIV-1 viral load, with the 90% virologic success rate, meeting the WHO target in most clinical settings. The aim of this study was to analyse antiretroviral treatment efficacy in Poland and to identify variables associated with virologic suppression. Methods: Cross-sectional data on 5152 (56.92% of the countrywide treated at the time-point of analysis) patients on cART for more than six months with at least one HIV-RNA measurement in 2016 were collected from 14 Polish centres. Patients' characteristics and treatment type-based outcomes were analysed for the virologic suppression thresholds of <50 and <200 HIV-RNA copies/ml. CART was categorized into two nucleos(t)ide (2NRTI) plus non-nucleoside reverse transcriptase (NNRTI) inhibitors, 2NRTI plus protease (PI) inhibitor, 2NRTI plus integrase (InI) inhibitor, nucleos(t)ide sparing PI/r+InI and three drug class regimens. For statistics Chi-square and U-Mann Whitney tests and adjusted multivariate logistic regression models were used. Results: Virologic suppression rates of <50 copies/mL were observed in 4672 (90.68%) and <200 copies/mL in 4934 (95.77%) individuals. In univariate analyses, for the suppression threshold <50 copies/mL higher efficacy was noted for 2NRTI+NNRTIbased combinations (94.73%) compared to 2NRTI+PI (89.93%), 2NRTI+InI (90.61%), nucleos(t)ide sparing PI/r+InI (82.02%) and three drug class regimens (74.49%) (p < 0.0001), with less pronounced but significant differences for the threshold of 200 copies/mL [2NRTI+NNRTI-97.61%, 2NRTI+PI-95.27%, 2NRTI+InI-96.61%, PI/r+InI- 95.51% and 86.22% for three drug class cART) (p < 0.0001). However, in multivariate model, virologic efficacy for viral load <50 copies/mL was similar across treatment groups with significant influence by history of AIDS [OR:1.48 (95%CI:1.01-2.17) if AIDS diagnosed, p = 0.046], viral load < 5 log copies/mL at care entry [OR:1.47 (95%CI:1.08-2.01), p = 0.016], baseline lymphocyte CD4 count =200 cells/µL [OR:1.72 (95%CI:1.04-2.78), p = 0.034] and negative HCV serology [OR:1.97 (95%CI:1.29-2.94), p = 0.002]. For viral load threshold <200 copies/mL higher likelihood of virologic success was only associated with baseline lymphocyte CD4 count =200 cells/µL [OR:2.08 (95%CI:1.01-4.35), p = 0.049] and negative HCV status [OR:2.84 (95%CI:1.52-5.26), p = 0.001]. Conclusions: Proportion of virologically suppressed patients is in line with WHO treatment target confirming successful application of antiretroviral treatment strategy in Poland. Virological suppression rates depend on baseline patient characteristics, which should guide individualized antiretroviral tre0atment decisions. [ABSTRACT FROM AUTHOR]

Objectives: To report predictors of outcomes of second-line ART for HIV treatment in a resource-limited setting.Methods: All adult ART-naïve patients who initiated standard first-line treatment between April 2004 and February 2012 at four public-sector health facilities in Johannesburg, South Africa, experienced virologic failure and initiated standard second-line therapy were included. We assessed predictors of attrition (death and loss to follow-up [≥3 months late for a scheduled visit]) using Cox proportional hazards regression and predictors of virologic suppression (viral load <400 copies/ml ≥3 months after switch) using modified Poisson regression with robust error estimation at 1 year and ever after second-line ART initiation.Results: A total of 1236 patients switched to second-line treatment in a median (IQR) of 1.9 (0.9-4.6) months after first-line virologic failure. Approximately 13% and 45% of patients were no longer in care at 1 year and at the end of follow-up, respectively. Patients with low CD4 counts (<50 vs. ≥200, aHR: 1.85; 95% CI: 1.03-3.32) at second-line switch were at greater risk for attrition by the end of follow-up. About 75% of patients suppressed by 1 year, and 85% had ever suppressed by the end of follow-up.Conclusions: Patients with poor immune status at switch to second-line ART were at greater risk of attrition and were less likely to suppress. Additional adherence support after switch may improve outcomes. [ABSTRACT FROM AUTHOR]

