Rate Of Virological Failure Research Articles

Use of long-acting injectable cabotegravir/rilpivirine in people with HIV and adherence challenges.

Recent changes in US Department of Health and Human Services and International AIDS Society USA guidelines now endorse use of long-acting injectable cabotegravir and rilpivirine (LA-CAB/RPV) in people with HIV (PWH) who have adherence challenges, including those with viremia. We sought to summarize clinical trial and real-world study data on outcomes and implementation strategies, highlight key unanswered questions, and provide recommendations for best practices. Studies of LA-CAB/RPV in PWH with adherence challenges demonstrate excellent virologic outcomes, although the rate of virologic failure is higher than that in registrational trials conducted in PWH with stable viral suppression. However, viral suppression is attainable on alternate antiretroviral regimen, including those that employ lenacapavir, another long-acting injectable antiretroviral drug, even after virologic failure on LA-CAB/RPV. Successful implementation strategies for long-acting programs include centralized multidisciplinary clinic teams (ideally with pharmacist/pharmacy technician involvement), small incentives to promote patient retention on injections, allowing for drop-in injections, outreach after late injections, and partnerships with home nursing, street medicine, and harm reduction sites. Creating programs that can support PWH with adherence challenges, their providers, and their clinics to use LA-CAB/RPV in service of sustained viral suppression is an urgent priority, particularly for PWH with CD4+ cell count <200 cells/mm3.

Long-acting antiretroviral therapy in the context of viral suppression.

Long-acting antiretroviral therapy (ART), such as with cabotegravir and rilpivirine, is a new and exciting paradigm shift that could change the face of HIV treatment if it were universally available to all who want it. In countries where there is access, uptake has been slow - partly because of capacity issues and partly because of hesitancy around remaining clinical questions. We summarized clinical trial data and emerging real-world evidence to shed light on these questions. Phase 2b/3/3b clinical trials have shown CAB+RPV injections to be both well tolerated and efficacious. Real-world cohort (RWC) studies with larger numbers of people demonstrate high levels of adherence and persistence, and low rates of virological failure in clinical practice. Although the risk of virological failure in the context of CAB+RPV is low, it remains a pertinent issue because of the high risk of developing two-class resistance. The use of multiple definitions of virological failure in RWC studies currently makes understanding the available evidence difficult and could have deleterious effects on clinical decision-making. Longer term real-world evidence in diverse populations is needed to better understand the durability of CAB+RPV and its suitability in different contexts.

Emergent resistance-associated mutations at first- or second-line HIV-1 virologic failure with second-generation InSTIs in two- and three-drug regimens: the Virostar-1 study.

Second-generation integrase strand transfer inhibitors (InSTIs) have a high barrier to resistance and potent antiretroviral activity. They are recommended as first- or second-line (FL and SL) options in two- and three-drug regimens (2DR and 3DR) in international treatment guidelines. However, there are limited real-world data on emerging resistance at the time of virological failure (VF) with these regimens. The Virostar-1 study objective is to analyse the emergence of resistance-associated mutations (RAMs) over 3 years with DTG-based 2DRs and DTG- or bictegravir (BIC)-based 3DRs in people living with HIV (PLWH) experiencing a VF (FL or SL). Retrospective analysis of genotypic resistance detected at the time of a FL or SL VF with BIC/FTC/TAF, DTG/ABC/3TC, DTG/3TC and DTG/RPV between 2019 and 2022 was conducted from a French multicentre database. VF was defined as two consecutive HIV-1 plasma viral loads > 50 c/mL. Sanger assays were performed at VF within standard clinical care. Resistance mutations were reported using the ANRS algorithm. Selection biases prevent group comparisons. During the period, N = 5986 PLWH were followed either in FL or SL. The VF rate was overall low: BIC/FTC/TAF, 6.8%; DTG/ABC/3TC, 7.5%; DTG/3TC, 5.1%; and DTG/RPV, 2.1%. Some emergent InSTI or NRTI RAMs were detected with BIC/FTC/TAF 4%, DTG/ABC/3TC 8.5%, DTG/3TC 18% and 39% emergent NNRTI RAMs with DTG/RPV. However, a complete absence of dual resistance against NRTIs and InSTIs was observed. We detected rare emergent InSTI RAMs and few emergent NRTI RAMs in PLWH failing DTG- or BIC-based regimens in FL or SL. The observed rates of emergent RAMs at VF were 4% with BIC/FTC/TAF, 8.5% with DTG/ABC/3TC, 18% with DTG/3TC and 39% with DTG/RPV.

