Reinfection following direct-acting antiviral therapy for hepatitis C infection among people in prison with recent injecting drug use: the SHARP-P study.

Adolescents and young adults living with HIV (AYHIV) face complex psychosocial and adherence challenges that compromise long-term treatment success. Long-acting injectable therapies (LA-ART), such as cabotegravir and rilpivirine, may improve adherence, reduce stigma, and facilitate treatment retention. We conducted a retrospective, multicenter study of AYHIV enrolled in the Spanish pediatric HIV cohort (CoRISpe) and its adult extension (CoRISpe-FARO), who initiated LA-ART. Demographic, clinical, virological, immunological and biochemical data were analyzed up to March 2025. Outcomes before and after LA-ART initiation were analyzed, including CD4/CD8 ratio, viral suppression, and body mass index (BMI). Among 681 individuals in active follow-up, 26 AYHIV (65.4% women, median age 28) initiated LA-ART, primarily for treatment simplification. Most had acquired HIV perinatally and had extensive ART histories; 30% had received more than ten different ART regimens. Twenty-one patients had documented virological failures prior to LA-ART. Despite this, all patients achieved or maintained virological suppression after a median follow-up of 11 months. This included three individuals who initiated LA-ART with detectable viral load. CD4 and CD8 counts remained stable; the CD4/CD8 ratio showed an upward trend (p = 0.057), suggesting improved immune balance. Notably, AYHIV with BMI < 30 kg/m² showed significant increases in CD4 count, CD4%, and CD4/CD8 ratio. Overall BMI increased post-LA-ART (p = 0.036), especially in women. Treatment was well tolerated, with only one discontinuation due to injection site pain. LA-ART was safe, well tolerated, and effective in maintaining virological suppression, and showed positive immunological trends in AYHIV, including those with prior adherence issues or detectable viral load at baseline. These results support the potential of LA-ART as a valuable therapeutic strategy in AYHIV, especially in those with complex treatment histories and adherence challenges. Further prospective studies are warranted to confirm long-term outcomes.

The aim of this study was to evaluate the effectiveness of treatment of onychomycosis of the feet in HIV-infected patients depending on the effectiveness of antiretroviral therapy (ART). Patients and methods. 96 HIV-infected patients with onychomycosis of the feet were under observation. The diagnosis of HIV infection was established according to the International Classification of Diseases of the 10th revision (ICD-10) and verified by the detection of specific serological and molecular biological markers of HIV. The number of CD4+-lymphocytes and viral load (copies/ml) were recorded in all patients. Considering the effectiveness of ART, HIV-infected patients with onychomycosis of the feet were divided into four groups. Group I included patients with virological and immunological ART success; to the II group – patients with a decrease in viral load without an increase in the number of CD4+-lymphocytes or with an increase in the level of CD4+&gt;500 cells/μl without a decrease in viral load; to the III group – patients with an immunological response, but without a decrease in the viral load; to IV group – persons with virological and immunological failures of ART. Thus, 30 people were under observation in the 1st group; in the II group – 20; in the III group – 11; in the IV group – 35 patients. From the systemic antifungal therapy, HIV-infected patients of the I group received terbinafine 250 mg per day for 12 weeks. Patients of the II group received itraconazole 200 mg 2 times a day according to the scheme of pulse therapy on the 1st, 5th and 9th weeks of treatment. In groups III-IV, patients were prescribed fluconazole at a dose of 150 mg once a week for 6 months. The results. On the 6th month of observation, the effectiveness of antifungal therapy for onychomycosis of the feet in patients with virological and immunological successes of antiretroviral therapy was significantly higher than in patients with virological and immunological failures of antiretroviral therapy (p&lt;0.01). At the 12th month of observation, the mycological, clinical and full effectiveness of antifungal therapy for onychomycosis of the feet was statistically significantly higher in the case of virological and immunological success of antiretroviral treatment, compared to the group of patients in whom such a result of etiotropic therapy of HIV infection could not be achieved (р&lt;0.01). Conclusions. Evaluation of the effectiveness of antifungal therapy for onychomycosis of the feet in HIV-infected patients in groups formed depending on the effectiveness of antiretroviral treatment showed the best results in the group with a successful option of using antiretroviral drugs and the worst in the group with a negative result of such treatment. In representatives of the group with a lack of positive dynamics of one of the indicators (viral load or the number of CD4+-lymphocytes), the combined therapy of onychomycosis of the feet showed intermediate results.

