Virological Failure Research Articles

Genetic Diversity and Drug Resistance Mutations in HIV-1 pol Gene Sequences in the Philippines: A Retrospective Genomic Analysis

The Philippines has experienced a significant increase in HIV-1 infections in recent years, with a growing epidemic driven by the CRF01_AE strain. Understanding the genetic diversity of HIV-1 in the Philippines is crucial for the development of effective treatment strategies and the prevention of drug resistance. This study analyzed comprehensive data on common resistance mutation patterns from 2009 to 2017, revealing an increasing trend of mutations observed in NRTI and NNRTI resistance among the predominant CRF01_AE strains. The most common NRTI mutations observed were M184V, K65R, and S68G, whereas the most common NNRTI mutations were K103N, Y181C, and G190A. The study also found a high prevalence of M184V minority variants (0.5-20%) in treatment-naive patients, which could increase the risk of virological failure in 3TC-containing regimens. The findings of this study highlight the importance of comprehensive drug resistance surveillance and access to resistance testing to guide optimal first-line antiretroviral treatment selection and to manage the growing HIV-1 epidemic in the Philippines. The development of effective strategies to prevent and manage drug resistance is crucial to ensuring the long-term success of HIV treatment programs in the country.

Direct Antivirals Can Achieve a Cure in All Patients With Chronic Hepatitis C due to Genotype 5: A French Multicentre Study.

Hepatitis C virus genotype 5 (HCV-GT-5) is found mainly in South Africa. In our area in central France, the prevalence of HCV-GT-5 is 14%. Here we evaluated sustained virological response at week 12 post-treatment (SVR12) in 147 HCV-GT-5 patients from 14 French university hospitals (2014-2021) treated with direct-acting antivirals (DAA) in real-life. Patients had mainly received sofosbuvir/ledipasvir ± ribavirin, sofosbuvir/velpatasvir, and glecaprevir/pibrentasvir. Overall SVR12 was 98% (144/147). Two patients experienced relapse: one was successfully retreated with the same DAAs (sofosbuvir/ledipasvir) plus ribavirin, and the other refused further DAA treatment. One patient with virological failure (sofosbuvir/velpatasvir) had received a second treatment (sofosbuvir/velpatasvir/voxilaprevir) and progressed to cure. HCV-GT-5 patients treated with a DAA regimen had a 99% SVR12 in intention-to-treat (including initial therapy and retreatment) and 100% SVR12 per protocol. Sofosbuvir/ledipasvir, sofosbuvir/velpatasvir, and glecaprevir/pibrentasvir show very good efficacy in real-world HCV-GT-5 patients.

Dolutegravir with enteral feeds in intensive care: nutrition vs viral suppression

Abstract Introduction People living with HIV requiring admission to intensive care often receive enteral nutrition via feeding tubes. Enteral feeds contain cations which may interfere with dolutegravir (DTG) absorption due to chelation1. For this reason, temporal spacing (six hours before/ two hours after DTG administration2) is recommended, possibly leading to suboptimal caloric intake3. The clinical significance of the interaction between enteral feeds and DTG when co-administered is not fully understood and public data are sparse. Aim We aim to evaluate the impact and outcomes of co-administering DTG and enteral feeds. Methods Review of prospectively collected data on therapeutic drug monitoring (TDM) and electronic patient records of patients on DTG and enteral feeds, whilst in intensive care unit (ITU) between 2022 and 2023. Maximum (Cmax) and trough (Ctrough) DTG concentrations were measured and compared to reference ranges (DTG 50 mg once daily: Cmax 3340 ng/mL; Ctrough 830 ng/mL). All data were anonymised and collected as part of routine care for analysis. According to the National Research Ethics Service guidelines, further patient consent and ethical approval were not required. Results Six cases were identified with eight incidences of TDM sampling: 2 (33%) female; median age 34 (IQR 33-42); 3 (50%) non-white ethnicity; mean number of days on ITU 46 days; mean number of days into feeds 28 days; all (100%) suffered from hypoalbuminaemia (18-26 g/L). All patients were taking tenofovir-based regimens as their backbone antiretroviral therapy and once daily DTG, unless when co-administered with rifampicin where twice daily DTG is required to overcome enzyme induction effects of rifampicin. In three of the eight samples, temporal spacing with enteral feeds occurred as per SPC guidance2. The highest Cmax with once daily DTG seen in this cohort was 2201 ng/mL which was achieved without temporal spacing, whilst the lowest Ctrough (44 ng/mL) was observed in a different individual with sufficient temporal spacing. The viral loads measured while patients were receiving feeds varied, with 3 (50%) remaining suppressed. All (100%) patients had a fully suppressed viral load after enteral feeds ceased, including one patient who was naïve to treatment prior to admission with a high viral load. Discussion/Conclusion DTG Cmax were lower than those observed in literature regardless of temporal spacing from enteral feeds. Ctrough concentrations were also lower than expected in all cases. Six of eight Ctrough were lower than the DTG minimum effective concentration (MEC) of 300 ng/mL, however, only one was below IC90 for wildtype virus (64 ng/mL). Virological failure or onset of resistance was not observed in any of the patients. Multiple factors are likely to be contributing to low DTG concentrations, of which the most significant is likely impaired drug absorption, whilst nutritional feed co-administration seems to not be relevant.