Prevalence, rate, and predictors of virologic failure among adult HIV-Infected clients on second-line antiretroviral therapy (ART) in Tanzania (2018–2020): a retrospective cohort study

BackgroundAntiretroviral therapy (ART) has been proven to be highly effective in reducing the impact of human immunodeficiency virus (HIV) infection. However, as more people receive initial ART treatment, the risk of developing resistance and eventual treatment failure increases, leading to the need for second-line treatment regimens. Understanding the factors that contribute to virologic failure to second-line ART is crucial in preventing switching to the more expensive and toxic third-line regimens. This study provides information on the prevalence, rate, and predictors of virologic failure (VF) among clients on second-line ART in Tanzania.ResultsWe followed 4718 clients for 15100 person-years (PY) of observations. Of them, 1402 (29.72%) experienced virologic failure at a rate of 92.85 per 1000 PY of observations (95% CI 88.11, 97.84). Factors that were associated with VF included: having a viral load count of ≥ 1000 copies/mL during first-line ART, with a hazard ratio (HR) 4.65 (95% CI 3.57, 6.07), using lopinavir (LPV/r) as a protease inhibitor during second-line ART (HR 4.20 (95% CI 3.12, 7.10), having a CD4 count < 200 cells/mm3 during second-line ART (HR 1.89 (95% CI 1.46, 2.44), and being on ART for 13–35 months (HR 8.22 (95% CI 2.21, 30.61). Paradoxically, having a CD4 count < 200 cells/mm3 during first-line ART treatment was associated with a reduced risk of virologic failure (HR 0.77 (95% CI 0.60, 0.99).ConclusionsIn Tanzania, approximately 30% of adult clients on second-line ART experience VF at a rate of 92.71 per 1000 person-years. This high virologic failure rate underscores the urgent need for targeted interventions, such as enhancing adherence support, optimizing drug regimens, and regular viral load monitoring. These interventions will reduce the need for switching to the more costly and toxic third-line ART therapy and are also crucial for achieving the UNAIDS goal of 95% viral suppression among treated individuals by 2030.

People living with HIV co-infected with the Kaposi Sarcoma-associated Herpes Virus have a distinct HIV Tat profile and higher rates of antiretroviral virologic failure, more evident among those with Kaposi's sarcoma.

Kaposi sarcoma (KS) is a neoplasm of vascular origin that promotes angiogenesis and the growth of endothelial cells triggered by the Kaposi Sarcoma-associated Herpes Virus (KSHV). When associated with HIV, KSHV becomes more aggressive and rapidly evolves. The HIV-1 TAT protein can be essential in developing AIDS-associated KS by promoting angiogenesis and increasing KSHV replication. Therefore, we evaluated the genetic profile of the first exon of tat gene among groups of people living with HIV (PLHIV) with (case group, n = 36) or without KS, this later with (positive control group, n = 46) and without KSHV infection (negative control group, n = 24); all individuals under antiretroviral therapy. The genetic diversity, the DN/DS ratio, and the genetic entropy of the first exon of tat were higher in the case group, followed by the positive control group, which was higher than the negative control group. The number of tat codons under positive selection was seven in the case group, six in the positive control group, and one in the negative control group. The prevalence of HIV viral loads below the detection limit was equal in the case and positive control groups, which were lower than in the negative control group. The mean CD4+ T cell counts were higher in the negative control group, followed by the positive control group, and followed by the case group. These results emphasize the negative influence of KSHV in antiretroviral treatment, as well as the HIV-specific TAT profile among PLHIV who developed KS.

Safety and Effectiveness From the Cabotegravir and Rilpivirine Implementation Study in European Locations Study: Phase 3b Hybrid Type III Implementation Study Integrating Cabotegravir + Rilpivirine Long-Acting Into European Clinical Settings.

