Rates Of Virologic Suppression Research Articles

Effectiveness and safety of dolutegravir plus lamivudine in treating HIV in China, including outcomes of patients coinfected with tuberculosis.

Antiretroviral regimens for human immunodeficiency virus (HIV) infection have continuously evolved; however, antiretrovirals can cause severe adverse reactions. Two-drug regimen therapy can decrease lifetime cumulative drug exposure and long-term toxicities associated with multiple antiretrovirals. The preferred 2-drug regimen constitutes dolutegravir (DTG) and lamivudine (3TC). This study determined the rate of virological suppression and incidence of adverse events at week 48 in treatment-naïve people living with HIV initiated on DTG + 3TC. This was a single-center, retrospective, observational study. Treatment-naïve people aged ≥18 years who received at least 1 DTG + 3TC dose between May 2020 and May 2022 were included. Eighty-nine people living with HIV were enrolled. Twenty-five (28.1%) patients with a DTG + 3TC regimen at baseline were analyzed because of comorbidities, and 48% because of concomitant tuberculosis (TB). Viral suppression at 48 weeks was achieved in 91.67% of patients, and TB was well controlled. At week 48, 84 (94.38%) patients had viral loads < 50 copies/mL, and 21 (91.31%) of the 23 participants with a baseline HIV-1-RNA level ≥ 1 × 105 copies/mL achieved virological success. Fifteen (88.23%) of the 17 participants with a baseline CD4 + cell count of <200 cells/µL achieved virological suppression. The median CD4 + cell count change from baseline was 539.5 cells/µL. No significant changes in triglycerides, low-density lipoprotein cholesterol, weight, or creatinine were observed from baseline to 48 weeks. One patient had severe insomnia at 4 weeks. Our findings support the real-world effectiveness and low metabolic impact of DTG + 3TC. Using DTG + 3TC in patients coinfected with TB and HIV has favorable therapeutic outcomes.

Effectiveness, safety and discontinuation rates of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) in people with HIV using real-world data: a systematic review and meta-analysis.

The use of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) is based on the results of robust clinical trials. To assess the effectiveness and safety of BIC/FTC/TAF in treatment-naïve (TN) and treatment-experienced (TE) people with HIV using available real-world cohort studies. Systematic review and meta-analysis of publications and communications identified via Boolean search in Medline, PubMed and Embase, and conference abstracts reporting retrospective real-world use of BIC/FTC/TAF, published until 31 January 2024. The primary endpoint was the proportion of TN and TE people with HIV with viral load (VL) < 50 copies/mL at 48 weeks while on treatment. Of the 38 identified publications and conference abstracts, for the present analysis we included 12 publications (comprising 792 TN and 6732 TE individuals). For the three publications including 507 TN participants reporting the primary outcome, VL suppression was 97% [95% confidence intervals (CI): 89-100]. For the nine publications including 4946 TE participants reporting the primary outcome, VL suppression was 95% (95% CI: 94-96), with suppression >93% in all studies. Total discontinuations at 48 weeks in TE individuals were 3% (95% CI: 2-5), 1% (95% CI: 0-2) due to side effects. A total of four publications with 151 TE individuals with previous presence of M184V substitution were identified, reporting a suppression rate at 48 weeks of 95% (95% CI: 88-100). Real-world studies demonstrate low discontinuation rates and high rates of virologic suppression in individuals treated with BIC/FTC/TAF, both TN and TE with and without previous detection of M184V substitution.

Effect of dolutegravir on ferritin, iron, and C-reactive protein among people living with HIV and co-infections.

Dolutegravir-based antiretroviral therapy (ART) is currently recommended as the preferred first-line ART in many resource-limited settings. However, little is known about the clinical experience of dolutegravir within a context of prevalent co-infections. To assess virological outcomes, and iron, ferritin and C-reactive protein (CRP) levels among people living with HIV (PLWH) and co-infections after initiating or re-initiating dolutegravir-based ART. This prospective study was conducted between August 2022 and August 2023. Study participants were recruited from an HIV opportunistic infection clinic. Screening for co-infections (syphilis, hepatitis B virus, cytomegalovirus and herpes simplex virus) was performed at baseline, prior to ART initiation. Plasma HIV viral load (VL), CRP, ferritin and iron levels were measured at baseline and at the 6-month follow-up period. A total of 100 participants (51 women and 49 men) were enrolled in this study. The median age of the participants was 39 years. The prevalence of co-infections was 30%. Prior to ART initiation, participants with co-infections had higher VL, CRP and ferritin, and lower iron levels, compared to those without co-infections (P < 0.001). Following 6 months of ART, CRP and ferritin levels decreased while iron levels increased, regardless of co-infection status. However, CRP and ferritin remained significantly higher in those with co-infections despite similar and high rates of virologic suppression in both groups. The presence of co-infections in PLWH is associated with higher VL and with chronic inflammation. Ferritin and CRP decreased on dolutegravir-based ART but remained higher in people with co-infections despite similar rates of virologic suppression.

