A numbers game: mosquito-based arbovirus surveillance in two distinct geographic regions of Latin America.

Aedes mosquitoes, as vectors of medically important arthropod-borne viruses (arboviruses), constitute a major public health threat that requires entomological and epidemiological surveillance to guide vector control programs to prevent and reduce disease transmission. In this study, we present the collaborative effort of 1 year of Aedes ageypti (Linnaeus, 1762) mosquito-based arbovirus surveillance in 2 geographically distinct regions of Latin America (Nicaragua and Ecuador). Adult female mosquitoes were collected using backpack aspirators in over 2,800 randomly selected households (Nicaragua, Ecuador) and 100 key sites (Nicaragua) from 8 distinct communities (Nicaragua: 2, Ecuador: 6). A total of 1,358 mosquito female pools were processed for RNA extraction and viral RNA detection using real-time reverse transcription-polymerase chain reaction. Ten positive dengue virus (DENV) pools were detected (3 in Nicaragua and 7 in Ecuador), all of which were found during the rainy season and matched the serotypes found in humans (Nicaragua: DENV-1 and DENV-4; Ecuador: DENV-2). Infection rates ranged from 1.13 to 23.13, with the Nicaraguan communities having the lowest infection rates. Our results demonstrate the feasibility of detecting DENV-infected Aedes mosquitoes in low-resource settings and underscore the need for targeted mosquito arbovirus sampling and testing, providing valuable insights for future surveillance programs in the Latin American region.

Viral eradication reduces all-cause mortality in patients with chronic hepatitis C virus infection who had received direct-acting antiviral therapy.

BACKGROUND AND AIMS: The impact of hepatitis C virus (HCV) eradication via direct-acting antiviral (DAA) therapy on overall mortality, particularly non-liver-related mortality, is understudied. METHODS: We recruited 4180 patients with chronic HCV infection who achieved sustained virological response (SVR) (HCV eradication) through DAA therapy (n = 2501, SVR group) or who did not receive antiviral therapy (n = 1679, non-SVR group); 1236 from each group were chosen using propensity score matching. Causes of death and all-cause mortality, including non-liver-related diseases, were investigated. RESULTS: Of the 4180 patients, 592 died during the follow-up period. In the SVR group, the mortality rates from liver-related and non-liver-related diseases were 16.5% and 83.5%, respectively. Compared to the non-SVR group, mortality rates from liver-related and non-liver-related diseases were 50.1% and 49.9%, respectively (p < .001). In non-cirrhotic patients, multivariable analysis revealed that SVR was an independent factor associated with both liver-related (hazard ratio [HR], .251; 95% confidence interval [CI], .092-.686) and non-liver-related (HR, .641; 95% CI, .415-.990) mortalities. In cirrhotic patients, multivariable analysis revealed that SVR remained an independent factor significantly associated with liver-related mortality (HR, .151; 95% CI, .081-.279). In propensity score-matched patients, the eradication of HCV (SVR group) decreased both liver-related (p < .001) and non-liver-related mortality (p = .008) rates compared to persistent HCV infection (non-SVR group). CONCLUSIONS: The elimination of HCV via DAA therapy reduced not only liver-related mortality but also non-liver-related mortality in patients with chronic HCV.

Impact analysis of SARS-CoV-2 vaccination in patients treated with monoclonal antibodies: A monocentric experience.