Cabotegravir + rilpivirine long-acting (CAB + RPV LA) dosed every 2 months (Q2M) is a complete regimen for the maintenance of HIV-1 virologic suppression. In this study, we report month 12 clinical outcomes in patient study participants (PSPs) in the CAB and RPV Implementation Study in European Locations (CARISEL) study. CARISEL is a phase 3b implementation-effectiveness study. CARISEL was designed as a 2-arm, unblinded study with centers randomized to either enhanced or standard implementation arms. For PSPs, this study is single arm, unblinded, and interventional; all PSPs switched from daily oral therapy to CAB + RPV LA dosed Q2M. The primary objective was to evaluate the perceived acceptability, appropriateness, and feasibility of CAB + RPV LA implementation for staff participants (presented separately). Clinical secondary endpoints assessed through month 12 included the proportion of PSPs with plasma HIV-1 RNA ≥50 and <50 copies/mL (Snapshot algorithm), incidence of confirmed virologic failure (CVF; 2 consecutive plasma HIV-1 RNA levels ≥200 copies/mL), adherence to injection visit windows, and safety and tolerability. Four hundred thirty PSPs were enrolled and treated; the mean age was 44 years (30% ≥50 years), 25% were women (sex at birth), and 22% were persons of color. At month 12, 87% (n = 373/430) of PSPs maintained HIV-1 RNA <50 copies/mL, with 0.7% (n = 3/430) having HIV-1 RNA ≥50 copies/mL. One PSP had CVF. The safety profile was consistent with previous findings. Overall, the results were similar between implementation arms. CAB + RPV LA Q2M was well tolerated and highly effective in maintaining virologic suppression with a low rate of virologic failure.

Impact of Human Immunodeficiency Virus Drug Resistance Mutations Detected in Women Prior to Antiretroviral Therapy With Efavirenz + Tenofovir Disoproxil Fumarate + Lamivudine (or Emtricitabine).

Two large studies suggest that resistance mutations to only nonnucleoside reverse transcriptase inhibitors (NNRTI) did not increase the risk of virologic failure during antiretroviral therapy (ART) with efavirenz/tenofovir disoproxil fumarate/lamivudine (or emtricitabine). We retrospectively evaluated a third cohort to determine the impact of NNRTI resistance on the efficacy of efavirenz-based ART. Postpartum women living with human immunodeficiency virus (HIV) were studied if they initiated efavirenz-based ART because of the World Health Organization's recommendation for universal ART. Resistance was detected by Sanger genotyping plasma prior to efavirenz-based ART and at virologic failure (HIV RNA >400 copies/mL). Logistic regression examined relationships between pre-efavirenz genotypes and virologic failure. Pre-efavirenz resistance was detected in 169 of 1223 (13.8%) participants. By month 12 of efavirenz-based ART, 189 of 1233 (15.3%) participants had virologic failure. Rates of virologic failure did not differ by pre-efavirenz NNRTI resistance. However, while pre-efavirenz nucleos(t)ide reverse transcriptase inhibitors (NRTI) and NNRTI resistance was rare (8/1223 [0.7%]) this genotype increased the odds (adjusted odds ratio, 11.2 [95% confidence interval, 2.21-72.2]) of virologic failure during efavirenz-based ART. Age, time interval between last viremic visit and efavirenz initiation, clinical site, viremia at delivery, hepatitis B virus coinfection, and antepartum regimen were also associated with virologic failure. Resistance to NNRTI alone was prevalent and dual-class (NRTI and NNRTI) resistance was rare in this cohort, with only the latter associated with virologic failure. This confirms others' findings that, if needed, efavirenz-based ART offers most people an effective alternative to dolutegravir-based ART.

Multicentre service evaluation of injectable cabotegravir and rilpivirine delivery and outcomes across 12 UK clinics (SHARE LAI-net).