HIV-1 Resistance Analysis of Participants With HIV-1 and Hepatitis B Initiating Therapy With Bictegravir/Emtricitabine/Tenofovir Alafenamide or Dolutegravir Plus Emtricitabine/Tenofovir Disoproxil Fumarate: A Subanalysis of ALLIANCE Data

Background: In the Phase 3 ALLIANCE study, both bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) and dolutegravir plus emtricitabine/tenofovir disoproxil fumarate (DTG + F/TDF) achieved high rates of HIV-1 RNA suppression through Week 96 in adults with HIV-1 and hepatitis B virus (HBV) initiating treatment (NCT03547908). Here, we quantify preexisting HIV-1 resistance, evaluate its effect on HIV-1 virologic suppression, and describe postbaseline HIV-1 resistance through Week 96. Methods: Preexisting HIV-1 resistance was assessed by historical and/or screening genotyping. HIV-1 RNA suppression to &lt;50 copies (c)/mL at Week 96 was assessed by preexisting resistance category. Postbaseline resistance was assessed in participants with HIV-1 RNA ≥200 c/mL through Week 96. Results: Primary nucleoside/nucleotide reverse transcriptase inhibitor, non-nucleoside reverse transcriptase inhibitor, and protease inhibitor resistance substitutions were present at baseline in 4 (1.7%), 19 (7.9%), and 5 (2.1%) of 241 participants, respectively. Virologic suppression rates were high, irrespective of preexisting primary resistance substitutions, including M184I. Six participants (3 per group) had confirmed HIV-1 RNA ≥200 c/mL and did not resuppress to &lt;50 c/mL while on study drugs; none of the 5 with postbaseline resistance data had treatment-emergent primary resistance substitutions. One participant on DTG + F/TDF with multiple virologic failures and documented nonadherence by pill count had treatment-emergent K70E and M184V/I, and subsequently resuppressed. Conclusion: In people with HIV-1 and HBV treated with first-line B/F/TAF or DTG + F/TDF, preexisting HIV-1 resistance was uncommon and did not affect virologic suppression. No treatment-emergent HIV-1 resistance occurred with B/F/TAF, further supporting the high barrier to resistance of this regimen.

Clinical benefits of novel non-nucleoside reverse transcriptase inhibitors: A prospective cohort study.

The efficacy and safety of ainuovirine+lamivudine+tenofovir (ANV+3TC+TDF) and efavirenz+lamivudine+tenofovir (EFV+3TC+TDF) have been confirmed in previous clinical trials; however, there are no related studies on patient-reported outcomes. This study aimed to evaluate the effectiveness and safety of these 2 antiretroviral therapy regimens and to understand the patient's symptom experience and subjective experience of sleep quality through patient-reported outcomes. This is a single-center prospective cohort study with 243 patients evaluated from October 1, 2021 to June 30, 2022. Virological effectiveness and patient-reported outcomes results were analyzed. The primary endpoint was the proportion of HIV viral load <50 copies/mL (virological suppression rate) at 48 weeks and the changes in the HIV symptom index and Pittsburgh sleep quality index. The virological suppression rates in the ANV+3TC+TDF and EFV+3TC+TDF groups were 83.6% (102/122) and 87.6% (106/121), respectively, at 48 weeks. In the ANV+3TC+TDF group, the scores of HIV symptom index and pittsburgh sleep quality index in the 48th week were lower than the baseline level (p < 0.05). Logistic regression results showed that the baseline regimen EFV+3TC+TDF was a risk factor for dizziness/lightheadedness (odds ratio = 3.153, 95% confidence interval: 1.473-6.748, p = 0.003), sadness/depression odds ratio = 2.404, 95% confidence interval:1.188-4.871, p = 0.015), and difficulty sleeping (odds ratio = 2.802, 95% confidence interval: 1.437-5.463, p = 0.002) at 48 weeks. Both regimens showed good virological effectiveness; however, compared with ANV+3TC+TDF, the EFV+3TC+TDF regimen reduced the prevalence of HIV-related symptoms.

Reasons, Efficacy and Safety of Switching to Dolutegravir-Based Regimens Among Virologically Suppressed PLWH: A Retrospective Cohort Study of 96 Weeks.