Impact of point-of-care birth test-and-treat on clinical outcomes among infants with HIV: A cluster randomized trial in Mozambique and Tanzania.

We assessed the impact of point-of-care (PoC) test-and-treat at birth on clinical outcomes and viral suppression among HIV-positive infants in Mozambique and Tanzania. This cluster-randomized trial allocated health facilities to intervention, providing PoC-testing and antiretroviral treatment (ART) at birth and week 4-8, or control, starting these at week 4-8. The primary outcome was proportions of clinical events (mortality, morbidity, retention, virological failure, toxicity) among HIV-positive infants at month-18. We estimated incidence rate ratios adjusted for timing of HIV-detection (aIRR) and reported viral suppression <1000 copies/mL. Among 6602 neonates enrolled October 2019-September 2021, 125 were diagnosed HIV-positive by week 12. In the intervention arm, 38/69 (55.1%) were diagnosed at birth with 35 initiating ART within two days. In the control arm, 27/56 (48.2%) were retrospectively detected HIV-positive at birth, of whom 6/56 (10.7%) died or were lost to follow-up before testing. Median age at ART initiation was 6 (intervention) versus 33 days (control). Birth test-and-treat was not associated with a significant reduction in clinical outcomes up to month-18 [53 (76.8%) versus 48 (85.7%); aIRR 0.857; 95% CI 0.505-1.492], but showed a 68% relative reduction in 6-month mortality. Viral suppression was poor overall, but improved in the intervention group at month 18 (65.7% versus 29.6%; p=0.005). PoC test-and-treat at birth is feasible in resource-poor settings and resulted in clinically-relevant reduction of early infant mortality, though improved clinical outcomes were not sustained to month-18. Poor viral suppression may undermine early survival benefits, calling for better paediatric treatments and tailored adherence interventions.

HIV-related outcomes among migrants living in Europe compared with the general population: a systematic review and meta-analysis

Compared with the general population, international migrants arriving in Europe face severe socioeconomic challenges that result in higher HIV prevalence and limited access to health care, potentially leading to negative outcomes. In this systematic review and meta-analysis, we aimed to investigate the incidence of HIV-related outcomes among international migrants arriving in Europe compared with the incidence among the general population. We did a systematic review and meta-analysis to identify studies investigating HIV-related outcomes in migrants and the general population living with HIV in Europe. Six authors (EDV, VP, VS, SDG, MC, and RN) independently searched PubMed, Scopus, and Web of Science from database inception until July 22, 2023 (with an update on March 3, 2024), then screened titles and abstracts of all potentially eligible articles. Studies were included if they were observational studies; investigated clinical, virological, or immunological outcomes in migrants living with HIV; were conducted in Europe; had at least one control group of non-migrants living in a European country; and were in English. Titles and abstracts were screened for eligibility followed by a full-text assessment by two authors (EDV, VP, VS, SDG, MC, or RN). Data were extracted from articles using a structured Redcap form. Primary outcomes of our systematic review were (1) mortality, (2) AIDS-defining condition, (3) combined outcome of AIDS or death, (4) treatment discontinuation, (5) rate of loss to follow-up, (6) virological failure, and (7) immunological failure. Data were reported as relative risks (RRs) or odds ratios with their 95% CIs. The study is registered with PROSPERO, CRD42024501191. Of the 1316 articles identified (1297 in the initial search and 19 in the updated search), 19 were included in our systematic review, consisting of 104 676 participants who were followed up for a mean of 79·3 months. The meta-analysis, adjusted for potential confounders, showed that migrants present similar mortality risk (RR 0·88, 95% CI 0·75-1·04), but higher risk for AIDS-defining conditions (1·23, 1·14-1·34), treatment discontinuation (2·39, 1·49-3·29), loss to follow-up (2·53, 1·41-4·53), virological failure (1·80, 1·25-2·60), and immunological failure (3·70, 2·17-12·50) compared with the general population. In subanalyses for WHO regions, people originally from the African region had higher risk for HIV-related adverse outcomes. Compared with the non-migrant population, migrants living in Europe with HIV face higher risks for progression to AIDS, loss to follow-up, treatment discontinuation, and virological and immunological failure. Interventions aimed to improve HIV care among migrants living in Europe are urgently needed. None.

