Virological Failure Research Articles

Dolutegravir-Based Antiretroviral Therapy in People with HIV with Solid Organ Transplantation: A Single-Arm Pilot Clinical Trial (DTG-SOT)

Abstract Background This study assessed the pharmacokinetic interactions between dolutegravir (DTG)-based antiretroviral therapy (ART) and immunosuppressants in solid organ transplantation (SOT) recipients with human immunodeficiency virus (HIV) and ART safety. Methods Phase IV, single-center, open-label, single-arm clinical trial (DTG-SOT, NCT03360682) including adult SOT recipients with HIV conducted between 2017 and 2019. People with HIV (PHIV) with plasma viral load <50 copies/mL during ≥12 months and receiving stable raltegravir-based ART during ≥6 months were switched to tenofovir disoproxil fumarate (TDF)/Emtricitabine (FTC) or Lamivudine (3TC)/Abacavir (ABC)+DTG and followed up for 48 weeks. Immunosuppressant pharmacokinetic parameters were compared before and two weeks after ART switch (primary outcome). Efficacy and safety were analyzed at 48 weeks by intention-to-treat analysis (ITT). Results Nineteen consecutive participants (median 57 years, IQR 51-60), mostly liver recipients (63·2%), received DTG/3TC/ABC (63·2%) and DTG+FTC/TDF (36·8%). Pharmacokinetic parameters changed, albeit not significantly, before and after ART, for mycophenolic acid (MPA) (Cmax +63%, Cmin +53%, AUC +16%; n=7) and cyclosporine A (Cmax -64%, Cmin +14%, AUC -47%; n=2), with smaller changes for tacrolimus (Cmax +14%, Cmin -29%, AUC -9%; n=7). No participants experienced acute rejection or virological failure and CD4+ cell counts and percentages remained unchanged during follow-up. Three (15·8%) discontinued treatment due to AEs. Estimated glomerular filtration rate decreased (p=0·0015) and creatinine increased (p=0·0001) slightly. Conclusions DTG-based ART lacked clinically significant drug-drug interactions with tacrolimus and MPA. Switching to DTG-based ART was effective in PHIV SOT recipients. More studies are needed to evaluate DTG safety in this setting.

Drug Resistance in Anti-viral Medications: A Case Study of Human Immunodeficiency Virus

HIV drug resistance (HIVDR) is an ongoing challenge in the management of HIV, with global prevalence rising significantly since the widespread adoption of antiretroviral therapy (ART). Resistance mutations compromise treatment effectiveness, leading to virological failure and the transmission of resistant strains, including newly infected individuals. Pregnant women face heightened risks, as resistant strains complicate treatment options and increase the likelihood of vertical transmission. Addressing this issue is critical to sustaining the success of ART and advancing global HIV control efforts. This review examines drug resistance in antiviral medications using HIV as a case study. A systematic literature review was conducted using PubMed, Google Scholar, and reports from WHO and UNAIDS, focusing on peer-reviewed publications from the past 20 years. Search terms included “HIV drug resistance,” “antiretroviral resistance,” and “mother-to-child transmission.” Articles were selected based on their relevance to resistance mechanisms, prevalence, and management strategies, ensuring a comprehensive analysis of the topic. Findings indicate that HIVDR remains a barrier to effective treatment, driven by the virus’s high mutation rate and genetic diversity. Resistance has emerged across all major antiretroviral drug classes, particularly in low- and middle-income countries, where limited access to resistance testing and poor treatment adherence exacerbate the problem. Addressing HIVDR requires enhanced surveillance, the development of innovative therapies, and strategies to improve adherence and reduce selective pressure. Additionally, integrating resistance data into treatment guidelines and utilizing advanced technologies such as artificial intelligence can optimize treatment outcomes and support global HIV/AIDS control efforts.

Impact of switching to long-acting injectable cabotegravir plus rilpivirine on rectal HIV-1 RNA shedding and implications for transmission risk.

