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Abstract Background HIV/AIDS has left a profound impact, leading to significant mortality, morbidity, economic strain, and disability on a global scale. The introduction of antiretroviral therapy (ART) has played a pivotal role in mitigating the economic burden of HIV and enhancing overall productivity. However, the emergence of virological failure presents a critical contemporary challenge within global health, reflecting the complexity of effectively managing HIV treatment outcomes in the 21st century. Methods An institutional based, cross-sectional study was conducted. Data were collected using a pretested, structured checklist. Data were edited and cleaned using Microsoft Excel 2016 and analyzed using SPSS version 25. Baseline demographic and clinical data were summarized using descriptive statistics. Multiple logistic regression analysis was run to identify association between dependent and independent variables, by computing odds ratio and 95% confidence interval. A p-value

Abstract Background In Uganda, 20% (19,073/94,579) of children and adolescents (0-19 years) living with HIV (CALHIV) were receiving second-line antiretroviral therapy (ART) by the end of March 2020. Data on incidence and predictors of virological failure among these CALHIV on second-line ART is limited. Lack of this information and limited access to HIV drug resistance testing prevents early identification of CALHIV at risk of virological failure on second-line ART. The aim of this study was to determine the incidence and predictors of virological failure among CALHIV on second-line ART in Uganda. Methodology This was a retrospective cohort study of all CALHIV aged 0-19 years who were switched to second-line ART regimen between June 2010 and June 2019 at the Baylor Uganda Centre of Excellence clinic. Data was analysed using STATA 14. Cumulative incidence curves were used to assess incidence of virological failure. Factors associated with virological failure were identified using sub-distributional hazard regression analysis for competing risks considering death, transfer out and loss to follow-up as competing risks. Results Of 1104 CALHIV, 53% were male. At switch to Protease Inhibitor (PI) based second-line ART, majority (47.7%) were aged 5 – 9 years,56.2% had no/mild immune suppression for age while 77% had viral load copies < 100,000 copies/mL. The incidence of virological failure on second-line ART regimen among CALHIV was 3.9 per 100 person-years (PY) with a 10-year cumulative incidence rate of 32%. Factors significantly associated with virological failure were age 10 – 19 years (HR 3.2, 95% 1.6 – 6.2, p < 0.01) and HIV viral load count > 100,000 copies/mL (HR 2.2, 95% CI 1.5 – 3.1), p < 0.01) prior to second-line ART switch. Conclusion Treatment outcomes for children and adolescents on second-line ART are favourable with one third of them developing virological failure at 10 years of follow up. Adolescent age group and high HIV viral load at the start of second-line ART were significantly associated with virological failure on second-line ART. There is need to determine optimal strategies to improve ART treatment outcomes among adolescents with high viral load counts at second-line ART switch.

Background: HIV/AIDS has left a profound impact, leading to significant mortality, morbidity, economic strain, and disability on a global scale. The introduction of antiretroviral therapy (ART) has played a pivotal role in mitigating the economic burden of HIV and enhancing overall productivity. However, the emergence of virological failure presents a critical contemporary challenge within global health, reflecting the complexity of effectively managing HIV treatment outcomes in the 21st century. Methods: An institutional based, cross-sectional study was conducted. Data were collected using a pretested, structured checklist. Data were edited and cleaned using Microsoft Excel 2016 and analyzed using SPSS version 25. Baseline demographic and clinical data were summarized using descriptive statistics. Multiple logistic regression analysis was run to identify association between dependent and independent variables, by computing odds ratio and 95% confidence interval. A p-value < 0.05 was considered significant. Results: The study delved into the health profile of 117 individuals who were receiving treatment with a third-line antiretroviral therapy (ART) regimen. The findings revealed that the median age of the participants stood at 44 (IQR = ± 17) years and male accounted 53%. The median duration of after HIV diagnosis was found to be 14.25 (± IQR = 5.71) years. Overall virological suppression after third line ART was 76.9% at 6 months. Following adjustment with multiple variable logistic regression, good adherence to medication showed statistical significance in achieving virologic suppression (AOR = 8.48(95% CI: 2.3–30.8), p = 0.001). In contrast, the absence of a change in the second line regimen (AOR = 3.0(95% CI: 0.36–24.8), p = 0.31) and receiving second-line medication for less than three years (AOR = 1.07(95% CI: 0.39–2.95), p = 0.89), and baseline viral load above 100,000 (AOR = 1.74(0.64–2.95), p = 0.27) shows statistically non-significant association with virologic suppression. Clinical trial number: Not applicable. Conclusion: This multicenter study provides strong evidence on virological suppression following the use of third-line antiretroviral therapy drugs in Ethiopia. The results of the study indicate rate of Virological suppression after starting third-line ART drugs is significantly linked to good adherence. [ABSTRACT FROM AUTHOR]

Background: In Uganda, 20% (19,073/94,579) of children and adolescents (0-19 years) living with HIV (CALHIV) were receiving second-line antiretroviral therapy (ART) by the end of March 2020. Data on incidence and predictors of virological failure among these CALHIV on second-line ART is limited. Lack of this information and limited access to HIV drug resistance testing prevents early identification of CALHIV at risk of virological failure on second-line ART. The aim of this study was to determine the incidence and predictors of virological failure among CALHIV on second-line ART in Uganda. Methodology: This was a retrospective cohort study of all CALHIV aged 0-19 years who were switched to second-line ART regimen between June 2010 and June 2019 at the Baylor Uganda Centre of Excellence clinic. Data was analysed using STATA 14. Cumulative incidence curves were used to assess incidence of virological failure. Factors associated with virological failure were identified using sub-distributional hazard regression analysis for competing risks considering death, transfer out and loss to follow-up as competing risks. Results: Of 1104 CALHIV, 53% were male. At switch to Protease Inhibitor (PI) based second-line ART, majority (47.7%) were aged 5 – 9 years,56.2% had no/mild immune suppression for age while 77% had viral load copies < 100,000 copies/mL. The incidence of virological failure on second-line ART regimen among CALHIV was 3.9 per 100 person-years (PY) with a 10-year cumulative incidence rate of 32%. Factors significantly associated with virological failure were age 10 – 19 years (HR 3.2, 95% 1.6 – 6.2, p < 0.01) and HIV viral load count > 100,000 copies/mL (HR 2.2, 95% CI 1.5 – 3.1), p < 0.01) prior to second-line ART switch. Conclusion: Treatment outcomes for children and adolescents on second-line ART are favourable with one third of them developing virological failure at 10 years of follow up. Adolescent age group and high HIV viral load at the start of second-line ART were significantly associated with virological failure on second-line ART. There is need to determine optimal strategies to improve ART treatment outcomes among adolescents with high viral load counts at second-line ART switch. [ABSTRACT FROM AUTHOR]

Background Long-acting (LA) injectable therapy with cabotegravir (CAB) and rilpivirine (RPV) is currently used as maintenance treatment for human immunodeficiency virus type 1, and has a low risk for virological failure (VF). Although the risk is low, the circumstances and impact of VF in the real-world setting merit further evaluation. Methods We performed an in-depth clinical, virological, and pharmacokinetic analysis on the reasons behind and the impact of VF during LA CAB/RPV therapy in 5 cases from the Netherlands. Genotypic resistance testing was performed after the occurrence of VF, and drug plasma (trough) concentrations were measured after VF was established and on any other samples to assess on-treatment drug levels. CAB and RPV drug levels that were below the first quartile of the population cutoff (≤Q1) were considered to be low. Results Five cases who were eligible for LA CAB/RPV experienced VF despite a low predicted risk at baseline. Genotypic resistance testing revealed extensive selection of nonnucleoside reverse transcriptase inhibitor–associated mutations in all cases, and integrase strand transfer inhibitor mutations in 4 cases. All cases displayed low drug levels of either CAB, RPV, or both during the treatment course, likely contributing to the occurrence of VF. In 3 cases, we were able to identify the potential mechanisms behind these low drug levels. Conclusions This is the first in-depth multiple case analysis of VF on LA CAB/RPV therapy in a real-world setting. Our observations stress the need to be aware for (evolving) risk factors and the yield of a comprehensive clinical, virological, and pharmacokinetic approach in case of failure. [ABSTRACT FROM AUTHOR]

Objective: To study the prevalence of low‐level viraemia (LLV) and its association with virological failure (VF). Methods: We conducted a retrospective analysis of 3498 participants at YRG CARE, Chennai, India (2013–2018) on antiretroviral therapy (ART) for ≥6 months with two or more plasma viral load (pVL) measurements. Results were stratified for those with pVL <1000 copies/mL: fully suppressed (FS) (pVL <40), low‐LLV (pVL 40–199), mid‐LLV (pVL 200–399), and high‐LLV (pVL 400–999). The study assessed the association with VF (pVL >1000 copies/mL) using Cox proportional hazard model. Results: Among 3498 participants, 2965 (84.8%) were FS and 533 (15.2%) were LLV. During the follow‐up, 348 (10%) experienced VF, with 222 (6.3%) experienced after LLV (42% of LLV) and 126 (3.6%) experienced after FS (4.3% of FS). When compared with FS, those with LLV had a greater risk of VF [adjusted hazard ratio (aHR) = 12.7; 95% confidence interval (CI): 10.2–15.9]. First‐line participants had a higher VF incidence (aHR = 15.8, 95% CI: 11.4–21.9) than second‐line participants (aHR = 5.6, 95% CI: 4.1–7.7). Those with high‐LLV had the highest VF risk (aHR = 22.856, 95% CI: 15.204–34.359 vs. aHR = 8.186, 95% CI: 5.564–12.043, for first‐line vs. second‐line participants, respectively), followed by those with mid‐LLV (aHR = 13.375, 95% CI: 8.327–21.483 vs. aHR = 6.261, 95% CI: 4.044–9.695) and low‐LLV (aHR = 12.976, 95% CI: 7.974–21.118 vs. aHR = 4.158, 95% CI: 2.826–6.119). Conclusions: The prevalence of LLV was intermediate in our study population. There was a higher risk of VF among individuals with LLV, and this risk increased with the increasing levels of LLV. Close monitoring of individuals experiencing LLV could help in the early identification of VF. [ABSTRACT FROM AUTHOR]

Background: Antiretroviral drug simplification is a strategy to reduce drug exposure and improve treatment adherence. Nowadays, dolutegravir plus lamivudine is the most preferred regimen, which might lead in the future with problems related to drug resistance or drug intolerance. This meta-analysis aimed to assess the safety of HAART simplification without integrase inhibitors. Methods: We conducted a systematic review and meta-analysis using the Embase and Medline databases to include clinical trials and observational studies published between 2008 and March 2024. The studies focused on HIV-positive individuals with suppressed viral load who either simplified their treatment to dual therapy without integrase inhibitors or continued triple therapy. The primary outcome of interest was the likelihood of viral failure within 48 weeks. Results: Ten studies were included, with a total of 1,977 patients. Boosted Protease Inhibitors (PI) were the core of antiretroviral simplification therapy. The simplification group did not show an increased risk of virological failure, with a pooled RR in 48 weeks of 1.29 (0.61‒2.73, I² = 51 %) when compared to control group. Boosted protease inhibitors were preferred combined with lamivudine, nevirapine, efavirenz, and maraviroc). Only maraviroc plus boosted PI combination was associated with a higher risk of virological failure with an RR of 4.49 (1.99‒10.11). Conclusion: Simplification therapy with boosted PI plus lamivudine or non-nucleoside transcriptase reverse inhibitors was a safe strategy and not associated with a higher risk of virological failure. This approach might be an alternative to dolutegravir-based simplification regimens if needed.