BACKGROUND: Since the discovery of SARS-CoV-2, no treatment has been able to completely eradicate the virus. The study aimed to evaluate the virological and clinical impact of the vaccination in SARS-CoV-2 infected patients treated with monoclonal antibodies (mAbs). METHODS: This single-centre, observational, retrospective, real-life study was performed on SARS-CoV-2 symptomatic outpatients and inpatients treated with mAbs from March 2021 to November 2022 includes 726 patients. Each patient received available mAbs (bamlanivimab-etesevimab or casirivimab-indevimab or sotrovimab or tixagevimab-cilgavimab) according to the circulating virus strains. Age, comorbidities, vaccination status, death rates, duration of virological clearance, average length of stay, risk factors, and hospitalization or ICU admission were recorded. RESULTS: Of 726 patients with complete data analyzed (median age 64), 516 outpatients and 210 inpatients were included. Vaccination status was known for all participants: 74.4 % and 51.7 % were vaccinated against SARS-CoV-2 among inpatients and outpatients, respectively. A shorter duration of virological clearance was observed in the vaccinated group, with a median of 16 days (IQR 15-17), compared to 19 days (IQR 18-21) in the unvaccinated group [HR 1.21; p < 0.032]. Multivariate analysis of virological clearance also showed statistical significance with tixagevimab cilgavimab 300 mg/300 mg (HR 2.73, p value < 0.001). No significant difference was found in worsening [OR 1,29; p = 0.57] and mortality [OR 0.65; p = 0.81] rates between vaccinated and unvaccinated patients treated with mAbs. CONCLUSIONS: Key findings include a shorter duration of virological clearance in vaccinated outpatients but no significant differences in worsening or mortality rates between vaccinated and unvaccinated patients treated with mAbs. The study suggests a potential synergistic role of mAbs in accelerating virological clearance in vaccinated patients with mild to moderate COVID-19, with differing effects in hospitalized patients. Therefore, it is essential to implement health surveillance in high-risk patients with comorbidities in order to identify early any variants that might otherwise escape neutralizing antibodies.

No impact of HIV coinfection on the mortality in patients with hepatitis C virus infection after sustained virological response.

BACKGROUND: In patients with hepatitis C virus (HCV) chronic infection and advanced liver disease, the impact of human immunodeficiency virus (HIV) coinfection on the clinical outcome after sustained virological response (SVR) has not been sufficiently clarified. The aim of this study was to compare the mortality after SVR of patients bearing HCV chronic infection and advanced liver fibrosis, with and without HIV-coinfection after a prolonged follow-up. METHODS: This was a prospective multicenter cohort study including individuals with HIV/HCV-coinfection and patients with HCV-monoinfection from Spain, fulfilling: 1) Liver stiffness (LS) ≥9.5 kPa before treatment; 2) SVR with a direct-acting antiviral (DAA) based regimen; 3) LS measurement available at SVR. The main outcome was overall survival. Mortality attributable to liver disease and non-hepatic causes was also assessed. RESULTS: 1,118 patients were included, of whom 676 (60.5%) were living with HIV. The median (Q1-Q3) follow-up was 76 months (57-83). After SVR, 46 (10%) HCV-monoinfected and 74 (11%) HIV/HCV-coinfected patients died. The overall mortality rate (95% CI) was 1.9 (1.6-2.2) per 100 person-years, 1.9 (1.4-2.5) per 100 person-years in patients with HCV-monoinfection and 1.8 (1.6-2.3) per 100 person-years in people living with HIV. In the multivariable analysis, HIV-coinfection was not associated with a shorter survival [0.98 HR (95% confidence interval, CI) = (0.61-1.58), p=0.939]. CONCLUSIONS: In patients with HCV chronic infection and advanced fibrosis, HIV-coinfection does not reduce the overall survival after SVR.

HIV-1 resistance and virological failure to treatment with the integrase inhibitors bictegravir, cabotegravir, and dolutegravir: a systematic literature review.

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

Effectiveness and safety of tenofovir amibufenamide in chronic hepatitis B patients.

This letter to the editor relates to the study entitled "Tenofovir amibufenamide vs tenofovir alafenamide for treating chronic hepatitis B: A real-world study", which was recently published by Peng et al. Hepatitis B virus infection represents a significant health burden worldwide and can lead to cirrhosis and even liver cancer. The antiviral drugs currently used to treat patients with chronic hepatitis B infection still have many side effects, so it is crucial to identify safe and effective drugs to inhibit viral replication.

Hepatitis C treatment outcome among people in prison: The SToP-C study.