The study aimed to explore the reasons, efficacy, and safety of switching to dolutegravir (DTG) based regimens in virologically suppressed people living with HIV (PLWH) in tertiary hospitals in China. Therefore, the study could provide a valuable reference for the rational clinical use of DTG. PLWH's basic information, treatment details, and reasons for switching were collected, through the electrical clinical medical record system and telephone follow-up. Data included the proportion of PLWH with HIV RNA <50 copies/mL, changes in immunological indicators, and metabolic metrics at week 48 and week 96. 319 PLWH were included in the analysis. The three major reasons for switching were neurological toxicity (16.30%), simplification (13.79%), and renal toxicity (11.29%). Our study showed high rates of virologic suppression in the per-protocol analysis (week 48: 99.69%; week 96: 99.29%) after switching to DTG-based regimens. The median CD4+ T cell count increased from 579 cells/μL (IQR 420.5-758) to 642 cells/μL (IQR 466.5-854) at week 96 (p<0.0001). An improvement was observed in liver function (ALT: p<0.0001; AST: p<0.0001) and fasting glucose (p<0.0001). However, there was an elevation in creatinine (Cr) (p<0.0001) and a slight decrease in the estimated glomerular filtration rate (eGFR) (p<0.0001). Regarding lipid profile, triglyceride (TG) levels declined, while total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels increased. Further analysis revealed that the increase in TC and LDL-C was associated with the withdrawal of tenofovir disoproxil fumarate (TDF). This observed increase in lipid parameters only concerned the PLWH who switched from a TDF-containing regimen to a non-TDF regimen. This study confirmed the virologic efficacy of switching to DTG-based regimens in virologically suppressed PLWH over a 96-week period. The findings also expanded the evidence of immune reconstitution and metabolic safety associated with this switch.

Case Series of People With HIV on the Long-Acting Combination of Lenacapavir and Cabotegravir: Call for a Trial.

Injectable cabotegravir (CAB)/rilpivirine (RPV) is the only combination long-acting (LA) antiretroviral regimen approved for HIV. RPV may not be effective among individuals with non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance, which has >10% prevalence in many countries. Lenacapavir (LEN) is an LA capsid inhibitor given every 6 months, but has not been studied in combination with other LA agents. We assembled a case series from 4 US academic medical centers where patients with adherence challenges were prescribed LEN subcutaneously every 26 weeks/CAB (+/- RPV) intramuscularly every 4 or 8 weeks. Descriptive statistics, including viral load (VL) outcomes, were summarized. All patients (n = 34: 76% male; 24% cis/trans female; 41% Black; 38% Latino/a; median age [range], 47 [28-75] years; 29% and 71% on CAB every 4 or 8 weeks) reported challenges adhering to oral ART. The reasons for using LEN/CAB with or without RPV were documented or suspected NNRTI mutations (n = 21, 59%), integrase mutations (n = 5, 15%), high VL (n = 6, 18%), or continued viremia on CAB/RPV alone (n = 4, 12%). Injection site reactions on LA LEN were reported in 44% (32% grade I, 12% grade 2). All patients but 2 (32/34; 94%) were suppressed (VL <75 copies/mL) after starting LEN at a median (range) of 8 (4-16) weeks, with 16/34 (47%) suppressed at baseline. In this case series of 34 patients on LEN/CAB, high rates of virologic suppression (94%) were observed. Reasons for using LEN/CAB included adherence challenges and underlying resistance, mostly to NNRTIs. These data support a clinical trial of LEN/CAB among persons with NNRTI resistance.

Advances in discovery of novel investigational agents for functional cure of chronic hepatitis B: A comprehensive review of phases II and III therapeutic agents.

Chronic hepatitis B virus (HBV) infection affects over 295 million people globally and an estimated 1.6 million people in the United States. It is associated with significant morbidity and mortality due to cirrhosis, liver failure, and liver cancer. Antiviral therapy with oral nucleos(t)ide analogues is associated with high rates of virologic suppression, which in turn has been associated with a decreased risk of liver complications. However, current antiviral regimens are limited by concerns with adverse effects, adherence, resistance, long-term treatment, and ongoing risk for liver events. Novel investigational agents are currently in development and are targeted at achieving functional cure with sustained hepatitis B surface antigen (HBsAg) loss and suppression of HBV DNA. Herein we review key evidence from phases II and III trials defining the efficacy and safety profiles for key investigational agents for functional cure of chronic hepatitis B, including core/capsid inhibitors, entry inhibitors, RNA interference (siRNA/ASO), HBsAg inhibitors, Toll-like receptor agonists, checkpoint inhibitors, and therapeutic vaccines.