Mitiku Desalegn,1 Tewoderos Shitemaw,2 Mesfin Tesfaye,3 Genanew Kassie Getahun3 1Department of Anesthesia, College of Medicine and Health Science, Wachemo University, Hossana, Ethiopia; 2Menelik II Medical and Health Science College, Addis Ababa, Ethiopia; 3Department of Public Health, Menelik II Medical and Health Science College, Addis Ababa, EthiopiaCorrespondence: Mitiku Desalegn, Email mitikudesalegn44@gmail.comBackground: The causes of virological failure are poorly recognized and investigated. This study aimed to identify determinant factors of viral failure in children taking first-line ART at a randomly selected federal hospital in Addis Ababa, Ethiopia.Methods: A facility-based unmatched case–control study was carried out from May 10, 2022, to July 20, 2022, G.C. among HIV-infected children on first-line antiretroviral therapy. There were 209 HIV-positive youngsters in the study’s overall sample size, comprising 53 cases and 156 controls. Data was gathered by chart review using an organized checklist in English. The data were entered using Epi-data 4.2 and exported into SPSS version 24 for analysis. The relationship between each explanatory variable and the result variable was described using both bivariate and multivariate analysis. An adjusted odds ratio with 95% confidence intervals was conducted, and a p-value < 0.05 was considered statistically significant.Results: Being male (AOR= 4.504; 95% CI: 1.498, 13.539), duration on ART exceeding 47 months (AOR=40.6; 95% CI:9.571,172.222), fair and poor drug adherence (AOR=16.348; 95% CI:4.690,56.990), missed clinical appointments (AOR = 3.177; 95% CI: 1.100– 9.174), and baseline WHO clinical stage 4 disease (AOR = 6.852; 95% CI: 1.540– 30.49) were associated with an increased risk of virological failure. Conversely, a history of drug change and a CD4 count ranging from 250 to 500 cells/mm3 were significantly protective factors (AOR = 0.071; 95% CI: 0.024– 0.214 and AOR=0.118; 95% CI: 0.030, 0.464, respectively).Conclusion: Being male, duration on ART > 47 months, fair and poor adherence, missed clinical appointments, and baseline WHO Stage 4 are factors that increase the odds of virological failure. History of ART Drug change and a CD4 count between 250 and 500 cells/mm3 are factors that decrease the odds of virological failure.Keywords: retrospective, virological failure, antiretroviral therapy, children, Ethiopia

Francesca Alberton,1 Laura Galli,2 Riccardo Lolatto,2 Caterina Candela,1 Nicola Gianotti,2 Matteo Chiurlo,2 Martina Ranzenigo,2 Martina Strano,2 Alessia Uglietti,3 Antonella Castagna1,2 1Infectious Diseases Unit, Vita Salute San Raffaele University, Milan, Italy; 2Infectious Diseases Unit, San Raffaele Scientific Institute, Milan, Italy; 3Medical Affairs Department, Infectious Diseases and Vaccines & Rare Diseases, Johnson&Johnson, Milan, ItalyCorrespondence: Alessia Uglietti, Medical Affairs Department, Infectious Disease and Vaccines & Rare Diseases, Johnson&Johnson, viale Fulvio Testi 280/6, Milan, 20126, Italy, Tel +39-344 2665502, Email augliett@its.jnj.comObjective: To evaluate the virological outcome of darunavir–cobicistat (DRVc)‐based regimens in adults living with HIV who had experienced virological failure (VF) on any previous drug combination.Methods: This was a retrospective cohort study (CSLHIV Cohort) of adults living with HIV who started a DRVc‐based regimen with HIV‐RNA > 50 copies/mL after VF on any previous drug combination. Data on demographics, antiretroviral treatment since HIV diagnosis, and immunological and metabolic parameters from baseline (start of DRVc) to 48 weeks were analyzed in order to assess the cumulative proportion of those who achieved virological success (VS), defined as at least one instance of HIV‐RNA < 50 copies/mL within 12 months from baseline. Follow-up lasted from the start of the DRVc-based regimen (baseline) to the first instance of HIV-RNA < 50 copies/mL, last available visit, or loss to follow‐up or death, whichever occurred first. Univariate and multivariate Cox proportional-hazard regression models were used to identify baseline factors associated with VS.Results: A total of 176 individuals were included, and 120 (68.2%) achieved < 50 HIV‐RNA copies/mL within 12 months since baseline. On multivariate analysis, baseline HDL cholesterol was independently associated with the occurrence of VS (adjusted HR 1.021, 95% CI 1.004– 1.038; p=0.014). Among the 120 subjects with VS, 27 (22.5%) had had VF during a median follow-up of 20.8 months since the first undetectable HIV-RNA. Resistance testing after VF was available in two cases, which harboured the HIV variant–bearing protease inhibitor–resistance mutations D30N, I50V, and N88D. During a median follow-up of 38.4 months, 65 of 176 (36.9%) individuals discontinued DRVc for any reason (37 of 120, 30.8%) and achieved VS vs. 28 of 56 (50%) without VS (p=0.019). Time to discontinuation was longer in people with VS (41.5 vs. 23.0 months, p=0.0007). No statistically significant changes were observed in immunological or lipid profiles during follow-up.Conclusion: Most individuals in this study achieved VS within 12 months from the beginning of a DRVc-based regimen; therefore, this treatment represent a viable option for people who have experienced VF on other regimens.Keywords: HIV infection, antiretroviral therapy, ART, darunavir–cobicistat, DRVc, virological failure, VF

Supplemental Digital Content is Available in the Text. Background: Dolutegravir exposure is reduced after switching from efavirenz, which could select for dolutegravir resistance if switching occurs during virologic failure. Methods: We measured serial dolutegravir trough concentrations after switching from efavirenz in a clinical trial, which randomized some participants to a supplemental dolutegravir dose or placebo for the first 14 days. Changes in dolutegravir trough concentrations between days 3, 7, 14, and 28 were evaluated. The primary outcome was the geometric mean ratio of dolutegravir trough concentrations on day 7 versus day 28. Results: Twenty-four participants received double-dose dolutegravir (50 mg twice daily) and 11 standard dose for the first 14 days. Baseline characteristics were 77% female, median age 36 years, CD4 cell count 254 cells/mm3, and HIV-1 RNA 4.0 log10 copies/mL. The geometric mean ratio (90% CI) of dolutegravir trough concentrations on day 7 versus day 28 was 0.637 (0.485 to 0.837) in the standard-dose group and 1.654 (1.404 to 1.948) in the double-dose group. There was a prolonged induction effect at day 28 in participants with efavirenz slow metaboliser genotypes. One participant in the double-dose group had a dolutegravir trough concentration below the protein-binding adjusted concentration needed to inhibit 90% of HIV-1 (PA-IC90) at day 3. Conclusions: No participants on standard-dose dolutegravir had dolutegravir trough concentrations below the PA-IC90. Slow efavirenz metaboliser genotypes had higher baseline efavirenz concentrations and more pronounced and longer period of induction postswitch. These findings suggest that a 14-day lead-in supplemental dolutegravir dose may not be necessary when switching from a failing efavirenz-based first-line regimen. [ABSTRACT FROM AUTHOR]

Background Confirming the efficacy of dolutegravir/lamivudine in clinical practice solidifies recommendations on its use. Methods Prospective cohort study (DUALING) in 24 human immunodeficiency virus (HIV) treatment centers in the Netherlands. HIV RNA–suppressed cases were on triple-drug antiretroviral regimens without prior virological failure or resistance and started dolutegravir/lamivudine. Cases were 1:2 matched to controls on triple-drug antiretroviral regimens by the use of dolutegravir-based regimens, age, sex, transmission route, CD4+ T-cell nadir, and HIV RNA zenith. The primary endpoint was the treatment failure rate in cases versus controls at 1 year by intention-to-treat and on-treatment analyses with 5% noninferiority margin. Results The 2040 participants were 680 cases and 1380 controls. Treatment failure in the 390 dolutegravir-based cases versus controls occurred in 8.72% and 12.50% (difference: −3.78% [95% confidence interval {CI}, −7.49% to.08%]) by intention-to-treat and 1.39% and 0.80% (difference: 0.59% [95% CI, –.80% to 1.98%]) by on-treatment analyses. The treatment failure risk in 290 non-dolutegravir-based cases was also noninferior to controls. Antiretroviral regimen modifications unrelated to virological failure explained the higher treatment failure rate by intention-to-treat. A shorter time on triple-drug antiretroviral therapy and being of non-Western origin was associated with treatment failure. Treatment failure, defined as 2 consecutive HIV RNA >50 copies/mL, occurred in 4 cases and 5 controls but without genotypic resistance detected. Viral blips occured comparable in cases and controls but cases gained more weight, especially when tenofovir-based regimens were discontinued. Conclusions In routine care, dolutegravir/lamivudine was noninferior to continuing triple-drug antiretroviral regimens after 1 year, supporting the use of dolutegravir/lamivudine in clinical practice. Clinical Trials Registration NCT04707326. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