Long-acting injectable cabotegravir + rilpivirine (CAB + RPV LAI) was approved for use in virally suppressed adults in the England and Wales national health service in November 2021. We describe a service evaluation of delivery processes and outcomes in 12 clinics. Centres populated a database using information from local policies and clinical records. Services were asked to describe approval processes, clinic pathways, and adherence to national guidelines. Additional data were collected on reasons for regimen choice, treatment discontinuations, and management of viraemia. In total, 518 adults from 12 clinics were approved for CAB + RPV LAI between February 2022 and December 2023. Of the 518 people approved for CAB + RPV LAI, 423 received at least one injection. Median duration on CAB + RPV was 7.5 months (interquartile range 3.7-11.3). In total, 97% of injections were administered within the ±7-day window. Virological failure occurred in 0.7%, and 6% discontinued CAB + RPV. In this large UK-based cohort, robust approval processes and clinic protocols facilitated on-time injections and low rates of both discontinuation and virological failure.

Transition times across the HIV care continuum in Spain from 2005 to 2022: a longitudinal cohort study

Ending AIDS by 2030 requires improvements across all stages of the HIV care continuum. We used a longitudinal approach to assess changes in the HIV care continuum in Spain and transition probabilities across different stages. We used data from the prospective Cohort of the Spanish HIV/AIDS Research Network to analyse the time from diagnosis to linkage to care, linkage to care to antiretroviral therapy (ART), and ART to viral suppression in five calendar periods defined by milestones in ART, from 2005 to 2022. We used the Kaplan-Meier method and Cox proportional hazard models to estimate cumulative probabilities of stage transition within 1, 3, 6, and 12 months of stage eligibility, by period. We included 18 529 participants. Comparing the initial (2005-09) and final (2020-22) periods, time to linkage to care decreased from a median of 6·0 weeks to 1·3 weeks, time to ART initiation from 15·9 weeks to 0·4 weeks, and time to viral suppression from 13·3 weeks to 7·1 weeks. Adjusted hazard ratios for the comparison between the last period and the initial period were 3·1 (95% CI 2·8-3·4) for linkage to care within 1 month, 11·4 (10·1-12·3) for ART initiation within 1 month, and 2·2 (1·2-2·4) for viral suppression within 3 months. The aggregate proportion of late diagnoses was 38·6%, increasing after 2012 to 46·4% in the 2020-22 period. Same-day ART initiation increased from 18% to 39% from 2005 to 2022. The overall incidence rate of virological failure was 1·05 failures per 1000 person-years and showed a non-significant decline throughout the study. The great improvement in transition times through the HIV care cascade might put Spain on the verge of achieving the UNAIDS targets for HIV elimination. However, late diagnosis remains a challenge that should be addressed. Instituto de Salud Carlos III and Spanish AIDS Research Network.

Effectiveness and safety of glecaprevir/pibrentasvir for 8 weeks in the treatment of patients with acute hepatitis C: A single-arm retrospective study.

No direct-acting antiviral is currently approved for acute HCV infection, delaying treatment. We investigated the effectiveness and safety of 8-week glecaprevir/pibrentasvir (G/P) in patients with acute HCV infection. This noninterventional, single-arm, retrospective chart review was designed to enroll adults/adolescents with acute HCV infection. Analyses were conducted on a full analysis set (FAS; all enrolled) and modified FAS (FAS excluding nonvirologic failures). The primary end point (modified FAS) was sustained virologic response at posttreatment week 12 (SVR12) with superiority to 92.6% threshold determined by historic chronic HCV G/P SVR12 rates. Secondary end points (FAS) included SVR12, on-treatment virologic failure, posttreatment relapse, and reinfection. Adverse events and safety laboratory values were assessed.Overall, 202 adults were enrolled; in the modified FAS, 150/151 (99.3%; 95% CI: 96.3-99.9) achieved SVR12, demonstrating superiority to efficacy threshold. In the FAS, the SVR12 rate was 74.3% and the on-treatment virologic failure rate was 0%. Relapse and reinfection rates after the final treatment visit (FAS) were 0.5% and 3%, respectively; 39 patients had missing SVR12 data. No on-treatment alanine aminotransferase elevations > 3 × upper limit of normal with total bilirubin > 2 × upper limit of normal were reported. All 53 patients with alanine aminotransferase Grade ≥ 2 at baseline improved to Grade 0/1 on treatment. No adverse eventss of hepatic decompensation/failure or leading to G/P discontinuation occurred. Two patients had serious adverse events unrelated to G/P. Eight-week G/P therapy was effective and well-tolerated in patients with acute HCV infection. Data support further investigation of G/P in acute HCV to shorten care cascades, reduce transmission, and support HCV elimination.