Efficacy and safety of switching to dolutegravir/lamivudine in virologically suppressed people with HIV-1 aged ≥ 50 years: week 48 pooled results from the TANGO and SALSA studies

BackgroundAs the population of people with HIV ages, concerns over managing age-related comorbidities, polypharmacy, immune recovery, and drug-drug interactions while maintaining viral suppression have arisen. We present pooled TANGO and SALSA efficacy and safety results dichotomized by age (< 50 and ≥ 50 years).MethodsWeek 48 data from the open-label phase 3 TANGO and SALSA trials evaluating switch to once-daily dolutegravir/lamivudine (DTG/3TC) fixed-dose combination vs continuing current antiretroviral regimen (CAR) were pooled. Proportions of participants with HIV-1 RNA ≥ 50 and < 50 copies/mL (Snapshot, intention-to-treat exposed) and safety were analyzed by age category. Adjusted mean change from baseline in CD4 + cell count was assessed using mixed-models repeated-measures analysis.ResultsOf 1234 participants, 80% of whom were male, 29% were aged ≥ 50 years. Among those aged ≥ 50 years, 1/177 (< 1%) DTG/3TC participant and 3/187 (2%) CAR participants had HIV-1 RNA ≥ 50 copies/mL at 48 weeks; proportions with HIV-1 RNA < 50 copies/mL were high in both treatment groups (≥ 92%), consistent with overall efficacy and similar to observations in participants aged < 50 years (≥ 93%). Regardless of age category, CD4 + cell count increased or was maintained from baseline with DTG/3TC. Change from baseline in CD4 + /CD8 + ratio was similar across age groups and between treatment groups. One CAR participant aged < 50 years had confirmed virologic withdrawal, but no resistance was detected. In the DTG/3TC group, incidence of adverse events (AEs) was similar across age groups. Proportions of AEs leading to withdrawal were low and comparable between age groups. Although drug-related AEs were generally low, across age groups, drug-related AEs were more frequent in participants who switched to DTG/3TC compared with those who continued CAR. While few serious AEs were observed in both treatment groups, more were reported in participants aged ≥ 50 years vs < 50 years.ConclusionsAmong individuals with HIV-1, switching to DTG/3TC maintained high rates of virologic suppression and demonstrated a favorable safety profile, including in those aged ≥ 50 years despite higher prevalence of concomitant medication use and comorbidities.Trial registration number: TANGO, NCT03446573 (February 27, 2018); SALSA, NCT04021290 (July 16, 2019).

Virological Suppression and its Predictors Among HIV/AIDS Patients on Antiretroviral Therapy in Ethiopia: Systematic Review and Meta-analysis.

Achieving viral load suppression is crucial for the prevention of complications and deaths related to HIV infection. Ethiopia has embraced the worldwide 95-95-95 target, but there is no national representative information regarding virological suppression. Therefore, this review aims to determine the pooled virological suppression rate and identify the pooled effect of contributing factors of viral suppression for HIV-positive patients on antiretroviral therapy in Ethiopia. We systematically searched websites and databases, including online repositories, to obtain primary studies. Two reviewers assessed the quality of the included articles using the Newcastle-Ottawa Scale appraisal checklist. Publication bias was checked using Egger's regression test, the heterogeneity of the studies was assessed using I2 statistics and Q statistics, and a sensitivity analysis was performed to identify any outlier results in the included studies. The Der Simonian Laird random-effects model was used to estimate the overall proportion of viral suppression, and STATA 17 statistical software was used for all types of analysis. A total of 21 eligible articles primarily conducted in Ethiopia using HIV program data were used for this quantitative synthesis. The overall pooled virological suppression rate was 71% (95% CI, 64%-77%). The pooled effects of poor adherence to ART (adjusted odds ratio [AOR], 0.33; 95% CI, 0.28-0.40), body mass index (18.5-24.9 kg/m2; AOR, 1.8; 95% CI, 1.37-2.36), disclosure (AOR, 1.41; 95% CI, 1.05-1.89), absence of opportunistic infection (AOR, 1.68; 95% CI, 1.43-1.97), and high baseline viral load count (AOR, 0.65; 95% CI, 0.52-0.81) were identified as significant predictors of viral suppression. The overall pooled percentage of virological suppression was low compared with the global target of viral suppression and the Ethiopian Public Health Institute report. Poor adherence, normal body mass index, disclosure, absence of opportunistic infection, and high baseline viral load count were factors contributing to viral suppression in Ethiopia. Responsible stakeholders should maximize their efforts to achieve the global target of virological suppression by addressing significant predictors.

Outcomes of severely ill patients with AIDS treated with efavirenz or dolutegravir: a multicenter, observational study.