The elimination of mother-to-child transmission of human immunodeficiency virus (HIV) is a key global public health priority. In Africa, virologic failure among people living with HIV continues to pose a significant public health challenge, affecting both individual well-being and community health. Maintaining viral load suppression is crucial to prevent vertical transmission of HIV and to minimize maternal morbidity and mortality. To stop the vertical transmission of HIV and lower the risk of maternal morbidity and mortality, it is important to achieve viral load suppression. Although many African countries have adopted the global 95-95-95 targets, comprehensive data on virologic suppression among pregnant and lactating mothers across the continent remains limited. The objective of this systematic review and meta-analysis was to determine the pooled estimate of virologic suppression and to examine the factors associated with it among HIV-positive pregnant and lactating women on antiretroviral therapy in Africa. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The study protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO; CRD420251186121). We carried out a thorough systematic review by examining PubMed, ScienceDirect, Hinari, and Google Scholar for relevant studies. Data from the studies were retrieved using an Excel sheet and analyzed with STATA version 17. The Joanna Briggs Institute appraisal tool was used to evaluate the methodological quality of studies. A random-effects model with restricted maximum likelihood (REML) was applied to determine the pooled prevalence of virologic suppression (viral load threshold ≤1000 copies/ml) among pregnant and lactating mothers in Africa. A funnel plot and the Egger's test were used to investigate publication bias. Statistical heterogeneity was assessed using the I2statistic and Cochrane's Q test. A total of 55 eligible studies, comprising 304,883 participants, were included in the quantitative meta-analysis. Accordingly, the overall prevalence of virologic suppression among HIV-positive pregnant and breastfeeding women in Africa was 80.86% (95% CI: 77.63%, 84.09%, I2 = 99.84%). In contrast, the pooled estimate for achieving an undetectable viral load was substantially lower, at 60.92% (95% CI: 52.46%, 69.39%; I2 = 99.91%). Virologic suppression was significantly associated with women's age (15-24 years) (AOR = 0.49; 95% CI: 0.32-0.77), disclosure of HIV status to a partner (AOR = 1.66; 95% CI: 1.31-2.11), first-line antiretroviral therapy regimen (AOR = 6.53; 95% CI: 1.93-22.06), and good antiretroviral drug adherence (AOR = 3.61; 95% CI: 1.18-11.02). In addition, other socio-demographic variables, higher educational level, being married/cohabitant, urban residency, healthcare utilization (time of ANC booking, time of ART initiation, duration of ART), fear of stigma, distance to health facility, shortage of health professionals, ART drug stock-out, and lack of HIV care commodities were significantly associated with virologic suppression among HIV-positive pregnant and lactating women in Africa. The pooled estimate of virologic suppression among HIV-positive pregnant and breastfeeding women in Africa was approximately 81%, below the global target of 95% virological suppression. This emphasizes the necessity of targeted strategies for younger HIV-positive women, disclosing HIV status, initiating first-line antiretroviral regimens, and promoting antiretroviral treatment adherence. Upgrading health care systems to enable regular viral load monitoring, as well as addressing socio-demographic and antiretroviral therapy-related variables, are vital steps towards attaining and sustaining VS in these groups of population, ultimately assisting in achieving elimination of MTCT of HIV.

Chronic hepatitis C virus (HCV) infection is a systemic disease frequently associated with extrahepatic autoimmune conditions, including rheumatoid arthritis (RA). Immune dysregulation and immunomodulatory therapy may raise concerns about the effectiveness and safety of direct-acting antivirals (DAAs), while real-world data in RA patients remain limited. To assess whether the presence of RA influences the severity of liver disease and the outcomes of direct-acting antiviral (DAA) therapy in HCV-infected patients. This retrospective multicenter study included adult HCV-infected patients treated with DAAs between 2015 and 2024 in Polish centers. We compared patients with RA with those without autoimmune disease (non-AID). Of 20 645 patients included in the analysis, 206 (1.0%) had RA. They were older, predominantly female, had lower BMI, and less advanced liver fibrosis as compared to the non-AID group. The SVR rates were high and comparable between RA and non-AID populations (98.4% vs 97.7%). RA was not associated with treatment failure. Independent predictors of virologic failure included male sex, genotype 3 infection, prior treatment, advanced liver disease, and Child-Pugh class B/C. Mild adverse events were more frequent in RA patients, while serious adverse events, deaths, and treatment discontinuation rates were comparable. RA does not contribute to increased severity or progression of HCV-related liver disease and does not negatively affect the effectiveness or safety of DAA therapy. Liver disease stage and hepatic dysfunction, rather than the presence of RA, are the key determinants of treatment outcomes in patients with chronic HCV infection.