We describe and analyze resistance-associated mutations (RM) and virological failures (VF) on antiretroviral therapy using the latest approved integrase inhibitors (INIs) dolutegravir (DTG), bictegravir (BIC), and cabotegravir (CAB), together with their companion drugs in fixed-dose formulations: BIC/emtricitabine/tenofovir; CAB/rilpivirine; DTG/abacavir/lamivudine; DTG/emtricitabine/tenofovir; and DTG/lamivudine. Systematic literature searches were conducted in PubMed and other electronic databases for clinical studies published between January 2010 and May 2023, according to preferred reporting items for systematic reviews and meta-analyses guidelines (PRISMA), which analyzed VFs and RMs of INIs. Fifty clinical studies were included in the synthesis. VF in antiretroviral treatment (ART)-naïve patients occurred in 0.7-4.0%, 0.6-1.4%, and 0.6-9.0% of patients treated with DTG, BIC, and CAB, respectively. VF was reported in patients with previous ART in 0-8.1%, 0-2.0%, and 0.4-2.3% of those treated with DTG, BIC, and CAB, respectively. RMs were detected in ART-naïve patients in only one study with DTG (0.3%), none of the studies with BIC, and three of the studies with CAB (0.1-5.4%). In ART-experienced patients, RMs were detected in 0-1.9% of DTG-treated patients. No cases of RM were detected in the 11 BIC studies reviewed. In the case of CAB, RMs were detected in eight studies, ranging from 0.3% to 1.9% of patients. In conclusion, RM rates in the studies reviewed were generally low using the latest INIs. This review identified BIC as the INI with the lowest number of observed VF and lack of RM. [ABSTRACT FROM AUTHOR]

Abstract Background HIV virological failure is one of the main problems in HIV-infected patients, and identifying the main predictors of such treatment failure may help in combating HIV/AIDS. Methodology This cross-sectional study included 1800 HIV-infected patients with either virological failure or treatment response. HIV viral load, CD4 count, and other tests were performed. Statistical analysis was used to determine the predictors of virological failure. Results Clinical stage, treatment with reverse transcriptase inhibitors (RTIs), under therapy for three years or more, suboptimal adherence to antiretroviral treatment (ART), age > 40 years, CD4 count

Objective: Although the tenofovir alafenamide/emtricitabine/bictegravir (TAF/FTC/BIC) regimen is recommended in national and international guidelines for changing treatment in treatment-experienced patients living with HIV (PLwHIV), there are limited real-life data reported in Türkiye. We aimed to evaluate the changes in virological and immunological indicators, renal functions, and lipid profiles in the follow-up of patients who switched to TAF/FTC/BIC. Methods: The study included treatment-experienced PLwHIV aged 18 years or older who were followed at the infectious diseases outpatient clinic between January 2020 and December 2021. Follow-up parameters before and after switching to TAF/FTC/BIC were evaluated retrospectively. Results: A total of 77 PLwHIV were included. Of those, 71 (92.2%) were male, and the median age was 42 years. The 24th and 48th week median HIV RNA values of patients whose viral loads were measured were 35 (27-77) copies/ml and 34 (24-49) copies/ml, respectively, after switching. We did not detected a significant difference in CD4+T lymphocyte count, CD4+ T lymphocyte percentage, and CD4+/CD8+ ratio when compared with pre-treatment values. Virological suppression was not maintained in 24.7% (n=19/77) of PLwHIV. While "incomplete virological response" was not detected in any patients, 2.6% (n=2/77) had virological rebound, 1.3% (n=1/77) were virological non-responders, 10.4% (n=8/77) had low-level viremia, and 20.8% (n=16/77) had virological blip. Glomerular filtration rate (GFR) (101 ml/min./1.73m² vs. 96 ml/min./1.73m², p=0.05) and total cholesterol level (199 mg/dl vs. 185 mg/dl, p=0.05) decreased at 48th week. In switching from tenofovir alafenamide/emtricitabine/elvitegravir/cobicistat (TAF/FTC/EVG/Cob) to TAF/FTC/BIC, significant decreases were detected in GFR (101 ml/min./1.73m² vs. 95 ml/min./1.73m², p=0.016) and total cholesterol levels (205 mg/dl vs. 182 mg/dl, p<0.001). Conclusion: Even if virological suppression is achieved before switching, virological suppression may be impaired in patients after switching to TAF/FTC/BIC. Moreover, renal functions should be closely monitored due to the significant decrease in GFR, especially when switching from TAF/FTC/EVG/Cob to TAF/FTC/BIC. [ABSTRACT FROM AUTHOR]

Background Human immunodeficiency virus low-level viremia (LLV) is associated with subsequent treatment failure at least with non nucleoside reverse transcriptase inhibitor (NNRTI)-containing antiretroviral therapy. Data on implications of LLV occurring under dolutegravir, which has largely replaced NNRTIs in Africa, are scarce, however. Methods We included adults with human immunodeficiency virus in Lesotho who had ≥2 viral loads (VLs) taken after ≥6 months of NNRTI- or dolutegravir-based antiretroviral therapy. Within VL pairs, we assessed the association of viral suppression (<50   copies/mL) and low- and high-range LLV (50–199 and 200–999   copies/mL, respectively) with virological failure (≥1000   copies/mL) using a mixed-effects regression model. Participants could contribute VLs to the NNRTI and the dolutegravir group. Results Among 18 550 participants, 12 216 (65.9%) were female and median age at first VL included was 41.2 years (interquartile range, 33.4–51.5). In both groups, compared with a suppressed VL, odds of subsequent virological failure were higher for low-range LLV (NNRTI: adjusted odds ratio; 95% confidence interval: 1.9; 1.4–2.4 and dolutegravir: 2.1; 1.3–3.6) and high-range LLV (adjusted odds ratio; 95% confidence interval, 4.2; 3.1–5.7 and 4.4; 2.4–7.9). Conclusions In the dolutegravir era, LLV remains associated with virological failure, endorsing the need for close clinical and laboratory monitoring of those with a VL ≥50 copies/mL. [ABSTRACT FROM AUTHOR]

Objectives: Although widely recommended, data on bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) efficacy in HIV‐1‐infected children/adolescents are mainly extrapolated from studies in adults and one paediatric trial in which subjects have good treatment adherence. This study aimed to provide data about the risk of virological failure (VF) and acquired genotypic resistance in children and adolescents receiving BIC/FTC/TAF in a real‐world setting. Methods: This retrospective monocentric study included 74 paediatric patients who received BIC/FTC/TAF during ≥6 months in 2019–2023. VF was defined as not achieving a plasma viral load <50 copies/mL within 6 months of BIC/FTC/TAF initiation or as experiencing virological rebound ≥50 copies/mL. Results: Most patients were antiretroviral therapy (ART)‐experienced (93.2%), previously exposed to integrase inhibitors (85.1%) and displayed viral suppression at baseline (67.6%). Their median age was 11.2 years [interquartile range (IQR): 8.8–15.2]. BIC/FTC/TAF introduction reduced treatment burden in most ART‐experienced subjects. Genotypic susceptibility score of BIC/FTC/TAF was ≥2 in all cases. Median follow‐up was 40 months (IQR: 21–46). VF occurred in 28 people (37.8%), more frequently in the case of VF versus viral suppression at baseline (68% vs. 26%, P = 0.02). BIC/FTC/TAF was interrupted for suspected intolerance in only one case (1.4%). Nucleoside reverse transcriptase inhibitor (NRTI) mutation (T69D/N) emerged in one patient (3.6% of VF) after 47 months of continuous detectable viraemia while on ART. No acquisition of mutations in the integrase gene was observed. Conclusion: Because of its high genetic barrier to resistance, BIC/FTC/TAF could be especially useful in the paediatric population, in which the risk of poor treatment adherence and VF is high. [ABSTRACT FROM AUTHOR]

Objectives: Australia has made significant progress towards achieving the UNAIDS's 95‐95‐95 cascade targets including HIV viral suppression. To investigate the burden of HIV viraemia, we assessed viral blips, low‐level viraemia (LLV) and virologic failure (VF) in an Australian cohort. Methods: We studied the proportion of people with viral suppression, viral blips, LLV and VF in the Australian HIV observational database (AHOD) between 2010 and 2021. The association between blips or LLV, and VF was investigated using Cox regression, and predictors of viral blips and LLV were assessed using repeated‐measured logistic regression. Results: Among 2544 AHOD participants who were in follow‐up and on antiretroviral therapy (ART) from 1 January 2010 (88.7% male), 444 had experienced VF (incidence rate: 2.45 [95% CI: 2.23–2.69] per 100 person‐years [PY]) during 18,125 PY of follow‐up (a median of 7.6 years). The proportion of people with VF decreased over time, whereas rates of blips and LLV remained stable. Participants with blips (hazard ratio, 2.89; 95% CI: 2.31–3.61) and LLV (4.46; 95% CI: 3.38–5.89) were at increased risk of VF. Hepatitis B co‐infection, longer documented treatment interruption duration, younger age and lower CD4 at ART initiation, and protease inhibitors‐based initial regimen were associated with an increased risk of VF. Common predictors of blips and LLV such as higher HIV‐1 RNA and lower CD4 at ART initiation, longer treatment interruption, more VL testing and types of care settings (hospitals vs. sexual health services) were identified. Conclusions: Blips and LLV predict subsequent VF development. We identified important predictors of HIV viraemia including VF among individuals on INSTI‐based regimens to help direct HIV management plans. [ABSTRACT FROM AUTHOR]

Objectives: Our objective was to characterize longitudinal patterns of viraemia and factors associated with viral suppression in people with HIV and low‐level viraemia (LLV) during antiretroviral therapy (ART). Methods: We included people with HIV in the EuResist Integrated Database with LLV following ART initiation after 2005. LLV was defined as two or more consecutive viral load (VL) measurements of 51–199 copies/mL 30–365 days apart after >12 months of ART. Viraemia patterns were analyzed over 24 months. Factors associated with viral suppression at 12 months after LLV episodes were identified using univariable and multivariable logistic regression. Results: Of 25 113 people with HIV, 2474 (9.9%) had LLV. Among 1387 participants with 24 months of follow‐up after LLV, 406 (29%) had persistent suppression, 669 (48%) had transient viraemic episodes, 29 (2%) had persistent LLV, and 283 (20%) had virological failure. Following LLV episodes, the proportion with detectable viraemia declined (p for trend <0.001 and 0.034, in the first and second year, respectively). At 12 months, 68% had undetectable VL, which was associated with suppression before LLV (adjusted odds ratio [aOR] 1.7; 95% confidence interval [CI] 1.2–2.4) and ART modification after LLV (aOR 1.6; 95% CI 1.0–2.4). The following factors were negatively associated with undetectable VL at 12 months: higher VL during LLV (aOR 0.57 per log10 copies/mL; 95% CI 0.37–0.89), injecting drug use (aOR 0.67; 95% CI 0.47–0.96), and regimens with protease inhibitors (aOR 0.65; 95% CI 0.49–0.87) or combined anchor drugs (aOR 0.52; 95% CI 0.32–0.85). Conclusion: Most people with LLV did not experience sustained viral suppression during 24‐month follow‐up, supporting the association between LLV and inferior treatment outcome. [ABSTRACT FROM AUTHOR]