The impact of long-acting injectable cabotegravir plus rilpivirine (CAB/RPV) on rectal HIV-1 RNA dynamics and the factors associated with viral shedding remain poorly understood. This prospective study evaluated HIV-1 RNA dynamics by analyzing sequential paired plasma and rectal fluid samples from virologically-suppressed individuals who transitioned from oral antiretroviral therapy (ART) to every-two-month CAB/RPV (preceded or not by oral lead-in), over a 9-month follow-up period. RPV trough concentrations were measured in 384 rectal samples. 597 plasma and 561 rectal samples from 90 participants were analyzed. HIV-1 RNA >50 (>1.69 log10) copies/swab was detected in 14.7% (59/401) of rectal samples (42.2% of participants) during intramuscular CAB/RPV, and in 17.5% (28/160) of rectal samples (29% of participants) during oral ART. Median (range) detectable rectal HIV-1 RNA level during intramuscular ART was 362 (226-659) copies/swab. The frequency and quantity of rectal shedding did not differ between groups with/without oral lead-in. No correlation was observed between rectal shedding and detectable plasma HIV-1 RNA. Median (Q1-Q3) rectal RPV concentration was 3.07 (2.83-3.35) log10 ng/swab, 1.6-fold above the EC90 for rectal tissue, and did not correlate with rectal HIV-1 RNA levels. Rectal shedding was associated with plasma pre-ART HIV-1 RNA >5 log10 in multivariate Cox regression, but was unrelated to established predictors of virological failure with CAB/RPV. Rectal HIV-1 shedding is common during bimonthly intramuscular CAB/RPV treatment and is also observed with oral ART. Shedding was independent of concurrent plasma HIV-1 RNA and rectal RPV concentrations, and was associated with pre-ART viral load.

Resistance to Dolutegravir in Treatment-experienced Patients in South Africa: A Retrospective Cohort Study.

Dolutegravir resistance has been reported more frequently in patients with prior treatment experience compared to those on dolutegravir in first-line antiretroviral therapy (ART). The widespread use of dolutegravir in resource-limited programmatic settings might facilitate the emergence of resistance. Data on the prevalence of dolutegravir resistance from programmatic settings in Africa are scarce. This retrospective observational cohort study assessed dolutegravir resistance in routine care settings of the Western Cape provincial public healthcare sector program between February 2021 and June 2024. Treatment-experienced adults who developed virologic failure (two HIV-1 RNA ≥1000 copies/mL), who had received dolutegravir-based ART for >24 months, were eligible for genotypic antiretroviral resistance testing (GART). Drug resistance mutations (DRMs) and resistance levels were classified using the Stanford database. Among 99 eligible patients, 76 had GART performed, and 68 had successful sequences. Among these 68, 43 (63%) had dolutegravir DRMs with: 1 potential low, 1 low, 15 intermediate, and 26 high resistance levels. The median time on dolutegravir-based ART was 24 months (IQR, 23-31). Of the 43 patients with dolutegravir DRMs, 21 (49%) were receiving zidovudine-lamivudine-dolutegravir and 19 (44%) were receiving tenofovir-lamivudine-dolutegravir; 42/43 had prior ART experience. Over 60% of patients with prior treatment experience who had been on dolutegravir-based ART for over two years and experienced virologic failure had intermediate or high level dolutegravir resistance. This suggests that criteria for GART used are too stringent, which has resource implications in programmatic settings where access to resistance testing for individual management is limited.

Next-generation sequencing and drug resistance mutations of HIV-1 subtypes in people living with HIV in Sicily, Italy, 2021-2023.

HIV-1 infection continues to be a significant public health concern, notwithstanding the expanded utilization of antiretroviral treatment (ART), due to the emergence of drug resistance. The prevalence of transmitted drug resistance remains uncertain, particularly concerning integrase inhibitors. This study aimed to assess the extent of HIV resistance in both ART-naïve and experienced individuals living with HIV (PLHIV) at the University Hospital in Palermo, Italy. Genotyping and mutation analysis were performed on ART naïve and experienced PLHIV admitted from June 2021 to October 2023 by the NGS method. Mutations were detected by testing different NGS frequency cut-offs: ≥5 %, ≥10 %, and ≥20 %. Demographic, clinical, virological, and immunological data were retrospectively collected. Of the PLHIV, 85 (70 %) were ART-naïve, while 36 (30 %) were ART-experienced with virological failure. The main HIV-1 subtype was B (54 %), which was significantly associated with Italy-born (P < 0.001) and experienced PLHIV (P = 0.024). In the remaining cases, A1 (6 %), C (3 %), F1 (7 %), G (2 %), and Circulating Recombinant Forms (28 %) were reported. At least one mutation for a drug class was detected in 39.7 %, 45.4 %, and 53.7 % of cases at HIV-1 NGS thresholds of 20 %, 10 %, and 5 %, respectively. Drug resistance was found in 18.2 %, 25.6 %, and 33.0 %, by NGS cut-off of 20 %, 10 %, and 5 % respectively. The lowering of NGS cut-offs mainly increased the rates of integrase strand transfer inhibitor resistance. For overall resistance, no difference was observed between B and non-B subtypes for any NGS cut-offs.