Tenofovir disoproxil fumarate (TDF) is widely used in the treatment of chronic hepatitis B (CHB) due to its high antiviral potency and genetic barrier to resistance. However, long-term use is associated with renal toxicity, bone mineral loss, and high treatment burden. The European Association for the Study of the Liver (EASL) 2017 guidelines allow for cessation of nucleoside analogues (NAs) in well-selected patients, but data on outcomes following TDF withdrawal in Middle Eastern populations remain limited. In this prospective cohort study, 44 Iranian patients with CHB who fulfilled the 2017 EASL criteria for safe TDF discontinuation were followed for 12 months. Virological failure was defined as HBV DNA >2000 IU/mL (HBeAg-negative) or >20000 IU/mL (HBeAg-positive). Biochemical failure was defined as alanine aminotransferase (ALT) >2× upper limit of normal (ULN). Patients were assessed quarterly through laboratory testing and imaging. Outcomes, relapse timing, and predictors of failure were evaluated. TDF discontinuation was successful in 22 patients (50%) who maintained both virological suppression and normal ALT without reinitiation of therapy. Relapse occurred in the remaining 22 patients, with most failures (81.8%) occurring within the first 6 months. No cases of hepatic decompensation were reported. Virological relapse was more frequent than biochemical relapse. Serum creatinine significantly improved post-cessation (1.14 ± 0.30 to 1.10 ± 0.28 mg/dL, P=0.05), and liver stiffness remained stable in 97.7% of patients (fibro scan result). Longer HBV infection duration and extended TDF treatment were significant predictors of relapse. TDF cessation in appropriately selected Iranian patients with CHB is safe and feasible, with half maintaining remission over 12 months. Relapse predominantly occurred early and was mild, supporting EASL 2017 guideline recommendations. These findings offer valuable insight into TDF discontinuation in genotype D-predominant populations and support the use of finite therapy strategies with careful post-withdrawal monitoring.

Objective Bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) is currently one of the most valuable switch options for antiretroviral therapy (ART)-experienced people with HIV (PWH). Nevertheless, studies on long-term impact of prior experience of integrase strand transfer inhibitors (INSTIs) on such switch option are currently lacking. Methods This observational retrospective real-life study presents a longitudinal analysis of data from a monocentric cohort of PWH who underwent a therapeutic switch to BIC/FTC/TAF from any other previous regimens. Results Overall, 441 PWH were included in the study: 318 INSTI-experienced and 123 INSTI-naïve, of which 65 switching from non-nucleoside reverse transcriptase inhibitors (NNRTI)-based regimens and 58 from protease inhibitors (PI)-based regimens. At the end of 12 months follow-up, the overall population presented significant improvements in immunological and lipidic parameters, especially benefitting PWH switching from boosted INSTI-based regimes and INSTI-naïve PWH switching from PI-based regimens. Hepatic profiles were stable and a minor, not clinically relevant decrement of eGFR was reported. Virological efficacy of BIC/FTC/TAF switch could be inferred by observing PWH with detectable viral loads at the moment of switch (73, 16.6%): only five of them subsequently discontinued the regimen due to virologic failure or persistently detectable low viraemia. After a median duration of follow-up of 181 ± 66 weeks (3.48 ± 1.27 years), a quarter of the overall population discontinued BIC/FTC/TAF, with a median time of discontinuation of 213 weeks (4.38 years), with no differences according to prior INSTI experience. Conclusions Our real-life data further support the role of BIC/FTC/TAF as a durable, safe and “lipid-friendly” ART switch option, also for PWH without prior INSTI experience.