Background: The successful detection of drug-resistance mutations (DRMs) in HIV-1 infected patients has improved the management of HIV infection. Next-generation sequencing (NGS) to detect low-frequency mutations is predicted to be useful for efficiently testing minority drug resistance mutations, which could contribute to virological failure. This study employed Sanger sequencing and NGS to detect and compare minority and majority drug resistance mutations in HIV-1 strains in treatment-naive patients from Ghana. Method: From a previous study, 20 antiretroviral therapy (ART)-naive participants were selected for a cross-sectional study. Sanger sequencing and NGS techniques were used to detect the majority and minority HIV drug resistance (HIVDR) mutations, respectively, in the protease (PR) and partial reverse transcriptase (RT) genes. NGS detected mutations at 1 % and 5 % frequencies and Sanger sequencing at ≥20 % frequencies. The sequences obtained from NGS and Sanger sequencing platforms were submitted to the Stanford HIV drug resistance database for subtyping, mutation identification, and interpretations. Results: Sequences from the twenty participants where the CRF02_AG was the predominant strain (16, 80 %) were analyzed. NGS detected 25 mutations in the RT and PR genes, compared to 21 mutations by Sanger sequencing. Minority DRMs were detected at the prevalence of 55.0 % with NGS against 35 % DRMs by Sanger sequencing. One of the patients had eight different HIVDR variants, with two minority variants. These mutations were directed against PI (K20I and D30DN), NNRTI (Y181C, M23LM and V108I) and NRTI (K65R, M184I, and D67N). Conclusion: The study affirms the usefulness of genomic sequencing for drug resistance testing in HIV. It further shows that Sanger sequencing alone may not be adequate to detect mutations and that NGS capacity should be developed and deployed in the Ghanaian clinical settings for patients living with HIV.

Thabo Ishmael Lejone,1,2 Ozayr Mahomed1 1SolidarMed, Lesotho, South Africa; 2Discipline of Public Health Medicine, University of KwaZulu Natal, Durban, South AfricaCorrespondence: Ozayr Mahomed, Howard College, University of KwaZulu Natal, 227 George Campbell Building, Durban, South Africa, Tel +27 31 2604382, Fax +27 31 260 9111, Email mahomedo@ukzn.ac.zaBackground: Lesotho has the second-highest HIV prevalence globally at an estimated 23%, with approximately 87% of the population between 15 and 59 years of age reported to be receiving antiretroviral treatment. There is an urgent need to increase access to effective ART due to increasing rates of first- and second-line treatment failure. Sustaining successful treatment and limiting the development of virological failure is essential, hence the need for early detection of increased viral load indicating drug resistance or rapid progression of viral replication.Aim: The aim of the study was to determine the proportion of patients with HIV with virological failure and to identify factors associated with virological failure in two districts of Lesotho.Methods: A retrospective cohort study was conducted in two districts (Butha-Buthe and Mokhotlong) in Lesotho. Data for all patients (age ≥ 15 years) in the viral load (VL) monitoring database with at least two consecutive viral load results between December 2015 and December 2019 from 22 health facilities were extracted. Descriptive data were presented using tables and figures. Bivariate and multivariate analyses were performed. A p-value < 0.05 was considered a statistically significant association.Results: Only 4% (n = 913) of the study participants had virological failure. Longer time on treatment > 65 months (AOR: 1.85 CI: 1.59– 2.15) and being on second-line ART regimen (AOR: 75.23 95% CI: 75.00– 99.15) were significantly (p < 0.001) associated with virological failure.Conclusion: Virological failure among the study participants is lower compared to other settings. The study identified duration on treatment, treatment regimen as high risk for virological failure. Targeted interventions should be developed for these high-risk group individuals, with continuous monitoring of virological response and appropriate drug switching to clients to achieve improved outcomes.Keywords: Lesotho, HIV prevalence, highly active antiretroviral treatment, virological failure

Abstract Background Antiretroviral treatment improves health related quality of life (HRQoL) of people with human immunodeficiency virus (PWH). However, one third initiating first-line treatment experience virological failure and the determinants of HRQoL in this key population are unknown. Our study aims to identify determinants of among PWH failing antiretroviral treatment in sub-Saharan Africa. Methods We analysed data from a cohort of PWH having virological failure (> 1,000 copies/mL) on first-line ART in South Africa and Uganda. We measured HRQoL using the EuroQOL EQ-5D-3L and used a two-part regression model to obtain by-country analyses for South Africa and Uganda. The first part identifies risk factors that were associated with the likelihood of participants reporting perfect health (utility = 1) versus non-perfect health (utility

Abebaw Abie,1 Mekonnen Damessa2 1Department of Pharmacy, College of Medicine and Health Science, Debre-Markos University, Debre-Markos, Ethiopia; 2Department of Pharmacy, Institute of Health, Jimma University, Jimma, EthiopiaCorrespondence: Mekonnen Damessa, P.O.box: 378, Tel +251924100153, Email mekonnenmoke4@gmail.comIntroduction: 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.Methods: 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 Results: 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.Conclusion: 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.Keywords: age-associated comorbidity, combination antiretroviral therapy, HIV, immunological failure, virological failure, sub-Saharan Africa

BackgroundDespite 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.ObjectiveThis 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.MethodsA 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

This study aimed to assess second-line antiretroviral therapy (ART) outcomes in a National HIV Treatment program. People living with HIV aged ≥18 years initiating first-line ART who switched to second-line protease inhibitor-based regimens from January 2008 to May 2019, with a minimum of 1-year follow-up were studied. The primary outcome was second-line treatment failure (two consecutive virological failure episodes (viral load ≥1000 copies/mL)). Of 318,506 PLH initiating ART, 29,015 (9.1%) switched to second-line regimens after a median (IQR) ART duration of 1.63 (0.60-3.59) years. Lost to follow-up (LTFU) occurred in 5316 (18.3%) of whom 1376 (5%) remained LTFU and alive; 4606 (15.9%) died. Cumulative second-line failure incidence was 9.8% at 6 years, more common in females, younger PLH those with lower switch CD4 cell counts. Multidisciplinary, innovative support systems are needed to improve second-line treatment outcomes, particularly those relating to modifiable risk factors. Plain Language Summary: Outcomes after switching to second line antiretroviral regimens in the Thai National Treatment program We assessed the rates of virological failure, losses to follow-up and death in 29,015 people who switched to second line antiretroviral therapy in Thailand. The cumulative rate of virological failure was a 9.8% at 6 years, loss to follow-up occurred in 18.3% (5% who remained alive) and 15.9% died. Women and those with lower CD4 counts at switch had the highest risk of virological failure. [ABSTRACT FROM AUTHOR]

Background: The aim of the study is to evaluate the effectiveness, safety, and tolerability of a two-drug regimen (2-DR) dolutegravir/lamivudine (DTG/3TC) versus a three-drug regimen (3-DR) tenofovir alafenamide/emtricitabine/bictegravir (TAF/FTC/BIC) in a real-life cohort of HIV-1 virologically suppressed treatment-experienced (TE) people living with HIV (PLWH). Methods: This was a single-center, retrospective, observational study analyzing adult TE PLWH who started the 2-DR or 3-DR between January 2018 and January 2023. All PLWH with a viral load (VL) <50 copies/mL at the time of switching, and a follow-up of more than 6 months or interruption of treatment at any time, were included. Results: A total of 324 PLWH were included; of these, 110 (34%) were on the 2-DR and 214 (66%) were on the 3-DR. Most patients remained on therapy in both groups (93.6% 2-DR versus 90.2% 3-DR) and, at the last control, 99.1% achieved VL < 50 copies/mL with the 2-DR versus 97.2% with the 3-DR (p = 0.260). No virological failures occurred in either group. Adverse events occurred in a few cases: four (3.6%) in the 2-DR group and five (2.3%) in the 3-DR group (p = 0.500). The median follow-up-time was 19.6 months for the 2-DR and 27.5 months for the 3-DR. Conclusion: Our study shows a similar effectiveness and safety profile in virologically suppressed PLWH switching to DTG/3TC or TAF/FTC/BIC. [ABSTRACT FROM AUTHOR]

A large proportion of people living with HIV (PLHIV) in sub-Saharan Africa reside in rural areas. Knowledge of enablers and barriers of adherence to antiretroviral treatment (ART) in these populations is limited. We conducted a cohort study of 501 adult PLHIV on ART at a rural South African treatment facility as a sub-study of a clinical trial (ClinicalTrials.gov NCT03357588). Socio-economic, psychosocial and behavioral characteristics were assessed as covariates of self-reported adherence difficulties, suboptimal pill count adherence and virological failure during 96 weeks of follow-up. Male gender was an independent risk factor for all outcomes. Food insecurity was associated with virological failure in males. Depressive symptoms were independently associated with virological failure in both males and females. Household income and task-oriented coping score were protective against suboptimal pill-count adherence. These results underscore the impact of low household income, food insecurity and depression on outcomes of ART in rural settings and confirm other previously described risk factors. Recognition of these factors and targeted adherence support strategies may improve patient health and treatment outcomes. [ABSTRACT FROM AUTHOR]

Abstract Background Treatment with effective antiretroviral therapy (ART) reduces viral load as well as HIV-related morbidity and mortality in HIV-positive patients. Despite the expanded availability of antiretroviral therapy around the world, virological failure remains a serious problem for HIV-positive patients. Thus, Machine learning predictive algorithms have the potential to improve the quality of care and predict the needs of HIV patients by analyzing huge amounts of data, and enhancing prediction capabilities. This study used different machine learning classification algorithms to predict the features that cause virological failure in HIV-positive patients. Method An institution-based secondary data was used to conduct patients who were on antiretroviral therapy at the University of Gondar Comprehensive and Specialized Hospital from January 2020 to May 2022. Patients’ data were extracted from the electronic database using a structured checklist and imported into Python version three software for data pre-processing and analysis. Then, seven supervised classification machine-learning algorithms for model development were trained. The performances of the predictive models were evaluated using accuracy, sensitivity, specificity, precision, f1-score, and AUC. Association rule mining was used to generate the best rule for the association between independent features and the target feature. Result Out of 5264 study participants, 1893 (35.06%) males and 3371 (64.04%) females were included. The random forest classifier (sensitivity = 1.00, precision = 0.987, f1-score = 0.993, AUC = 0.9989) outperformed in predicting virological failure among all selected classifiers. Random forest feature importance and association rules identified the top eight predictors (Male, younger age, longer duration on ART, not taking CPT, not taking TPT, secondary educational status, TDF-3TC-EFV, and low CD4 counts) of virological failure based on the importance ranking, and the CD-4 count was recognized as the most important predictor feature. Conclusion The random forest classifier outperformed in predicting and identifying the relevant predictors of virological failure. The results of this study could be very helpful to health professionals in determining the optimal virological outcome.