BACKGROUND AND AIMS: Hepatitis C virus (HCV) burden is higher among people in prison given high prevalence of injecting drug use. This study evaluated direct-acting antiviral (DAA) treatment outcome in prisons. METHODS: The Surveillance and Treatment of Prisoners with hepatitis C (SToP-C) study enrolled individuals incarcerated in four Australian prisons (2017-2019). Participants with detectable HCV RNA were offered sofosbuvir-velpatasvir for 12 weeks. Sustained virological response (SVR) was assessed in intention-to-treat (ITT; participants commencing treatment and due for SVR assessment before study close) and per-protocol (PP; participants with documented treatment completion and SVR assessment) populations. RESULTS: Among 799 participants with HCV, 324 (41%) commenced treatment (94% male; median age, 32 years; median duration of incarceration, 9 months). In ITT population (n = 310), 201 had documented treatment completion (65% [95% CI: 59-70]), and 137 achieved SVR (ITT-SVR: 44% [95% CI: 39-50]). In PP population (n = 143), 137 achieved SVR (PP-SVR: 96% [95% CI: 91-98]). Six participants had quantifiable HCV RNA at SVR assessment from treatment failure (n = 2) or reinfection (n = 4). Release or inter-prison transfer was common reasons for no documented treatment completion (n = 106/109 [97%]) and no SVR assessment (n = 57/58 [98%]). In ITT analysis, longer incarceration was associated with increased SVR (adjusted OR per month 1.03 [95% CI: 1.01-1.04]). CONCLUSION: Among participants who completed DAA treatment and were assessed for SVR, treatment outcome was consistent with non-prison clinical studies. However, most individuals did not complete treatment or lacked study-documented treatment outcome due to release or transfer. Strategies to accommodate dynamic prisoner populations are required to ensure continuity of HCV care, including treatment completion and post-treatment care.

Risk factors related to low-level viraemia in chronic hepatitis B patients receiving entecavir treatment.

Background: About 20% of on-treatment patients with chronic hepatitis B (CHB) experienced low-level viraemia (LLV), which is associated with persistent low-grade inflammation, fibrosis progression, and increased risk of hepatocellular carcinoma. We aimed to investigate the high-risk factors related to LLV. Methods: In this retrospective study, patients receiving entecavir (ETV) treatment from January 2018 to January 2023 were enrolled, and were divided into a LLV (HBV DNA 20-2000 IU/mL) cohort and a complete virological response (CVR) (HBV DNA < 20 IU/mL) cohort according to the virological response at week 48 posttreatment. Treatment baseline characteristics were retrieved from electronic medical records. Multivariate logistic regression was performed. Results: Totally, 1653 patients were enrolled, male patients accounted for 73.0%; the median age was 44 years; the mean HBV DNA level was 5.9 Log10 IU/ml. Among them, 472 (28.6%) experienced LLV. Multivariate analysis showed that HBeAg positivity (OR = 2.650, 95% CI: 2.000-3.511, p < 0.001), HBV DNA ≥ 6.0 Log10 IU/mL (OR = 1.370, 95% CI: 1.054-1.780, p = 0.019), qHBsAg ≥ 9000 IU/mL (OR = 4.472, 95% CI: 3.410-5.866, p < 0.001), cirrhosis (OR = 1.650, 95% CI: 1.234-2.207, P = 0.001), LSM ≥ 13.0 kPa (OR = 1.644, 95% CI: 1.203-2.246, p = 0.002), and PLT < 100×109/L (OR = 1.450, 95% CI: 1.094-1.922, p = 0.010) at baseline were related to the development of LLV. Conclusions: High HBV DNA/HBsAg quantification/LSM, low PLT, HBeAg positivity, and liver cirrhosis were high-risk factors associated with LLV in patients receiving entecavir treatment.

Immunological and virological response to fostemsavir in routine US clinical care: An OPERA cohort study.

OBJECTIVES: Fostemsavir is a novel attachment inhibitor used with other antiretrovirals in heavily treatment-experienced (HTE) adults with multidrug-resistant HIV-1. Real-world immunological and virological responses were assessed in individuals starting fostemsavir in the OPERA cohort. METHODS: Among adults with HIV-1 starting fostemsavir between 2 July 2020 and 1 September 2022, 6-month and 12-month changes in CD4 T-cell count and CD4%, and maintenance/achievement of viral load (VL) <50 copies/mL were described and stratified by baseline VL (suppressed: <50 copies/mL; viraemic: ≥50 copies/mL) and CD4 count (high: ≥350 cells/µL; low: <350 cells/µL). RESULTS: Of 182 individuals starting fostemsavir, 64% were viraemic (34% low CD4, 30% high CD4) and 36% were suppressed (16% low CD4, 20% high CD4). The suppressed/low CD4 group had the largest median increases in CD4 count (6-month: 30 cells/µL [interquartile range {IQR} 9-66], 12-month: 66 cells/µL [IQR 17-125]), and CD4% (6-month: 1.0% [IQR -0.3-2.8], 12-month: 1.9% [IQR 1.3-3.9]). Regardless of baseline VL, those with a high baseline CD4 count experienced a greater variability in immunological response than those with low CD4 counts (12-month standard deviation range 172-231 cells/µL vs. 69-90 cells/µL). VL <50 copies/mL was maintained in most suppressed individuals; nearly half of the viraemic/high CD4 group and a third of the viraemic/low CD4 group achieved a VL <50 copies/mL at either timepoint. CONCLUSIONS: After 6 or 12 months of fostemsavir use, virological response was low in viraemic individuals, although most suppressed individuals did maintain suppression. While immunological response varied across individuals, virologically suppressed HTE individuals with low CD4 counts may benefit from immunological improvements with fostemsavir.