Currently, integrase inhibitors (INIs)-based ART regimens are the preferred initial therapy for AIDS patients. There is scarce information on the use of dolutegravir (DTG) among late-presenter people living with HIV (PLHIV). To compare the effect of DTG- or efavirenz (EFV)-based regimens on the outcomes of patients with advanced AIDS. We compared two cohorts of consecutive symptomatic AIDS patients (WHO stage 4, CD4 count<50 cells/mL) starting therapy with DTG-based (2018-2021, prospective cohort) or EFV-based regimens (2013-2016, retrospective cohort) from five Brazilian cities. The main endpoints were early (all-cause) mortality, viral suppression at 24 and 48 weeks, changes in CD4 count, and changes in initial therapy (for any reason). We included all eligible patients in a consecutive way (in both groups) until we reached 92 individuals per arm. The median baseline CD4 count (20 vs. 21 cells/mL) and the median HIV plasma viral load (5.5 copies/mL log10) were identical across the groups. Viral suppression rates were higher in the DTG group than in the EFV group at 24 (67.4% vs. 42.4%,) and 48 weeks (65.2% vs. 45.7%, p < 0.001 for both comparisons). More patients in the DTG group presented with CD4 > 200 cells/mL compared to the EFV group at 48 weeks (45% vs. 29%, p = 0.03). Treatment changes (ITT, M = F) were significantly more frequent in the EFV group (1% vs. 17%, p < 0.0001). The relative mortality rate was 25% lower in the DTG group, but without statistical significance. We detected a higher rate of virological suppression and greater treatment durability in patients with advanced AIDS treated with DTG than in those treated with EFV.

Dolutegravir based therapy showed CD4+ T cell count recovery and viral load suppression among ART naïve people living with HIV AIDS: a pilot evaluation

Recently, dolutegravir (DTG)-based combined therapy, a more effective and safer first-line antiretroviral therapy (ART), has been recommended by the World Health Organization for the treatment of Human Immunodeficiency Virus (HIV) since July 2018. However, its effectiveness in CD4+ T-cells count recovery and viral load suppression has not been studied yet in Ethiopia, where HIV is endemic. Therefore, we aimed to conduct a pilot assessment on the effect of DTG-based therapy on CD4+ T-cell count and viral load count among people living with HIV (PLWH) in Ethiopia. A longitudinal prospective cohort study was conducted from July 2020 to February 2021. 109 PLWH who are ART naive but plan to initiate DTG-based therapy were recruited. HIV viral ribonucleic acid (RNA) copies were determined using polymerase chain reaction. To compute the difference in viral load and CD4+ T-cell counts between the baseline, 3rd, and 6th months, a Friedman test was used. The study included 109 PLWH who had never received antiretroviral medication. Participants taking DTG-based treatment showed significantly decreasing median (IQR) values of viral load count (copies/mL) from 446,812 (237649.5–732994.5) at baseline to 34 (23.5–46) at 3 months and 0.0 (0–19) at 6 months of treatment follow-up. Although the treatment increases the proportion of participants with HIV-1 RNA 50 copies/mL from 0 (0% at baseline) to 87 (79.8%) and 100 (91.7%) at the 3rd and 6th months of treatment, respectively, On the other hand, the CD4+ T-cell count increased significantly during treatment: median (IQR): 209 (81.5–417.5) versus 291 (132–522) versus 378 (181–632.5) cells/L at baseline, the 3rd and 6th months of the treatment follow-up period, respectively. We found dolutegravir-based therapy was a promising option with high virological suppression rates and CD4+ T-cell count recovery, demonstrating a restoration of cellular immunity. Moreover, Viral load suppression rates were high after the initiation of the treatment. We recommend further research should be conducted with a larger number of participants to acquire greater awareness of the treatment outcomes.

The Acceptability, Feasibility, and Preliminary Effectiveness of a Courier HIV-Treatment Delivery and SMS Support Intervention for Young People Living With HIV in South Africa.

Young people living with HIV (YPLWH) experience poorer rates of virological suppression compared with adults. Differentiated service delivery models for YPLWH are urgently needed to address this disparity. Participants were recruited from an HIV treatment clinic near Cape Town, South Africa. We conducted a longitudinal pilot study to examine the acceptability, feasibility, and preliminary effectiveness of a courier ART delivery and SMS support intervention to retain YPLWH (13-24 years) in care during COVID-19. YPLWH had the option to enroll in the courier service and were randomized 1:1 to receive adherence support via a weekly SMS. Modified Poisson regression was used to estimate the preliminary effectiveness of the courier intervention on viral suppression (HIV-1 RNA <200 copies/mL) at months 3 and 6. Among 215 participants, 82% elected to enroll in the courier ART service at baseline, 41% reported receiving a delivery in the past 3 months at month 3, and 49% reported receiving a delivery in the past 3 months at month 6. Among those who received a delivery, most (91%-100%) rated the intervention as acceptable. Participants who reported receiving a delivery in the past 3 months at month 3 were 1.26 (95% CI: 1.05, 1.54) times as likely to have a suppressed viral load at month 3 and 1.21 (0.99, 1.48) times as likely at month 6, controlling for potential confounders. Findings reveal high uptake and acceptability of a courier ART delivery intervention among YPLWH and promising evidence for its effectiveness in increasing the probability of viral suppression. A fully powered trial is warranted.