Background: Human immunodeficiency virus (HIV)-positive students at a rural university in Limpopo province are followed-up according to the national guidelines for the treatment of HIV. Blood monitoring revealed that some students on antiretroviral (ARV) treatment were not virologically suppressed despite adherence and compliance being emphasised at every visit. Objectives: The study sought to identify the students’ experiences that were hindering the viral load from improving. Method: A two-phase qualitative, explorative, descriptive study design was followed. Convenience purposive sampling methods were taken on. By means of a semi-structured interview guide, face-to-face interviews were directed. Thematic content analysis was applied. Results: Non-disclosure, noisy ARV packaging, stigma, and service delivery played a role in determining levels of student adherence and compliance with ARVs in the study sample. Conclusion: Study findings suggest practical recommendations to improve compliance among students on ARVs: provision of HIV education to all students to help reduce stigma and make it easier to disclose HIV status; use of user-friendly noise-free packaging by pharmaceutical companies to enclose medication, such as blister packs; a supermarket approach in service delivery points to reduce the stigmatising effects of consulting rooms for ARV services. Contribution: There is scope to examine the relevance of these findings for other students in the country, to compare them, and to use material from larger studies to guide targeted interventions that could improve adherence among young people.

This study aimed to determine the HIV-1 subtype distribution and HIV drug resistance (HIVDR) in patients with ART failure from 2014 to 2020 in Hainan, China. A 7-year cross-sectional study was conducted among HIV/AIDS patients with ART failure in Hainan. We used online subtyping tools and the maximum likelihood phylogenetic tree to confirm the HIV subtypes with pol sequences. Drug resistance mutations (DRMs) were analyzed using the Stanford University HIV Drug Resistance Database. A total of 307 HIV-infected patients with ART failure were included, and 241 available pol sequences were obtained. Among 241 patients, CRF01_AE accounted for 68.88%, followed by CRF07_BC (17.00%) and eight other subtypes (14.12%). The overall prevalence of HIVDR was 61.41%, and the HIVDR against non-nucleoside reverse transcriptase inhibitors (NNRTIs), nucleotide reverse transcriptase inhibitors (NRTIs), and protease inhibitors (PIs) were 59.75%, 45.64%, and 2.49%, respectively. Unemployed patients, hypoimmunity or opportunistic infections in individuals, and samples from 2017 to 2020 increased the odd ratios of HIVDR. Also, HIVDR was less likely to affect female patients. The common DRMs to NNRTIs were K103N (21.99%) and Y181C (20.33%), and M184V (28.21%) and K65R (19.09%) were the main DRMs against NRTIs. The present study highlights the HIV-1 subtype diversity in Hainan and the importance of HIVDR surveillance over a long period. [ABSTRACT FROM AUTHOR]

Background: Antiretroviral treatment improves health related quality of life (HRQoL) of people with human immunodeficiency virus (PWH). However, one third initiating first-line treatment experience virological failure and the determinants of HRQoL in this key population are unknown. Our study aims to identify determinants of among PWH failing antiretroviral treatment in sub-Saharan Africa. Methods: We analysed data from a cohort of PWH having virological failure (> 1,000 copies/mL) on first-line ART in South Africa and Uganda. We measured HRQoL using the EuroQOL EQ-5D-3L and used a two-part regression model to obtain by-country analyses for South Africa and Uganda. The first part identifies risk factors that were associated with the likelihood of participants reporting perfect health (utility = 1) versus non-perfect health (utility < 1). The second part identifies risk factors that were associated with the EQ-5 L-3L utility scores for participants reporting non-perfect health. We performed sensitivity analyses to compare the results between the two-part model using tobit models and ordinary least squares regression. Results: In both countries, males were more likely to report perfect health and participants with at least one comorbidity were less likely to report perfect health. In South Africa, participants with side effects and in Uganda those with opportunistic infections were also less likely to report perfect health. In Uganda, participants with 100% ART adherence were more likely to report perfect health. In South Africa, high HIV viral load, experiencing ART side effects, and the presence of opportunistic infections were each associated with lower HRQoL, whereas participants with 100% ART adherence reported higher HRQoL. In Uganda participants with lower CD4 count had lower HRQoL. Conclusion: Markers of advanced disease (opportunistic infection, high viral load, low CD4), side effects, comorbidities and lack of ART adherence negatively impacted HRQoL for PWH experiencing virological failure. Trial registration: ClinicalTrials.gov: NCT02787499. Highlights: What we already know: As antiretroviral treatment (ART) access has expanded for people with HIV (PWH) and the condition has transitioned from a routinely fatal to chronic disease in sub-Saharan Africa, longer term health-related quality of life (HRQoL) has become the primary focus of care. ART generally improves HRQoL, but up to one third of PWH initiating first-line ART will experience virological failure. The gap: The determinants of HRQoL for PWH suffering virologic failure in sub-Saharan Africa are unknown. What our study adds: Markers of advanced disease (opportunistic infection, high viral load, low CD4), side effects, comorbidities and lack of ART adherence negatively impacted HRQoL for PWH experiencing virological failure. [ABSTRACT FROM AUTHOR]

Background There are conflicting data regarding baseline determinants of virological nonsuppression outcomes in persons with human immunodeficiency virus (HIV) starting antiretroviral treatment (ART). We evaluated the impact of different baseline variables in the RESPOND cohort. Methods We included treatment-naive participants aged ≥18 who initiated 3-drug ART, in 2014–2020. We assessed the odds of virological suppression (VS) at weeks 48 and 96 using logistic regression. Viral blips, low-level viremia (LLV), residual viremia (RV), and virological failure (VF) rates were assessed using Cox regression. Results Of 4310 eligible participants, 72% started integrase strand transfer inhibitor (INSTI)-based regimens. At 48 and 96 weeks, 91.0% and 93.3% achieved VS, respectively. At 48 weeks, Kaplan-Meier estimates of rates were 9.6% for viral blips, 2.1% for LLV, 22.2% for RV, and 2.1% for VF. Baseline HIV-1 RNA levels >100 000 copies/mL and CD4+ T-cell counts ≤200/µL were negatively associated with VS at weeks 48 (adjusted odds ratio, 0.51 [95% confidence interval,.39–.68] and.40 [.27–.58], respectively) and 96 and with significantly higher rates of blips, LLV, and RV. CD4+ T-cell counts ≤200/µL were associated with higher risk of VF (adjusted hazard ratio, 3.12 [95% confidence interval, 2.02–4.83]). Results were consistent in those starting INSTIs versus other regimens and those starting dolutegravir versus other INSTIs. Conclusions Initial high HIV-1 RNA and low CD4+ T-cell counts are associated with lower rates of VS at 48 and 96 weeks and higher rates of viral blips, LLV, and RV. Low baseline CD4+ T-cell counts are associated with higher VF rates. These associations remain with INSTI-based and specifically with dolutegravir-based regimens. These findings suggest that the impact of these baseline determinants is independent of the ART regimen initiated. [ABSTRACT FROM AUTHOR]

BACKGROUND:Understanding factors driving virological failure, including the contribution of HIV drug resistance mutations (DRM), is critical to ensuring HIV treatment remains effective. We examine the contribution of drug resistance mutations for low viral suppression in HIV-positive participants in a population-based sero-prevalence survey in rural South Africa. METHODS:We conducted HIV drug resistance genotyping and ART analyte testing on dried blood spots (DBS) from HIV-positive adults participating in a 2014 survey in North West Province. Among those with virologic failure (> 5000 copies/mL), we describe frequency of DRM to protease inhibitors (PI), nucleoside reverse transcriptase inhibitors (NRTI), and non-nucleoside reverse transcriptase inhibitors (NNRTI), report association of resistance with antiretroviral therapy (ART) status, and assess resistance to first and second line therapy. Analyses are weighted to account for sampling design. RESULTS:Overall 170 DBS samples were assayed for viral load and ART analytes; 78.4% of men and 50.0% of women had evidence of virologic failure and were assessed for drug resistance, with successful sequencing of 76/107 samples. We found ≥1 DRM in 22% of participants; 47% were from samples with detectable analyte (efavirenz, nevirapine or lopinavir). Of those with DRM and detectable analyte, 60% showed high-level resistance and reduced predicted virologic response to ≥1 NRTI/NNRTI typically used in first and second-line regimens. CONCLUSIONS:DRM and predicted reduced susceptibility to first and second-line regimens were common among adults with ART exposure in a rural South African population-based sample. Results underscore the importance of ongoing virologic monitoring, regimen optimization and adherence counseling to optimize durable virologic suppression.