Predictors of Injection Visit Adherence in Those Receiving Injectable Cabotegravir/Rilpivirine.

There is limited data evaluating potential predictors of adherence to injection visits and the impact of late injections on viral suppression in those receiving long-acting injectable (LAI) cabotegravir/rilpivirine (CAB/RPV) for the treatment of HIV. A retrospective cohort study was conducted among adult people with HIV (PWH) receiving LAI CAB/RPV for at least 6 months between May 2021 and August 2023. Data collected included demographics, office visit no-shows one year prior to switching to LAI CAB/RPV, injection visit no-shows, injections outside the dosing window, and virologic outcomes. Cox-proportional hazards regression was performed to evaluate predictors of no-show to injection visits or late injections. Included were 287 PWH with a median follow up time (IQR) of 450 days (344-548 days). Younger age [HR 0.97 (95%CI 0.95-0.98)] and ≥ 1 office visit no-show in the year prior to switch to LAI CAB/RPV [HR 2.03 (1.32-3.12]) were associated with having a no-show to an injection visit (32.1%). Male sex assigned at birth [HR 9.18 (1.26-66.9)] with a trend towards younger age [HR 0.98 (0.95-1.0)] were associated with having a late injection (15.3%). There was no relationship between late injections and having a detectable viral load or virologic failure (n=3) after switch to LAI CAB/RPV. Having office visit no-shows prior to switching to LAI CAB/RPV was associated with missed injection visits, and younger age was associated with both missed injection visits and late injections. Resources to reduce and manage missed injection appointments need to be considered when implementing LAI CAB/RPV.

Epidemiological and virological characteristics of people living with HIV on antiretroviral treatment for more than 6 months in virological failure in Brazzaville, Republic of Congo

Introduction. Virological failure is one of the main causes of failing to treat, and better management of HIV infection requires understanding and controlling the factors that contribute to this phenomenon. The main objective was to characterize the patients of the active file of the Brazzaville Outpatient Treatment Center in virological failure to identify predictive factors leading to virological failure. Methods. Conducted between June and December 2020, this was a cross-sectional study. Patients enrolled were HIV-1-infected patients from the Brazzaville Outpatient Treatment Center receiving a potent combination therapy for at least 6 months but experiencing virological failure. Viral load was measured using the automated Abbott Real-time HIV-1 m2000rt System. Sociodemographic and clinical data were collected from a computerized patient record software called Santia. For the identification of the independent predictors of virological failure, statistical analysis was performed. Results. A total of 109 patients with virological failure were recruited. The median age of the patients was 45 years (interquartile range: 37–52 years) and women were more represented (74%). More than half of the patients had World Health Organization stage IV HIV and the median duration of antiretroviral treatment was 96 months. The most followed treatment regimen was AZT+3TC+EFV (or nevirapine) with 48%, while the median viral load was 12985 copies ml−1. Conclusion. In our study, we did not identify any sociodemographic or clinical variables predictive of virological failure. However, we felt that it would be desirable to carry out a study with temporal follow-up and the possibility of sequencing in order to identify the different circulating genotypes and resistance mutations.

Spectrum of Non-Nucleoside Reverse Transcriptase Inhibitor-Associated Drug Resistance Mutations in Persons Living with HIV-1 Receiving Rilpivirine

Introduction: Few data are currently available on the nonnucleoside reverse transcriptase (RT) inhibitors (NNRTI) resistance mutations selected in persons living with HIV-1 (PLWH) who develop virological failure while receiving rilpivirine (RPV). Methods: We analyzed pooled HIV-1 RT genotypic data from 280 PLWH in the multicenter EuResist database and 115 PLWH in the Stanford HIV Drug Resistance Database (HIVDB) who received RPV as their only NNRTI. Results: Among the 395 PLWH receiving RPV, 180 (45.6%) had one or more NNRTI-associated DRMs. Overall, 44 NNRTI-associated DRMs were identified, including 26 that occurred in two or more PLWHs. Seven mutations had a prevalence ≥10% among the 180 PLWH with one or more NNRTI-associated DRM: E138K (32.2%), V90I (25.0%), K101E (17.8%), Y181C (17.2%), E138A (13.9%), H221Y (12.2%), and K103N (10.6%). Y181C was significantly more likely to co-occur with K101E, V179F, H221Y, and M230L. Ten novel non-polymorphic mutations at known NNRTI-associated mutation positions were also identified, usually in just one PLWH: L100F, V108A, T139I, P225S, M230V, Y232C, and T240A/I/M/S. Conclusions: Our analysis extends the spectrum of mutations emerging in PLWH receiving RPV. Additional phenotypic characterization of RPV-selected mutations is necessary to better understand their biological and possible clinical significance.