Clinical and virological characteristics of coexistent hepatitis B surface antigen and antibody in treatment-naive children with chronic hepatitis B virus infection.

Serological pattern of simultaneous positivity for hepatitis B surface antigen (HBsAg) and antibody against HBsAg (anti-HBs) is considered a specific and atypical phenomenon among patients with chronic hepatitis B virus (HBV) infection, especially in pediatric patients. Unfortunately, there is limited understanding of the clinical and virological characteristics among children having chronic HBV infection and the coexistence of HBsAg and anti-HBs. Hence, our objective was to determine the prevalence of coexistent HBsAg and anti-HBs and to explore the associated clinical and virological features in this patient population. The researchers conducted a retrospective cohort study on the 413 pediatric patients with chronic HBV infection from December 2011 to June 2022. The patients were stratified into two groups based on their anti-HBs status. Demographic, serum biochemical and virological parameters of two group were compared. Of the total 413 enrolled subjects, 94 (22.8%) were tested positive for both HBsAg and anti-HBs. Patients with anti-HBs were younger and demonstrated significantly higher ratio of albumin to globulin (A/G), elevated serum levels of alanine transaminase (ALT), lower ratio of aspartate transaminase (AST)/ALT (AST/ALT) and reduced serum levels of globulin, HBsAg and HBV DNA, Additionally, these patients were more likely to show coexistent HBeAg and anti-HBe when compared to patients without anti-HBs. The results of multivariate logistical analysis revealed that AST/ALT, serum levels of globulin and HBsAg were negatively associated with coexistence of HBsAg and anti-HBs. Our data demonstrated a considerable prevalence of coexisting HBsAg and anti-HBs in pediatric patients. Children with this specific serological pattern were commonly of a younger age, seemly predisposing them to early liver impairment and lower HBV replication activity.

Genetic landscape for majority and minority HIV-1 drug resistance mutations in antiretroviral therapy naive patients in Accra, Ghana.

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

Efficacy of Pegylated Interferon-alpha-2a in Chronic Hepatitis Delta: Experience from a Tertiary Care Hospital in Karachi.

Background: Chronic hepatitis D (CHD) along with chronic hepatitis B (CHB) is an important cause of morbidity and mortality in patients with cirrhosis. It is a potentially curable infection that has long awaited a good treatment option. Objective: To ascertain the efficacy of pegylated interferon (PEG-IFN)-alpha-2a in patients suffering from CHD. A tertiary care hospital experience from Pakistan. Materials and methods: The study included 207 CHD polymerase chain reaction (PCR)-positive patients treated with PEG-IFN-alpha-2a between July 2020 and October 2022. Virological response rate (PCR negative) at weeks 24 and 48 was the primary endpoint. Secondary outcomes included partial response (>2 log reduction in PCR) and treatment failure rate (<2 log reduction in PCR). Results: A total of 187 patients started PEG-IFN therapy, and 148 patients completed the assigned 48 weeks of therapy. Patients' mean age was 25.7 years with 65% being males. The virological response rate was 40.5% at week 24 and 32.4% at week 48. The partial response rate was 24% at both weeks 24 and 48. The treatment failure rate was 36% at week 24 and 44% at week 48. Hemoglobin, white blood cell (WBC) count, and total bilirubin were found to be predictive of treatment response. Side effects led to treatment discontinuation among eighteen patients and one patient died due to hepatic failure. Conclusion: Therapy with PEG-IFN-alpha-2a shows suboptimal outcomes in patients with CHD. There is a strong need for more effective alternate therapies for CHD patients. How to cite this article: Butt N, Usmani MT, Hussain R, et al. Efficacy of Pegylated Interferon-alpha-2a in Chronic Hepatitis Delta: Experience from a Tertiary Care Hospital in Karachi. Euroasian J Hepato-Gastroenterol 2024;14(1):51-55.