James Samwel Mundamshimu,1 Kija Malale,1 Benson R Kidenya,1 Daniel W Gunda,1 Logious Bwemelo,1,&ast; Mwakile Mwashiuya,1,&ast; Salhida Shamnte Omar,1,&ast; Neema Mlowe,1,&ast; Magwa Kiyumbi,1 James S Ngocho,2,3 Emmanuel Balandya,4 Bruno Sunguya,4 Stephen E Mshana,1 Kien Mteta,2 John Bartlett,5,6 Eligius Lyamuya,4 Blandina Theophil Mmbaga,2,3 Samuel Kalluvya1 1Catholic University of Health and Allied Sciences, Mwanza, Tanzania; 2Kilimanjaro Christian Medical University College, Moshi, Tanzania; 3Kilimanjaro Clinical Research Institute, Moshi, Tanzania; 4Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania; 5Kilimanjaro Christian Medical University College, Mosh, Tanzania; 6Duke Global Health Institute, Duke University Medical Center, Durham, NC, USA&ast;These authors contributed equally to this workCorrespondence: James Samwel Mundamshimu, Tel +255746999249, Email jamessamwel913@yahoo.comBackground: Introduction and expansion of antiretroviral therapy (ART) have turned the tide of HIV pandemic, thus helping people living with HIV (PLHIV) achieve viral suppression. This success may need to be complemented by intensified adherence counseling (IAC) to improve adherence to treatment. However, some PLHIV still face higher than acceptable viral loads despite being on treatment.Purpose: We investigated the factors associated with the failure to suppress HIV viral load after three months of IAC sessions.Patients and Methods: This cross-sectional study analyzed secondary data from PLHIV-attended care and treatment clinics in Mwanza between January 2018 and December 2019 who had unsuppressed VL after being on ART for at least six months. We identified PLHIV in first-line ART with viral load evaluation before receiving IAC and had viral load results done at 90 days after IAC. We conducted descriptive statistics to examine the magnitude of viral suppression. Wilcoxon signed-rank test used to compare the median viral load before and after IAC sessions, and logistic regressions predicted the factors associated with failure.Results: This study included 212 subjects. After intervention, most participants 85.9% (182) had significantly improved adherence compared to baseline. More than half 75.5% (160) of the participants had viral suppression after the intervention. Participants aged 18– 25 years (AOR = 5.6, 95% CI, 1.1– 29.6), unstable client during ART initiation (AOR = 0.3, 95% CI, 0.13– 0.62), and poor adherence to ART (AOR = 4, 95% CI, 1.3– 12.3) remained the main predictors of virological failure after IAC intervention.Conclusion: Even though virological suppression is influenced by ART adherence, the findings in this study have shown co-existence of other factors to be addressed. Unstable during ART initiation is a new factor identified in this study.Keywords: people living with HIV, virological failure, intensified adherence counseling, factors, Tanzania

Background: Even though highly active antiretroviral therapy (HAART) for HIV (Human Immune Deficiency) patients has considerably improved viral load suppression, more people still struggle to reduce viral loads. The aim of the study was to determine the associated factors of virological failure in HIV patients on antiretroviral therapy (ART) in the Upper East Region of Ghana. Methods: A retrospective cross-sectional study involving 366 participants aged 15 years and above who were on HAART for six (6) months or longer with viral load results in 2020. Bivariate and multiple logistic regression analyses were conducted to identify the determinants of virological failure among HIV patients at 95% confidence interval (C.I.) with a significant level pegged at a p value less than 0.05. Results: The prevalence of viral load failure was 47.0% and adherence to antiretroviral therapy was 62.6% among patients on HAART. The significant predicators of virological failure were basic education (AOR (adjusted odds ratio) = 7.36, 95% C.I = 4.91–59.71), High school/Vocational /Technical education (AOR = 4.70, 95% C.I. = 1.90–9.69), monthly salary/income ˂ GHS 375.00 (AOR = 7.20, 95% C.I. = 1.73–29.95), duration on ART for ˂1 year (AOR = 0.27, 95% C.I. = 0.10–0.75), ART regimen (Tenofovir + Lamivudine + Efavirenz) (AOR = 3.26, 95% C.I. = 1.95–11.25), 3–5 times missed medication per month (AOR = 2.86, 95% C.I. = 1.34–6.08) and ≥6 missed medication per month (AOR = 23.87, 95% C.I. = 10.57–53.92). Conclusion: Educational status, salary/income, ART duration, ART combination regimen, and number of doses missed were statistically significantly associated with virological failure in patients on antiretroviral therapy. The majority of the respondents adhered to ART, which led to moderate viral load suppression but lower than the target for 2020. There is the need to strengthen the ongoing accelerated social behavior change communication among patients on ART to enhance adherence in order to attain the new UNAIDS target of 95% viral load suppression by 2030 in the Upper East Region of Ghana.

According to the World Health Organization, sustained virological suppression of 90 % should be achieved among children and adolescents living with HIV / AIDS, which makes it important to assess the prevalence of virological failure of antiretroviral therapy. The aim of this study was to determine the prevalence of virological failure and the clinical factors associated with it, as well as therapeutic drug monitoring in groups divided by the viral load level among children and adolescents with HIV. Materials and Methods: A retrospective analysis of the medical records of 184 children and adolescents receiving antiretroviral therapy and registered at the Irkutsk Regional Center for the Prevention and Control of AIDS and Infectious Diseases, Irkutsk, was carried out. The study included 172 children aged 1-18 years with perinatal HIV infection. Patients were divided into groups depending on the level of viral load: group 1 – 21 patients with viral load > 1000 copies/ml of plasma, group 2 – 42 patients with viral load 50– 1000 copies/ml of plasma, group 3 – 109 patients with undetectable viral load (< 50 copies/ml). All patients underwent standard tests in accordance with clinical guidelines for the treatment of HIV infection in children, as well as therapeutic drug monitoring. Results. Against the background of ongoing antiretroviral therapy, a significant number of patients 21 / 172 (12,2 %) experienced virological failure. The proportion of children and adolescents with incomplete suppression of HIV replication is 42 / 172 (24,4 %). Statistically significant differences were obtained by changing the ART regimen (p = 0,031). In the first group, the proportion of patients who changed the therapy regimen is 7 / 21 (33,3 %), which is two times less than in the group with a zero viral load of 70 / 109 (64,2 %). There are differences in the proportion of children and adolescents with zero concentrations of ritonavir and lopinavir (p = 0,020 and p = 0,012) in the three compared groups. The distribution of patients with zero concentrations was as follows: for ritonavir in the first group 3 / 17 (17,6 %), in the second – 8/37 (21,6 %), in the third group – 4/80 (5 %); for lopinavir – 4/17 (23,5 %), 6/36 (16,7 %), 3/80 (3,8 %), respectively. Conclusion. This study demonstrates that the prevalence of virological failure among children and adolescents receiving ART remains high. To achieve sustained virological suppression in children and adolescents taking a protease inhibitor regimen, adherence to therapy must be increased. As one of the methods for assessing adherence, therapeutic drug monitoring can be used.

Abstract Background The number of people receiving second-line antiretroviral therapy (ART) has increased as global access to ART has expanded. Data on the burden and factors associated with second-line ART virologic failure (VF) from India remain limited. Methods We conducted cross-sectional viral load (VL) testing among adults (≥ 18 years) who were registered at a publicly funded ART center in western India between 2014 and 2015 and had received second-line ART for at least 6 months. Sociodemographic and clinical characteristics were abstracted from routinely collected programmatic data. Logistic regression evaluated factors associated with VF (defined as VL > 1000 copies/mL). Results Among 400 participants, median age was 40 years (IQR 34–44), 71% (285/400) were male, and 15% (59/400) had VF. Relative to participants without VF, those with VF had lower median CD4 counts (230 vs 406 cells/mm3, p

Background The World Health Organization (WHO) recommends viral load (VL) monitoring for HIV patients on antiretroviral therapy (ART). However, availability of VL monitoring in low-income countries remains limited. Objective To investigate factors associated with virological failure in HIV-infected children treated without routine VL monitoring. Methods This cohort study was done in children living with HIV (CLHIV) registered at Cipto Mangunkusumo General Hospital from 2004 to 2021. Viral load monitoring was not routinely done. Subjects with at least one VL result after 6 months on ART were included in the study. Virological failure was defined as a VL of >1,000 copies. Subjects’ data were obtained from medical records, laboratory reports, and dispensing pharmacies. Statistical analysis was done following survival analysis with hazard ratio. Results There were 384 children who had at least 1 VL result after ART was initiated. Median age at diagnosis was 30 months. Length of follow-up ranged from 6 to 216 months, with a mean frequency of VL monitoring of 0.7 times/person/year. Most subjects were already in clinical stages 3 and 4 (77.8%); 75% met severe immunodeficiency criteria. Virological failure was found in 45.8% of subjects after a median of 33 months on first-line ART, yielding an incidence of 3.3 per 1,000 person months. Independent associated factors were age at diagnosis of

Background: Since limited data are available, we aimed to compare the efficacy and durability of dolutegravir and darunavir in advanced naïve patients. Methods: Retrospective multicenter study including AIDS- or late-presenting (def. CD4 ≤ 200/µL) HIV-infected patients starting dolutegravir or ritonavir/cobicistat-boosted darunavir+2NRTIs. Patients were followed from the date of first-line therapy initiation (baseline, BL) to the discontinuation of darunavir or dolutegravir, or for a maximum of 36 months of follow-up. Results: Overall 308 patients (79.2% males, median age 43 years, 40.3% AIDS-presenters, median CD4 66 cells/µL) were enrolled; 181 (58.8%) and 127 (41.2%) were treated with dolutegravir and darunavir, respectively. Incidence of treatment discontinuation (TD), virological failure (VF, defined as a single HIV-RNA > 1000 cp/mL or two consecutive HIV-RNA > 50 cp/mL after 6 months of therapy or after virological suppression had been achieved), treatment failure (the first of TD or VF), and optimal immunological recovery (defined as CD4 ≥ 500/µL + CD4 ≥ 30% + CD4/CD8 ≥ 1) were 21.9, 5.2, 25.6 and 1.4 per 100 person-years of follow-up, respectively, without significant differences between dolutegravir and darunavir (p > 0.05 for all outcomes). However, a higher estimated probability of TD for central nervous system (CNS) toxicity (at 36 months: 11.7% vs. 0%, p = 0.002) was observed for dolutegravir, whereas darunavir showed a higher probability of TD for simplification (at 36 months: 21.3% vs. 5.7%, p = 0.046). Conclusions: Dolutegravir and darunavir showed similar efficacy in AIDS- and late-presenting patients. A higher risk of TD due to CNS toxicity was observed with dolutegravir, and a higher probability of treatment simplification with darunavir. [ABSTRACT FROM AUTHOR]