A Phase-IV Non-interventional Study to Assess Virological Effectiveness, Safety, and Tolerability of DTG-based Antiretroviral Therapy in HIV-1 Infected Indian Persons Living with HIV.

Dolutegravir (DTG) is a novel yet preferential first- and -second-line treatment for persons living with HIV (PLH). Owing to its recent introduction, DTG-based regimens have not undergone a comprehensive, systematic evaluation regarding their real-world utilization and safety profile among a sizeable Indian population. This study aimed to assess the 24 week immunovirological outcomes, anthropometric and metabolic changes, tolerability, and adverse events (AEs) of DTG-based antiretroviral (ART) regimens. A single-centre phase-IV non-interventional observational study involving 322 ART naïve and treatment-experienced PLH initiating DTG-based-regimens until October 2022 were followed up for outcomes at 24 weeks. At 24 weeks, all PLH (n = 113) in the naïve group, all PLH (n = 67) in the first-line substitution group, 93.9% PLH (n = 46) in the first-line failure group, and 95.7% PLH (n = 89) in the second-line substitution group were virologically suppressed to plasma HIV-RNA <1000 copies/mL. Virological suppression rates to plasma HIV-RNA <200 copies/mL and <50 copies/mL were consistent among PLH who received DTG as first- or second-line ART. The mean-unadjusted weight gain observed was 3.5 kg (SE: 0.330), and it was significantly higher in PLH with poorer health at baseline (either HIV-RNA ≥ 1000 copies/ml or CD4 cell count <350 cells/μL). Overall, 27.3% PLH (n = 88) gained ≥10% of their baseline body weight, corresponding to 3.7% incidence (n = 12) of treatment-emergent clinical obesity. DTG had an overall lipid-neutral effect, with an advantageous effect being observed in PLH switching from non-nucleoside analogue reverse-transcriptase inhibitors (NNRTI) or ritonavir-boosted protease inhibitors (b/PI), especially in dyslipidemic pre-treated PLH (median change in total cholesterol: 28.5 mg/dL and triglycerides: 51 mg/dL), possibly emanating from the withdrawal of the offending ART. The incidence of DTG-specific AEs, including CNS AEs, was low. Two PLH developed proximal myopathy and one developed transaminitis, warranting DTG discontinuation. Asymptomatic serum-CPK elevation and drug-induced transaminitis were seen in 25.2% (n = 27) and 3.2% (n = 10) PLH, respectively. No apparent negative effects on renal function were detected. Our results from a large Indian cohort indicate a favourable virological and metabolic response, with good tolerance of DTG-based ART at 24 weeks.

Efficacy and safety of bictegravir/emtricitabine/tenofovir alafenamide fumarate for adult patients with human immunodeficiency virus-1 in China: a retrospective real-world cohort study

ABSTRACT Background This study aimed to evaluate the therapeutic effect and tolerance of bictegravir/emtricitabine/tenofovir alafenamide fumarate (BIC/FTC/TAF) use for 24 weeks in anti-retroviral therapy (ART)-naïve patients in China. Methods This single-center retrospective cohort study included ART-naïve patients who received BIC/FTC/TAF from July 2021 to April 2022. The proportion of patients with HIV RNA < 50 copies/mL at the end point of 24 weeks (virological suppression rate) was the primary outcome, and the changes in CD4 cell count, CD4/CD8 ratio, weight, blood lipid, and safety were secondary outcomes. Results A total of 80 ART-naïve patients were enrolled. The virological suppression rate was 86.3% at 24 weeks. The median CD4 cell count increased from 212 cells/μL (interquartile range [IQR]: 90.3–398.3) at baseline to 348 cells/μL (IQR: 219.8–541.0) at 24 weeks. The median CD4/CD8 ratio increased from 0.25 (IQR: 0.13–0.37) at baseline to 0.40 (IQR: 0.26–0.66) at 24 weeks. During the follow-up of 80 ART-naïve patients using BIC/FTC/TAF, 16 participants had adverse events; however, these events did not lead to drug withdrawal. Conclusion This real-world cohort study showed that BIC/FTC/TAF could achieve good immunological and virological responses in ART-naïve patients. In addition, this study also shows good safety.

