Antiviral Therapy

To evaluate the impact of baseline resistance-associated substitutions (RASs) on direct-acting antiviral (DAA) treatment response among pegylated interferon in combination with ribavirin (PR) failing patients in a real-life setting.

Blood samples and clinical data from 171 patients who failed PR treatment were collected. All of them received rescue DAA regimens. RAS identified in the NS3, NS5A and NS5B regions by Sanger sequencing method were compared by DAA regimen and HCV subtypes. We assessed sustained virological response at 12 weeks (SVR12) and evaluated the impact of baseline RASs on the effectiveness of DAA regimens in clinical practice.

The overall SVR12 rates were: 89.47% (153/171), 92.1% (117/127) in patients without cirrhosis versus 81.8% (36/44) in those with cirrhosis, without significant difference (χ²=3.69, P=0.08); 87.9% in genotype (GT)1b patients (n=116) versus 93.8% in GT2a (n=32) versus 90.5% in GT3 (n=21) versus 100% in GT6 (n=2), without significant difference (χ²=1.02, P=0.84); 66.7% in asunaprevir (ASV) + daclatasvir (DCV) regimen (n=24) versus 94.0% in sofosbuvir (SOF)-based regimen (n=133), with significant difference (χ²=19.7, P=0.001). Our results showed that the prevalence of NS3, NS5A, NS5B RASs was 45.02%, 39.76% and 71.34%, respectively, and higher incidence of RASs in cirrhosis than without cirrhosis (81.8% versus 63.8%), with a statistically significant difference (χ²=4.92, P=0.03). In the ASV/DCV cohort (n=24), 4 of 11 patients (36.4%) with baseline NS3/NS5A RASs achieved SVR12, whereas 12 of 13 patients (92.3%) without RASs achieved SVR12, with significant difference (χ²=8.39, P=0.008). However, this relationship was not seen in the SOF-based subgroup (94.6% versus 92.7%; χ²=0.18, P=0.7). Treatment failure with DAAs occurred in 10.53% (n=18) of our study population, baseline NS5A substitution including L31M or Y93H (n=13) was the most frequently detected RAS, rescue regimen with velpatasvir (VEL)/SOF + ribavirin (RBV) for 12 weeks or 24 weeks was highly effective in patients who failed previous use of NS5A inhibitors, regardless of GT or cirrhosis.

Natural RASs are common in Chinese patients failing with PR treatment. High prevalence of clinically relevant RASs (such as L31M, Y93H) supports the appropriateness of HCV resistance tests to properly guide DAA-based therapy. These findings might be used to select salvage therapies.

Viral suppression in patients on antiretroviral treatment (ART) is critical to reducing HIV transmission and HIV-related mortality. Although many studies have evaluated factors associated with viral suppression, few have assessed the extent to which missing viral load data may bias results.

We included data on all patients starting ART from 2005 to 2019 in eight South African cohorts participating in the International epidemiology Databases to Evaluate AIDS (IeDEA) collaboration. Multivariable logistic regression models were used to determine factors associated with having a viral load measurement within 2 months of a scheduled testing date and having a viral load <400 RNA copies/ml (‘viral suppression’). In a sensitivity analysis, missing viral loads were imputed based on patients’ clinical and demographic characteristics and outcomes.

Viral load tests were scheduled in 603,549 and 77,423 intervals in adults and children, respectively, but test results were recorded in only 40.7% and 41.2%, respectively. The proportion of recorded results suppressed was 85.7% in adults and 72.4% in children. After imputation of missing viral load measurements, viral suppression reduced slightly in adults (85.3%) and increased in children (73.2%). Predictors of virological suppression in adults, which included female sex, older age, higher baseline CD4⁺ T-cell count and recent testing year, were similar in the main analysis and after imputing missing viral loads.

Although viral load information was frequently missing in the South African setting, estimates of viral suppression and predictors of viral suppression did not change substantially after adjusting for missing data.

For patients with HBV infection who have decompensated cirrhosis (DC), a higher dose (1.0 mg/day) of entecavir is recommended than that used for those with compensated disease (0.5 mg/day), though with very little supporting data. We therefore compared the viral suppression achieved with 0.5 mg/day and 1.0 mg/day of entecavir in patients with HBV-related DC (NCT03345498).