Antiretroviral treatment failure has emerged as a challenge in the management of pediatric human immunodeficiency virus (HIV) patients, especially in resource-limited countries despite accessibility to Highly Active Antiretroviral Therapy (HAART). A systematic review and meta-analysis was conducted to synthesize virological failure (VF) prevalence and ascertain its predictors in children in sub-Saharan Africa. An electronic database search strategy was conducted from January to September 2021 on PubMed, EMBASE, SCOPUS, HINARI, and CINAHL. Further, manual searching was conducted on non-indexed journals. Utilizing the JASP© version 0.17.2 (2023) statistical software, a meta-analysis of pooled prevalence of VF was estimated using the standardized mean differences. Further, selection models were used to assess the risk of bias and heterogeneity. The pooled odds ratios were estimated for the respective studies reporting on predictors of VF. The overall pooled estimate of the prevalence of VF in sub-Saharan Africa among the sampled population was 29% (95% CI: 27.0-32.0; p<0.001). Predictors of VF were drug resistance (OR: 1.68; 95% CI: 0.88-2.49; p < 0.001), poor adherence (OR: 5.35; 95% CI: 5.26-5.45; p < 0.001), nevirapine (NVP)-based regimen (OR: 5.11; 95% CI: 4.66-5.56; p < 0.001), non-usage of cotrimoxazole prophylaxis (OR: 4.30; 95% CI: 4.13-4.47; p < 0.001), higher viral load at the initiation of antiretroviral therapy (ART) (OR: 244.32; 95% CI: 244.2-244.47; p <0.001), exposure to the prevention of mother to child transmission (PMTCT) (OR: 8.02; 95%CI: 7.58-8.46; p < 0.001), increased age/older age (OR: 3.37; 95% CI: 2.70-4.04; p < 0.001), advanced World Health Organization (WHO) stage (OR: 6.57; 95% CI: 6.17-6.98; p < 0.001), not having both parents as primary caregivers (OR: 3.01; 95% CI: 2.50-3.53; p < 0.001), and tuberclosis (TB) treatment (OR: 4.22; 95% CI: 3.68-4.76; p <0.001). The mean VF prevalence documented is at variance with studies in other developing countries outside the sub-Saharan region. The high prevalence of HIV cases contrasting with the limited expertise in the management of pediatric ART patients could explain this variance. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the 9-month cost and health-related quality of life (HRQOL) outcomes of resistance versus viral load testing strategies to manage virological failure in low-middle income countries. We analyzed secondary outcomes from the REVAMP clinical trial: a pragmatic, open label, parallel-arm randomized trial investigating resistance versus viral load testing for individuals failing first-line treatment in South Africa and Uganda. We collected resource data, valued according to local cost data and used the 3-level version of EQ-5D to measure HRQOL at baseline and 9 months. We applied seemingly unrelated regression equations to account for the correlation between cost and HRQOL. We conducted intention-to-treat analyses with multiple imputation using chained equations for missing data and performed sensitivity analyses using complete cases. For South Africa, resistance testing and opportunistic infections were associated with statistically significantly higher total costs, and virological suppression was associated with lower total cost. Higher baseline utility, higher cluster of differentiation 4 (CD4) count, and virological suppression were associated with better HRQOL. For Uganda, resistance testing and switching to second-line treatment were associated with higher total cost, and higher CD4 was associated with lower total cost. Higher baseline utility, higher CD4 count, and virological suppression were associated with better HRQOL. Sensitivity analyses of the complete-case analysis confirmed the overall results. Resistance testing showed no cost or HRQOL advantage in South Africa or Uganda over the 9-month REVAMP clinical trial. • We analyzed cost and health-related quality of life (HRQOL) data using seemingly unrelated regression equations to account for joint correlation: this method is not widely published. • We undertook analysis in the context of a marginal, nonsignificant benefit in clinical primary outcome, proceeding based on strong economic hypotheses suggesting cost and HRQOL benefits for resistance testing. • Our study benefits from rich, primary, individual patient-level data to compare baseline and 9-month cost and HRQOL. • Notably, in contrast to high-income countries, resistance testing showed no 9-month cost or HRQOL advantage compared with viral load testing in low-middle income countries. • Results are key to informing multinational partners, nongovernment organizations, and public health policy makers about the use of resistance testing in clinical practice. • They are also important for informing the lifetime cost-effectiveness analysis of resistance testing in the era of new resistance testing methods and treatment regimens. [ABSTRACT FROM AUTHOR]

Background: Treatment with effective antiretroviral therapy (ART) reduces viral load as well as HIV-related morbidity and mortality in HIV-positive patients. Despite the expanded availability of antiretroviral therapy around the world, virological failure remains a serious problem for HIV-positive patients. Thus, Machine learning predictive algorithms have the potential to improve the quality of care and predict the needs of HIV patients by analyzing huge amounts of data, and enhancing prediction capabilities. This study used different machine learning classification algorithms to predict the features that cause virological failure in HIV-positive patients. Method: An institution-based secondary data was used to conduct patients who were on antiretroviral therapy at the University of Gondar Comprehensive and Specialized Hospital from January 2020 to May 2022. Patients' data were extracted from the electronic database using a structured checklist and imported into Python version three software for data pre-processing and analysis. Then, seven supervised classification machine-learning algorithms for model development were trained. The performances of the predictive models were evaluated using accuracy, sensitivity, specificity, precision, f1-score, and AUC. Association rule mining was used to generate the best rule for the association between independent features and the target feature. Result: Out of 5264 study participants, 1893 (35.06%) males and 3371 (64.04%) females were included. The random forest classifier (sensitivity = 1.00, precision = 0.987, f1-score = 0.993, AUC = 0.9989) outperformed in predicting virological failure among all selected classifiers. Random forest feature importance and association rules identified the top eight predictors (Male, younger age, longer duration on ART, not taking CPT, not taking TPT, secondary educational status, TDF-3TC-EFV, and low CD4 counts) of virological failure based on the importance ranking, and the CD-4 count was recognized as the most important predictor feature. Conclusion: The random forest classifier outperformed in predicting and identifying the relevant predictors of virological failure. The results of this study could be very helpful to health professionals in determining the optimal virological outcome. [ABSTRACT FROM AUTHOR]

BackgroundPeople living with human immunodeficiency virus (PLWH) are still being diagnosed late, rendering the benefits of "early" antiretroviral therapy (ART) unattainable. Therefore, we aimed to evaluate the benefits of "immediate" ART.MethodsA nationwide cohort of PLWH in China who initiated ART January 1, 2011, to December 31, 2014 and had baseline CD4 results >200 cells/μL were censored at 12 months, dropout, or death, whichever came first. Treatment dropout and virological failure (viral load ≥400 copies/mL) were measured. Determinants were assessed by Cox and log-binomial regression.ResultsThe cohort included 123605 PLWH. The ≤30 days group had a significantly lower treatment dropout rate of 6.72%, compared to 8.91% for the 91-365 days group and to 12.64% for the >365 days group. The ≤30 days group also had a significantly lower virological failure rate of 5.45% (31-90 days: 7.39%; 91-365 days: 9.64%; >365 days: 12.67%). Greater risk of dropout (91-365 days: adjusted hazard ratio [aHR] = 1.33, 95% confidence interval [CI] = 1.25-1.42; >365 days: aHR = 1.55, CI = 1.47-1.54), and virological failure (31-90 days: adjusted risk ratio [aRR] = 1.35, CI = 1.26-1.45; 91-365 days: aRR = 1.66, CI = 1.55-1.78; >365 days: aRR = 1.85, CI = 1.74-1.97) were observed for those who delayed treatment.ConclusionsART within 30 days of HIV diagnosis was associated with significantly reduced risk of treatment failure, highlighting the need to implement test-and-immediately-treat policies.

Hung-Chin Tsai,1– 5 I-Tzu Chen,1 Hui-Min Chang,6– 8 Susan Shin-Jung Lee,1,2 Yao-Shen Chen1,2 1Division of Infectious Diseases, Department of Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; 2Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; 3Department of Parasitology, Kaohsiung Medical University, Kaohsiung, Taiwan; 4Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan; 5Shu-Zen Junior College of Medicine and Management, Kaohsiung, Taiwan; 6Department of Pharmacy, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; 7Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 8Department of Pharmacy and Graduate Institute of Pharmaceutical Technology, Tajen University, Pingtung, TaiwanCorrespondence: Hung-Chin Tsai, Division of Infectious Diseases, Department of Medicine Kaohsiung Veterans General Hospital, #386 Ta-Chung 1st Road, Kaohsiung, 813, Taiwan, Tel +886 7 3422121 ext. 2029, Fax +886 7 346 8292, Email hctsai1011@yahoo.com.tw; tsaihungchin@gmail.comPurpose: This study aimed to investigate the prevalence of resistance to a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based single-tablet regimen (STR) in Taiwanese patients and clarify the clinical implications of using doravirine in patients who fail NNRTI treatment.Patients and Methods: Taiwanese patients infected with HIV-1 who failed NNRTI-based STR treatment were enrolled in this retrospective cohort study from 2015 to 2020. Mutations associated with drug resistance were identified using the 2019 International Antiviral Society-USA list of drug-resistant mutations in HIV, and drug susceptibility was assessed according to the Stanford HIV Drug Resistance Database version 9. Median values of continuous variables were compared between two groups using the Mann–Whitney U-test, and categorical variables were compared using the chi-square test or Fisher’s exact test.Results: A total of 107 patients were included, of whom 29 were treatment failure to the initial STRs, and 78 failed treatment after switching to an STR. Seventy-four patients failed treatment with TDF/FTC/EFV (Atripla), 30 with TDF/FTC/RPV (Complera) and 3 with TAF/FTC/RPV (Odefsey). The prevalence rates of resistance to nucleoside reverse transcriptase inhibitors (NRTIs), NNRTIs, protease inhibitors (PIs) and integrase strand transfer inhibitors (INSTIs) were 76%, 86%, 3% and 2%, respectively. Among the 29 patients failure to the initial STRs, 62% developed doravirine resistance, compared to 64% of the 78 the patients who failed treatment after switching to an STR. There were no significant differences in the prevalence of specific NNRTI or doravirine resistance-associated mutations between these two groups. The patients with K65R mutations were more likely to have NNRTI resistance (p = 0.037) and doravirine resistance (p < 0.001).Conclusion: Our findings showed a high rate of doravirine cross-resistance in patients with NNRTI-based STR treatment failure. Doravirine should be used cautiously as a salvage regimen in patients who fail NNRTI treatment.Keywords: HIV, doravirine, drug resistance, single-tablet regimen, virological failure

