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

This case-control study explored cumulative tenofovir exposure among patients with human immunodeficiency virus/hepatis B virus (HIV/HBV) coinfection with HIV viral suppression. Among patients taking tenofovir disoproxil fumarate, median TFV-DP levels in dried blood spots were ∼3-fold lower among patients with incomplete HBV viral suppression (n = 4) compared to those with complete suppression (n = 5) (516 vs 1456 fmol/punch). [ABSTRACT FROM AUTHOR]

Virologic failure of long-acting rilpivirine/cabotegravir is rare but may result in severely limited treatment options. Known risk factors cannot predict all cases. Therapeutic drug monitoring (TDM) may help identify patients at risk, but reliable thresholds are missing. We report retrospective TDM in a cohort of 5 patients, including 1 virological failure. [ABSTRACT FROM AUTHOR]

Abstract Background Antiretroviral therapy (ART) has been proven to be highly effective in reducing the impact of human immunodeficiency virus (HIV) infection. However, as more people receive initial ART treatment, the risk of developing resistance and eventual treatment failure increases, leading to the need for second-line treatment regimens. Understanding the factors that contribute to virologic failure to second-line ART is crucial in preventing switching to the more expensive and toxic third-line regimens. This study provides information on the prevalence, rate, and predictors of virologic failure (VF) among clients on second-line ART in Tanzania. Results We followed 4718 clients for 15100 person-years (PY) of observations. Of them, 1402 (29.72%) experienced virologic failure at a rate of 92.85 per 1000 PY of observations (95% CI 88.11, 97.84). Factors that were associated with VF included: having a viral load count of ≥ 1000 copies/mL during first-line ART, with a hazard ratio (HR) 4.65 (95% CI 3.57, 6.07), using lopinavir (LPV/r) as a protease inhibitor during second-line ART (HR 4.20 (95% CI 3.12, 7.10), having a CD4 count

Abstract Background Sexual and gender minorities (SGMs) are at higher risk of HIV incidence compared to their heterosexual cisgender counterparts. Despite the high HIV disease burden among SGMs, there was limited data on whether they are at higher risk of virologic failure, which may lead to potential disease progression and increased transmission risk. The All of Us (AoU) Research Program, a national community-engaged program aiming to improve health and facilitate health equity in the United States by partnering with one million participants, provides a promising resource for identifying a diverse and large volunteer TGD cohort. Leveraging various data sources available through AoU, the current study aims to explore the association between sexual orientation and gender identity (SOGI) and longitudinal virologic failure among adult people with HIV (PWH) in the US. Methods This retrospective cohort study used integrated electronic health records (EHR) and self-reported survey data from the All of Us (AoU) controlled tier data, version 7, which includes participants enrolled in the AoU research program from May 31, 2017, to July 1, 2022. Based on participants’ sexual orientation, gender identity, and sex assigned at birth, their SOGI were categorized into six groups, including cisgender heterosexual women, cisgender heterosexual men, cisgender sexual minority women, cisgender sexual minority men, gender minority people assigned female at birth of any sexual orientation, and gender minority people assigned male at birth of any sexual orientation. Yearly virologic failure was defined yearly after one’s first viral load testing, and individuals with at least one viral load test > 50 copies/mL during a year were defined as having virologic failure at that year. Generalized linear mixed-effects models were used to explore the association between SOGI and longitudinal virologic failure while adjusting for potential confounders, including age, race, ethnicity, education attainment, income, and insurance type. Results A total of 1,546 eligible PWH were extracted from the AoU database, among whom 1,196 (77.36%) had at least one viral failure and 773 (50.00%) belonged to SGMs. Compared to cisgender heterosexual women, cisgender sexual minority women (adjusted Odds Ratio [aOR] = 1.85, 95% CI: 1.05–3.27) were at higher risk of HIV virologic failure. Additionally, PWH who were Black vs. White (aOR = 2.15, 95% CI: 1.52–3.04) and whose insurance type was Medicaid vs. Private insurance (aOR = 2.07, 95% CI: 1.33–3.21) were more likely to experience virologic failure. Conclusions Maintaining frequent viral load monitoring among sexual minority women with HIV is warranted because it allows early detection of virologic failure, which could provide opportunities for interventions to strengthen treatment adherence and prevent HIV transmission. To understand the specific needs of subgroups of SGMs, future research needs to examine the mechanisms for SOGI-based disparities in virologic failure and the combined effects of multi-level psychosocial and health behavior characteristics.

Background: Sexual and gender minorities (SGMs) are at higher risk of HIV incidence compared to their heterosexual cisgender counterparts. Despite the high HIV disease burden among SGMs, there was limited data on whether they are at higher risk of virologic failure, which may lead to potential disease progression and increased transmission risk. The All of Us (AoU) Research Program, a national community-engaged program aiming to improve health and facilitate health equity in the United States by partnering with one million participants, provides a promising resource for identifying a diverse and large volunteer TGD cohort. Leveraging various data sources available through AoU, the current study aims to explore the association between sexual orientation and gender identity (SOGI) and longitudinal virologic failure among adult people with HIV (PWH) in the US. Methods: This retrospective cohort study used integrated electronic health records (EHR) and self-reported survey data from the All of Us (AoU) controlled tier data, version 7, which includes participants enrolled in the AoU research program from May 31, 2017, to July 1, 2022. Based on participants' sexual orientation, gender identity, and sex assigned at birth, their SOGI were categorized into six groups, including cisgender heterosexual women, cisgender heterosexual men, cisgender sexual minority women, cisgender sexual minority men, gender minority people assigned female at birth of any sexual orientation, and gender minority people assigned male at birth of any sexual orientation. Yearly virologic failure was defined yearly after one's first viral load testing, and individuals with at least one viral load test > 50 copies/mL during a year were defined as having virologic failure at that year. Generalized linear mixed-effects models were used to explore the association between SOGI and longitudinal virologic failure while adjusting for potential confounders, including age, race, ethnicity, education attainment, income, and insurance type. Results: A total of 1,546 eligible PWH were extracted from the AoU database, among whom 1,196 (77.36%) had at least one viral failure and 773 (50.00%) belonged to SGMs. Compared to cisgender heterosexual women, cisgender sexual minority women (adjusted Odds Ratio [aOR] = 1.85, 95% CI: 1.05–3.27) were at higher risk of HIV virologic failure. Additionally, PWH who were Black vs. White (aOR = 2.15, 95% CI: 1.52–3.04) and whose insurance type was Medicaid vs. Private insurance (aOR = 2.07, 95% CI: 1.33–3.21) were more likely to experience virologic failure. Conclusions: Maintaining frequent viral load monitoring among sexual minority women with HIV is warranted because it allows early detection of virologic failure, which could provide opportunities for interventions to strengthen treatment adherence and prevent HIV transmission. To understand the specific needs of subgroups of SGMs, future research needs to examine the mechanisms for SOGI-based disparities in virologic failure and the combined effects of multi-level psychosocial and health behavior characteristics. [ABSTRACT FROM AUTHOR]

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

Dolutegravir resistance is emerging in routine clinical contexts in southern Africa, primarily in patients with prior treatment experience failing dolutegravir-based antiretroviral therapy (ART). This potential issue was raised by The Nucleosides and Darunavir/Dolutegravir in Africa trial that compared dolutegravir and boosted protease inhibitor–based therapy as second-line ART, in which new dolutegravir resistance was observed at failure. However, recent data suggest that also at risk are patients who were transitioned to dolutegravir from non-nucleoside reverse transcriptase inhibitor–based ART while viremic. Identifying patients experiencing failure of dolutegravir with resistance will be difficult given current gaps in viral load monitoring and limited capacity for genotypic resistance testing. As a result, in the short term, most patients affected will go unrecognized, with particularly important implications for patients affected who have advanced HIV or who are pregnant/breastfeeding. Prospective research is needed to understand the scope of the problem, identify additional risk factors, and determine best management. In the short term, for most patients with dolutegravir resistance and prior non-nucleoside reverse transcriptase inhibitor exposure, the best option will be a timely switch to a regimen anchored by a boosted protease inhibitor, with a high genetic barrier to resistance. [ABSTRACT FROM AUTHOR]

HIV-associated wasting (HIVAW) is an underappreciated AIDS-defining illness, despite highly effective antiretroviral therapy (ART). We (a) assessed the association between incident HIVAW/low weight and all-cause mortality and (b) described virologic outcomes after people with HIV (PWH) experienced HIVAW/low weight while on ART. In the Observational Pharmaco-Epidemiology Research & Analysis (OPERA®) cohort, PWH without prior HIVAW/low weight who were active in care in 2016–2020 were followed through the first of the following censoring events: death, loss to follow-up, or study end (October 31, 2021). HIVAW/low weight was a diagnosis of wasting or low body mass index (BMI)/underweight or a BMI measurement <20 kg/m2. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between time-dependent HIVAW/low weight and mortality were estimated with extended Cox regression models. Over a median follow-up of 45 months (interquartile range: 27, 65), there were 4,755 (8%) cases of HIVAW/low weight and 1,354 (2%) deaths among 62,314 PWH. PWH who experienced HIVAW/low weight had a significantly higher risk of death than those who did not (HR: 1.96; 95% CI: 1.68, 2.27) after adjusting for age, race, ethnicity, and changes in viral load (VL) and Veterans Aging Cohort Study Mortality Index scores over follow-up. Among 4,572 PWH on ART at HIVAW/low weight, 68% were suppressed (VL of <200 copies/mL); subsequent virologic failure was uncommon (7%). Among viremic PWH, 70% and 60% achieved suppression and undetectability (VL of <50 copies/mL), respectively, over follow-up. HIVAW remains a challenge for some PWH. Particular attention needs to be paid to HIVAW/low weight and virologic control to restore health and potentially reduce the risk of death. [ABSTRACT FROM AUTHOR]