Risk of hepatocellular carcinoma occurrence after antiviral therapy for patients with chronic hepatitis C Infection: a systematic review and meta-analysis.

BACKGROUND AND AIMS: The risk of hepatocellular carcinoma (HCC) occurrence following antiviral therapy in patients with chronic hepatitis C (CHC) remains unclear. The current study aims to compare: (1) the HCC occurrence rate following sustained virological response (SVR) versus non-response (NR); (2) the HCC occurrence rate following direct-acting antiviral (DAA) therapy versus interferon (IFN)-based therapy, and (3) the HCC occurrence rate in SVR patients with or without cirrhosis. METHODS: A search was performed for articles published between January 2017 and July 2022. Studies were included if they assessed HCC occurrence rate in CHC patients following anti-HCV therapy. Random effects meta-analysis was used to synthesize the results from individual studies. RESULTS: A total of 23 studies including 29,395 patients (IFN-based = 6, DAA = 17; prospective = 10, retrospective = 13) were included in the review. HCC occurrence was significantly lower in CHC with SVR (1.54 per 100 person-years (py, 95% CI 1.52, 1.57) than those in non-responders (7.80 py, 95% CI 7.61, 7.99). Stratified by HCV treatment regimens, HCC occurrence following SVR was 1.17 per 100 py (95% CI 1.11, 1.22) and 1.60 per 100 py (95% CI 1.58, 1.63) in IFN- and DAA treatment-based studies. HCC occurrence was 0.85 per 100 py (95% CI 0.85, 0.86) in the non-cirrhosis population and rose to 2.47 per 100 py (95% CI 2.42, 2.52) in the cirrhosis population. Further meta-regression analysis showed that treatment types were not associated with a higher HCC occurrence rate, while cirrhosis status was an important factor of HCC occurrence rate. CONCLUSION: HCC occurrence was significantly lower in the SVR population than in the NR population. HCC risk following SVR occurred three times more frequently in patients with cirrhosis than patients without cirrhosis. However, we found no significant difference in HCC occurrence risk following SVR between DAA and IFN therapies. CLINICAL TRIAL NUMBER: CRD42023473033.

Assessment of hepatitis B virus relapse in cancer patients receiving chemotherapy with prophylactic nucleos(t)ide analogues: Implications for overall mortality.

BACKGROUND AND AIMS: We aimed to explore the risk factors associated with virological and clinical relapse, as well as their impact on overall mortality, in hepatitis B virus (HBV)-infected patients receiving nucleos(t)ide analogues (NUCs) therapy prior to chemotherapy initiation. METHODS: From 2010 to 2020, we conducted a prospective cohort study involving patients with HBV infection undergoing cytotoxic chemotherapy. We utilized the Kaplan-Meier method and Cox proportional hazard regression models to assess risk factors. RESULTS: We observed that TDF or TAF (HR: 2.16, 95% CI 1.06-4.41; p = .034), anthracycline (HR: 1.73, 95% CI 1.10-2.73; p = .018), baseline HBV DNA (HR: 1.55, 95% CI 1.33-1.81; p < .001) and end-of-treatment HBsAg titre >100 IU/mL (HR: 7.81, 95% CI 1.94-31.51; p = .004) were associated with increased risk of virological relapse. Additionally, TDF or TAF (HR: 4.91, 95% CI 1.45-16.64; p = .011), baseline HBV DNA (HR: 1.48, 95% CI 1.10-1.99; p = .009) and end-of-treatment HBsAg titre >100 IU/mL (HR: 6.09, 95% CI .95-38.87; p = .056) were associated with increased risk of clinical relapse. Furthermore, we found that virological relapse (HR: 3.32, 95% CI 1.33-8.32; p = .010) and clinical relapse (HR: 3.59, 95% CI 1.47-8.80; p = .005) significantly correlated with all-cause mortality in HBV patients receiving cytotoxic chemotherapy with prophylactic NUCs therapy. CONCLUSIONS: The risk of virological and clinical relapse was linked to baseline HBV DNA, end-of-treatment HBsAg levels and TDF or TAF for prophylaxis; additionally, experiencing relapse heightens the risk of all-cause mortality. Further research is warranted to explore potential strategies for preventing virological and clinical relapse in high-risk patients.