1575. Comparison of virologic suppression rates pre-, intra- and postpartum in women with HIV in an underserved US community

Abstract Background Antiretroviral therapy (ART) has significantly reduced mother-to-child transmission of HIV among pregnant women. Nonetheless, numerous factors can impede ART adherence and thus virologic suppression (HIV RNA &amp;lt; 200 copies/mL). Although there are limited data on current rates of virologic control in women with HIV around pregnancy, previous studies have highlighted lower rates at the start of pregnancy and 6 months postpartum. The objective of this study was to compare virologic suppression rates in women pre-pregnancy, intrapartum, and postpartum at a clinic serving a marginalized community and to identify factors associated with virologic control Methods This study was a single-center, retrospective chart review including pregnant patients receiving care at a hospital-based, NJ Ryan-White funded clinic between 2015-2022. The primary endpoint was to determine whether there is a difference in the proportion of patients with virologic suppression at the start of pregnancy, at delivery, and 6 months postpartum Results At the first visit, 64.4% of mothers were virologically suppressed. Our study found that the proportion of women remaining virologically suppressed was lower at 6 months postpartum compared to the time of delivery (82.2% versus 90.4%, p=0.017), regardless of virologic suppression at the first visit. Older age at pregnancy was associated with improved virologic suppression at 6 months postpartum (OR 1.13, 95% CI 1.01-1.27). However, perinatal HIV acquisition, as compared to heterosexual acquisition, was correlated with increased virologic failure at 6 months postpartum (OR 5.4, 95% CI 1.42-20.08). Conclusion Although a high percentage of patients were controlled at delivery, the drop in virologic suppression postpartum highlights the need for additional efforts to support the mother and child during that time. While further research is warranted to identify further confounders that may impact virologic control and other barriers to care, the healthcare team should work together holistically on frequent outreach and follow up during the entire pregnancy. Disclosures All Authors: No reported disclosures

A comparison of clinical outcomes among people living with HIV of different age groups attending queen Elizabeth central hospital outpatient ART Clinic in Malawi.

Adherence to Antiretroviral Treatment (ART) in children and adolescents living with HIV in low-resource settings is not extensively studied in large cohort studies including both adults and pediatric patients. We compared rates of virological suppression, adherence and defaulting among children, adolescents and adults attending a family ART clinic at Queen Elizabeth Central Hospital; a tertiary hospital situated in the southern region of Malawi. The study was longitudinal and made use of routinely collected data for all 27,229 clinic attendees. Clinical information obtained at routine clinical visits entered electronically since 2008 was extracted in February 2017. This data was used to ascertain differences across the different age groups. Logistic regression and Cox regression models were fitted to compare rates of Virological Suppression (VS), adherence, and defaulting, respectively. Younger and older adolescents (ages 10-14 years and 15-19 years respectively) were less likely to achieve VS compared to adults in the final model AOR 0.4 (0.2-0.9, 95% CI) and AOR 0.2 (0.1-0.4, 95% CI) respectively. Young children (ages 0-4 years), older children (ages 5-9 years) and younger adolescents were less adherent to ART compared to adults AOR 0.1 (0.1-0.2, 95% CI), AOR 0.2 (0.1-0.3, 95% CI), and AOR 0.4 (0.3-0.5, 95% CI) respectively. Young adults and younger children had an increased likelihood of defaulting compared to adults. Poor performance on ART of children and adolescents highlights unaddressed challenges to adherence. Ongoing research to explore these potential barriers and possible interventions needs to be carried out. The adherence assessment methods used and strategies for improving it among children and adolescents need to be revised at the clinic.

Retrospective longitudinal analysis of low-level viremia among HIV-1 infected adults on antiretroviral therapy in Kenya

HIV low-level viremia (LLV) (51-999 copies/mL) can progress to treatment failure and increase potential for drug resistance. We analyzed retrospective longitudinal data from people living with HIV (PLHIV) on antiretroviral therapy (ART) in Kenya to understand LLV prevalence and virologic outcomes. We calculated rates of virologic suppression (≤50 copies/mL), LLV (51-999 copies/mL), virologic non-suppression (≥1000 copies/mL), and virologic failure (≥2 consecutive virologic non-suppression results) among PLHIV aged 15 years and older who received at least 24 weeks of ART during 2015-2021. We analyzed risk for virologic non-suppression and virologic failure using time-dependent models (each viral load (VL) <1000 copies/mL used to predict the next VL). Of 793,902 patients with at least one VL, 18.5% had LLV (51-199 cp/mL 11.1%; 200-399 cp/mL 4.0%; and 400-999 cp/mL 3.4%) and 9.2% had virologic non-suppression at initial result. Among all VLs performed, 26.4% were LLV. Among patients with initial LLV, 13.3% and 2.4% progressed to virologic non-suppression and virologic failure, respectively. Compared to virologic suppression (≤50 copies/mL), LLV was associated with increased risk of virologic non-suppression (adjusted relative risk [aRR] 2.43) and virologic failure (aRR 3.86). Risk of virologic failure increased with LLV range (aRR 2.17 with 51-199 copies/mL, aRR 3.98 with 200-399 copies/mL and aRR 7.99 with 400-999 copies/mL). Compared to patients who never received dolutegravir (DTG), patients who initiated DTG had lower risk of virologic non-suppression (aRR 0.60) and virologic failure (aRR 0.51); similarly, patients who transitioned to DTG had lower risk of virologic non-suppression (aRR 0.58) and virologic failure (aRR 0.35) for the same LLV range. Approximately a quarter of patients experienced LLV and had increased risk of virologic non-suppression and failure. Lowering the threshold to define virologic suppression from <1000 to <50 copies/mL to allow for earlier interventions along with universal uptake of DTG may improve individual and program outcomes and progress towards achieving HIV epidemic control. No specific funding was received for the analysis. HIV program support was provided by the President's Emergency Plan for AIDS Relief (PEPFAR) through the United States Centers for Disease Control and Prevention (CDC).