Telemedicine virologic and immunologic outcomes in people living with HIV (PLWH) in a correctional setting during the SARS-CoV-2 pandemic

BackgroundIt is known that SARS-CoV-2 infection increases the risk of severe illness in patients who are immunocompromised as compared to the general public. To combat this issue, telemedicine was utilized to combat the issue of general access to care to decrease the risk of exposure of SARS-CoV-2 infection in various settings. However, there is very little data on adequate continuity of care (COC) and sustainability of telehealth throughout the SARS-CoV-2 pandemic. There is even less data on the effects of the SARS-CoV-2 pandemic in special populations, such as people living with human immunodeficiency virus (PLWH) who reside in the correctional setting. The purpose of this study was to investigate rates of HIV virologic suppression (VS) and the sustainability of telemedicine throughout the SARS-CoV-2 pandemic.MethodsThis was a retrospective, pre-post cohort study of PLWH who received antiretroviral therapy (ART) within Illinois Department of Corrections (IDOC)/University of Illinois at Chicago telemedicine clinic between March 2019– March 2021. Patients who were released from IDOC or reincarcerated during the study period were excluded. The primary endpoint compared the rate of HIV VS pre-, peri-, and post-SARS-CoV-2 restrictions. Secondary endpoints included change in immunologic function pre-, peri-, and post-SARS-CoV-2 restrictions, incidence of SARS-CoV-2 infection, number of hospitalizations, development of virologic failure, and change in ART post-restriction. Other factors known to influence COC were also collected.ResultsOf 320 patients screened, 225 were included. The majority were Black males (73.7%) where 95.1% had a CD4 T-cell count > 200 cells/mm3 at baseline. Approximately 88% of patients were on a single tablet regimen, with most receiving bictegravir/emtricitabine/tenofovir alafenamide (39.1%). Factors associated with disruption of COC included missed scheduled appointments (62.6%) and non-adherence to ART regimen (4.4%) in the post-restriction period. Regardless, VS (VL < 200 copies/mL) was maintained in 98.2% of people pre-pandemic, 97.8% of people peri-pandemic and 99.1% of people post-restriction.ConclusionsPLWH within IDOC had sustained VS and COC throughout the SARS-CoV-2 pandemic with telemedicine. These results describe how the pandemic impacted PLWH in a correctional setting and future studies could contribute to creating national guidance for telemedicine models to streamline clinical practice through the utilization of telemedicine.

Three Year Efectiveness of Bictegravir/Emtricitabine/Tenofovir Alafenamide as Switch Strategy in the Real-World

Abstract Introduction We previously described the effectiveness of bictegravir/emtricitabine/tenofovir alafenamide as a switch strategy in real-life in people with HIV (PWH) at 48 weeks. We did not find that previous nucleoside reverse transcriptase inhibitor (NRTI) resistance associated mutations (RAMs) had an impact on efficacy. Herein we report response rate after three years of follow-up. Methods Retrospective review of treatment-experienced PWH who switched to B/F/TAF in a single-centre cohort. HIV-RNA less than 50 copies/mL was analyzed at 96 and 144 weeks in an intention-to-treat (ITT) analysis (missing=failure) and per-protocol analysis (PP) (patients with missing data or changes for reasons other than virological failure were excluded). Results Five hundred and six PWH were included: 16.2% women, median age 52.3 years, median time of HIV infection 18.9 years, 13.6% with documented pre-existing NRTI RAMs. At 96 weeks of follow-up in the ITT and PP analysis, HIV-RNA &amp;lt; 50 copies/mL was seen in 73.1% and 95.4%, respectively. At 144 weeks these figures were 68.2% and 94%, respectively. There were no statistically significant differences between patients with or without previous NRTI RAMs. A total of 140 patients were excluded for the per-protocol analysis at week 144: 46 were lost to follow-up; 32 discontinued treatment due to toxicity; 34 simplified to dual ART therapy, 7 switched for other reasons and 20 patients died (no death was B/F/TAF related). Conclusion Through 3 years of follow-up, switching to B/F/TAF maintained high rates of virological suppression in long-term PWH. These results are seen even in patients with preexisting NRTI RAMS.