One Year of Long-Acting Cabotegravir and Rilpivirine in People With Human Immunodeficiency Virus and Long Exposure to Antiretroviral Therapy: Data From the SCohoLART Study.

Background: The aim of the study was to evaluate the 12-month cumulative probability of treatment discontinuation (TD) in people with human immunodeficiency virus (HIV; PWH) and a long exposure to antiretroviral therapy (ART) switching to long-acting cabotegravir and rilpivirine (CAB/RPV). Methods: SCohoLART is a single-center, prospective, cohort study designed to collect both samples and clinical data from PWH with virological suppression who switched to bimonthly long-acting CAB/RPV. TD occurred at switch to another regimen for any reason including virological failure (VF); VF was defined as HIV RNA levels ≥50 copies/mL at 2 consecutive measurements or a single HIV RNA level ≥1000 copies/mL. Results were reported as median (interquartile range [IQR]) or frequency (percentage). Cumulative probabilities of TD were estimated using Kaplan-Meier curves. Results: We evaluated 514 participants; 467 (90.9%) were male, and their median age (IQR) was 49 (40-56) years. At the time of switching, the median time from HIV diagnosis and the median duration of ART were 14.0 (IQR, 8.8-20.5) and 11.4 (7.9-17.4) years, respectively; before starting CAB/RPV, the median number of antiretroviral regimens was 3 (2-4). During a median study follow-up (IQR) of 13.1 (9.1-15.5) months, 52 PWH (10.1%) experienced TD, including 4 (0.8%) for VF. The 12-month cumulative probability of TD was 11% (95% confidence interval, 8%-14%). The main cause of TD was injection site reaction (15 participants [28.8%]). Conclusions: The 1-year cumulative probability of TD with long-acting CAB/RPV was quite low in this cohort of people with a median exposure to ART of 10 years, in whom injection site reaction was the leading cause of TD. VFs were rare during study follow-up.

Virologic Response and Reinfection Following HCV Treatment among Hospitalized People Who Inject Drugs: Follow-Up Data from the OPPORTUNI-C Trial.

Treatment of hepatitis C among people who inject drugs (PWID) may be complicated by loss to follow-up and reinfection. We aimed to evaluate sustained virologic response (SVR) and reinfection, and to validate complete pharmacy dispensation as a proxy for cure among PWID enrolled in a trial of opportunistic HCV treatment. Data were obtained by reviewing the electronic patient files and supplemented by outreach HCV RNA testing. Reinfection was defined based on clinical, behavioral, and virological data. Intention to treat SVR ≥ 4 within 2 years after enrolment was accomplished by 59 of 98 (60% [95% CI 50-70]) during intervention conditions (opportunistic treatment) and by 57 of 102 (56% [95% CI 46-66]) during control conditions (outpatient treatment). The time to end of treatment response (ETR) or SVR ≥ 4 was shorter among intervention participants (HR 1.55 [1.08-2.22]; p = 0.016). Of participants with complete dispensation, 132 of 145 (91%) achieved ETR or SVR > 4 (OR 12.7 [95% CI 4.3-37.8]; p < 0.001). Four cases of reinfection were identified (incidence 3.8/100 PY [95% CI 1.0-9.7]). Although SVR was similar, the time to virologic cure was shorter among intervention participants. Complete dispensation is a valid correlate for cure among individuals at risk of loss to follow-up. Reinfection following successful treatment remains a concern.

Elevated hepatitis B virus RNA levels in HBeAg-positive patients with low-level viraemia or previous low-level viraemia.