Understanding challenges experienced by adolescents and youth living with HIV (AYLWH) during COVID-19 can inform care during health crises. From 2021-2023, bi-monthly in-person/phone surveys were administered to assess trends in psychological, physical, and socioeconomic challenges, and antiretroviral nonadherence, among Kenyan AYLWH, alongside COVID-19 burden (casesloads and Oxford-Stringency-Index (OSI)). Biannual viral loads (VLs) were described as virologic suppression (VL < =40copies/mL), virologic failure (VL>40copies/mL), and treatment failure (VL>1,000copies/mL). Associations among caseloads/OSI, challenges, nonadherence, and treatment failure transitions (VL < =1,000 to >1,000copies/mL and vice versa) were evaluated using regression models, accounting for repeated-measures, age, gender, clinic, and between-visit days. Among 441 participants (mean age 16.9 years, 49% female, mean time on ART 11.9 years), 89% reported at enrollment challenges (48% psychological, 66% physical, 61% socioeconomic). Within-subject challenges, COVID-19 caseloads, and OSI scores varied over time alongside pandemic changes. During stringent periods and surges, physical challenges worsened (OR = 1.04 per 100-cases increase/day, CI = 1.00-1.08); psychological challenges were stable (OR = 1.02, CI = 0.98-1.06); socioeconomic challenges worsened during caseloads upticks (OR = 2.08, CI = 1.14-3.81). Higher challenges burden at enrollment was associated with slower reduction in challenges over time. Nonadherence (74% at enrollment) was associated with higher prior-visit challenges (Psychological: OR = 1.37, CI = 1.24-1.51; Physical: OR = 1.43, CI = 1.22-1.69; Socioeconomic: OR = 1.27, CI = 1.11-1.46). Virologic and treatment failure occurred in 19% and 10%; suppression-to-failure transition was associated with worsening adherence (OR = 1.26, CI = 1.00-1.58). Kenyan AYLWH experienced substantial wellness challenges during COVID-19, possibly prompting poor adherence and viral outcomes. While stability of non-physical challenges suggests COVID-19 adaptation, targeted interventions are warranted to support this vulnerable population during public health crises.

HIV reservoir is the main barrier to HIV cure but its size dynamics on antiretroviral therapy (ART) in various clinical settings is poorly characterized. Responders to a dolutegravir-based regimen (DBR) enrolled in the DRONE study were analyzed for longitudinal total HIV DNA and immune activation biomarkers (sCD14, sCD163, IL-6, IP-10). Overall, 169 participants were allocated to various groups: ART-naive acute infections (AI, n=20) or chronic infections (CI, n=21), and ART-treated individuals in virological success (VS, n=116) or failure (VF, n=12). HIV DNA significantly decreased at W48 of successful DBR in the AI (median: -1.3log10copies/million PBMCs), CI (-0.6), and VF (-0.5) groups, but not in the VS group. Activation biomarkers decreased on DBR only for individuals with ongoing HIV replication at baseline. Successful DBR was associated with rapid HIV DNA decline in ART-naive and ART-failing individuals but not in the context of ART switch.

Despite antiretroviral therapy (ART) scale-up in sub-Saharan Africa, treatment failure remains a significant challenge. We characterised virological and immunological outcomes among people living with HIV (PLHIV) attending tertiary care facilities in Nigeria, with exploratory analysis of potential mechanistic factors. This multi-centre cross-sectional study enrolled 517 HIV-positive adults from four Nigerian tertiary facilities between January 2019 and December 2021. Primary outcomes included viral load suppression (<1,000 copies/mL) and CD4 count. Exploratory mechanistic analyses examined drug resistance mutations (n = 50), immune activation markers (n = 40), and inflammatory biomarkers (n = 35) in pilot subsets. Among 412 participants with viral load data, only 111 (26.9%; 95% CI 22.7-31.5) achieved viral suppression, substantially below the UNAIDS 95% target. Of 387 with CD4 data, 149 (38.5%; 95% CI 33.6-43.6) had severe immunodeficiency (<200 cells/μL). Among 346 participants with complete data, discordant responses were common: 25.7% showed virological failure with preserved immunity, while 6.6% had immunological failure despite viral suppression. In pilot mechanistic subsets, 86% of viraemic participants harboured drug resistance mutations, with M184V (62%) and K103N (54%) predominating. CD8 T-cell activation (CD38+HLA-DR+) was significantly elevated in viraemic versus suppressed participants (median 28.6% vs. 12.4%; p < 0.001), correlating inversely with CD4 count (ρ = -0.46; p < 0.01). HIV treatment outcomes at Nigerian tertiary facilities fall substantially short of global targets. The high prevalence of discordant immune-virological responses and preliminary evidence of drug resistance and immune activation suggest multiple interacting pathways to treatment failure. Larger mechanistic studies are warranted to inform targeted interventions.