Abstract Background Low-level viremia (LLV) has been identified as a potential precursor to virologic failure (VF), yet its clinical implications, particularly within the context of Integrase Strand Transfer Inhibitors (INSTIs)-based regimens, remain insufficiently explored. The study aimed to investigate the relationship between LLV and VF within ART-naïve patients on INSTIs-based regimens in China. Methods A longitudinal cohort study was conducted with ART-naïve patients aged ≥ 18 years at Beijing Ditan Hospital, under the Chinese National Free Antiretroviral Treatment Program (NFATP). The LLV was defined as a viral load (VL) ranging from 50 to 199 copies/mL after six months of ART initiation, and VF as a VL ≥ 200 copies/mL. Sensitive analyses were also performed, defining LLV as 50–999 copies/mL and VF as exceeding 1000 copies/mL. Multivariate logistic regression, Kaplan-Meier (KM) curve, and Generalized Estimating Equation (GEE) models were used to evaluate the risk factors associated with LLV and VF events. Results The study involved 830 ART-naïve patients, comprising 600 in the INSTIs group and 230 in the protease inhibitors (PIs) group. LLV events were observed in 10.4% of patients on PIs-based regimens and and 3.2% on INSTIs-based regimens (P

Background: Low-level viremia (LLV) has been identified as a potential precursor to virologic failure (VF), yet its clinical implications, particularly within the context of Integrase Strand Transfer Inhibitors (INSTIs)-based regimens, remain insufficiently explored. The study aimed to investigate the relationship between LLV and VF within ART-naïve patients on INSTIs-based regimens in China. Methods: A longitudinal cohort study was conducted with ART-naïve patients aged ≥ 18 years at Beijing Ditan Hospital, under the Chinese National Free Antiretroviral Treatment Program (NFATP). The LLV was defined as a viral load (VL) ranging from 50 to 199 copies/mL after six months of ART initiation, and VF as a VL ≥ 200 copies/mL. Sensitive analyses were also performed, defining LLV as 50–999 copies/mL and VF as exceeding 1000 copies/mL. Multivariate logistic regression, Kaplan-Meier (KM) curve, and Generalized Estimating Equation (GEE) models were used to evaluate the risk factors associated with LLV and VF events. Results: The study involved 830 ART-naïve patients, comprising 600 in the INSTIs group and 230 in the protease inhibitors (PIs) group. LLV events were observed in 10.4% of patients on PIs-based regimens and and 3.2% on INSTIs-based regimens (P < 0.001). INSTIs-based regimens demonstrated a protective effect against LLV events (aHR = 0.27, 95% CI 0.137–0.532). VF events occurred in 10.9% of patients on PIs-based regimens and 2.0% on INSTIs-based regimens, respectively (P < 0.001). The occurrence of LLV events significantly increased the risk of VF by 123.5% (95% CI 7.5%-364.4%), while the integrase inhibitors were associated with a 76.9% (95% CI 59.1%-86.9%) reduction in VF risk. Conclusion: Our findings indicate that INSTIs-based regimens are critical protective factors against LLV and subsequent VF. These results underscore the importance of HIV viral load monitoring to ensuring effective treatment outcomes, highlighting the necessity for prompt and precise monitoring to refine HIV treatment methodologies. [ABSTRACT FROM AUTHOR]

Background This study examined the prevalence and factors associated with detectable viremia, as well as clinical outcomes among people with HIV (PWH) receiving antiretroviral therapy (ART) who initially achieved viral suppression in 2 southern states in Nigeria. Methods The retrospective cohort study used data from the electronic medical records of 96 comprehensive ART centers. PWH were followed up who achieved viral suppression (viral load [VL] ≤50 copies/mL) upon starting ART based on the first VL test. We examined the presence of detectable viremia in follow-up VL results, graded by the absolute VL count from the second and third consecutive VL tests as follows: transient viremia (second follow-up VL, 51–999 copies/mL; third, ≤50 copies/mL), persistent viremia (second follow-up VL, 51–999 copies/mL or ≥1000 copies/mL; third, >50 copies/mL), and virologic failure (second and third follow-up VL, >1000 copies/mL). We analyzed demographic and clinical factors associated with detectable viremia using logistic regression analysis on Stata 14. Results Overall, 15 050 PWH had achieved viral suppression following ART initiation (median age, 34 years; 71.3% female). On follow-up, 3101 (20.6%) had a viremic event: 11.6%, transient viremia; 8.8%, persistent viremia; 0.2%, virologic failure. Shorter duration of ART (P <.001), being 0 to 14 years of age (P <.001), and not being enrolled in a differentiated service delivery model (P <.001) were significantly associated with detectable viremia. Conclusions Our study shows that people who initially attain vial suppression upon starting ART remain at risk of detectable viremia. [ABSTRACT FROM AUTHOR]

This retrospective cohort study investigated older people living with HIV/AIDS (PLWHA) characteristics, HIV care, and treatment outcomes among all cases between 1996 and 2019 in Guangxi, China. Secondary data were extracted from two national surveillance databases. Older (≥50 years old) and younger (18-49 years old) PLWHA were compared regarding demographic and behavioral characteristics, HIV care, virologic failure, and all-cause mortality. Older PLWHA accounted for 41.6% of all HIV cases (N = 144,952) between 1996 and 2019. The proportion of older cases increased from 10.4% to 64.8% for men and from 2.4% to 66.7% for women between 2002 and 2019. Heterosexual contact accounted for 96.0% of older adults. Moreover, older PLWHA had a lower median CD4 count at the HIV diagnosis (193 vs. 212 cells/μL, p < 0.0001) and were less likely to receive antiretroviral therapy (ART) than younger adults (72.1% vs. 86.1%, p < 0.001). The all-cause mortality risk of older PLWHA was 2.87 times of younger adults [adjusted hazard ratio (AHR) 2.87; 95% confidence interval (CI) 2.76-2.98]. In addition, older PLWHA reported an 18% increase in odds for virologic failure than younger adults (AOR 1.18; 95% CI 1.08-1.30). Therefore, enhanced HIV prevention and care are urgently needed in older people. [ABSTRACT FROM AUTHOR]

Background The implications of bariatric surgery (BS) on virologic and metabolic outcomes in people with human immunodeficiency virus (HIV; PWH) on antiretroviral therapy (ART) are unknown. Methods Here, we report a retrospective analysis up to 18 months post-BS in PWH from the AIDS Therapy evaluation in The Netherlands (ATHENA) cohort with data from all dutch HIV treating Centers. Primary end points were a confirmed virologic failure (2 consecutive HIV-RNA measurements >200 copies/mL) and the percentage of patients who achieved >20% total body weight loss up to 18 months post-BS. Switches from baseline ART and trough plasma concentrations of antiretrovirals were also reported post-BS. Metabolic parameters and medication usage were compared pre- and post-BS. Results Fifty-one patients were included. One case of confirmed virologic failure and 3 cases with viral blips were detected in this cohort up to 18 months post-BS. Eighty-five percent of patients achieved >20% total body weight loss at 18 months post-BS, with a mean difference from baseline (95% confidence interval) of −33.5% (−37.7% to −29.3%). Trough plasma concentrations of measured antiretroviral agents were all above minimum effective concentrations, except for 1 sample of darunavir. Lipid profiles, but not serum creatinine and blood pressure, improved significantly (P <.01) post-BS. Total medications and obesity-related comedications declined from 203 to 103 and from 62 to 25, respectively, at 18 months post-BS. Conclusions BS was an effective intervention for weight loss and lipid control in PWH using ART in this cohort with no clear link to poor virologic outcomes. [ABSTRACT FROM AUTHOR]

Background: In South African antiretroviral guidelines, selected patients failing second-line protease inhibitor (PI)-based therapy qualify for genotypic resistance testing – those with PI resistance receive darunavir-based third-line regimens; those without PI resistance continue current regimen with adherence support. The Western Cape province, from September 2020, implemented a strategy of tenofovir-lamivudine-dolutegravir (TLD) for patients, provided there was no tenofovir resistance, irrespective of PI resistance. Objectives: To evaluate virologic outcomes with TLD among adults failing second-line PI regimens with no tenofovir resistance. Method: An observational cohort study comparing outcomes in patients switched to TLD with those continuing the same PI or switched to darunavir-based regimens. Follow-up was until virologic suppression (HIV-1 RNA 400 copies/mL), or at the point of censoring. Results: One hundred and thirty-three patients switched to TLD, 101 to darunavir-based regimens, and 121 continued with the same PI. By 12 months, among patients with PI resistance, 42/47 (89%) in the TLD group had HIV-1 RNA 400 copies/mL compared to 91/99 (92%) in the darunavir group (hazard ratio, 1.11; 95% confidence interval, 0.77–1.60). In patients without PI resistance, 66/86 (77%) in the TLD group had HIV-1 RNA 400 copies/mL compared to 42/120 (35%) in those continuing with the same PI (hazard ratio, 4.03; 95% confidence interval, 2.71–5.98). Two patients receiving TLD developed virologic failure with high-level dolutegravir resistance. Conclusion: Amongst patients failing second-line PI with no PI resistance, switching to TLD was associated with higher virologic suppression, likely due to improved adherence. Virologic outcomes were similar in patients with PI resistance switched to darunavir-based regimens or TLD.