Use of doravirine-based regimens in clinical practice in Europe: a real-life retrospective observational study.

We evaluated antiviral effectiveness and safety of doravirine (DOR)-based regimens in people with HIV (PWH) in routine clinical practice. A retrospective, noninterventional study across 16 sites in five European countries [United Kingdom (UK), France, Spain, Belgium, Netherlands]. The study was conducted in both treatment-experienced and treatment-naive PWH who either switched to, or initiated DOR-containing antiretroviral therapy (ART). The primary endpoints were virological success (defined as the percentage of participants with HIV RNA <50 copies/ml, using FDA Snapshot method) and virological failure (FDA Snapshot, HIV RNA ≥50 copies/ml) at 48 weeks after initiation of DOR regimen. Between August 2017 and February 2022, 394 participants were enrolled, 63 naive and 331 treatment-experienced. 75.4% were men, with a median age of 45 years, and 92.2% received DOR in combination with tenofovir disoproxil fumarate and lamivudine or emtricitabine. The proportion of participants with virological success at week 48 after initiation of DOR regimen was 90.6% [95% confidence interval (CI) 87.3-93.3] overall, 87.3% (95% CI 76.5-94.4) in the ART-naive group, and 91.2% (95% CI 87.7-94.1) in the switch group. The proportion of participants with virological failure was 3.3% (95% CI 1.8-5.6) overall, 1.6% (95% CI 0-8.5) in the ART-naive group and 3.6% (95% CI 1.9-6.2) in the switch group. Of the 394 included participants, two (0.5%) were lost to follow-up and 13 (3.3%) discontinued the DOR regimen, four (1%) due to adverse events. Our results show high levels of efficacy and low levels of side effects in DOR-containing regimens in both treatment-naive and treatment-experienced PWH.

Transmission of Dolutegravir resistance in treatment-naive individuals with HIV-1: A cohort study.

Transmission of Dolutegravir resistance in treatment-naive individuals with HIV-1: A cohort study.

'With age comes wisdom': effectiveness and tolerability of dolutegravir + lamivudine in virologically-suppressed people with HIV.

Results from clinical trials and observational studies suggest that dolutegravir plus lamivudine is a well tolerated option for simplification in people with HIV (PWH). We aimed to assess long-time effectiveness and safety in our cohort. We performed an observational study enrolling HIV-1-infected, virologically suppressed PWH, switching to dolutegravir plus lamivudine. Exclusion criteria were HBV-coinfection and the presence of the M184V mutation before the simplification. We performed survival analysis to evaluate time to virological failure (VF, defined by a single HIV-RNA ≥200 copies/ml or by two consecutive HIV-RNA ≥ 50 copies/ml) and treatment discontinuation (TD, defined as the interruption of either 3TC or DTG). Six hundred thirty-one PWH were considered for the analysis: 446 were males (70.7%), with a median age of 51.1 years [interquartile range (IQR) 42.6-57.6]. Estimated probabilities of maintaining virological suppression at 192 and 384 weeks were 95.1% [95% confidence interval (CI) 92.0-96.2] and 91.5% (95% CI 87.1-94.4), respectively. At multivariable analysis, including zenith HIV-RNA, time of virological suppression before switch, risk factors for HIV infection and age, only IDU [versus other risk factors, adjusted hazard ratio (aHR) 3.58, 95% CI 1.38-9.28, P = 0.009] independently predicted VF. A border-line significant association with VF emerged for age (per 10-years more, aHR 0.72, 95% CI 0.51-1.01, P = 0.058) and zenith HIV-RNA >500 000 cps/ml (versus. <500 000 cps/ml, aHR 2.31, 95% CI 0.98-5.46, P = 0.056).As to treatment tolerability, estimated probabilities of remaining on study regimen at 192 and 384 weeks were 87.8% (95% CI 84.5-90.5) and 85.1% (95% CI 81.0-88.5), respectively. Our findings confirm the long-term effectiveness and tolerability of dolutegravir plus lamivudine in virologically suppressed PWH.