Comparing the long-term effectiveness and safety of dolutegravir/lamivudine versus bictegravir/emtricitabine/tenofovir alafenamide fumarate as first-line regimens: a real life multicentre cohort.

We compared the effectiveness and safety of bictegravir/emtricitabine/tenofovir alafenamide fumarate (BIC/FTC/TAF) and dolutegravir plus lamivudine (DTG + 3TC) in our cohort of treatment-naive people with HIV (PWH). In a multicentre cohort of treatment-naive PWH starting a first-line regimen with either dolutegravir plus lamivudine or BIC/FTC/TAF, Kaplan-Meier survival analysis was used to estimate time to virological failure (VF) and time to treatment discontinuation (TD), whereas Cox regression was used to evaluate predictors of VF and TD. Changes in CD4+ cell count were assessed via non-parametric tests, and linear regression analyses were performed to explore predictors of CD4+ cell count changes. One hundred and seventy individuals were included: 66 started dolutegravir plus lamivudine (DTG group) and 104 started BIC/FTC/TAF (BIC group). During follow-up, we observed two VFs in the DTG group [1.7 per 100 person-years of follow-up (PYFU)] and two in the BIC group (1.7 per 100 PYFU). Estimated probability of remaining free from VF at Week 144 was 95.9% in the DTG group and 95.2% in the BIC group (log-rank P = 0.955). Four TDs were observed in the DTG group (3.4 per 100 PYFU) and 21 in the BIC group (17.6 per 100 PYFU). Estimated probability of maintaining the study regimen at Week 144 was 90.3% in the DTG group and 70.0% in the BIC group; individuals in the BIC group had a higher probability of TD (log-rank P = 0.003). In both groups, the CD4+ count improved significantly during follow-up. Our study shows that both strategies are effective and safe, with few VFs and TDs due to tolerability issues.

Effectiveness, safety, and patient-reported outcomes of emtricitabine/tenofovir alafenamide-based regimens for the treatment of HIV-1 infection: Final 24-month results from the prospective German TAFNES cohort study.

Tenofovir alafenamide (TAF) was introduced in the European Union in 2015 as a novel prodrug of tenofovir showing similar efficacy in clinical trials and a more favorable safety profile than tenofovir disoproxil fumarate (TDF). The German TAFNES cohort study (2016-2019) was conducted to generate real-world evidence. Treatment-naïve (TN) and treatment-experienced (TE) people with HIV (PWH) receiving elvitegravir/cobicistat/emtricitabine/TAF (E/C/F/TAF), rilpivirine/F/TAF (R/F/TAF) or F/TAF + 3rd agent were included. Month (M) 24 outcomes included virologic effectiveness (HIV RNA <50 copies/mL), treatment persistence, adverse drug reactions (ADRs) and patient-reported outcomes, using the HIV Symptom Index (HIV-SI), 36-Item Short Form Health Survey (SF-36) and HIV Treatment Satisfaction (HIVTSQ) questionnaires. The study included 767 PWH (92% men, median age 46 years; 301 TN, 466 TE; E/C/F/TAF [n = 318], R/F/TAF [n = 192], F/TAF + 3rd agent [n = 257]). Among TN, 35% had late HIV diagnosis (CD4 < 350/μL and/or AIDS). Of TE, 95% were on suppressive antiretroviral therapy (ART) before switching. D:A:D (Data Collection on Adverse Effects of Anti-HIV Drugs) 5-year risks for chronic kidney disease were high for about 1 in 10 TN and 4 in 10 TE. Overall treatment persistence at M24 was 81% (E/C/F/TAF: 88%; R/F/TAF: 86%; F/TAF + 3rd agent: 70%, with ART simplification of multiple-tablet regimens in 13%). M24 viral suppression (missing = excluded) was 96% (479/501). Discontinuations due to virologic failure or ADRs were rare, 2% (12/767) and 4% (30/767), respectively. HIV-SI and SF-36 summary scores improved in TN; HIVTSQ change scores showed an improvement in treatment satisfaction in TE. Real-world data confirmed a favorable safety profile and high virologic effectiveness with high treatment satisfaction on F/TAF-based ART.