Abstract Objective The purpose of this study is to investigate the incidence of determinants for virologic failure and to identify predisposing factors to enhance treatment efficacy. Tackling this global public health issue is the key to reducing the rate of virological failure and increasing the success of treatment for those living with HIV. Methods This umbrella review delves into various aspects of current anti-retroviral therapy (ART) which is the primary treatment for human immunodeficiency virus (HIV) infection. Comprehensive searches were conducted in online databases including PubMed, Embase, Scopus, and Web of Science, up to May 26, 2023. Following the screening and selection of relevant articles, eligible articles were included in the data extraction. This study adhered to the PRISMA guideline to report the results and employed the NIH quality and bias risk assessment tool to ensure the quality of included studies. Results In total, 40 review studies published from 2015 to 2023 were included. The bulk of these studies concurred on several major factors contributing to HIV drug resistance and virological failure. Key among these were medication adherence, baseline and therapeutic CD4 levels, the presence of co-infections, and the advanced clinical stage of the infection. Conclusion The resistance to HIV drugs and instances of determinants for virologic failure have a profound impact on the life quality of those infected with HIV. Primary contributors to this scenario include insufficient adherence to treatment, decreased CD4 T-cell count, elevated viral levels, and certain treatment regimens. Implementing appropriate interventions could address these issues. Sub-Saharan Africa exhibits elevated rates of determinants for virologic failure, attributed to the delay in HIV testing and diagnosis, and late initiation of antiretroviral therapy (ART). It is essential to undertake further research aimed at enhancing the detection of resistance in HIV patients and mitigating viral failure by addressing these underlying causes.

Background: Antiretroviral regimens containing a second-generation integrase strand-transfer inhibitor (INSTI) plus 2 nucleos(t)ide reverse-transcriptase inhibitors (NRTIs) are the recommended therapy for people with HIV (PWH) who are antiretroviral-naïve or on stable antiretroviral therapy (ART) with viral suppression. Real-world data on the virologic effectiveness of co-formulated bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) among PWH with virologic failure while receiving other ART remain sparse. Methods: We retrospectively reviewed the medical records of PWH who had viral rebound with plasma HIV RNA >1000 copies/mL and were switched to either dolutegravir combined with 2 NRTIs or BIC/FTC/TAF. The primary end point was re-achieving viral suppression within the first 48 weeks of switch. The association between NRTI-related resistance-associated mutations (RAMs) and virologic effectiveness was examined. Results: Seventy-nine PWH with viral rebound while receiving other antiretroviral regimens were included. Within the first 48 weeks of switch, the overall probability of re-achieving viral suppression was 79.7% (82.5% [33/40] and 76.9% [30/39] for BIC/FTC/TAF and dolutegravir-based regimens, respectively, p = 0.78). PWH with a higher CD4 lymphocyte count (adjusted odds ratio, per 100-cell/mm3 increase, 1.41; 95% confidence interval, 1.02–1.95) were more likely to re-achieve viral suppression. Among PWH switching to BIC/FTC/TAF who had pre-existing RAMs to NRTIs before switch, 14 of 15 (93.3%) successfully achieved viral suppression. Conclusions: Switching to BIC/FTC/TAF and dolutegravir-based regimens could re-achieve viral suppression in four-fifth of the PWH who experienced viral rebound during treatment with other antiretroviral regimens. Pre-existing NRTI-related RAMs did not have adverse impact on the effectiveness of dolutegravir combined with 2 NRTIs or BIC/FTC/TAF.

Low-frequency mutations associated with drug resistance have been related to virologic failure in subjects with no history of pre-treatment and recent HIV diagnosis. In total, 78 antiretroviral treatment (ART)-naïve subjects with a recent HIV diagnosis were selected and followed by CD4+ T lymphocytes and viral load tests to detect virologic failure. We sequenced the basal samples retrospectively using next-generation sequencing (NGS), looking for low-frequency mutations that had not been detected before using the Sanger sequencing method (SSM) and describing the response to ART. Twenty-two subjects developed virologic failure (VF), and thirteen of them had at least one drug-resistance mutation associated with Reverse Transcriptase Inhibitors (RTI) and Protease Inhibitors (PIs) at frequency levels ≤ 1%, not detected previously in their basal genotyping test. No resistance mutations were observed to Integrase Strand Transfer Inhibitors (INSTIs). We identified a possible cause of VF in ART-naïve subjects with low-frequency mutations detected. To our knowledge, this is the first evaluation of pre-existing drug resistance for HIV-1 minority variants carried out on ART-naïve people living with HIV/AIDS (PLWHA) by analyzing the HIV-1 pol gene using NGS in the country.

Objective: The purpose of this study is to investigate the incidence of determinants for virologic failure and to identify predisposing factors to enhance treatment efficacy. Tackling this global public health issue is the key to reducing the rate of virological failure and increasing the success of treatment for those living with HIV. Methods: This umbrella review delves into various aspects of current anti-retroviral therapy (ART) which is the primary treatment for human immunodeficiency virus (HIV) infection. Comprehensive searches were conducted in online databases including PubMed, Embase, Scopus, and Web of Science, up to May 26, 2023. Following the screening and selection of relevant articles, eligible articles were included in the data extraction. This study adhered to the PRISMA guideline to report the results and employed the NIH quality and bias risk assessment tool to ensure the quality of included studies. Results: In total, 40 review studies published from 2015 to 2023 were included. The bulk of these studies concurred on several major factors contributing to HIV drug resistance and virological failure. Key among these were medication adherence, baseline and therapeutic CD4 levels, the presence of co-infections, and the advanced clinical stage of the infection. Conclusion: The resistance to HIV drugs and instances of determinants for virologic failure have a profound impact on the life quality of those infected with HIV. Primary contributors to this scenario include insufficient adherence to treatment, decreased CD4 T-cell count, elevated viral levels, and certain treatment regimens. Implementing appropriate interventions could address these issues. Sub-Saharan Africa exhibits elevated rates of determinants for virologic failure, attributed to the delay in HIV testing and diagnosis, and late initiation of antiretroviral therapy (ART). It is essential to undertake further research aimed at enhancing the detection of resistance in HIV patients and mitigating viral failure by addressing these underlying causes. [ABSTRACT FROM AUTHOR]

Increasing HIV drug resistance (DR) among children with HIV (CHIV) on antiretroviral treatment (ART) is concerning. CHIV ages 1–14 years enrolled from March 2019 to December 2020 from five facilities in Kisumu County, Kenya, were included. Children were randomized 1:1 to control (standard-of-care) or intervention (point-of-care viral load (POC VL) testing every three months with targeted genotypic drug resistance testing (DRT) for virologic failure (VF) (≥1000 copies/mL)). A multidisciplinary committee reviewed CHIV with DRT results and offered treatment recommendations. We describe DR mutations and present logistic regression models to identify factors associated with clinically significant DR. We enrolled 704 children in the study; the median age was 9 years (interquartile range (IQR) 7, 12), 344 (49%) were female, and the median time on ART was 5 years (IQR 3, 8). During the study period, 106 (15%) children had DRT results (84 intervention and 22 control). DRT detected mutations associated with DR in all participants tested, with 93 (88%) having major mutations, including 51 (54%) with dual-class resistance. A history of VF in the prior 2 years (adjusted odds ratio (aOR) 11.1; 95% confidence interval (CI) 6.3, 20.0) and less than 2 years on ART at enrollment (aOR 2.2; 95% CI 1.1, 4.4) were associated with increased odds of major DR. DR is highly prevalent among CHIV on ART with VF in Kenya. Factors associated with drug resistance may be used to determine which children should be prioritized for DRT. [ABSTRACT FROM AUTHOR]

The concept of "undetectable = untransmittable (U = U)" has been revolutionary in both the prevention and treatment of persons with human immunodeficiency virus (HIV). Most studies proving the concept of U = U used an HIV RNA (viral load [VL]) cutoff of 200 copies/mL to define being undetectable. Since then, increasingly sensitive commercial VL assays, sometimes down to a lower limit of detection (LLD) of 20 copies/mL, lead to confusion about the definition of "undetectable" and when someone is truly considered untransmittable. VLs between the LLD and 200 copies/mL have been associated with future virologic failure; however, no data exist to suggest that intervening in those patients leads to any meaningful benefits. In the absence of a demonstrable benefit of reporting such low VLs, we view this practice as harmful. We suggest recommendations for adjusting VL reporting and improving provider counseling, and call for research designs to mitigate the harms of overly sensitive VL testing. [ABSTRACT FROM AUTHOR]

Abstract Background Since January 2017, the recommended first-line antiretroviral regimen in Brazil is the fixed-dose combination of tenofovir plus lamivudine with dolutegravir (TL + D). According to the literature, integrase resistance-associated mutations (INRAMs) are rarely found upon virologic failure to first-line dolutegravir plus two nucleoside reverse transcriptase inhibitors. We evaluated the HIV antiretroviral genotypic resistance profile of patients referred for genotyping in the public health system who failed first-line TL + D after at least six months of therapy on or before December 31, 2018. Methods HIV Sanger sequences of the pol gene were generated from plasma of patients with confirmed virologic failure to first-line TL + D in the Brazilian public health system before December 31, 2018. Results One hundred thirteen individuals were included in the analysis. Major INRAMs were detected in seven patients (6.19%), four with R263K, one with G118R, one with E138A, and one with G140R. Four patients with major INRAMs also had the K70E and M184V mutations in the RT gene. Sixteen (14.2%) additional individuals presented minor INRAMs, and five (4,42%) patients had both major and minor INRAMS. Thirteen (11.5%) patients also presented mutations in the RT gene selected by tenofovir and lamivudine, including four with both the K70E and M184V mutations and four with only M184V. The integrase mutations L101I and T124A, which are in the in vitro pathway for integrase inhibitor resistance, were found in 48 and 19 patients, respectively. Mutations not related to TL + D, thus probable transmitted resistance mutations (TDR), were present in 28 patients (24.8%): 25 (22.1%) to nucleoside reverse transcriptase inhibitors, 19 (16.8%) to non-nucleoside reverse transcriptase inhibitors, and 6 (5.31%) to protease inhibitors. Conclusions In marked contrast to previous reports, we report a relatively high frequency of INRAMs among selected patients failing first-line TL + D in the public health system in Brazil. Possible reasons for this discrepancy include delays in detecting virologic failure, patients inadvertently on dolutegravir monotherapy, TDR, and/or infecting subtype.