With over 1 million new HCV infections in 2022, treating acute HCV is essential to achieve WHO's HCV elimination goal. Although guidelines recommend prompt treatment, no direct-acting antiviral is approved for acute HCV outside of the US, leading to loss of patients to care while waiting for chronicity, and increased onward transmission. This single-arm, phase IIIb study evaluated the efficacy and safety of an 8-week glecaprevir/pibrentasvir regimen in treatment-naïve adults with acute HCV. Analyzed populations included intention-to-treat (ITT; all patients receiving ≥1 glecaprevir/pibrentasvir dose) and modified ITT, which excluded non-virologic failures (mITT-VF). The primary and key secondary efficacy endpoints were achievement of sustained virologic response at post-treatment Week 12 (SVR12) in the ITT and mITT-VF populations. Secondary endpoints included on-treatment virologic failure, post-treatment relapse, and reinfection in the ITT population. Treatment-emergent adverse events (TEAEs) and safety laboratory values were assessed. Overall, 286 adults were enrolled and treated; 14.3% were recent/current users of injection drugs, 49.7% were HCV/HIV coinfected, and 64.2% had HCV genotype 1. SVR12 was achieved by 96.2% (95% CI 93.2%-97.8%) in the ITT population (n = 286), and 100% in the mITT-VF population (n = 275). No TEAEs of hepatic decompensation/failure occurred; 1 (0.3%) patient discontinued due to a non-treatment-related TEAE; 3.5% of patients experienced serious TEAEs, none treatment-related; no deaths occurred. No patient with baseline alanine aminotransferase elevations of Grade 1-3 worsened to a higher grade during treatment, and all patients with baseline Grade 2-4 improved to a lower grade at the final treatment visit. An 8-week glecaprevir/pibrentasvir regimen was efficacious and well-tolerated in patients with acute HCV. These results support glecaprevir/pibrentasvir use in HCV test-and-treat models, potentially streamlining the care cascade, reducing transmission, and supporting HCV elimination. Currently, approved hepatitis C treatments are available only for chronic HCV in most geographies, with glecaprevir/pibrentasvir recently approved in the US for acute HCV. The lack of therapeutic options delays treatment initiation, increasing the risk of disengagement among people who inject drugs and other vulnerable groups, and contributing to onward transmission. This study demonstrates that 8-week glecaprevir/pibrentasvir therapy is efficacious and safe in patients with acute HCV infection, supporting its role as a recently approved treatment for acute HCV. Availability of an approved treatment for acute HCV will support the implementation of test-and-treat strategies in outreach settings for key prevalent populations, reducing delays and improving care retention, particularly among high-risk individuals. NCT04903626.

Introduction Loss to follow-up (LTFU) has been reported as a recurrent challenge affecting the success of antiretroviral treatment among HIV-infected patients in low- and middle-income countries. Additionally, loss of follow-up is a significant problem associated with increased treatment failure, which can be presented through clinical, immunological, and virological failure. Lastly, LTFU exacerbates the rates of morbidity, mortality, and drug resistance among people living with HIV. The study explores factors associated with loss to follow-up among patients living with HIV in selected public clinics under the DIMAMO surveillance area in the Capricorn district of Limpopo province. Material and Methods A qualitative research approach, particularly Phenomenology, was adopted to explore and understand the experiences of registered nurses and community health workers who work with patients on antiretroviral treatment at the selected public clinics. Twenty-eight (28) participants were purposively selected. Furthermore, data were collected using semi-structured interviews. Lastly, data was analysed using Delve narrative analysis as guided by Delve and Limpaecher. Results Following the process of data analysis, the study revealed that patients living with HIV often face diverse internal conflicts and significant barriers leading to loss of follow-up. The following themes emerged: 1.) Patient-related factors identified in a form of denial related to perceptions of HIV, perceptions of being healed or healthy, and lastly, not accepting responsibility for HIV health status. 2.) Significant barriers associated with disengagement from HIV care among patients were identified in the form of non-disclosure of HIV status to significant others, fear of stigmatisation, perceived breach of confidentiality, and lastly, resistance to or non-use of community healthcare interventions. Discussion In summary, the study identified the key challenges affecting HIV care, including internal conflicts, which manifested in the form of denial, and misconceptions about health status as reported by the participants. Thus, the significant barriers to care disengagement included non-disclosure of HIV status, fear of stigma, perceived breaches of confidentiality, and resistance to community healthcare interventions. Conclusion Furthermore, these findings highlight the need for targeted interventions to improve patient retention rates. Notably, a comprehensive training program and information guide for healthcare providers can enhance their ability to support antiretroviral patients and improve treatment adherence and health outcomes.