Rapid Initiation of Antiretroviral Therapy Under the Treat-All Policy Reduces Loss to Follow-Up and Virological Failure in Routine Human Immunodeficiency Virus Care Settings in China: A Retrospective Cohort Study (2016-2022).

Following the World Health Organization's guidelines for rapid antiretroviral therapy (ART) initiation [≤7 days after human immunodeficiency virus (HIV) diagnosis], China implemented Treat-All in 2016 and has made significant efforts to provide timely ART since 2017. This study included newly diagnosed HIV adults from Tianjin, China, between 2016 and 2022. Our primary outcome was loss to follow-up (LTFU) at 12 months after enrollment. The secondary outcome was 12-month virological failure. The association between rapid ART and LTFU, as well as virological failure, was assessed via Cox regression and logistic regression. A total of 896 (19.1%) of 4688 participants received ART ≤7 days postdiagnosis. The rate of rapid ART has increased from 7.5% in 2016 to 33.3% by 2022. The rapid ART group had an LTFU rate of 3.3%, as opposed to 5.0% in the delayed group. The rapid ART group had a much reduced virological failure rate (0.6% vs. 1.8%). Rapid ART individuals had a reduced likelihood of LTFU [adjusted hazard ratio: 0.65, 95% confidence intervals (CI): 0.44-0.96] and virological failure (adjusted odds ratio: 0.35, 95% CI: 0.12-0.80). The real-world data indicated that rapid ART is practicable and beneficial for Chinese people with HIV, providing evidence for its widespread implementation and scaling up.

Incidence and predictors of virological failure among children receiving first-line anti-retroviral treatment in public comprehensive specialized hospitals found in Northeast Ethiopia: a retrospective follow-up study.

Despite anti-retroviral treatment coverage in resource-limited countries being highly appreciated, the occurrence of first-line virological failure remains a priority agenda. Therefore, this study serves as an input for evidence of virological failure among children. This study aimed to assess the incidence and predictors of virological failure among children receiving first-line anti-retroviral treatment in public comprehensive specialized hospitals found in Northeast Ethiopia through a retrospective follow-up study. A multicenter institution-based retrospective follow-up study was conducted on the medical records of 481 human immunodeficiency virus (HIV)-infected children who were on first-line anti-retroviral therapy from 1 January 2017 to 31 December 2021. Data were retrieved from 15 May to 15 June 2022 at three public comprehensive specialized hospitals. Study participants were recruited using a simple random sampling technique. STATA-14 was used to analyze the data, which was entered using EpiData version 4.6.2.0. The Kaplan-Meier estimator was used to estimate the survival. Both bivariable and multivariable Cox regression models were fitted to identify predictors. Finally, adjusted hazards ratios (AHRs) with 95% confidence intervals (CIs) were computed, and variables with a P-value of <0.05 were considered statistically significant predictors of virological failure. A total of 481 children records were included in the final analysis, with an observed follow-up period of 16,379 person-months. Among these, 60 (12.47%) had developed virological failure, resulting in an overall incidence density rate of 3.67 (95% CI; 2.84, 4.73) per 1000 person-month observations. The hazards of virological failure (VF) among children were found to be increased by being in recent WHO stages III and IV (AHR = 3.688; 95% CI: 1.449-6.388), poor adherence to anti-retroviral treatment (ART) (AHR = 3.506; 95% CI: 1.711-7.234), and living in a rural environment (AHR = 5.013; 95% CI: 1.958-8.351). Conversely, the hazard of VF was reduced by 60% when the age of caregivers was less than 40 years (AHR = 0.405; 0.003-0.449). The incidence rate of virological failure was relatively high. Living in a rural area, poor adherence to ART, being in a recent advanced WHO clinical stage, and having a caregiver of 40 years of age or older were all independent predictors of virological failure in children. Patients or parents (caregivers) need to be aware of the importance of strictly adhering to treatment regimens to prevent virological failure.