Summary: Background: HIV low-level viremia (LLV) (51–999 copies/mL) can progress to treatment failure and increase potential for drug resistance. We analyzed retrospective longitudinal data from people living with HIV (PLHIV) on antiretroviral therapy (ART) in Kenya to understand LLV prevalence and virologic outcomes. Methods: We calculated rates of virologic suppression (≤50 copies/mL), LLV (51–999 copies/mL), virologic non-suppression (≥1000 copies/mL), and virologic failure (≥2 consecutive virologic non-suppression results) among PLHIV aged 15 years and older who received at least 24 weeks of ART during 2015–2021. We analyzed risk for virologic non-suppression and virologic failure using time-dependent models (each viral load (VL)

Antiretroviral therapies (ARTs) have revolutionized the management of human immunodeficiency virus (HIV) infection, significantly improved patient outcomes, and reduced the mortality rate and incidence of acquired immunodeficiency syndrome (AIDS). However, despite the remarkable efficacy of ART, virologic failure remains a challenge in the long-term management of HIV-infected individuals. Virologic failure refers to the persistent detectable viral load in patients receiving ART, indicating an incomplete suppression of HIV replication. It can occur due to various factors, including poor medication adherence, drug resistance, suboptimal drug concentrations, drug interactions, and viral factors such as the emergence of drug-resistant strains. In recent years, extensive efforts have been made to understand and address virologic failure in order to optimize treatment outcomes. Strategies to prevent and manage virologic failure include improving treatment adherence through patient education, counselling, and supportive interventions. In addition, the regular monitoring of viral load and resistance testing enables the early detection of treatment failure and facilitates timely adjustments in ART regimens. Thus, the development of novel antiretroviral agents with improved potency, tolerability, and resistance profiles offers new options for patients experiencing virologic failure. However, new treatment options would also face virologic failure if not managed appropriately. A solution to virologic failure requires a comprehensive approach that combines individualized patient care, robust monitoring, and access to a range of antiretroviral drugs. [ABSTRACT FROM AUTHOR]

Low-frequency mutations associated with drug resistance have been related to virologic failure in subjects with no history of pre-treatment and recent HIV diagnosis. In total, 78 antiretroviral treatment (ART)-naïve subjects with a recent HIV diagnosis were selected and followed by CD4+ T lymphocytes and viral load tests to detect virologic failure. We sequenced the basal samples retrospectively using next-generation sequencing (NGS), looking for low-frequency mutations that had not been detected before using the Sanger sequencing method (SSM) and describing the response to ART. Twenty-two subjects developed virologic failure (VF), and thirteen of them had at least one drug-resistance mutation associated with Reverse Transcriptase Inhibitors (RTI) and Protease Inhibitors (PIs) at frequency levels ≤ 1%, not detected previously in their basal genotyping test. No resistance mutations were observed to Integrase Strand Transfer Inhibitors (INSTIs). We identified a possible cause of VF in ART-naïve subjects with low-frequency mutations detected. To our knowledge, this is the first evaluation of pre-existing drug resistance for HIV-1 minority variants carried out on ART-naïve people living with HIV/AIDS (PLWHA) by analyzing the HIV-1 pol gene using NGS in the country. [ABSTRACT FROM AUTHOR]

Background Antiretroviral therapy (ART) is recommended for people with HIV (PWH), irrespective of CD4 cell count, to improve their health and reduce the risk of transmission to sexual partners through long-term viral suppression. We identified risk factors for viral rebound among patients with a period of stable viral suppression to inform counseling and monitoring. Methods We conducted a multisite, retrospective study of PWH with a 2-year period of sustained viral suppression in the United States using the Centers for AIDS Research Network of Integrated Clinical Systems cohort. We used multivariable logistic regression to identify characteristics independently associated with any viral rebound (viral load [VL] ≥200 copies/mL) and sustained viral rebound (VL ≥200 copies/mL followed by a VL that was also ≥200 copies/mL within 6 months), within 2 years of follow-up. Results Among 3496 eligible patients with a 2-year period of sustained viral suppression, most (90%) continued to have viral suppression over 2 additional years; 10% experienced viral rebound, and 4% experienced sustained viral rebound. In multivariable analyses, Black race, current smoking, integrase strand transfer inhibitor use, and 5- to 9-year duration of ART were positively associated, and being age ≥50 years was negatively associated, with any viral rebound. Only current smoking and 5- to 9-year (vs 2- to 4-year) duration of ART were positively associated, and being age ≥60 years was negatively associated, with sustained viral rebound. Conclusions Most people retained in clinical care and with HIV viral suppression on ART will have persistent viral suppression. However, some patients may benefit from additional treatment adherence support. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is Available in the Text. Background: Women with HIV (WHIV) in the United States face many challenges with adherence to antiretroviral therapy (ART), and suboptimal adherence often leads to virologic failure. This study aimed to determine the association between ART adherence trajectories and the risk of virologic failure. Methods: We included WHIV (aged 18 years or older) enrolled in the Women's Interagency HIV Study in the United States from April 2014 to September 2019 who had at least 2 consecutive measurements of HIV RNA and ≥3 measurements of self-reported adherence. Group-based trajectory modeling was used to identify adherence trajectories. Cox proportional hazard ratios were used to measure the association. Main Outcome Measure: Virologic failure was defined as HIV RNA ≥200 copies/mL at 2 consecutive visits. Results: We included 1437 WHIV (median age 49 years). Of all women, 173 (12.0%) experienced virologic failure. Four adherence trajectories were identified, namely "consistently high" (26.3%), "moderate increasing" (9.5%), "moderate decreasing" (30.6%), and "consistently low" (33.5%). Women in the consistently low adherence group consumed alcohol and experienced depression more than other groups. Compared with the "consistently high" trajectory, the risk of virologic failure was higher among women with "consistently low" [adjusted hazard ratio (aHR) 2.8; 95% confidence interval (CI): 1.6 to 4.9; P < 0.001] and "moderate decreasing" adherence trajectories (aHR 1.8; 95% CI: 1.0 to 3.2; P = 0.04), but it was similar to those with "moderate increasing" adherence trajectory (aHR 1.0; 95% CI: 0.4 to 2.5; P = 0.94). Conclusions: Adherence to ART remains a challenge among WHIV. Multilevel behavioral interventions to address poor adherence, alcohol consumption, and depression are needed. [ABSTRACT FROM AUTHOR]

IntroductionReal-time electronic adherence monitoring (EAM) systems could inform on-going risk assessment for HIV viraemia and be used to personalize viral load testing schedules. We evaluated the potential of real-time EAM (transferred via cellular signal) and standard EAM (downloaded via USB cable) in rural Uganda to inform individually differentiated viral load testing strategies by applying machine learning approaches.MethodsWe evaluated an observational cohort of persons living with HIV and treated with antiretroviral therapy (ART) who were monitored longitudinally with standard EAM from 2005 to 2011 and real-time EAM from 2011 to 2015. Super learner, an ensemble machine learning method, was used to develop a tool for targeting viral load testing to detect viraemia (>1000 copies/ml) based on clinical (CD4 count, ART regimen), viral load and demographic data, together with EAM-based adherence. Using sample-splitting (cross-validation), we evaluated area under the receiver operating characteristic curve (cvAUC), potential for EAM data to selectively defer viral load tests while minimizing delays in viraemia detection, and performance compared to WHO-recommended testing schedules.ResultsIn total, 443 persons (1801 person-years) and 485 persons (930 person-years) contributed to standard and real-time EAM analyses respectively. In the 2011 to 2015 dataset, addition of real-time EAM (cvAUC: 0.88; 95% CI: 0.83, 0.93) significantly improved prediction compared to clinical/demographic data alone (cvAUC: 0.78; 95% CI: 0.72, 0.86; p = 0.03). In the 2005 to 2011 dataset, addition of standard EAM (cvAUC: 0.77; 95% CI: 0.72, 0.81) did not significantly improve prediction compared to clinical/demographic data alone (cvAUC: 0.70; 95% CI: 0.64, 0.76; p = 0.08). A hypothetical testing strategy using real-time EAM to guide deferral of viral load tests would have reduced the number of tests by 32% while detecting 87% of viraemia cases without delay. By comparison, the WHO-recommended testing schedule would have reduced the number of tests by 69%, but resulted in delayed detection of viraemia a mean of 74 days for 84% of individuals with viraemia. Similar rules derived from standard EAM also resulted in potential testing frequency reductions.ConclusionsOur machine learning approach demonstrates potential for combining EAM data with other clinical measures to develop a selective testing rule that reduces number of viral load tests ordered, while still identifying those at highest risk for viraemia.