Durability of doravirine/dolutegravir dual combination in a multicentre cohort of elderly people with HIV.

Even though the doravirine/dolutegravir combination is not mentioned by guidelines, real-life data has begun to emerge on its use. We aimed to describe the durability of doravirine/dolutegravir in a multicentre Italian cohort of elderly people with HIV (EPWH). We included all EPWH who ever started the doravirine/dolutegravir combination in six Italian centres and were followed up until treatment discontinuation (TD) for any reason (virological failure, death, treatment interruption for other reasons) on 31 March 2024. Descriptive statistics were used to describe the study population; Kaplan-Meier curves and Cox regression analyses were used to estimate incidence and associated predictors of time to TD. We included 157 people; 61.1% were male, the median age was 59 years (IQR: 55-64), 75.2% had multimorbidity, 38.9% were on polypharmacy, and 91.1% had HIV-RNA of <50 copies/mL. No genotype resistance test was available for 19.4% of people who started doravirine/dolutegravir. The main reasons for starting doravirine/dolutegravir were high cardiovascular risk (51.6%), simplification (52.9%) and drug-drug interactions (25.5%). During a median follow-up of 27.85 (IQR: 22.92-31.79) months, 8 (5.1%) participants experienced TD (2 toxicities, 2 virological failures, 2 switches to long-acting drugs, 1 death and 1 transferred). The incidence of TD was 2.27 per 100 person-years of follow-up. Multivariable Cox regression analyses did not show any factors as predictors of TD. In this multicentre cohort of EPWH with clinical complexity, the doravirine/dolutegravir combination showed good durability over time. TD probability was very low, and no significant factors seem to predict it, likely due to the limited number and heterogeneity of cases of TD.

Predicting antiretroviral medication adherence among substance-using people with HIV: test and extension of the information-motivation-behavioral skills model.

Antiretroviral therapy (ART) is effective in reducing HIV transmission and mortality, yet daily adherence remains a challenge for many people with HIV (PWH). Suboptimal adherence can lead to virological failure and increased mortality, particularly among those with substance use disorders, such as cocaine use disorder (CUD). The Information-Motivation-Behavioral (IMB) skills model offers a framework to understand and enhance ART adherence by addressing individual and social barriers. In this study, we tested the IMB skills model among 80 cocaine-using PWH currently on ART, and found that behavioral skills significantly predicted adherence. In the extension of the IMB skills model, the addition of practical barriers altered the relationship by showing that motivational barriers such as treatment fatigue and practical barriers significantly affected ART adherence. The findings suggest that for PWH with substance use disorders, addressing practical barriers and motivational factors may be crucial for improving ART adherence, in addition to building behavioral skills.

Development of HIV Drug-Resistance Mutations and Antiretroviral Efficacy Among Vietnamese Patients After Failure of 5-Year First-Line Therapy.

The emergence of drug-resistant mutations in human immunodeficiency virus (HIV) over time presents a challenge to treatment. We describe the development of drug-resistance mutations and ART efficacy reduction in Vietnamese patients with failure of first-line ART during a 5-year period. This is a 5-year observational cohort study with HIV viral loads of patients evaluated annually for 5 years (2017-2022) at the hospitals in Vietnam. Patients with a viral load ≥ 1000 copies/mL were subjected to identifying mutations in reverse transcriptase, protease, and integrase to evaluate HIV resistance and the efficacy of ART. After 5 years of monitoring the HIV load of 2932 patients on ART, 75 (2.56%) patients had concurrent virological failure at all 5 years. In 2017, only 2/75 HIV strains possessed Protease Inhibitor (PI) resistance mutations, while 75/75 HIV strains had both Nucleoside Reverse Transcriptase Inhibitors (NRTIs) and Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) resistance mutations. Only four PI resistance variants were found, while 40 and 32 mutations were resistant to NRTIs and NNRTIs. After 5 years, the number of HIV PI resistance mutations had increased to 14, with 13 new mutations emerging. There were six novel mutations associated with resistance to NRTIs, NNRTIs, and the proportion of preexisting mutations increased from 1.3% to 13.3%. Furthermore, HIV sensitivity to ART decreased from 2.7% to 18.6%. After 5 years, HIV had increased resistance mutations to PIs, NRTIs, and NNRTIs, with PI resistance mutations increasing the most rapidly, and the decrease in HIV sensitivity to PIs was higher than that to NRTIs and NNRTIs.