Hamdi Fekredin Zakaria,1 Temam Beshir Raru,1 Fila Ahmed Hassen,2 Galana Mamo Ayana,1 Bedasa Taye Merga,2 Gebiso Roba Debele,3 Genet Kiflemariam,4 Sewnet Adem Kebede,5 Tadesse Awoke Ayele5 1Department of Epidemiology and Biostatistics, School of Public Health, College of Health and Medical Sciences, Haramaya University, Harar, Ethiopia; 2Department of Public Health and Health Policy, School of Public Health, College of Health and Medical Sciences, Haramaya University, Harar, Ethiopia; 3Department of Public Health, College of Health Sciences, Metu University, Metu, Ethiopia; 4International Institute for Primary Health Care, Addis Ababa, Ethiopia; 5Department of Epidemiology and Biostatistics, Institute of Public Health, College of Medical and Health Sciences, University of Gondar, Gondar, EthiopiaCorrespondence: Temam Beshir Raru, Department of Epidemiology and Biostatistics, School of Public Health, College of Health and Medical Sciences, Haramaya University, P.O. Box: 235, Harar, Ethiopia, Email temam.b1@gmail.comIntroduction: Virological suppression for persons living with HIV (PLHIV) on antiretroviral therapy (ART) reached 85% at the end of 2018, still falling short of the UNAIDS target of 95%. In Ethiopia, there were studies on treatment failure focusing on viral suppression and immunological failure of ART users, but none of them have addressed virological failure for second-line regimens.Objective: This study was aimed to estimate the incidence and predictors of virological failure among HIV patients who were switched to second-line ART at the selected public hospitals in Addis Ababa.Methods: An institutional-based retrospective follow-up study was conducted from September 2018 to January 2021 at public hospitals in Addis Ababa. The sample size was determined by using the Schoenfeld formula. Data entry were done by Epi Data version-4.6.0.0 and exported to R-software version-4.1.0 for analysis. Kaplan–Meier methods were used to compare the survival estimates. Cox proportional hazard model was used to identify predictors of virological failure and model adequacy was checked by using the Cox–Snell residuals plot.Results: Overall 44 (12.22%) HIV/AIDS patients developed virological failure with incidence density of 3.57/1000 Person-Month (PM) with 95% CI of [2.65– 4.79]. Age > 45 years (AHR=0.36, 95% CI: 0.12– 0.99), CD4 count < 100cell/mm3 (AHR=3.02, 95% CI: 1.17– 7.78), TB co-infection (AHR=2.48, 95% CI: 1.10– 6.33), ATV/r-based second-line regimen (AHR=0.27, 95% CI: 0.11– 0.70), and poor adherence at the start of second-line ART (AHR=6.18, 95% CI: 1.93– 19.76) were the significant predictors of virological failure.Conclusion: A high incidence of virological failure was noticed. The rate of virological failure was higher for patients who had poor ART adherence, small CD4count, and TB co-infection. Therefore, targeted HIV care interventions shall be provided to young ages and efforts stepped up to improve adherence to ART, which helps to increase immunity and suppress viral replication. In addition, prevention and early detection of TB co-infection are crucial to the patients.Keywords: incidence, second-line antiretroviral therapy, predictors, virological failure, HIV/AIDS

Introduction: The Thai National AIDS programme (NAP) treatment guidelines have recommended rapid antiretroviral therapy (ART) initiation, regardless of CD4 count since 2014. We assessed treatment outcomes among youth living with HIV (YLHIV), initiating first‐line ART and assessed the association between virological failure (VF) and timing of ART initiation. Methods: We retrospectively reviewed data for YLHIV aged 15–24 years, initiating non‐nucleoside reverse transcriptase inhibitor‐based ART from 2014 to 2019, through the NAP database. We classified the timing of ART into three groups based on duration from HIV‐positive diagnosis or system registration to ART initiation: (1) <1 month (rapid ART); (2) 1–3 months (intermediate ART); and (3) >3 months (delayed ART). VF was defined as viral load (VL) ≥ 1000 copies/ml after at least 6 months of first‐line ART. Factors associated with VF were analysed using generalized estimating equations. Results: Of 19,825 YLHIV who started ART, 78% were male. Median (interquartile range, IQR) age was 21 (20–23) years and CD4 count was 338 (187–498) cells/mm3. After registration, 12,216 (62%) started rapid ART, 4272 (22%) intermediate ART and 3337 (17%) delayed ART. The proportion of YLHIV starting ART <30 days significantly increased from 43% to 57% from 2014–2016 to 2017–2019 (p < 0.001). The median duration of first‐line therapy was 2 (IQR 1–3) years and 89% started with efavirenz‐based regimens. Attrition outcomes showed that 325 (2%) died (0.73 [95% CI 0.65–0.81] per 100 person‐years [PY]) and 1762 (9%) were loss to follow‐up (3.96 [95% CI 3.78–4.15] per 100 PY). Of 17,512 (88%) who had VL checked from 6 to 12 months after starting treatment, 80% achieved VL <200 copies/ml. Overall, 2512 experienced VF 5.87 (95% CI 5.65–6.11) per 100 PY). In a multivariate model, the adjusted incidence rate ratio for VF was 1.47 (95% CI 1.33–1.63, p < 0.001) in the delayed ART group and 1.14 (95% CI 1.03–1.25, p< 0.001) in the intermediate ART group, compared to YLHIV in the rapid ART group. Conclusions: Rapid ART initiation after diagnosis was associated with significantly reduced risks of VF and death in YLHIV, supporting the implementation of rapid ART for optimizing health outcomes. [ABSTRACT FROM AUTHOR]

Background: Even though highly active antiretroviral therapy (HAART) for HIV (Human Immune Deficiency) patients has considerably improved viral load suppression, more people still struggle to reduce viral loads. The aim of the study was to determine the associated factors of virological failure in HIV patients on antiretroviral therapy (ART) in the Upper East Region of Ghana. Methods: A retrospective cross-sectional study involving 366 participants aged 15 years and above who were on HAART for six (6) months or longer with viral load results in 2020. Bivariate and multiple logistic regression analyses were conducted to identify the determinants of virological failure among HIV patients at 95% confidence interval (C.I.) with a significant level pegged at a p value less than 0.05. Results: The prevalence of viral load failure was 47.0% and adherence to antiretroviral therapy was 62.6% among patients on HAART. The significant predicators of virological failure were basic education (AOR (adjusted odds ratio) = 7.36, 95% C.I = 4.91–59.71), High school/Vocational /Technical education (AOR = 4.70, 95% C.I. = 1.90–9.69), monthly salary/income ˂ GHS 375.00 (AOR = 7.20, 95% C.I. = 1.73–29.95), duration on ART for ˂1 year (AOR = 0.27, 95% C.I. = 0.10–0.75), ART regimen (Tenofovir + Lamivudine + Efavirenz) (AOR = 3.26, 95% C.I. = 1.95–11.25), 3–5 times missed medication per month (AOR = 2.86, 95% C.I. = 1.34–6.08) and ≥6 missed medication per month (AOR = 23.87, 95% C.I. = 10.57–53.92). Conclusion: Educational status, salary/income, ART duration, ART combination regimen, and number of doses missed were statistically significantly associated with virological failure in patients on antiretroviral therapy. The majority of the respondents adhered to ART, which led to moderate viral load suppression but lower than the target for 2020. There is the need to strengthen the ongoing accelerated social behavior change communication among patients on ART to enhance adherence in order to attain the new UNAIDS target of 95% viral load suppression by 2030 in the Upper East Region of Ghana. [ABSTRACT FROM AUTHOR]

To broaden access to HIV viral load monitoring (VLM), the use of blood samples from dried blood spots (DBS) or point-of-care (POC) devices, could be of great help in settings where plasma is not easily accessible. The variety of assays available makes the choice complex. This systematic review and meta-analysis aims to estimate the sensitivity and specificity of DBS and POC devices to identify patients in virological failure using World Health Organization (WHO) recommendations (viral load ≥1000 copies/mL), compared with plasma, for the assays currently available. Four databases were searched for articles, and two reviewers independently identified articles reporting sensitivity and specificity of DBS and/or POC to identify patients in virological failure. We excluded articles that used other thresholds as well as articles with a total number of participants below 50 to avoid reporting bias. Heterogeneity and factors associated with assays' performances were assessed by I2 statistics and metaregression. The protocol of this review follows the PRISMA guidelines. Out of 941 articles, 47 were included: 32 DBS evaluations and 16 POC evaluations. Overall, when using DBS, the Abbott RT HIV-1, Roche CAP-CTM, NucliSENS BioMerieux and Aptima assays presented sensitivity and specificity exceeding 85%, but reported results were highly heterogeneous. Factors associated with better performances were high volume of blood and the use of the same assay for DBS and plasma VLM. Regarding the POC devices, SAMBA I, SAMBA II, and GeneXpert devices presented high sensitivity and specificity exceeding 90%, with less heterogeneity. DBS is suitable VLM, but performances can vary greatly depending on the protocols, and should be performed in trained centers. POC is suitable for VLM with less risk of heterogeneity but is more intensive in costs and logistics. [ABSTRACT FROM AUTHOR]

Population-level uptake of direct-acting antiviral (DAA) treatment for hepatitis C virus (HCV) infection, including retreatment, can be estimated through administrative pharmaceutical dispensation data. However, the reasons for retreatment are not captured in these data. We developed a machine learning model to classify retreatments as reinfection or treatment failure at a national level. Retreatment data from the REACH-C cohort (n = 10,843 treated with DAAs; n = 320 retreatments with known reason), were used to train a random forest model. Nested cross validation was undertaken to assess model performance and to optimise hyperparameters. The model was applied to data on DAA retreatment dispensed during 2016-2021 in Australia, to identify the reason for retreatment (treatment failure or reinfection). Average predictive accuracy, precision, sensitivity, specificity and F 1 -score for the model were 96.3%, 96.5%, 96.3%, 96.3% and 96.3%, respectively. Nationally, 95,272 individuals initiated DAAs, with treatment uptake declining from 32,454 in 2016 to 6,566 in 2021. Of those treated, 6,980 (7%) were retreated. Our model classified 51.8% (95% CI 46.7–53.6%; n = 3,614) of cases as reinfection and 48.2% (95% CI 46.4–53.3%; n = 3,366) as treatment failure. Retreatment for reinfection increased steadily over the study period from 14 in 2016 to 1,092 in 2020, stabilising in 2021. Retreatment for treatment failure increased from 73 in 2016 to 1,077 in 2019, then declined to 515 in 2021. Among individuals retreated for treatment failure, 50% had discontinued initial treatment. We used a novel methodology with high classification accuracy to evaluate DAA retreatment patterns at a national level. Increases in retreatment uptake for treatment failure corresponded to the availability of pangenotypic and salvage regimens. Increasing retreatment uptake for reinfection likely reflects increasing reinfection incidence. This study used machine learning methodologies to analyse national administrative data and characterise trends in HCV retreatment due to reinfection and treatment failure. Retreatment for reinfection increased over time, reflecting increasing numbers of people at risk for reinfection following HCV cure. Increased retreatment for treatment failure corresponded to the availability of pangenotypic and salvage DAA regimens. The findings of this study can be used by public health agencies and policy makers to guide and assess HCV elimination strategies, while the novel methodology for monitoring trends in HCV retreatment has the potential to be used in other settings, and health conditions. [Display omitted] • Seven percent of people treated for HCV in Australia were retreated. • Machine learning was used to classify retreatments based on national administrative data. • Overall, 52% of retreatment was for reinfection and 48% was for treatment failure. • Retreatment for reinfection increased over time, reflecting increasing numbers of people at-risk for reinfection following cure. • Retreatment for treatment failure increased when salvage DAAs became available. [ABSTRACT FROM AUTHOR]