We reviewed the medical charts of 1,700 patients diagnosed with HIV who referred to a central HIV clinic in Tehran between 2004 and 2017. Participants who had a viral load of > 200 copies/mL after six months or more on antiretroviral therapy (ART) were grouped as virologic failure (VF). We assessed the demographic characteristics, diagnosis date, first ART regimen, and resistance to various ART drugs. Out of 1,700 patients, 72 (4.2%) had a treatment failure. Among those with treatment failure, 51.3% were on zidovudine + lamivudine + efavirenz, 13.9% were on tenofovir + lamivudine + lopinavir/ritonavir, and 12.5% were on tenofovir + emtricitabine + efavirenz. In patients with treatment failure, the highest resistance was to nucleoside reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs) combination (44.4%). In these patients, resistance to tenofovir (one of the NRTIs) was 29.1%. The highest treatment failure was observed among patients treated with nevirapine (NVP) and efavirenz (EFV)-based regimen. Our findings suggest that protease inhibitors should be considered as first-line drugs in ART regimens in VF patients in Iran.

Background: The growing number of people on antiretroviral therapy in Kenya has led to a decrease in HIV morbidity and mortality. However, virologic failure (VF) threatens to reverse these gains. In Makueni County, existing data indicate challenges in achieving viral load (VL) suppression among persons living with HIV (PLHIV). Few studies have been carried out investigating VF in the region despite its high incidence of HIV infections. Methods: An analytical cross-sectional study was conducted among PLHIV in Makueni County to investigate the determinants and estimate the prevalence of VF. The prevalence of VF and its associated 95% exact binomial confidence interval was estimated, and a mixed-effects logistic regression model used to evaluate the relationship between the predictors and VF. Results: The estimated period prevalence of VF between October 2018 and June 2019 was 13.2% (95% CI: 12.7%–13.8%). Being 15 years or older (aOR=0.53; 95% CI: 0.44 – 0.645) and having blood samples tested for reasons other than baseline VL measurement was associated with lower odds of VF: breastfeeding mothers (aOR=0.1; 95% CI: 0.01 – 0.97); clinical failure (aOR=0.08; 95% CI: 0.01 – 0.44); confirmation of VF (aOR=0.2; 95% CI: 0.07 – 0.62); no VL data (aOR=0.06; 95% CI: 0.01 – 0.31); routine VL (aOR=0.04; 95% CI: 0.01 – 0.12); drug substitution (aOR=0.03; 95% CI: 0.01 – 0.08). Taking ABC-based, AZT-based, or other non-TDF-Based regimens increased the odds of VF (aOR=1.61; 95% CI: 1.34 – 1.94), (aOR=1.75; 95% CI: 1.52 - 2.01), and (aOR=1.55; 95% CI: 0.99 - 2.44) respectively. Conclusion: This study showed that over 13% of HIV patients on ART in Makueni County had VF between October 2018 and June 2019. The significant risk factors associated with VF were found to be age lower than 15 years, taking a non-TDF-based ART regimen, and blood sampling for baseline VL measurements.

Background: Since January 2017, the recommended first-line antiretroviral regimen in Brazil is the fixed-dose combination of tenofovir plus lamivudine with dolutegravir (TL + D). According to the literature, integrase resistance-associated mutations (INRAMs) are rarely found upon virologic failure to first-line dolutegravir plus two nucleoside reverse transcriptase inhibitors. We evaluated the HIV antiretroviral genotypic resistance profile of patients referred for genotyping in the public health system who failed first-line TL + D after at least six months of therapy on or before December 31, 2018. Methods: HIV Sanger sequences of the pol gene were generated from plasma of patients with confirmed virologic failure to first-line TL + D in the Brazilian public health system before December 31, 2018. Results: One hundred thirteen individuals were included in the analysis. Major INRAMs were detected in seven patients (6.19%), four with R263K, one with G118R, one with E138A, and one with G140R. Four patients with major INRAMs also had the K70E and M184V mutations in the RT gene. Sixteen (14.2%) additional individuals presented minor INRAMs, and five (4,42%) patients had both major and minor INRAMS. Thirteen (11.5%) patients also presented mutations in the RT gene selected by tenofovir and lamivudine, including four with both the K70E and M184V mutations and four with only M184V. The integrase mutations L101I and T124A, which are in the in vitro pathway for integrase inhibitor resistance, were found in 48 and 19 patients, respectively. Mutations not related to TL + D, thus probable transmitted resistance mutations (TDR), were present in 28 patients (24.8%): 25 (22.1%) to nucleoside reverse transcriptase inhibitors, 19 (16.8%) to non-nucleoside reverse transcriptase inhibitors, and 6 (5.31%) to protease inhibitors. Conclusions: In marked contrast to previous reports, we report a relatively high frequency of INRAMs among selected patients failing first-line TL + D in the public health system in Brazil. Possible reasons for this discrepancy include delays in detecting virologic failure, patients inadvertently on dolutegravir monotherapy, TDR, and/or infecting subtype. [ABSTRACT FROM AUTHOR]

BackgroundThe clinical management of low-level viremia (LLV) remains unclear. The objective of this study was to investigate the association of blips and LLV with virologic failure.MethodsWe enlisted patients who newly enrolled into the HIV Research Network between 2005 and 2015, had HIV-1 RNA more than 200 copies/ml, and were either antiretroviral therapy (ART)-naive or ART-experienced and not on ART. Patients were included who achieved virologic suppression (≤50 on two consecutive viral loads) and had at least two viral loads following suppression. Blips and LLV (≥2 consecutive >51 copies/ml) were categorized separately into three categories: no blips/LLV, 51-200, 201-500. Cox proportional hazards regression was used to assess association between rates of blips/LLV and virologic failure (two consecutive >500).ResultsThe 2795 patients were mostly male (75.4%), black (50.3%), and MSM (52.9%). Median age was 38 years old (interquartile range 29-48). Most patients (88.8%) were ART-naive at study entry. Overall, 283 (10.1%) patients experienced virologic failure. A total of 152 (5.4%) patients experienced LLV to 51-200 and 110 (3.9%) patients experienced LLV to 201-500. Both LLV 51-200 [adjusted hazard ratio (aHR) 1.83 (1.10,3.04)] and LLV 201-500 [aHR 4.26 (2.65,6.86)] were associated with virologic failure. In sensitivity analysis excluding ART-experienced patients, the association between LLV 51 and 200 and virologic failure was not statistically significant.ConclusionLLV between 201 and 500 was associated with virologic failure, as was LLV between 51 and 200, particularly among ART-experienced patients. Patients with LLV below the current Department of Health and Human Services threshold for virologic failure (persistent viremia ≥200) may require more intensive monitoring because of increased risk for virologic failure.

BackgroundGuidelines for initial antiretroviral treatment (ART) regimens have evolved, with integrase strand transfer inhibitors (INSTIs) increasingly prominent. Research on virologic failure (VF) with INSTI therapy is predominantly from clinical trials not care settings, especially for recently approved medications including dolutegravir. We compared outcomes among people living with HIV (PLWH) who initiated recommended regimens in clinical care across the United States.SettingWe examined 2 groups of PLWH at 8 clinics who initiated ART regimens (August 1, 2013-March 31, 2017): those ART treatment-naive at initiation, and those treatment-experienced.MethodsThe outcome in this longitudinal cohort study was VF, defined as a viral load of ≥400 copies/mL ≥6 months after ART initiation. We examined the proportion of individuals who remained on, switched, or discontinued the regimen. Associations between regimens and outcomes were examined with adjusted Cox proportional hazards models.ResultsAmong 5177 PLWH, a lower proportion experienced VF on dolutegravir- versus other INSTI- or darunavir-based regimens for previously treatment-naive (7% vs. 12% vs. 28%) and treatment-experienced PLWH (6% vs. 10% vs. 21%). In adjusted analyses, hazard ratios were similar across regimens for the combined outcome of regimen discontinuation or treatment switch. The hazard ratios for VF comparing dolutegravir- to darunavir-based regimens was 0.30 (95% CI: 0.2 to 0.6) among previously treatment-naive PLWH and was 0.60 (95% CI: 0.4 to 0.8) among treatment-experienced PLWH.ConclusionsThe proportion of previously treatment-naive PLWH remaining on recommended ART regimens did not differ by regimen. The likelihood of VF was lower with dolutegravir- than darunavir-based regimens for previously treatment-naive and treatment-experienced PLWH.