Doravirine is a non-nucleoside reverse transcriptase inhibitor (NNRTI) recommended for first-line antiretroviral therapy (ART), and for suppressed switching, in combination with a two nucleos(t)ide reverse transcriptase inhibitor (NRTI) backbone. Doravirine does not have a high barrier to resistance, and genotypic resistance testing (GRT) pre-switch is recommended. Data on its use without pre-switching GRT is limited. This retrospective cohort study presents data on doravirine use in virologically suppressed people with and without prior GRT. A retrospective single centre review of health records was conducted among prescribed doravirine-based ART at a London HIV service. Of the 582 adults included, 75% were men, 56% were of White ethnicity. The median age at baseline was 51-years (IQR: 44-58). Median time on doravirine was 127-weeks (IQR:93-175). GRT showing no doravirine resistance was available for 78% (n = 454) of individuals before switching to doravirine, of which, 2% experienced virological failure (n = 9); including two people with NNRTI and NRTI resistance. Among those without pre-switching GRT (n = 97), 1% experienced virological failure (n = 1), with NNRTI and NRTI resistance. There was no statistical significant difference in virologic suppression (viral load <50 copies/ml) rates (GRT 95% versus no-GRT 95%; p = 0.823). A similar proportion of people with (24%) and without (27%) pre-switching GRT switched away from doravirine, most commonly due to adverse effects. We did not find differences in efficacy and tolerability in people switched to doravirine-based ART with or without GRT. As expected, emergent NNRTI and NRTI resistance was common amongst those with virological failure on doravirine.

Antiretroviral therapy (ART) potently inhibits HIV replication but does not eliminate HIV proviruses integrated within the genomes of infected cells. Though ART normally suppresses HIV to clinically undetectable levels in blood, some individuals experience non-suppressible viremia (NSV) that is not attributable to suboptimal drug exposure (e.g., incomplete medication adherence or pharmacological issues) nor emerging HIV drug resistance, and that does not resolve following ART regimen modification. We now understand that NSV can originate from expanded cell clones harboring genetically identical proviruses that reactivate to produce clinically detectable viremia. NSV can even originate from proviruses with genomic defects, particularly within HIV's major splice donor (MSD) site, which render the viremia non-infectious. But, because only a limited number of such cases have been described, all in HIV subtype B, the mechanisms that allow cells harboring such proviruses to produce prolonged viremia without being eliminated remain incompletely understood. We characterized a case of MSD-defective, replication-impaired NSV that lasted >4 years in an individual with non-B HIV. Our results reveal that proviruses with MSD deletions can persist by integrating into minimally differentiated CD4+ T-cell subsets that then give rise to the full spectrum of memory and effector subpopulations, and by exhibiting an HIV protein expression profile that would allow these cells to evade both cellular and humoral immunity. Our results highlight the need to better understand the biological implications of persistent HIV protein and virion production by clonally expanded cells harboring genomically defective proviruses, and for clinical guidelines to acknowledge this type of viremia.IMPORTANCEHIV cure efforts focus on eliminating the viral reservoir, strictly defined as cells harboring proviruses that can produce infectious HIV. But this definition excludes proviruses with defects in HIV's major splice donor site (MSD), which persist readily. Our results confirm that clonally expanded, MSD-defective proviruses can produce HIV transcripts, proteins, and clinically detectable viremia over long periods, underscoring the need to investigate the biological consequences of these activities. Our findings also have clinical implications. Most HIV treatment guidelines do not acknowledge that persistent viremia during ART can originate from clonally expanded infected cells, and all recommend that viremia >200 HIV copies/mL be managed as virologic failure. Clear clinical frameworks should be developed to discriminate persistent viremia that is due to suboptimal drug exposure and/or emerging drug resistance (that is clinically actionable), from NSV (that is not). HIV MSD genotyping could also help assess viral infectivity, and thus potential transmission risk, during NSV.

Treatment failure in second-line antiretroviral therapy (ART) among people living with HIV remains a critical concern in Zambia. This study investigated virological failure and factors associated with treatment failure among patients on second-line ART at two tertiary hospitals in Zambia. A cross-sectional study was conducted on 257 patient records from 1 January 2022 to 30 April 2025 on second-line ART from two tertiary hospitals. Multivariable logistic regression data analysis was performed using Stata 14.2. The prevalence of treatment failure was found to be 12.06% (95% CI 8 to 16%). Key predictors of treatment failure included younger age (<15-35 y), male gender (adjusted OR [aOR]-3.05; 95% CI 1.28 to 7.27) and ART initiation at WHO Clinical Stage 2 or above (aOR=1.62; 95% CI 0.68 to 3.82). Additionally, patients on a zidovudine/lamivudine/dolutegravir second-line regimen demonstrated significantly lower odds of failure compared with those on zidovudine/lamivudine/darunavir (aOR=0.34; 95% CI 0.16 to 0.77). This study found that treatment failure among people living with HIV on second-line ART in Zambia remains a significant concern. To improve treatment outcomes and reduce HIV-associated morbidity and mortality in Zambia, strengthening routine viral load monitoring and adherence support initiatives is essential.