Treatment-naive patients with HBV-related DC and serum HBV DNA titre exceeding 100,000 IU/ml received either dose of entecavir for 24 weeks. HBV DNA concentration was measured in blood specimens collected at baseline and after 2, 4, 8, 12 and 24 weeks of entecavir treatment.

Participants in the 0.5 mg/day (n=13) and 1.0 mg/day (n=16) groups had similar baseline hepatitis B e antigen (HBeAg) positivity rates (12/13 and 12/16; P=0.34) and median (range) log₁₀ serum HBV DNA levels (6.81 [5.01–8.12] and 7.45 [5.24–8.65]; P=0.17). The two doses led to similar reductions in serum HBV DNA levels after 2, 4, 8, 12 and 24 weeks of entecavir administration. At 24 weeks, 3 of the 13 patients receiving 0.5 mg/day and 1 of the 16 patients receiving 1.0 mg/day of entecavir had undetectable serum HBV DNA. Serum albumin level showed significant and similar improvement at the end of 24 weeks in the two groups.

Treatment-naive patients with HBV-related DC can be treated with entecavir in a 0.5 mg/day dose instead of the higher 1.0 mg/day dose, without compromising the degree of virological suppression. ClincialTrials.gov number NCT03345498.

Comprehensive treatment and clinical management are central to improving outcomes for people living with HIV (PLHIV). We explored trends in HIV clinical care, treatment outcomes, and chronic kidney disease (CKD) and diabetes monitoring.

We included patients ≥18 years in care at ten clinical sites in eight Asian countries. Proportions of patients on antiretroviral therapy (ART), with annual viral load, and with viral load suppression (VLS; <1,000 copies/ml) were estimated by year for 2011– 2016, stratified by country income level (lower-middle income [LMIC] and high-income countries [HIC]). Among those on ART in 2016 we evaluated factors associated with annual CKD and diabetes monitoring.

Among 31,346 patients (67% male), the proportions of patients on ART (median ART initiation year 2011, IQR 2007–2013), with annual viral load and VLS had substantially increased by 2016 (to 94%, 42% and 92%, respectively, in LMIC and 95%, 97% and 93%, respectively, in HIC) with the larger increases over time seen in LMIC. Among those on ART in 2016, monitoring proportions in LMIC were 53% for CKD and 26% for diabetes compared with 83% and 59%, respectively, in HIC. Overall, a decreased odds of monitoring was observed for male gender, heterosexual HIV exposure, no viral load and LMIC. Diabetes monitoring was also decreased in those with viral failure.

Our findings highlight suboptimal monitoring of viral load, CKD and diabetes in PLHIV in Asia. There is a need for affordable and scalable monitoring options to improve the joint care for HIV and non-communicable diseases.

Researchers must often rely on creatinine measurements to assess kidney function because direct glomerular filtration rates (GFR) and cystatin-c are rarely measured in routine clinical settings. However, HIV treatments often include dolutegravir, raltegravir, rilpivirine or cobicistat, which inhibit the proximal tubular secretion of creatinine without impairing kidney function, thus leading to measurement bias when using creatinine-based estimated GFR (eGFR). We developed eGFR correction factors to account for this potential bias.

11,359 treatment-naive HIV-positive individuals in OPERA were included if they initiated dolutegravir, elvitegravir/cobicistat, darunavir/cobicistat, raltegravir, rilpivirine or efavirenz (control) with an eGFR >60 ml/min/1.73 m². The eGFR was corrected by adding the median decrease reported in the literature to the calculated eGFR; correction factors were not validated. Incidence rates of eGFR <60 ml/min/1.73 m² (Poisson regression) and the relationship between regimens and eGFR <60 ml/min/1.73 m² (multivariate Cox proportional hazards models) were estimated with and without eGFR correction.

Without eGFR correction, dolutegravir, elvite-gravir/cobicistat, darunavir/cobicistat, raltegravir and rilpivirine based regimens were statistically significantly associated with a higher likelihood of eGFR <60 ml/min/1.73 m² than efavirenz. With eGFR correction, each of these regimens was associated with a statistically significantly lower likelihood of eGFR <60 ml/min/1.73 m² compared with efavirenz.

With increasing use of agents that inhibit tubular creatinine secretion, artificially low eGFR values could lead to erroneous conclusions in studies of HIV treatment and kidney outcomes measured with creatinine-based eGFR equations. Sensitivity analyses assessing the potential magnitude of bias arising from creatinine secretion inhibition should be performed.