Drug resistance testing at regimen failure in individuals diagnosed with HIV-1 between 2010 and 2018 in Israel.

Assess virological failures, analyze the results of resistance testing (RET), and investigate factors associated with acquired drug resistance mutations (aDRM). A retrospective longitudinal cohort study. Virological failures (viral load >50 copies/ml) from a cohort of 1130 individuals, diagnosed with HIV-1 in 2010-2018 and followed up until 2020, were included. Demographic, clinical, and virological data were collected. A piecewise exponential additive mixed model was employed to estimate the association of various factors with aDRM. Only 82 individuals had virological failure, 20/82 had multiple virological failures. The majority of virological failures (77%) were men, 48% were Israeli-born,79% were diagnosed in 2010-2014. Only 18% initiated with second-generation integrase-inhibitor (INI) based regimens. Although no baseline differences were identified between those with single and multiple virological failures, the latter had lower CD4+ levels before first virological failure. NRTI M184IV and INI N155H were identified in more than 10% of the cases. In those with additional failures, INI N155H was more prominent in cases with subtype B compared to those with non-B subtypes (P = 0.039). Diagnoses with CD4+ cell count less than 200 cells/μl and AIDS [hazard ratio = 3.46, 95% confidence interval (95% CI): 1.51-7.92, P = 0.003], second-generation INI at the first virological failure (HR = 0.32, 95% CI: 0.11-0.91, P = 0.033), and RET at baseline (hazard ratio = 0.34, 95% CI: 0.13-0.86, P = 0.022) had a significant and persistent relative effect on aDRM. The risk for aDRM is reduced in those who are treated with second-generation INI-based regimens. Diagnosis with low CD4+ cell counts and AIDS is associated with detection of aDRM.

Transient Viremia Among People with HIV Receiving Injectable Cabotegravir Plus Rilpivirine.

Long-acting injectable (LAI) cabotegravir/rilpivirine (CAB/RPV) provides an effective treatment option for people with HIV (PWH). Studies suggest that PWH on LAI CAB/RPV may experience isolated episodes of transient viremia (HIV RNA > 20 copies/mL) defined as virologic blips (VB). The risk factors for VB in PWH receiving LAI CAB/RPV are limited. We aimed to describe a cohort of PWH on LAI CAB/RPV and evaluate risk factors and time to VB following LAI CAB/RPV initiation. We obtained DC Cohort data from PWH who initiated LAI CAB/RPV prior to July 2023 and used Kaplan-Meier curves and Cox proportional hazards models to evaluate the association between participant demographics, HIV clinical factors, and time to VB. Among 98 PWH who initiated LAI CAB/RPV, 9 (9.2%) experienced at least one VB (median HIV RNA = 50 copies/mL; ranges 30-12,000 copies/mL) during a median follow-up period of five months (IQR: 2-10). The median CD4 count among PWH was 754 cells/µL (IQR: 598, 980) at the time of LAI CAB/RPV initiation. Having a high CD4 (≥ 500 cells/μL) at LAI CAB/RPV initiation was significantly associated with a lower hazard for VB when compared to baseline CD4 < 200 cells/µL [hazard ratios (HR): 0.15 [95% confidence intervals (CI): 0.03, 0.77]; aHR: 0.07 (95% CI: 0.01, 0.50); log-rank p = .026]. No other characteristics were significantly associated with time to VB, and no participants experienced virologic failure. Considerations for baseline CD4 may be important when initiating a patient on LAI CAB/RPV, and future studies will help evaluate the VB occurrence and associated factors among PWH.