Factors involved in gastroesophageal varix-related events in patients with hepatitisC virus-related compensated and decompensated cirrhosis after direct-acting antiviral therapy.

The incidence of and factors involved in gastroesophageal varix-related events in hepatitisC virus-related cirrhosis patients, including decompensated cirrhosis, after direct-acting antiviral therapy are unclear. We conducted a multicenter study using prospective data from 478 hepatitisC virus-related cirrhosis patients treated with direct-acting antiviral therapy from February 2019 to December 2021 at 33 Japanese hospitals. Gastroesophageal varices were classified as F1 (small-caliber), F2 (moderately enlarged), or F3 (markedly enlarged) according to the Japanese criteria. Patients without varix or with F1 without red color signs were defined as low-risk varix, and patients with ≥F2 or red color signs or a history of rupture were defined as high-risk varix. Varix-related events were defined as prophylactic treatment or rupture of gastroesophageal varix. The median age was 70years, 43% of patients had decompensated cirrhosis, and 16% had high-risk varices (13% in compensated and 33% in decompensated, p<0.001). Sustained virologic response rates were 94.9% for compensated cirrhosis and 91.3% for decompensated cirrhosis (p=0.120). Across 35.7months, 25 patients received prophylactic treatment, and four experienced varix rupture. The 3-year incidence rate of varix-related events was 6.2% (3.5% in compensated and 9.9% in decompensated, p=0.001). In the multivariate analysis, high-risk varix (p<0.001), high baseline gamma-glutamyl transpeptidase levels (p<0.001), and virologic failure (p=0.004) were significantly involved in varix-related events. The cumulative incidence rate of varix-related events was significantly higher in decompensated cirrhosis than in compensated cirrhosis. Baseline varix status, baseline gamma-glutamyl transpeptidase levels, and virologic response were related to varix-related events after direct-acting antiviral therapy.

Prevalence and Risk Factors of HIV Drug Resistance in Zimbabwe: Evidence from Zimbabwe Population-Based HIV Impact Assessment (ZIMPHIA) 2020 Survey

(1) Background: HIV drug resistance (HIVDR) poses a significant challenge to the effectiveness of antiretroviral therapy and the overall management of HIVand AIDS. Understanding the predictors of HIVDR is critical for developing strategies to mitigate its impact. The objectives of this study were to identify the predictors of HIVDR among Zimbabwe Population-Based HIV Impact Assessment (ZIMPHIA 2020) study participants, a national population-based survey. (2) Methods: Data from people living with HIV who participated in the ZIMPHIA 2020 were used to determine the predictors of HIVDR. (3) Results: The prevalence of HIVDR was 44.9%. Acquired HIVDR was present in 76.1% of people with a virological failure and transmitted resistance is 22.6% in naïve individuals. Factors associated with HIVDR in adjusted analysis were the number of lifetime sexual partners (aOR = 1.03, 95% CI: 1.01–1.06, p = 0.017), each additional year since the first HIV positive result (aOR = 1.17, 95% CI: 1.09–1.25, p &lt; 0.01), each additional year on ART (aOR = 1.14, 95% CI: 1.06–1.23, p = 0.001), initiating ART before 2014 (aOR = 3.08, 95% CI: 1.72–5.49, p = 0.020), ever had switched antiretrovirals (aOR = 2.47, 95% CI: 1.15–5.29, p = 0.020) or had ever had a viral load test (aOR = 2.54, 95% CI: 1.54–4.17, p &lt; 0.001) and a CD4 count &lt; 350 (aOR = 2.04, 95% CI: 1.48–2.83, p &lt; 0.01), while age ≥ 50 (aOR = 0.56, 95% CI: 0.32–0.98, 32 p = 0.04), condom use at last encounter (OR: 0.49, 95%CI: 0.33–0.73, p &lt; 0.001), and not being on ART (aOR = 0.09, 95% CI: 0.06–0.13, p &lt; 0.01) were associated with reduced odds of HIVDR. Conclusions: HIVDR was high among the participants. There is a need to address HIVDR and enhance the mechanisms already in place. This study introduces more information that would help in developing targeted interventions to prevent HIVDR and improve patient outcomes.

Emerging integrase resistance in an international perinatal virtual clinic.