DOLAMA 200: Effectiveness and Safety of a Dual Therapy with Dolutegravir Plus Lamivudine in Treatment-Experienced HIV-1 Infected Real World Participants in Spain.

The continuous pharmacological advances in antiretroviral treatment (ART) and the increasing understanding of HIV drug resistance has led to a change in the paradigm of ART optimization in the setting of the viral suppression of treatment-experienced patients with the emerging evidence of the effectiveness and safety of dual therapies. The aim of this study is to determine the antiviral efficacy and safety of switching to Dolutegravir + Lamivudine in people living with HIV, and to analyze the rate of patients with virologic failure (VF). A total of 200 patients were included with a median age of 51 years, 189 cells/µL of nadir CD4+, 13 years on ART and four previous ART regimens. Among the 168 patients who completed a follow-up at 48 weeks, a total of five VFs occurred, resulting in a 2.98% (5/168) VF rate. The results of the intention-to-treat analysis were a VF rate of 2.54% (5/197), and the rate of patients/year with viral suppression was 98.3% (298/303) in the observed data analysis. We observed a significant improvement in mean CD4 lymphocytes, the CD4/CD8 ratio and lipid profiles. The optimization of ART to DTG plus 3TC is a cost-effective switch option for treatment-experienced HIV patients, and also improves their lipid profiles.

Durability of doravirine with dolutegravir dual regimen compared with other dolutegravir-based dual combinations.

The availability of doravirine (DOR) allowed clinicians to prescribe a dolutegravir (DTG)-based two-drug regimen (2DR) in individuals not eligible to receive lamivudine (3TC) or rilpivirine (RPV). The aims of this study were to describe the durability of DTG + DOR compared with DTG/3TC and DTG/RPV and the rate of virological failure and target not-detected maintenance over time. This retrospective, monocentric analysis included all subjects who started a DTG-based 2DR from 2018 to 2022 as a simplification. Descriptive statistics and non-parametric tests to describe and compare the groups were applied. Kaplan-Meier probability curves and Cox regression models for regimens durability were used. The study enrolled 710 individuals: 499 treated with DTG/3TC, 140 with DTG/RPV, and 71 with DTG + DOR. A 2DR with DOR was prescribed to older subjects who had a longer infection, greater exposure to different antiretroviral regimens, a higher proportion of resistance-associated mutations, and a worse immune-virologic status. Over a cumulative follow-up of 68 152 weeks, 42 discontinuations were registered (5.9%). DTG + DOR had a risk of treatment interruption of 7.8% at 48 weeks and 9.8% at 96 weeks, significantly higher than the other 2DRs. In the multivariate Cox model, DTG + DOR and DTG/RPV were significantly associated with discontinuation. The maintenance of target not detected during follow-up was similar among groups. The rate of virological failure was higher for DTG + DOR through different event definitions. DTG + DOR durability was high over a long follow-up albeit lower than for other 2DRs. This combination might be an effective option in people with HIV that has proven difficult to treat.

Evaluating Second-line ART Efficacy in Pediatric HIV1 Infections: A Study at Albert Royer Children's Hospital

Introduction: In developing countries, around 15% of children infected with the Human Immunodeficiency Virus (HIV) have access to early diagnosis, and 28% are eligible for antiretroviral treatment (ART). The evaluation studies carried out in Senegal have been limited to children on first-line ART. The main objective of our study was to evaluate the efficacy of second-line ART.&#x0D; Methodology: Data were collected at 3 different sites. This was a retrospective, longitudinal and analytical study, conducted from March 4 to August 28, 2015. The study population consisted of 65 HIV1-infected children. BD FACSCountTM Flow Cytometer for TCD4 lymphocyte counting. For genotyping, 2 sets of PCRs were required. Data were entered and analysed using Word/Excel 2013 and Epi-info7 software.&#x0D; Results: We had 43 boys and 22 girls, giving a sex ratio of 1.95. The extreme ages were 5 and 15 years, and the mean age was 11.43 years. The majority belonged to stage 4 and 2 of the WHO classification. The clinical evolution was favourable in 86.15%, unfavourable in 3.07% and unspecified in 10.76%. We found 9 genotypes and recombinant forms; 80% of the strains were sequenced.&#x0D; Discussion: The general aim of ART is the same as in adults. Clinical stages were not specified in 15.38% of cases. In total, 58.46% had an excellent immunovirological response. We conclude from this that a good IR doesn’t mean a good immunovirological evolution. Initiation of ART should be guided by genotyping.&#x0D; Conclusion-Recommendations: ART reduced morbidity and mortality. Our study showed a virological failure rate of 21.53% and an IR rate of 86.15%.