Efficacy and safety of the novel capsid inhibitor lenacapavir to treat multidrug-resistant HIV: week 52 results of a phase 2/3 trial

Lenacapavir, a first-in-class HIV-1 capsid inhibitor, is in development as a long-acting agent for treating and preventing HIV-1. We aimed to evaluate the efficacy and safety of lenacapavir with an optimised background regimen in adults living with multidrug-resistant HIV-1 up to 52 weeks. This ongoing, international, phase 2/3 trial at 42 sites included adults living with multidrug-resistant HIV-1. In cohort 1, 36 participants were randomly assigned (2:1) to add oral lenacapavir (600 mg, days 1 and 2; 300 mg, day 8) or placebo to an existing failing regimen. At day 15, those on oral lenacapavir received subcutaneous lenacapavir 927 mg every 26 weeks; those on placebo started lenacapavir (2-week oral lead-in then subcutaneous). Cohort 1 started an optimised background regimen on day 15. In cohort 2 (non-randomised), 36 participants started an optimised background regimen concurrent with lenacapavir (oral to subcutaneous). Here we report the secondary endpoints of plasma HIV-1 RNA of less than 50 copies per mL or less than 200 copies per mL at week 52 (US Food and Drug Administration snapshot algorithm) in cohort 1 along with results for cohorts 1 and 2 combined. This trial is registered with ClinicalTrials.gov, NCT04150068, and clinicaltrialregister.eu, EudraCT 2019-003814-16 and is ongoing. Of 72 participants, 46 (64%) had CD4 counts of less than 200 cells per μL and 38 (53%) had no more than one fully active antiretroviral drug at baseline. In cohort 1, 30 of 36 participants (83%, 95% CI 67-94) had less than 50 HIV-1 RNA copies per mL and 31 of 36 participants (86%, 71-95) had less than 200 HIV RNA copies per mL, at week 52. In all, nine participants (four in cohort 1, five in cohort 2) had emergent lenacapavir resistance; four resuppressed (HIV-1 RNA <50 copies per mL) while maintaining lenacapavir use. One participant discontinued study drug owing to injection site reaction. In participants with multidrug-resistant HIV-1, subcutaneous lenacapavir in combination with an optimised background regimen resulted in a high rate of virological suppression up to 52 weeks. Gilead Sciences.

Prevalence of Comorbidities and Polypharmacy in a Historically Minoritized Community and Their Impact on Virologic Suppression in Persons with HIV.

Improved life expectancy from advances in antiretroviral therapy (ART) has been followed by a rise in comorbidities and polypharmacy in this aging population. Historically, polypharmacy has been associated with suboptimal virologic outcomes in persons with HIV, although data in the current ART era and among historically marginalized populations in the United States are limited. We measured the prevalence of comorbidities and polypharmacy, evaluating their impact on virologic suppression. This retrospective IRB-approved cross-sectional study reviewed health records of adults with HIV on ART and receiving care (≥2 visits) in 2019 at a single center in a historically minoritized community. Virologic suppression (HIV RNA <200 copies/mL) based on polypharmacy (≥5 non-HIV medications) or multimorbidity (≥2 chronic conditions) was evaluated. Logistic regression analyses were performed to identify factors associated with virologic suppression, with age, race/ethnicity, and CD4 < 200 cells/mm3 as covariates. Of the 963 individuals that met the criteria, 67%, 47%, and 34% had ≥1 comorbidity, multimorbidity, and polypharmacy, respectively. The cohort demographics were: mean of 49 years (range, 18-81), 40% cisgender women, 46% Latinx individuals, 45% Black individuals, 8% White individuals. Virologic suppression rates were 95% among patients with polypharmacy compared with 86% in those with a lower pill burden (p = 0.0001). The odds of virologic success were higher for individuals with polypharmacy [adjusted odds ratio, aOR = 2.3 (95% confidence interval, CI: 1.2-4.4)] and Latinx identity [aOR = 2.4 (95% CI: 1.5-3.8)], but lower if a CD4 count <200 cells/mm3 [aOR = 0.07 (95% CI: 0.04-0.1)]. The comorbidity burden was higher than previously described, which are driving polypharmacy rates. In the current ART era, polypharmacy is not inherently associated with worse virologic outcomes.