The aim of this study was to identify the prevalence of emergent integrase drug resistance mutations (INSTI-DRMs) in international referrals to a perinatal virtual clinic (PVC). A retrospective cohort study. Monthly multidisciplinary PVC reviewing complex case management for children and adolescents with perinatally acquired HIV (CAWHIV). One hundred fourteen cases referred for virological failure between October 2018 and January 2024. Data collected included age, sex, weight, country of residence, antiretroviral therapy (ART) history, HIV viral load, CD4+ cell count, and comorbidities. Resistance mutations were interpreted using the Stanford HIV Drug Resistance database with emergent major INSTI-DRMs described. Of 114 referrals, 103 (90%) had resistance sequences available. Prior INSTI exposure was documented in 61/103 (59%) with 19/61 (31%) having INSTI-DRMs. For these 19, median (IQR) age was 11 years (6-14), weight 25 kg (17-50), CD4+ cell count 485 cells/μl (153-805), and viral load 84 000 copies/ml (2380-137 000). Twelve of 19 (65%) were from low/middle-income countries (LMIC), 6/19 (32%) had current AIDS diagnoses with 14/19 (74%) referred from 2022 onwards. There were a median three prior regimens with 13/19 (68%) having at least 3 class resistance. Two developed INSTI-DRMs on first-line dolutegravir (DTG)-based ART, 17 on second+ line therapy. PVC recommendations were for tenofovir+ lamivudine/emtricitabine (six split adult tablets) with boosted darunavir [19; six twice daily (b.i.d.)], with b.i.d. DTG (6), plus fostemsavir (1) and ibalizumab (1). Although uncommon, INSTI resistance is emerging, mainly in highly treatment experienced CAWHIV from LMIC, highlighting the global need for access to boosted protease inhibitors and novel classes, including formulations for children less than 35 kg.

Virologically suppressed switch to Dolutegravir/Lamivudine 2-Drug regimen versus switch to commonly prescribed 3-Drug regimens in the United States

BackgroundTwo-drug regimens (2DRs) have been introduced in recent years to potentially reduce antiretroviral therapy (ART) toxicities and drug-drug interactions while demonstrating comparable efficacy to three-drug regimens (3DRs) for people with HIV (PWH). The objective of this study was to compare the real-world effectiveness and durability of a single-tablet 2DR of dolutegravir/lamivudine (DTG/3TC) with that of commonly prescribed 3DRs in ART-experienced, virologically suppressed PWH during the first 24 months of DTG/3TC availability in the United States.MethodsVirologically suppressed (viral load [VL] < 200 copies/mL) adult PWH initiating DTG/3TC 2DR, bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF), or a DTG-based 3DR between 01MAY2019 and 31OCT2020 were identified in the OPERA® cohort and followed through 30APR2021. Univariate Poisson regression (incidence rates) and marginal structural Cox proportional hazards models with inverse probability of treatment weights (hazard ratios) were used to quantify relationships between regimen type and confirmed virologic failure (2 consecutive VLs ≥ 200 copies/mL) or regimen discontinuation. Reasons for discontinuation were examined.ResultsA total of 8,037 ART-experienced, virologically suppressed PWH met the inclusion criteria and switched to DTG/3TC (n = 1,450), BIC/FTC/TAF (n = 5,691), or a DTG-based 3DR (n = 896). Incidence rates of confirmed virologic failure were low for all groups, at 0.66 (DTG/3TC), 0.84 (BIC/FTC/TAF), and 1.78 (DTG 3DR) per 100 person-years (py). Compared to DTG/3TC, only the DTG 3DRs were associated with a statistically significant increased hazard of confirmed virologic failure (hazard ratio: 5.21, 95% confidence interval: 1.85, 14.67). Discontinuation rates per 100 py were highest in the DTG 3DR group (24.90), followed by the DTG/3TC group (17.69) and the BIC/FTC/TAF group (8.30). Regardless of regimen, discontinuations were infrequently attributed to effectiveness (VL ≥ 200 copies/mL; 4%) or tolerability (adverse diagnoses, side effects, or lab abnormalities; 6%).ConclusionsAmong virologically suppressed PWH initiating a new regimen, few individuals experienced virologic failure in real-world clinical care. While rates of regimen discontinuation were high, most discontinuations could not be attributed to a lack of virologic control or poor tolerability. These findings suggest that DTG/3TC is an effective option for ART-experienced, virologically suppressed PWH.