Virological outcomes and genotypic resistance on dolutegravir-based antiretroviral therapy versus standard of care in children and adolescents: a secondary analysis of the ODYSSEY trial.

Virological outcomes and genotypic resistance on dolutegravir-based antiretroviral therapy versus standard of care in children and adolescents: a secondary analysis of the ODYSSEY trial.

The impact of adherence counseling incorporating a point of care urine tenofovir assay on virologic suppression among individuals failing tenofovir-lamivudine-dolutegravir: A pre-post intervention study.

The impact of adherence counseling incorporating a point of care urine tenofovir assay on virologic suppression among individuals failing tenofovir-lamivudine-dolutegravir: A pre-post intervention study.

Efficacy of dolutegravir plus lamivudine in treatment-naive people living with HIV without baseline drug-resistance testing available (D2ARLING): 48-week results of a phase 4, randomised, open-label, non-inferiority trial.

Efficacy of dolutegravir plus lamivudine in treatment-naive people living with HIV without baseline drug-resistance testing available (D2ARLING): 48-week results of a phase 4, randomised, open-label, non-inferiority trial.

Receipt of long-acting injectable antiretroviral therapy among people with HIV in Southern US states: an assessment using electronic health records and claims data

BackgroundIn January 2021, the United States (US) Food and Drug Administration (FDA) approved the first long-acting injectable antiretroviral therapy (LAI ART) regimen for the treatment of HIV providing an alternative to daily oral regimens. We analyzed electronic health records (EHRs) to provide real-world evidence of demographic and clinical characteristics associated with the receipt of LAI ART among people with HIV (PWH).MethodsLeveraging EHRs from a large clinical research network in the Southern US - OneFlorida + linked with Medicaid (updated to 08/2022) - we identified a cohort of PWH who have been prescribed at least one dose of LAI ART since January 2021 and characterized their demographics, clinical characteristics, and HIV care outcomes.ResultsA total of 233 LAI ART recipients were identified: 56.7% female, 45.1% aged 30 to 44, 51.3% non-Hispanic Black, 78.1% on Medicaid and 4.7% on private insurance. Approximately three-quarters of injections (71.2%) were received within 37 days of the previous dose, and 84.4% were received within 67 days. About 8% of LAI ART recipients did not have optimal care engagement the year before LAI ART initiation; one in five recipients had a diagnosis of alcohol or substance use disorder in lifetime. All achieved viral suppression (< 50 copies/mL) before starting LAI ART. Of a subset of patients with HIV viral load test records, only 1 record of virologic failure (viral load > 200 copies/ml) was observed after the initiation of LAI ART.DiscussionThere has been an increasing trend of LAI ART initiation since approval. People with suboptimal care engagement and with substance use disorder in lifetime were not excluded from LAI ART treatment.

Viral Suppression and HIV Drug Resistance Among Patients on Second-Line Antiretroviral Therapy in Selected Health Facility in Ethiopia.

HIV drug resistance (HIVDR) presents a significant challenge to antiretroviral therapy (ART) success, particularly in resource-limited settings like Ethiopia. This cross-sectional study investigated viral suppression rates and resistance patterns among patients on second-line ART across 28 Ethiopian health facilities. Blood samples collected from 586 participants were analyzed to measure CD4 count and viral load and assess HIVDR in patients experiencing virological failure (VF) (viral load ≥ 1000 copies/mL). Demographic and clinical data were analyzed using logistic regression to identify factors associated with VF. Results showed that 13.82% of participants experienced VF, with 67.57% of genotyped samples exhibiting at least one drug resistance mutation. Resistance to nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), and protease inhibitors (PIs) was detected in 48.64%, 64.86%, and 18.92% of cases, respectively. Dual-class resistance was identified in 48.64% of patients, while triple-class resistance was detected in 18.92%. VF was more likely among students and those with CD4 counts below 200 cells/mm³, but less likely in patients on second-line treatment for 12 months or more. Our findings highlight a substantial HIVDR burden among patients on second-line ART with VF, emphasizing the need for comprehensive HIV care, including adherence support, regular viral load monitoring, and HIVDR testing.