Cabotegravir and rilpivirine long-acting (CAB+RPV LA) is a novel switch strategy for people living with HIV. Our aim was to identify factors associated with therapeutic failure (TF) and virological failure (VF). We conducted a single-centre prospective cohort study. We reviewed all people living with HIV who initiated CAB+RPV LA between 14 February 2023 and 6 May 2025 in the hospital. Reasons for treatment discontinuation (VF, toxicity, poor adherence, death, pregnancy, transfer to another centre or oral bridging) were analysed, as well as virological effectiveness and the emergence of resistance mutations. Safety, adherence and overall regimen durability were also evaluated. The proportion of patients with HIV-RNA < 50 copies/mL at months 1, 7 and 13 was analysed using intention-to-treat (ITT) and on-treatment (OT) approaches. CAB+RPV LA was administered to 35% of the hospital's cohort (151/429). Of the 151 patients, 80% were male, with a median age of 40 years. A total of 116 patients reached 13 months of treatment. After a median follow-up of 18.8 months (interquartile range [IQR]: 11-23.7), 28 (18.5%) patients discontinued treatment, 3 (2%) of them due to VF (one with resistance mutations to both rilpivirine and cabotegravir). The proportions of patients with HIV-RNA < 50 copies/mL at months 1, 7 and 13 were 96%, 91% and 85% (ITT) and 96%, 95% and 93% (OT), respectively. Reasons for discontinuation included VF (2%), adverse events (4%), poor adherence (3%), transfer to another hospital (5%), oral bridging (4%) and difficulty attending appointments (1%). The modified therapeutic failure rate (excluding oral bridging and transfers) was 7.42 (95% confidence interval [CI]: 4.3-12.0) per 100 person-years. CAB+RPV LA appears to be an effective, safe and durable option for a switch strategy.

Islatravir (ISL), a nucleoside reverse transcriptase translocation inhibitor, and lenacapavir (LEN), a capsid inhibitor, have pharmacokinetic profiles supporting once-weekly (QW) oral dosing. In a Phase 2 study, QW ISL+LEN maintained a high rate (94.2%) of viral suppression (VS; HIV-1 RNA <50 copies/mL) at Week 48. We report resistance analyses through Week 48. Virologically suppressed participants received ISL (2 mg QW) plus LEN (600 mg Days 1+2, then 300 mg QW; n=52) or once-daily bictegravir/emtricitabine/tenofovir alafenamide (50/200/25 mg; n=52). Proviral DNA sequencing of HIV-1 protease, reverse transcriptase, and integrase was performed at screening; available historical genotypes were collected. Participants with primary nucleoside reverse transcriptase inhibitor (NRTI) or non-NRTI (NNRTI) resistance-associated mutations (RAMs) were excluded. Post-baseline resistance analyses were performed for participants with HIV-1 RNA ≥200 copies/mL at virologic failure (≥50 copies/mL at two consecutive visits) or ≥50 copies/mL at study drug discontinuation/last visit. Of 104 enrolled participants, five randomized with historical genotypes were subsequently found to have primary NRTI and/or NNRTI RAMs; all five maintained VS, including two participants with M184V/I (one/group). One participant receiving ISL+LEN with low-level viremia on Day 1 (HIV-1 RNA 251 copies/mL) met criteria for resistance analysis; no emergent resistance was observed, and they subsequently resuppressed on ISL+LEN. Longitudinal analysis of plasma virus detected identical viruses with no evidence of viral evolution. ISL+LEN maintained high rates of VS, including in one participant with pre-existing M184V. No participants developed drug resistance. These findings support the ongoing evaluation of QW oral ISL+LEN for HIV-1 treatment.