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

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

Benchmarking of an Intervention Aiming at the Micro-Elimination of Hepatitis C in Vulnerable Populations in Perpignan, France, to Inform Scale-Up and Elimination on the French Territory

Hepatitis C virus (HCV) is an important cause of chronic liver disease. Among at-risk populations, access to care is challenging. The French Ministry of Health has supported a seek-and-treat pilot intervention aiming at micro-elimination in Perpignan, France, to inform scale-up of elimination efforts across the whole territory. University College Dublin (UCD) led a successful EU funded project, called HepCare, focusing on the micro-elimination of HCV. UCD was contracted to evaluate and benchmark the Perpignan results against results from HepCare. Using mixed-method approaches including qualitative interviews with patients, a focus group with healthcare professionals, and quantitative analyses of the cascade of care against results obtained at other European sites, we analyse the acceptability, reproducibility, replicability, and effectiveness of the Perpignan intervention. A total of 960 participants were recruited in the Perpignan area. HCV antibody test results were obtained for 928 (96.6%), of which 150 (15.6%) were antibody-positive. Of the antibody-positive participants, 68 (45.3%) tested positive for HCV-RNA, 141 (94%) were linked to care, and of the HCV-RNA-positive participants, 60 (88%) started treatment. Of those who underwent treatment, 34 (56.7%) completed treatment and achieved a sustained viral response (SVR) at dataset closure, 18 (30%) were still in treatment, 5 (8.3%) defaulted from treatment, and 3 (5%) had a virologic failure or died. The intervention in Perpignan was acceptable to patients, but had limitations in effectiveness, as shown in comparisons with HepCare results. To engage harder-to-reach cohorts in France, future models of care in the territory should incorporate peer support.

Patterns of HIV-1 Drug Resistance Observed Through Geospatial Analysis of Routine Diagnostic Testing in KwaZulu-Natal, South Africa.

HIV-1 drug resistance (HIVDR) impedes treatment and control of HIV-1, especially in high-prevalence settings such as KwaZulu-Natal (KZN) province, South Africa. This study merged routine HIV-1 genotypic resistance test (GRT) data with Geographic Information Systems coordinates to assess patterns and geographic distribution of HIVDR in KZN, among ART-experienced adults with virological failure. We curated 3133 GRT records generated between 1 January 2018 and 30 June 2022, which includes the early phase of dolutegravir (DTG) rollout, of which 2735 (87.30%) had HIVDR. Of the 2735, major protease, nucleoside, and non-nucleoside reverse transcriptase inhibitor mutations were detected in 41.24%, 84.97% and 88.08% of GRTs, respectively. Additional genotyping of HIV-1 integrase for 41/3133 (1.31%) GRTs showed that 17/41 (41.46%) had integrase strand transfer inhibitor resistance. Notably, of 26 patients on DTG with integrase genotyping, 9 (34.62%) had DTG-associated resistance mutations. Dual- or triple-class resistance was observed in four of every five GRTs. The odds of HIVDR increased significantly with age, with ≥60 years having 5 times higher odds of HIVDR compared to 18-29 years (p = 0.001). We identified geospatial differences in the burden of HIVDR, providing proof of concept that this could be used for data-driven public health decision making. Ongoing real-time HIVDR surveillance is essential for evaluating the outcomes of the updated South African HIV treatment programme.

Epidemiological dynamics and molecular characterization of HIV drug resistance in eastern China from 2020 to 2023.

HIV drug resistance (HIVDR) has become a threat to the elimination of the AIDS epidemic due to the global scale-up of antiretroviral therapy (ART) for HIV-infected individuals. This study aims to investigate the epidemiological dynamics and molecular characterization of HIV pretreatment drug resistance (PDR) and acquired drug resistance (ADR) in Hangzhou, a developed region in China. An epidemiological survey combined with a molecular transmission network and Bayesian analysis was conducted. A total of 3,596 individuals with newly confirmed HIV infections (from 2020 to 2023) and 164 individuals with ART failure (from 2021 to 2023) were included. The molecular transmission network was used to identify key drug-resistant transmission clusters, while the Bayesian analysis was utilized to trace the origins and spread of these clusters. The overall prevalence of PDR was found to be 8.4% (303/3596). Among these cases, PDR to non-nucleoside reverse transcriptase inhibitors (NNRTIs) accounted for 4.7% (170/3596), significantly higher than the resistance observed for protease inhibitors (PIs; 2.8%, p < 0.001) and nucleoside reverse transcriptase inhibitors (NRTIs; 1.4%, p < 0.001). Multivariate logistic regression analysis revealed a significantly higher PDR value among individuals infected with the CRF07_BC subtype compared to those with the CRF08_BC subtype (aOR = 0.56, 95% CI = 0.359-0.859, p = 0.008). The molecular transmission network analysis identified the transmission of the drug resistance mutation (DRM) Q58E within the clusters of the CRF07_BC subtype. The Bayesian analysis suggested that these clusters were introduced into Hangzhou from Shenzhen between 2005 and 2012. Furthermore, the study highlighted 50.6% (83/164) prevalence of ADR among individuals experiencing ART failure. The combined molecular network analysis of virological failure and newly confirmed HIV infections indicated the transmission of the K103N mutation between these groups. In conclusion, targeted interventions may be necessary for specific subtypes and transmission clusters to control the spread of drug-resistant HIV. Continuous monitoring of resistance patterns is critical to inform treatment strategies and optimize ART regimens.