Background: Antiretroviral therapy (ART) expansion and viral load as a treatment monitoring approach have increased the demand for viral load testing. Many hurdles affect the coverage, quality, and use of viral load results. Estimates of viral load monitoring and viral suppression rates are needed to assess the performance of ART programs and improve human immunodeficiency virus (HIV) management outcomes., Methods: People with HIV (PWH) viral load monitoring data were routinely collected in 84 health facilities in Kinshasa, Democratic Republic of the Congo (DRC), between 2013 and 2020. The number of PWH under ART, the number of participants with at least 1 viral load test result, the rate of viral suppression (defined as ≤1000 HIV ribonucleic acid copies per mL), and the mean turnaround time from sample collection to release of viral load test results were collected together with clinical data., Results: A total of 14 057 PWH were included in the analysis. People with HIV were mainly enrolled after the "test and treat" implementation. The patients were followed for a median period of 27 months. The proportion of PWH with at least 1 available viral load largely increased in recent years. The delay from sample collection to release of viral load test results decreased overtime, from 35 days in 2018 to 16 days in 2020. Pregnancy and advanced HIV disease were associated with a lower chance of viral suppression., Conclusions: There has been considerable success in increasing viral load access for all PWH under therapy in DRC. Nevertheless, viral load testing should be intensified with a particular effort to be made in groups at higher risk of viral failure., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Objectives: To investigate HIV virologic suppression and drug resistance among HIV-infected patients receiving first-line antiretroviral treatment (ART) in hospitals while community care and outreach through local health workers in Guangxi, China.Design: This was a series of cross-sectional surveys from 2004 to 2012 in Guangxi, supported by the Chinese National HIVDR Surveillance and Monitoring Network Working Group.Settings: Guangxi, ChinaMethods: Demographic, ART and laboratory data (CD4+ cell count, viral load, and drug resistance) were analyzed. Factors associated with virologic suppression were identified by logistic regression analysis. Results: A total of 780 patients were included in this study. The median treatment duration was 20.6 months (IQR 6.6-35.9). Of 780 study participants, 95.4% of patients (744/780) had HIV virologic suppression. Among these, of the 143 patients who were infected through drug injection, only 10(7.0%) experienced virologic failure. and the overall prevalence of HIVDR was 2.8% (22/789). Factors associated with virologic suppression in the final multivariate models included: self-reported missing doses in the past month (compared to not missing doses in the past month, AOR=0.2, 95% CI: 0.1-0.6) and initial ART regimen without 3TC (compared to initial ART regimen with 3TC, AOR=0.2, 95% CI: 0.1-0.4). Moreover, the trend chi-square test showed that the proportion of virologic suppression increased over time from 2004 to 2012 (P=0.002).Conclusions: This study first demonstrated that HIV patients infected through various transmission routes can achieve an excellent treatment outcome in hospitals at or above the county level for free first-line ART in Guangxi. It is a important of ART education and adherence to intervention for achieving better treatment outcomes.

Introduction: Treatment options are limited for HIV-1-infected individuals who have received extensive previous antiretroviral therapy. ETV has shown significant clinical benefits in treatment-experienced HIV-1+ patients with antiretroviral resistance. The aim of this study was to evaluate the effectiveness of ETV plus optimized background regimen in real-life conditions in a cohort of highly HIV-1 antiretroviralexperienced patients. Methodology: Retrospective cohort of treatment-experienced HIV-1-infected adults with virological failure who started therapy with an ETVcontaining regimen. The effectiveness was evaluated using HIV-1 RNA viral load and changes in CD4+ cell count after 48 weeks of treatment. Results: Forty-two patients ≥ 16 years of age were included; 74% were men, and the median age was 45 years (IQR 41-53). All participants had prior non-nucleoside reverse transcriptase inhibitor use (55% nevirapine, 83%, efavirenz, and 28% both). Baseline median HIV-1 RNA viral load was 15,598 copies/mL (IQR 2651-84,175) and CD4+ cell count was 276 cells/mL (IQR 155-436). After 48 weeks of treatment, 90.5% (95% CI 78-96) of patients had HIV-1 RNA viral load < 200 copies/mL and 76% (95% CI 61-86) had < 50 copies/mL. CD4+ cell counts increased from baseline to 48 weeks of treatment to a median of 407 cells/mL (IQR 242-579); p < 0.001. Virological outcome was associated with virological failure at baseline HIV-1 RNA viral load ≥ 100,000 copies/mL (OR 7.6; 95% CI 1.2-44.80; p = 0.025). Conclusions: Our study provides clinically important evidence of the effectiveness and safety of ETV in highly antiretroviral-experienced HIV- 1-infected patients. [ABSTRACT FROM AUTHOR]