The understanding of viral transcription and replication activity in HBeAg-positive chronic hepatitis B (CHB) patients with low-level viraemia (LLV) or previous low-level viraemia (pre-LLV) remains unclear. Our aim was to evaluate and compare circulating hepatitis B virus (HBV) RNA levels in these patient groups with those achieving maintained virological response (MVR). This cross-sectional study included 147 patients: 43 in the LLV group, 25 in the pre-LLV group and 79 in the MVR group. Serum HBV RNA levels were assessed using specific RNA target capture combined with simultaneous amplification and testing method. Propensity score matching (PSM) was used to balance baseline characteristics between groups. Median HBV RNA levels were 6.9 copies/mL in the LLV group, 6.1 copies/mL in the pre-LLV group and 3.8 copies/mL in the MVR group. After PSM, significantly higher HBV RNA levels were observed in the LLV group compared to the MVR group (p < .001), and the pre-LLV group also showed higher HBV RNA levels than the MVR group (p < .001). Both LLV and pre-LLV HBeAg-positive CHB patients exhibited elevated circulating HBV RNA levels compared to those achieving MVR.

Virological outcomes of third-line antiretroviral therapy in a global context: a systematic reviews and meta-analysis.

BACKGROUND: Despite remarkable progress, HIV's influence on global health remains firm, demanding continued attention. Understanding the effectiveness of third-line antiretroviral therapy in individuals who do not respond to second-line drugs is crucial for improving treatment strategies. The virological outcomes of third-line antiretroviral therapy vary from study to study, highlighting the need for robust global estimates. METHODS: A comprehensive search of databases including PubMed, MEDLINE, International Scientific Indexing, Web of Science, and Google Scholar, was conducted. STATA version 17 statistical software was used for analysis. A random-effects model was applied to compute the pooled estimates. Subgroup analysis, heterogeneity, publication bias, and sensitivity analysis were also performed. The prediction interval is computed to estimate the interval in which a future study will fall. The GRADE tool was also used to determine the quality of the evidence. RESULTS: In this systematic review and meta-analysis, 15 studies involving 1768 HIV patients receiving third-line antiretroviral therapy were included. The pooled viral suppression of third-line antiretroviral therapy was 76.6% (95% CI: 71.5- 81.7%). The viral suppression rates at 6 and 12 months were 75.5% and 78.6%, respectively. Furthermore, third-line therapy effectively suppressed viral RNA copy numbers to ≤ 50 copies/mL, ≤ 200 copies/mL, and ≤ 400 copies/mL with rates of 70.7%, 85.4%, and 85.7%, respectively. CONCLUSION: More than three-fourths of patients on third-line antiretroviral therapy achieve viral suppression. Consequently, improving access to and timely initiation of third-line therapy may positively impact the quality of life for those with second-line treatment failure.

Association of comprehensiveness of antiretroviral care and detectable HIV viral load suppression among pregnant and postpartum women in the Democratic Republic of the Congo: a cross-sectional study.

Introduction: Worldwide, over two-thirds of people living with HIV are on antiretroviral therapy (ART). Despite increased ART access, high virological suppression prevalence remains out of reach. Few studies consider the quality of ART services and their impact on recipients' viral suppression. We assessed the association between ART service readiness and HIV viral load suppression among pregnant and breastfeeding women living with HIV (WLH) receiving ART in maternal and child health (MCH) clinics in Kinshasa, Democratic Republic of Congo. Methods: We performed a cross-sectional analysis leveraging data from a continuous quality improvement intervention on WLH's long-term ART outcomes. From November 2016 to May 2020, we enrolled WLH from the three largest clinics in each of Kinshasa'Ls 35 health zones. We measured clinic's readiness using three WHO-identified ART care quality indicators: relevant guidelines in ART service area, stocks of essential ART medicines, and relevant staff training in ≥24 months, scoring clinics 0-3 based on observed indicators. We defined viral load suppression as ≤1,000 cp/ml. Multilevel mixed-effect logistic models were used to estimate prevalence odds ratios (ORs) measuring the strength of the association between ART service readiness and viral suppression. Results: Of 2,295 WLH, only 1.9% received care from a clinic with a score of 3, 24.1% received care from a 0-scoring clinic, and overall, 66.5% achieved virologically suppression. Suppression increased from 65% among WLH receiving care in 0-scoring clinics to 66.9% in 1-scoring clinics, 65.8% in 2-scoring clinics, and 76.1% in 3-scoring clinics. We did not observe a statistically significant association between ART service readiness score and increased viral suppression prevalence, however we did find associations between other factors, such as the location of the health center and pharmacist availability with suppressed viral load. Discussion: A lack of comprehensive ART care underscores the need for enhanced structural and organizational support to improve virological suppression and overall health outcomes for women living with HIV..