Rates of Viral Non-Suppression and Acquired HIV-1 Drug Resistance Emergence among Children during the Sociopolitical Crisis in the Northwest Region of Cameroon: A Call for Improved Monitoring Strategies.

Virological failure (VF) among children remains concerning, with high risks of HIV drug resistance (HIVDR) emergence and increased disease progression. Therefore, monitoring of viral non-suppression and emerging HIVDR is crucial, especially in the frame of sociopolitical unrest. The study sought to determine the prevalence of VF and evaluate the acquired HIVDR and viral genetic diversity among children in the northwest region of Cameroon during the ongoing sociopolitical crisis. A cross-sectional facility-based study was conducted among HIV-infected children aged ≤18 years, receiving antiretroviral therapy (ART) in urban and rural settings of Northwest Cameroon, from November 2017 through May 2018. Viral load (VL) was done using the Abbott m2000RealTime. Unsuppressed VL was defined as viral load ≥1,000 copies/ml. HIVDR testing was performed by sequencing of HIV-1 protease-reverse transcriptase at the Chantal Biya International Reference Center (CIRCB) using an in-house protocol. Drug resistance mutations (DRM) were interpreted using Stanford HIVdbv8.5 and phylogeny using MEGAv.6. Data were compared between urban and rural areas with p<0.05 considered statistically significant. A total of 363 children were recruited, average age of 12 years (urban) and 8 years (rural). VL coverage was 100% in the urban setting and 77% in the rural setting. Overall, VF was 40.5% (39% [130/332] in the urban setting and 41% (13/31) in the rural setting; p=0.45). Overall, viral undetectability (defined as VL<40 copies/ml) was 45.5% (46% (urban) and 45% (rural); p=0.47). Among those experiencing confirmed virological failure and who were successfully sequenced (n=35), the overall rate of HIVDR was 100% (35/35). By drug class, HIVDR rates were 97.1% (34/35) for non-nucleoside reverse transcriptase inhibitors (NNRTIs), 97.1% (34/35) for NRTIs and 17.1% (6/35) for protease inhibitors (22.7% (5/22) in the urban setting and 7.7% [1/13] in the rural setting). CRF02_AG was the most prevalent viral clade (75%), followed by other recombinants (09_cpx, 11_cpx, 13_cpx, 22_01A1, 37_cpx) and pure subtypes (A1, F2, G, H). In this population of children and adolescents living with HIV in a context of socio-political instability in the North-West region of Cameroon, rates of viral non-suppression are high, and accompanied by HIVDR selection. Our suggests the need for a more differentiated care of these CAHIV, especially those in these regions faced with significant socio-economic and health impacts due to the ongoing crisis.

Burden of virologic failure, and its determinants among HIV positive children in East Africa: a systematic review and meta-analysis

Background: There are many studies regarding the prevalence of Virologic failure and its associated factors in East Africa, but they are inconclusive. In this study, the prevalence of Virologic failure and its associated factors in east Africa were determined. Methods: Published articles that were conducted in English language were prepared based on preferred reporting items for systematic reviews and meta-analysis (PRISMA) statement. Web of Science, PubMed, and Google Scholar were explored to find out the articles. STATA Version 14 software was used for computing the pooled estimates of both the prevalence of virologic failure and associated factors. The pooled estimates were computed using both random and fixed effect models. Results were presented by using the randomand fixed effect models. . The pooled estimates were presented with 95% CI. Publication bias was assessed by looking the symmetry in the funnel plot. Result: The pooled prevalence of virologic failure was, 25.90 (19.49, 32.32, p ≤ 0:001) in the random effect model. Four factors, poor adherence (2.91 (Pooled odds ratio(POR): 2.91, 95%CI: 1.93, 4.40), being male (1.17 (POR: 1.17, 95%CI: 1.08, 1.27)), wasting as an under nutrition (3.1 (POR:3.1, 95%CI: 1.63, 5.95), and Nevirapine(NVP) based regimen (2.76 (POR: 2.76 (1.65,95%CI: 4.62)) were found to be independent predictors of virologic failure. Conclusion: The prevalence of virologic failure in East Africa is remarkably high. Four factors were found to be the determining factors Different strategies must be designed to address (poor adherence, being male, wasting as an under nutrition, and NVP based regimen). Keywords: HIV; virologic failure; adherence; viral load suppression.