Antiretroviral single-tablet regimens (STRs) have several advantages over multiple-tablet regimens (MTRs), including increased adherence and improved treatment satisfaction for people with HIV (PWH). This analysis has systematically reviewed and compared STRs and MTRs in adult PWH receiving integrase strand transfer inhibitor (INSTI)-based regimens. MEDLINE and Embase databases were searched on November 28, 2023, to identify studies published from 2013 to 2023 that evaluated INSTI-based STRs compared with ≥ 1 INSTI-based MTRs. Study quality was assessed based on the University of York Centre for Reviews and Dissemination guidelines. Pairwise meta-analyses were conducted to provide pooled relative estimates for key clinical outcomes. Twenty-five publications were included in the quantitative syntheses. STRs were associated with improved adherence based on 3 retrospective studies [rate ratio (RR) = 1.64 (95% confidence interval: 1.46-1.83)] but there was no difference in adherence in the 1 randomized controlled trial (RCT) that assessed adherence [RR = 1.02 (0.77-1.35)], though, due to blinding, both STR and MTR groups took multiple pills. STRs were associated with higher persistence than MTRs based on 7 retrospective studies [RR = 1.33 (1.17-1.52)]. PWH treated with MTRs versus STRs were more likely to discontinue therapy in retrospective studies [hazard ratio = 1.62 (1.52-1.72), 6 studies] and prospective cohort studies [RR = 4.43 (1.62-12.09), 3 studies], but not within RCTs where there was no difference in discontinuation [RR = 0.83 (0.55-1.26), 4 trials]. Risk of virologic failure was comparable between STRs and MTRs in RCTs [RR = 1.00 (0.35-2.84), 5 trials] and retrospective studies [odds ratio = 1.30 (0.30-5.53), 5 studies]. INSTI-based STRs were associated with improved adherence and persistence, and lower discontinuation rates compared with INSTI-based MTRs in observational, real-world studies, whereas no differences in adherence or discontinuation were seen in RCTs. Neither RCTs nor real-world studies showed any difference in virologic failure for STRs and MTRs. STRs are a potential tool for supporting adherence and persistence in real-world settings. PROSPERO number CRD42024525515.

Engagement in HIV care is essential for viral suppression, and care coordination programs have shown improved retention and adherence. In New York Medicaid HIV Special Needs Plans (SNP), health-homes provide enhanced care coordination for people with HIV (PWH) at risk of non-adherence; however, evidence of their impact on virologic outcomes is limited. Using a matched case-control design and 2016-2018 data from a New York City Medicaid HIV SNP, this study examined associations between health-homes and virologic failure. Cases had virologic failure, defined as two consecutive viral loads > 200 copies/mL. Controls matched 1:1 on age (18+), race, and second viral load date, had no virologic failure. Conditional logistic regression examined virologic failure and health-home use duration, Social Deprivation Index (SDI), gender identity, HIV-infection stage, SNP enrollment, comorbidities, and polypharmacy. There were 2,566 PWH (62% male, mean age 42.9 years, mean SDI 92.3). Virologic failure was associated with HIV Stage III (OR = 2.01, 95% CI: 1.61-2.49), substance use disorder (OR = 2.09, 95% CI: 1.68-2.58), and < 6 months of health-home use (OR = 2.08, 95% CI: 1.27-3.42). The association attenuated with 6 + months of health-home use (reference=none; OR = 0.98, 95% CI: 0.77-1.25). Polypharmacy (OR = 0.72, 95% CI: 0.59-0.89) and mental health diagnoses (OR = 0.74, 95% CI: 0.59-0.94) had lower odds of virologic failure. Although further research is needed to clarify the roles of polypharmacy and mental health care, sustained health-home use may reduce disparities in virologic failure among PWH at high risk of falling out of care.

Extensive real-world data in people with HIV (PWH) switching from non-nucleoside reverse transcriptase inhibitors (NNRTIs), in particular from rilpivirine (RPV)-based regimens to bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF), are lacking. This is a single-center retrospective study. Inclusion criteria were PWH aged ≥ 18years, virologically suppressed on NNRTI triple antiretroviral regimens. The primary endpoint was the proportion of PWH with HIV-RNA < 50 cp/mL at 12months from time of switch to B/F/TAF. Overall, 214 PWH were included, of whom 105 (49.1%) were switching from RPV/FTC/TAF. After 12months, the proportion of PWH with HIV-RNA < 50 copies/mL was 82.7% (95% confidence interval, CI, 77.1-87.2) at intention-to-treat (ITT) and 95.7% (95% CI 91.7-97.8) at missing=excluded (M=E) analysis. In the group switching from RPV/FTC/TAF, the proportion of PWH with HIV-RNA < 50 copies/mL at 12months was 74.3% (95% CI 65.2-81.7) at ITT and 95.1% (95% CI 88.1-98.1) at M=E analysis. Two PWH (0.93%, 95% CI 0.26-3.34) experienced virological failure after switching to B/F/TAF, with no resistance mutations detected. Six treatment discontinuations were observed (2.8%, 95% CI 1.3-5.6). A decrease in low-density lipoprotein (LDL) cholesterol was documented when switching from RPV/FTC/TAF to B/F/TAF. Switching to B/F/TAF from NNRTI-based regimens, particularly if RPV-based, showed high virological effectiveness and rare treatment discontinuations. No resistance mutations were detected at failure.