Incidence and predictors of virological failure among HIV infected children and adolescents on first-line antiretroviral therapy in East Shewa hospitals, Oromia Region, Ethiopia: A retrospective follow up study.

Despite gains made from improved antiretroviral therapy coverage in resource limited countries, the occurrence of first line drug resistance remains a priority agenda. To reduce the emergence of resistant viruses, HIV viral load monitoring plays a critical role. However, many resource limited countries have difficulty of monitoring viral load due to economic constraints.There is also limited study regarding viral failure in developing countries. Therefore, this study aimed to assess the incidence and predictors of virological failure among HIV-infected children and adolescents on first-line ART Ethiopia, 2021. Institution based retrospective follow-up study was employed on 492 children and adolescents. Data were collected by trained nurses who have experience working in ART clinics. Data were entered using Epi-data version 4.6 and exported to Stata version 14 for analysis. The proportional hazard assumption was checked, and the Weibull regression was fitted. Cox-Snell residual was used to test the goodness of fit, and the appropriate model was selected by AIC. Finally, an AHR with a 95% CI was computed, and variables with a P-value < 0.05 in the multivariable analysis were taken as significant predictors of virological failure. The overall incidence rate of virological failure was 4.2, (95% CI: 3.41, 5.22) per 1000 person-months of observation with 20,169 person-months follow-up time. In multivariable analysis living in rural area (AHR = 1.97, 95% CI: 1.15-3.36), poor adherence (AHR = 2.20, 95% CI: 1.24-3.91), lower CD4 Count <200 cells/mm3 (AHR = 2.57, 95% CI: 1.27-5.18) and 201-350 cells/mm3 (AHR = 2.44, 95% CI: 1.28-4.67) respectively, and recent OI (AHR = 4.60, 95% CI: 2.38-8.90) are significantly associated with virological failure. The incidence rate of virological failure was high. Living in a rural, poor adherence, lower CD4 count, and recent opportunistic infection were independent risk factors associated with virological failure. Hence, it is better to give priority to strengthening the focused evaluation of important variables and managing accordingly.

Relación entre adherencia a entecavir y efectividad en pacientes con hepatitis B crónica

Purposeto evaluate adherence of patients with chronic hepatitis B initiated on entecavir as first-line treatment and to correlate adherence with effectiveness. Methodsobservational retrospective study performed between January 2007 and June 2013. Patients treated with entecavir for at least one year were included. A patient was considered to be adherent if median adherence was > 95%. Virological response (HBV DNA < 20UI/ml by Polymerase Chain Reaction), biochemical response (normalized level of alanine amino transferase [AAT]) and serological response (loss of hepatitis B surface antigen [HBsAg]) was assessed at month 12. Results85 patients were included. The median adherence rate was 94.2 (SD 12.8)%. 85.7% of the adherent patients achieved a virological response in contrast with 71.4% of the nonadhe-rent patients (OR:2,40; IC95%:0,60-9,54;p = 0,19). 87.9% of the adherent patients and 85.7% of the nonadherent patients showed normalized level of AAT (OR:1,21; IC95%:0,22-6,60;p = 0,56). Two adherent patients showed clearance of hepatitis B surface antigen. Conclusionthe median adherence is not high. Nonadherent patients have a trend towards a higher rate of virological failure so it is necessary to promote improved adherence to treatment.

Long-term outcomes of highly experienced people with HIV undergoing salvage therapy with raltegravir.