Increasing HIV drug resistance (DR) among children with HIV (CHIV) on antiretroviral treatment (ART) is concerning. CHIV ages 1–14 years enrolled from March 2019 to December 2020 from five facilities in Kisumu County, Kenya, were included. Children were randomized 1:1 to control (standard-of-care) or intervention (point-of-care viral load (POC VL) testing every three months with targeted genotypic drug resistance testing (DRT) for virologic failure (VF) (≥1000 copies/mL)). A multidisciplinary committee reviewed CHIV with DRT results and offered treatment recommendations. We describe DR mutations and present logistic regression models to identify factors associated with clinically significant DR. We enrolled 704 children in the study; the median age was 9 years (interquartile range (IQR) 7, 12), 344 (49%) were female, and the median time on ART was 5 years (IQR 3, 8). During the study period, 106 (15%) children had DRT results (84 intervention and 22 control). DRT detected mutations associated with DR in all participants tested, with 93 (88%) having major mutations, including 51 (54%) with dual-class resistance. A history of VF in the prior 2 years (adjusted odds ratio (aOR) 11.1; 95% confidence interval (CI) 6.3, 20.0) and less than 2 years on ART at enrollment (aOR 2.2; 95% CI 1.1, 4.4) were associated with increased odds of major DR. DR is highly prevalent among CHIV on ART with VF in Kenya. Factors associated with drug resistance may be used to determine which children should be prioritized for DRT.

Awoke Seyoum Tegegne,1 Mitiku Wale Muluneh,2 Setegn Bayabil Agegn,2 Hailegebrael Birhan Biresaw2 1Department of Statistics, Bahir Dar University, Bahir Dar, Ethiopia; 2Department of Statistics, Debre Tabor University, Debre Tabor, EthiopiaCorrespondence: Mitiku Wale Muluneh, Tel + 251-923-23-27-68, Email mitikuwale@gmail.comBackground: Medication adherence plays a significant in the success of combination antiretroviral therapy (cART). Therefore, the current investigation was conducted with the objective of comparing adherence and CD4 cell count with respect to virologic failure among HIV-infected adults under cART.Methods: A retrospective study design was conducted on 792 randomly selected HIV-infected adult patients who initiated first-line cART enrolled in the first 10 months of 2012 and followed up to August 2018 by using a simple random sampling technique based on their identification number.Results: The main outcome for the current investigation was the virologic failure which was decreased with successive visits. The area under the receiver operating characteristic curve for adherence and CD4 cell count change were 0.68 and 0.63 with χ2 = 21.2; p-value < 0.001 for the 12-month assessment. Similarly, these areas for the 36th and 60th month assessments were 0.71 and 0.66, with χ2 = 23.2; p-value < 0.001, and 0.73 and 0.71 with χ2 = 24.3; p-value < 0.001 for adherence and CD4 cell count, respectively.Conclusion: Pill count adherence was more accurate compared to CD4 cell count change for assessing virologic responses. Therefore, because of its easy access, simple use, cost-effectiveness, and accuracy, the adherence to cART was in favor of CD4 cell count change for monitoring the healthcare quality of HIV-infected patients.Keywords: adherence to cART, CD4 cell count, viral load, HIV, virologic failure, Ethiopia

BackgroundChronic pain occurs in up to 85% of persons living with HIV and is commonly treated with long-term opioid therapy (LTOT). We investigated the impact of chronic pain and LTOT on HIV outcomes.MethodsThis was prospective cohort study conducted between July 2015 and July 2016 in 5 HIV primary care clinics. Chronic pain was defined as ≥moderate pain for ≥3 months on the Brief Chronic Pain Questionnaire. Chronic pain and LTOT were assessed at an index visit. Suboptimal retention, defined as at least one "no-show" to primary care, and virologic failure were measured over the subsequent year. Multivariable logistic regression models were built for each outcome adjusting for site.ResultsAmong 2334 participants, 25% had chronic pain, 27% had suboptimal retention, 12% had virologic failure, and 19% were prescribed LTOT. Among individuals not on LTOT, chronic pain was associated with increased odds of suboptimal retention [adjusted odds ratio (aOR) 1.46, 95% confidence interval (CI): 1.10 to 1.93, P = 0.009] and virologic failure (aOR 1.97, 95% CI: 1.39 to 2.80, P < 0.001). Among individuals with chronic pain, there was no association between LTOT and retention, but LTOT was associated with lower rates of virologic failure (aOR 0.56, 95% CI: 0.33 to 0.96, P = 0.03).ConclusionsChronic pain in participants not on LTOT was associated with virologic failure. This reinforces the need to identify effective chronic pain treatments for persons living with HIV and investigate their impact on HIV outcomes. The apparent protective association between LTOT and virologic failure in those with pain merits further exploration.

Antiretroviral therapy (ART) uptake continues to increase across sub-Saharan Africa and emergence of drug-resistant HIV mutations poses significant challenges to management of treatment-experienced patients with virologic failure. In Zambia, new third-line ART (TLART) guidelines including use of dolutegravir (DTG) were introduced in 2018. We assessed virologic suppression, immunologic response, and HIV drug-resistant mutations (DRMs) among patients on TLART at the University Teaching Hospital (UTH) in Lusaka, Zambia. We conducted a retrospective review of patients enrolled at UTH on TLART for >6 months between January 2010 and June 30, 2021. CD4 and HIV viral load (VL) at TLART initiation and post-initiation were assessed to determine virologic and immunologic outcomes. Regression analysis using bivariate and multivariate methods to describe baseline characteristics, virologic, and immunologic response to TLART was performed. A total of 345 patients met inclusion criteria; women comprised 57.6% (199/345) of the cohort. Median age at HIV diagnosis was 30 (interquartile range: 17.3–36.8). In 255 (73.8%) patients with at least two VLs, VL decreased from mean of 3.45 log10 copies/mL (standard deviation [SD]: 2.02) to 1.68 log10 copies/mL (SD: 1.79). Common ARVs prescribed included DTG (89.9%), tenofovir disoproxil fumarate (68.7%), and darunavir boosted with ritonavir (66.4%); 170 (49.3%) patients had genotypes; mutations consisted of 88.8% nucleoside reverse transcriptase inhibitor, 86.5% non-nucleoside reverse transcriptase inhibitor, and 55.9% protease inhibitor. VL suppression to <1,000 copies/mL was achieved in 225 (78.9%) patients. DRM frequency ranged from 56% to 89% depending on drug class. Treatment-experienced patients receiving TLART in Zambia achieved high rates of suppression despite high proportions of HIV mutations illustrating TLART effectiveness in the DTG era. [ABSTRACT FROM AUTHOR]

Aim: It is unclear whether a low-level viremia (LLV) status is maintained in HIV-infected patients. Materials & methods: HIV-infected patients with LLV were enrolled and followed up for 5 years. Factors associated with virological outcomes were assessed via regression analyses. Results: A total of 39 patients maintained an LLV status, whereas 19 had disease progression with a viral load of ≥1000 copies/ml. LLV duration and drug resistance (DR) were associated with virological failure. Among the DR cases, the most frequent mutations were M184V/I (70.4%) and K103N (40.7%). Protease inhibitor (PI) mutations were rare. Conclusion: There is an increased risk for virologic failure in HIV-1-infected patients maintaining LLV for a long time. DR was not a rare phenomenon in LLV patients. The outcomes of HIV-infected patients in a state of active virus replication for a long period of time remain unknown. After 5 years of follow-up, approximately 71.6% of patients with persistent HIV replication maintained a state of active virus replication and 46.6% experienced drug resistance (DR), although their immune function has recovered to a certain extent. The duration of active virus replication and DR were independently associated with poor outcomes. For cases with DR, the most commonly used antiretroviral drugs were nevirapine, efavirenz, abacavir and lamivudine. Routine monitoring and drug-resistance testing in patients with persistent HIV replication are necessary. [ABSTRACT FROM AUTHOR]

Qun Li,1,2,&ast; Meiling Chen,2,3 Hongxin Zhao,1,2 Fengting Yu,2,4 Liting Yan,1,2 Jiang Xiao,1,2 Guiju Gao,1,2 Di Yang,1,2 Fujie Zhang1,2,&ast; 1Department of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Clinical Center for HIV/AIDS, Capital Medical University, Beijing, People’s Republic of China; 3The Medical Statistic Department, Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of China; 4Laboratory of Infectious Diseases Center, Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fujie ZhangClinical and Research Center of Infectious Disease, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, People’s Republic of ChinaTel +86 10 84322581Email treatment@chinaaids.cnBackground: Whether intermittent low-level viremia (iLLV/blip) or persistent low-level viremia (pLLV) increases the risk of virologic failure (VF) in HIV-1 patients is controversial. The objective of this study was to investigate the incidence of blip/pLLV and the association between blip/pLLV and VF in a Chinese antiretroviral therapy cohort.Methods: HIV-1 patients who underwent antiretroviral therapy (ART) from 2005 to 2018 and had at least two viral load (VL) measurements after a minimum of 6 months ART treatment were included. VF was defined as one or more VL measurements of ≥ 1000 copies/mL. Blip was described as an isolated VL measurement between 50 and 999 copies/mL, and pLLV was defined as two or more consecutive VL measurements between 50 and 999 copies/mL. Blip and pLLV were categorized separately into three groups: 50– 200, 201– 400 and 401– 999 copies/mL. The Cox proportional hazard model was used to explore the association between blip/pLLV and VF.Results: In total, 8098 participants were enrolled in this long-term cohort study. A 94.3% of the participants were male and among which 77.3% were infected through homosexual transmission. Blip occurred in 4.0% (325/8098) of the patients with an incidence of 0.73 per 100 person-years (/100 PYS) of follow-up (95% CI: 0.71– 0.76), whereas pLLV occurred in 1.3% of the patients (102/8098) with an incidence of 0.23/100 PYS of follow-up (95% CI: 0.21– 0.25). All the three categories of pLLV were associated with VF: pLLV 50– 200 [aHR: 3.82 (1.95– 7.47)], pLLV 201– 400 [aHR: 5.36 (2.35– 12.22)] and pLLV 401– 999 [aHR: 13.51 (8.28– 22.02)]. However, blip is not significantly associated with VF in any category.Conclusion: Our study suggested that patients with pLLV had an increased risk of subsequent VF. Therefore, if pLLV occurs in patients, monitoring and corresponding measurements must be strengthened to avoid the subsequent VF.Keywords: HIV-1, blip, persistent low-level viremia, virologic failure