Raltegravir and other third-line drugs have shown promise in improving outcomes in treatment-experienced patients. However, the efficacy and tolerability of these agents vary. This study assessed real-life virologic success, long-term survival, and adverse events in patients receiving raltegravir or other third-line drugs as salvage regimens. This retrospective cohort study included adults who experienced treatment failure (human immunodeficiency syndrome-1 RNA plasma viral load >1000 copies/mL) and subsequently initiated raltegravir or other third-line drugs (darunavir/ritonavir, maraviroc, or etravirine). Propensity score matching methods were employed to account for differences at the time of switching from failing antiretroviral therapy regimens. The matched subset was analyzed using the Kaplan-Meier method and Generalized Wilcoxon tests to evaluate the probability of achieving virologic suppression (plasma viral load <50 copies/mL). Mortality rates, toxicity, treatment interruption, virologic failure, and loss to follow-up were determined using Poisson regression. One hundred and sixty-eight patients initiating salvage regimens were included, with 123 receiving raltegravir and 45 other third-line drugs. Propensity score matching resulted in a subset of 90 patients, 45 in each group. During the follow-up period, there were no significant differences observed between the groups in terms of virologic suppression (77.8% vs 82.2%, P = .73), mortality rates (4.04 vs 6.18 persons per 100 person-years [p-y]; P = .67), drug toxicity (0.00 vs 2.06 persons per 100 p-y; P = .49), treatment interruption (8.07 vs 0.00 persons per 100 p-y; P = .06), virologic failure (2.02 vs 4.12 persons per 100 p-y; P = .61), and loss of follow-up (6.05 vs 4.12 persons per 100 p-y; P = .70). Our findings indicate comparable survival and virological success rates between raltegravir and other drugs used in salvage regimens. Similar rates of drug toxicity, treatment interruption, virologic failure, and loss of follow-up were also observed. These results suggest that raltegravir may be a viable option for salvage therapy, demonstrating outcomes comparable to other third-line drugs in real life.

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).

The Influence of Age-Associated Comorbidities on Responses to Combination Antiretroviral Therapy Among People Living with HIV, at the ART Clinic of Jimma Medical Center, Ethiopia: A Hospital-Based Nested Case-Control Study.

Despite the high prevalence of age-associated comorbidities in HIV patients in sub-Saharan Africa, there is a lack of data on their influence on treatment outcomes in HIV patients. Therefore, this study aimed to assess the impact of age-associated comorbidities on responses to antiretroviral therapy (ART) among people living with HIV. A hospital-based nested case-control study was conducted among adult HIV-infected patients at the Jimma Medical Center from January 3 to June 2, 2022. Data were recorded by interviewing the patients and their medical chart and analyzed using The Statistical Package for Social Science (SPSS) v. 23, and at p <0.05. The overall immunological and virologic failure rates were 13.8% and 13.4%, respectively. Being male [AOR = 3.079,95% CI (1.139-8.327)], having age-associated comorbidity [AOR:10.57,95% CI (2.810-39.779)], age ≥ 50 years [AOR = 2.855, 95% CI (1.023-7.9650)], alcohol intake [AOR = 3.648,95% CI (1.118-11.897)], and having a baseline CD4+ count of < 200 cells/uL [AOR:3.862, 95% CI (1.109-13.456) were an independent predictor of immunological failure; Whereas Being alcoholic [AOR:3.11, 95% CI (1.044-9.271)], having a baseline CD4+ count of < 200 cells/uL [AOR:5.11, 95% CI (1.547-16.892)], a low medication adherence [AOR:5.92, 95% CI (1.81-19.36)], bedridden baseline functional status [AOR:3.902, 95% CI (1.237-12.307)], and lack of cotrimoxazole prophylaxis [AOR:2.735,95% CI (1.084-6.902)] were found to be an independent predictor of virologic treatment failure, but being younger (age < 50 years) was protective for virologic failure. Out of the eight patients who were treated for HIV at least one patient had developed immunological and/or virological failure. Age-associated comorbid chronic non-communicable diseases highly influence immunological outcomes compared with virological outcomes. Health providers should pay attention to age-associated comorbidities, encourage lifestyle modifications, and counsel on medication adherence to improve clinical outcomes in patients with HIV.