Attaining viral load (VL) suppression for over 95% of the people living with HIV on antiretroviral therapy is a fundamental step in enabling Uganda and other sub-Saharan African countries to achieve global Sustainable Development Goal targets to end the HIV/AIDS epidemic by 2030. In line with the 2013 World Health Organization recommendations, several sub-Saharan African countries, including Uganda, use a threshold of 1000 HIV viral RNA copies/mL to determine HIV viral non-suppression. The United States Centers for Disease Control and Prevention and the International Association of Providers of AIDS Care deem this threshold very high, and hence recommend using 200 copies/mL to determine viral non-suppression. Using 1000 copies/mL as a threshold ignores people living with HIV who have low-level viraemia (LLV; HIV VL of at least 50 copies/mL but less than 1000 copies/mL). Despite the 2021 World Health Organization recommendations of using intensive adherence counselling for people living with HIV with LLV, several sub-Saharan African countries have no interventions to address LLV. However, recent studies have associated LLV with increased risks of HIV drug resistance, virologic failure and transmission. The purpose of this narrative review is to provide insights on the emerging concern of LLV among people living with HIV receiving antiretroviral therapy in sub-Saharan Africa. The review also provides guidance for Uganda and other sub-Saharan African countries to implement immediate appropriate interventions like intensive adherence counselling, reducing VL thresholds for non-suppression and conducting more research to manage LLV which threatens progress towards ending HIV by 2030.

Antiretroviral therapies (ARTs) have revolutionized the management of human immunodeficiency virus (HIV) infection, significantly improved patient outcomes, and reduced the mortality rate and incidence of acquired immunodeficiency syndrome (AIDS). However, despite the remarkable efficacy of ART, virologic failure remains a challenge in the long-term management of HIV-infected individuals. Virologic failure refers to the persistent detectable viral load in patients receiving ART, indicating an incomplete suppression of HIV replication. It can occur due to various factors, including poor medication adherence, drug resistance, suboptimal drug concentrations, drug interactions, and viral factors such as the emergence of drug-resistant strains. In recent years, extensive efforts have been made to understand and address virologic failure in order to optimize treatment outcomes. Strategies to prevent and manage virologic failure include improving treatment adherence through patient education, counselling, and supportive interventions. In addition, the regular monitoring of viral load and resistance testing enables the early detection of treatment failure and facilitates timely adjustments in ART regimens. Thus, the development of novel antiretroviral agents with improved potency, tolerability, and resistance profiles offers new options for patients experiencing virologic failure. However, new treatment options would also face virologic failure if not managed appropriately. A solution to virologic failure requires a comprehensive approach that combines individualized patient care, robust monitoring, and access to a range of antiretroviral drugs.

Supplemental Digital Content is Available in the Text. Background: Little is known about the long-term outcomes of children living with HIV in Latin America. Few studies have examined antiretroviral therapy (ART) regimen switches in the years after the introduction of ART in this population. This study aimed to assess clinical outcomes among children who started second-line ART in the Caribbean, Central and South America network for HIV epidemiology. Methods: Children (<18 years old) with HIV who switched to second-line ART at sites within Caribbean, Central and South America network for HIV epidemiology were included. The cumulative incidence and relative hazards of virologic failure while on second-line ART, loss to follow-up, additional major ART regimen changes, and all-cause mortality were evaluated using competing risks methods and Cox models. Results: A total of 672 children starting second-line ART were included. Three years after starting second-line ART, the cumulative incidence of death was 0.10 [95% confidence interval (CI) 0.08 to 0.13], loss to follow-up was 0.14 (95% CI: 0.11 to 0.17), and major regimen change was 0.19 (95% CI: 0.15 to 0.22). Of those changing regimens, 35% were due to failure and 11% due to toxicities/side effects. Among the 312 children with viral load data, the cumulative incidence of virologic failure at 3 years was 0.62 (95% CI: 0.56 to 0.68); time to virologic failure and regimen change were uncorrelated (rank correlation −0.001; 95% CI −0.18 to 0.17). Conclusions: Poor outcomes after starting second-line ART in Latin America were common. The high incidence of virologic failure and its poor correlation with changing regimens was particularly worrisome. Additional efforts are needed to ensure children receive optimal ART regimens. [ABSTRACT FROM AUTHOR]

Introduction: Standard therapy for HIV treatment has consisted of two nucleoside analogue reverse transcriptase inhibitors (NRTI) paired with a third agent. Use of two-drug regimens (2DR) has been considered for selected patients in part to avoid toxicities associated with the use of NRTIs. This study aimed to compare the real-world outcomes of integrase inhibitor (INSTI)-based three-drug regimens (3DR) versus 2DR of dolutegravir (DTG) + rilpivirine (RPV) or DTG + lamivudine (3TC). Methods: All patients in the Spanish VACH cohort switching to INSTI-based 3DR or a 2DR consisting of DTG + RPV or DTG + 3TC between May 2, 2016 and May 15, 2019 were included. Kaplan–Meier curves and Cox proportional hazard models were used to assess time to/risk of discontinuation due to treatment failure (TF) (defined as virologic failure [VF], immunologic failure, or disease progression) and adverse events (AEs). Three secondary analyses were performed: (1) in restricting the analysis to patients who were virologically suppressed (HIV RNA < 50 copies/mL) at switch; (2) matched analysis (2:1, matched by age, sex, number of previous VFs, and line of regimen), and (3) using VF as the primary endpoint in all patients. Results: Overall, 5047 3DR and 617 2DR patients were analyzed. Baseline characteristics differed between groups; 2DR patients were older, more treatment experienced, and more likely to be virologically suppressed at switch. Time to discontinuation due to TF was significantly shorter for 2DR (P = 0.002). The hazard ratio (HR) for discontinuation due to TF on 2DR vs 3DR was 2.33 (P = 0.003). No difference was observed for time to discontinuation (P = 0.908) or risk of discontinuation due to AEs (HR = 0.80; P = 0.488). Results were qualitatively similar in virologically suppressed patients, matched analysis, and for VF. Conclusion: In the real world, the risks of discontinuation due to TF and VF were more than two times higher in patients switching to DTG-based 2DR than INSTI-based 3DR, with no difference in discontinuation due to AEs. Plain Language Summary: People living with HIV (PLHIV) need lifelong treatment to prevent progression to AIDS. Standard HIV treatments use three different drugs in combination, but these can potentially cause unwanted side effects. Treatments using just two drugs have been developed. These aim to reduce side effects and treat HIV effectively. This study included 5664 participants in Spain who were split into two groups: 5047 participants switched from their old treatment to a three-drug regimen (3DR), and 617 participants switched to a two-drug regimen (2DR). The researchers measured how long it took for the participants to stop taking their treatment because it was not working, or it caused too many side effects. At the end of the study, more than 70% of participants in either group were still taking the same treatment. Of the 30% of participants who stopped treatment because it stopped working, those taking a 2DR stopped sooner than those taking a 3DR. This difference started to appear at about 18 months and got bigger until the study ended, which was 3 years after starting treatment. Participants taking a 2DR were twice as likely to stop treatment because it was not working than those taking a 3DR. There was no difference between the groups for how long it took for participants to stop their treatment because of side effects. These results show that for some PLHIV, the 2DR stopped working sooner than 3DR, without the benefit of fewer side effects. [ABSTRACT FROM AUTHOR]

Lina Fan,&ast; Aiping Yu,&ast; Defa Zhang, Ziyu Wang, Ping Ma Department of Infectious Diseases, Tianjin Second People’s Hospital, Nankai University, Tianjin, 300192, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ping MaDepartment of Infectious Diseases, Tianjin Second People’s Hospital, Nankai University, No. 7, Sudi Road, Naikai District, Tianjin, 300192, People’s Republic of ChinaTel +86-22-27468019Email maping@tj.gov.cnIntroduction: Although syphilis is a frequent co-infection in patients with human immunodeficiency virus (HIV) infection, the influence of syphilis on immune response and virologic failure in HIV-infected patients following initiation of antiretroviral therapy (ART) is not well-defined.Methods: A retrospective study was conducted at Tianjin Second People’s Hospital to evaluate the prevalence of syphilis and immune status in 4171 ART-naïve patients. The study included patients who initiated ART between August 2009 and June 2019.Results: The prevalence of syphilis was 40.1% in all ART-naïve patients and 42.5% in ART-naïve men who have sex with men. HIV/syphilis co-infection was associated with higher virologic failure (odds ratio (95% confidence interval): 1.30 (1.04, 1.63)). Patients with HIV/syphilis co-infection had lower median CD4+ T cell counts and CD4/CD8 ratios at baseline. After initiation of ART, patients co-infected with HIV/syphilis had smaller increases in CD4+ T cell counts and CD4/CD8 ratios than patients infected only with HIV. The rate of recurrence of syphilis or reinfection was 9% (n = 128) during seven years of ART.Conclusion: HIV/syphilis co-infection had a negative impact on immune recovery and antiretroviral effectiveness. RPR titer and HIV viral load should be monitored in patients co-infected with HIV/syphilis, especially in patients with high RPR titers.Keywords: HIV/syphilis, co-infection, antiretroviral therapy, virologic failure, CD4 response

Abstract Background Understanding the impact of food insecurity on HIV outcomes is critical for the development and implementation of effective, evidence-based interventions to address food insecurity and improve the HIV care cascade. We conducted a prospective, longitudinal study to determine the impact of food insecurity on HIV outcomes in Senegal, West Africa. Methods HIV-infected individuals presenting for care and initiation of ART through the Senegalese National AIDS program in Dakar and Ziguinchor were eligible for enrollment. Data were collected using interviews, clinical evaluations, laboratory analyses, and chart review at enrollment, month 6, and month 12. Logistic regression was used to determine the association between food insecurity and HIV outcomes. Results Among the 207 participants in this study, 70% were female and the median age was 37 years. The majority (69%) were food insecure at enrollment, 29% were severely food insecure, and 38% were undernourished. Nearly a third (32%) had no formal education, 23% practiced agriculture, and 40% owned livestock. The median daily food expenditure per person was $0.58. The median round trip transportation time to clinic was 90 min (IQR 30–240). The median cost of transportation to clinic was $1.74. At month 12, 69% were food insecure, 23% were severely food insecure, and 14% were undernourished. At month 12, 43% had not disclosed their HIV status; food insecurity was associated with non-disclosure of HIV-status due to fear of stigmatization and feelings of shame. Severe food insecurity was a strong predictor of loss to follow-up (OR 3.13 [1.08–9.06]) and persistent severe food insecurity was associated with virologic failure (OR 5.14 [1.01–26.29]) and poor adherence to ART 8.00 [1.11–57.57]. Poor nutritional status was associated with poor immunologic recovery (OR 4.24 [1.56–11.47]), virologic failure (OR 3.39 [1.13–10.21]), and death (OR 3.35 [1.40–8.03]). Conclusion Severity and duration of food insecurity are important factors in understanding the relationship between food insecurity and HIV outcomes. Our findings highlight the importance of nutritional status, socioeconomic opportunity, and self-stigmatization in the complex pathway between food insecurity and HIV outcomes. Interdisciplinary, multisectoral efforts are needed to develop and implement effective interventions to address food insecurity among people living with HIV.

Background The late recognition of virologic failure (VF) places persons with HIV in Sub-Saharan Africa at risk for HIV transmission, disease progression, and death. We conducted a systematic review and meta-analysis to determine if the recognition and response to VF in the region has improved. Methods We searched for studies reporting CD4 count at confirmed VF or at switch to second-line antiretroviral therapy (ART). Using a random-effects metaregression model, we analyzed temporal trends in CD4 count at VF—or at second-line ART switch—over time. We also explored temporal trends in delay between VF and switch to second-line ART. Results We identified 26 studies enrolling patients with VF and 10 enrolling patients at second-line ART switch. For studies that enrolled patients at VF, pooled mean CD4 cell count at failure was 187 cells/mm3 (95% CI, 111 to 263). There was no significant change in CD4 count at confirmed failure over time (+4 cells/year; 95% CI, –7 to 15). Among studies that enrolled patients at second-line switch, the pooled mean CD4 count was 108 cells/mm3 (95% CI, 63 to 154). CD4 count at switch increased slightly over time (+10 CD4 cells/year; 95% CI, 2 to 19). During the same period, the mean delay between confirmation of VF and switch was 530 days, with no significant decline over time (–14 days/year; 95% CI, –58 to 52). Conclusions VF in Africa remains an event recognized late in HIV infection, a problem compounded by ongoing delays between VF and second-line switch. [ABSTRACT FROM AUTHOR]

Objective: To determine viral load (VL) nonsuppression (VLN) rates, HIV drug resistance (HIVDR) prevalence, and associated factors among female sex workers (FSWs) in Ethiopia. Methods: A cross-sectional biobehavioral survey was conducted among FSWs in 11 cities in Ethiopia in 2014. Whole blood was collected, and HIVDR genotyping was performed. Logistic regression analysis was performed to identify factors associated with VLN and HIVDR. Results: Among 4900 participants, 1172 (23.9%) were HIV-positive and 1154 (98.5%) had a VL result. Participants were categorized into antiretroviral therapy (ART) (n = 239) and ART-naive (n = 915) groups based on self-report. From the 521 specimens (ART, 59; ART-naive, 462) with VL >=1000 copies/mL, genotyping was successful for 420 (80.6%) and 92 (21.9%) had drug resistance mutations (DRMs). Pretreatment drug resistance (PDR) was detected in 16.5% (63/381) of the ART-naive participants. Nucleoside reverse transcriptase inhibitor (NRTI), non-NRTIs (NNRTIs), and dual-class DRMs were detected in 40 (10.5%), 55 (14.4%), and 35 (9.2%) of the participants, respectively. Among 239 participants on ART, 59 (24.7%) had VLN. Genotyping was successfully performed for 39 (66.1%). DRMs were detected in 29 (74.4%). All 29 had NNRTI, 23 (79.3%) had NRTI or dual-class DRMs. VLN was associated with age 35 years or older, CD4+ T-cell count <350 cells/mm3, and being forced into selling sex. PDR and acquired drug resistance were associated with CD4+ T-cell count <350 cells/mm3 (P < 0.001). Conclusions: The high VLN and HIVDR rates among FSWs underscore the need for targeted interventions to improve ART access and virologic monitoring to maximize the benefit of ART and limit the spread of HIV and HIVDR. [ABSTRACT FROM AUTHOR]

Background: Children with perinatally acquired HIV, growing into adolescence, go through a period of change during which adherence to antiretroviral therapy can decrease, and mental health disorders are most often diagnosed for the first time. Objective: To investigate the prevalence of depressive disorders and factors associated with virologic failure in adolescents with perinatally acquired HIV under care at a tertiary hospital in Northeast Thailand. Materials and Methods: The present study was a cross-sectional study conducted between June 2017 and October 2018 at Srinagarind Hospital, Faculty of Medicine, Khon Kaen University. Participants with perinatally acquired HIV aged 12 to 24 years old who disclosed their HIV status and had been taking antiretroviral therapy for at least one year were interviewed by the psychiatrist, using DSM-5 criteria of depressive disorders. The diagnosis was made concurrently with psychiatric interventions in those who met indications for treatment. Virologic failure was defined as plasma HIV-1 RNA greater than 1,000 copies/mL. Factors associated with virologic failure were evaluated by univariable and multivariable analyses. Results: Seventy-nine participants were enrolled. Their median age was 17.5 years old, with an interquartile range of 14.9 to 18.9, and 57% were female. Nine had virologic failure and 14 (17.7%) were diagnosed with depressive disorders. On multivariable analysis, depressive disorders were associated with virologic failure (adjusted odds ratio 7.55, 95% CI 1.65 to 34.65). Conclusion: The prevalence of depressive disorders in adolescents with perinatally acquired HIV was 17.7%. Depressive disorders were found to be one of the factors associated with virologic failure. Keywords: Depressive disorders; Adolescents; Perinatally acquired HIV; Virologic failure [ABSTRACT FROM AUTHOR]

Background & Aims: Direct-acting antiviral (DAA) regimens provide a cure in >95% of patients with chronic HCV infection. However, in some patients in whom therapy fails, resistance-associated substitutions (RASs) can develop, limiting retreatment options and risking onward resistant virus transmission. In this study, we evaluated RAS prevalence and distribution, including novel NS5A RASs and clinical factors associated with RAS selection, among patients who experienced DAA treatment failure. Methods: SHARED is an international consortium of clinicians and scientists studying HCV drug resistance. HCV sequence linked metadata from 3,355 patients were collected from 22 countries. NS3, NS5A, and NS5B RASs in virologic failures, including novel NS5A substitutions, were examined. Associations of clinical and demographic characteristics with RAS selection were investigated. Results: The frequency of RASs increased from its natural prevalence following DAA exposure: 37% to 60% in NS3, 29% to 80% in NS5A, 15% to 22% in NS5B for sofosbuvir, and 24% to 37% in NS5B for dasabuvir. Among 730 virologic failures, most were treated with first-generation DAAs, 94% had drug resistance in ≥1 DAA class: 31% single-class resistance, 42% dual-class resistance (predominantly against protease and NS5A inhibitors), and 21% triple-class resistance. Distinct patterns containing ≥2 highly resistant RASs were common. New potential NS5A RASs and adaptive changes were identified in genotypes 1a, 3, and 4. Following DAA failure, RAS selection was more frequent in older people with cirrhosis and those infected with genotypes 1b and 4. Conclusions: Drug resistance in HCV is frequent after DAA treatment failure. Previously unrecognized substitutions continue to emerge and remain uncharacterized. Lay summary: Although direct-acting antiviral medications effectively cure hepatitis C in most patients, sometimes treatment selects for resistant viruses, causing antiviral drugs to be either ineffective or only partially effective. Multidrug resistance is common in patients for whom DAA treatment fails. Older patients and patients with advanced liver diseases are more likely to select drug-resistant viruses. Collective efforts from international communities and governments are needed to develop an optimal approach to managing drug resistance and preventing the transmission of resistant viruses.