Antiviral Therapy

This 5-year follow-up of the CCgenos cross-sectional study aimed to observe real-life outcomes in a cohort of 997 Han Chinese patients with chronic HCV infection and to explore the impacts of HCV genotype, patient characteristics and treatment status.

Clinical information and centralized HCV RNA measures were collected every 6/3 months for untreated/treated patients. Overall disease progression was defined as ≥1 of: de novo development of cirrhosis, Child-Turcotte-Pugh score increased by ≥2 points (if cirrhosis at baseline), progression to decompensated cirrhosis, hepatocellular carcinoma (HCC), liver transplant or death. Cox regression assessed risk factors for the time from estimated infection to cirrhosis or HCC. Logistic regression assessed risk factors for incidence rates of cirrhosis and overall disease progression.

281 of 514 patients enrolled across China completed 5 years of follow-up. Overall disease progression occurred in 36/364 (9.9%) treated patients and 35/148 (23.6%) untreated patients (odds ratio = 0.35; 95% CI 0.21, 0.59; P<0.0001). Overall disease progression occurred in 6/231 (2.6%) patients achieving sustained virological response at 24 weeks (SVR24) versus 11/82 (13.4%) who did not (P=0.0002). Cirrhosis development was significantly associated with abnormal aspartate aminotransferase (AST), age ≥40 years, body mass index ≥28 kg/m², HCV GT1, platelet count <100x10⁹/l, and AST to platelet ratio index (APRI) ≥2 (multivariate Cox regression, P<0.05). HCC was significantly associated with HCV GT1 and platelet count <100x10⁹/l (multivariate Cox regression, P<0.05).

Achieving SVR24 significantly reduced the probability of overall disease progression but no significant difference was seen for both cirrhosis and HCC during 5 years of follow-up.

This real-world clinical setting study characterized the virological patterns in genotype-1 patients failing interferon (IFN)-free regimens and evaluated the efficacy of re-treatment.

A total of 73 consecutive patients failing IFN-free regimens were enrolled (17 genotype-1a and 56 −1b). At failure Sanger sequencing of NS3, NS5A and NS5B regions was performed by home-made protocols.

In patients having failed an NS3 inhibitor, the prevalence of NS3-RASs was higher in the 10 with genotype-1a than in the 24 with genotype-1b (80% versus 41.6%). In patients treated with an NS5A inhibitor, the prevalence of NS5A-RASs was very high in the 14 with genotype-1a and the 27 with genotype-1b (78.6% and 92.5%, respectively). In patients having failed sofosbuvir, the prevalence of NS5B-RASs was more frequently identified in the 45 with genotype-1b than in the 10 with genotype-1a (37.7% versus 10%). The prevalence of NS5B-RASs in patients having failed dasabuvir was high in both genotypes, 66.6% in the 6 with genotype-1a and 45.5% in the 11 with genotype-1b.

The 6 patients re-treated with genotype-1a less frequently (50%) showed sustained virological response (SVR) than the 18 with genotype-1b (88.8%; P=0.07). SVR was more frequent in the 21 patients with an effective second-line direct-acting antiviral (DAA) regimen than the 3 without (90.4% versus 0%; P<0.005).

The prevalence of RASs was high in our real-world population. NS3, NS5A and NS5B sequencing seems mandatory in the choice of DAA re-treatment.

Influenza virus infections in lung transplant recipients (LTRs) have an increased risk of unfavourable outcomes. Early initiation of treatment is associated with improved outcomes. In clinical practice, empirical oseltamivir treatment is therefore commonly started prior to diagnostic microbiological confirmation. There is limited data on the patient characteristics, outcomes and safety of this practice. This study investigated outcomes and safety of this pre-emptive treatment strategy using oseltamivir.

Descriptive analysis of LTRs who received oseltamivir for ≥2 days for suspected influenza infection between July 2011 and June 2012. Analyses were based on data from electronic medical records and our standardized LTR database with prospective documentation of clinical information including medication, laboratory and radiological results, outcomes and adverse events.

We included 133 patients with a total of 261 oseltamivir treatment episodes (87.4% as outpatients). Median duration of oseltamivir treatment was 4 days (range 2 to 67) and 98.5% had concomitant antibiotic pharmacotherapy. Indications for oseltamivir included acute respiratory infection (66.7%), non-distinctive inflammatory reaction (51.3%) and influenza-like illness (2.7%). Influenza virus infection was confirmed by PCR in only 7%. Rhinovirus was the most frequent pathogen detected (14.9%). We discovered a wide range of adverse events but none occurred in >5%, and most were mild and of questionable causal relationship to oseltamivir administration.

This non-controlled retrospective analysis suggests that the pre-emptive use of oseltamivir for respiratory tract infections pending microbiological results is safe in LTRs.

Vitamin D deficiency is underdiagnosed and undertreated, especially among people living with HIV (PLWH). Recently, there has been an increased interest in the role of vitamin D in cardiovascular disease (CVD). While vitamin D deficiency has been associated with CVD in observational studies in the general population, there are limited data in PLWH. We therefore performed an analysis to assess the relationship of vitamin D and coronary atherosclerosis using coronary CT angiography (CCTA).

Women living with HIV (WLWH) without known CVD were included. Based on the median value of serum vitamin D levels, participants were dichotomized to either the <25 ng/ml (lower vitamin D group) or ≥25 ng/ml (higher vitamin D group). CCTA was used to assess plaque characteristics.

Forty-three WLWH were included in the analyses (mean age 46 ±8 years, 56% African American, duration of HIV 15 ±6 years, 83% undetectable HIV viral load). WLWH in the lower vitamin D group (n=22) had significantly higher numbers of segments with any coronary plaque (2.27 ±3.01 versus 0.38 ±0.97; P=0.02) and segments with non-calcified coronary plaque (1.41 ±1.82 versus 0.29 ±0.64; P=0.03) compared with WLWH in the higher vitamin D group (n=21). After adjusting for Framingham CHD risk point score, body mass index, diabetes and race, the relationship remained significant.

Our study demonstrates a significant, independent relationship between lower vitamin D status and higher numbers of noncalcified coronary plaque segments in WLWH. Further studies are warranted to evaluate the effect of vitamin D on CVD in PLWH. Trial Registration Identifier: NCT00455793.

The use of dual antiretroviral therapy (ART) regimens for treatment of HIV is increasing. The contemporary combination of boosted darunavir with dolutegravir has not been widely studied.

This was a retrospective cohort study that evaluated treatment-experienced individuals within three large urban clinics prescribed boosted darunavir with dolutegravir (study regimen) dual therapy. Follow-up was defined as the number of days from regimen initiation until the last HIV RNA determination on the study regimen. Virological outcomes, HIV RNA ≤50 copies/ml (undetectable), were assessed overall and by baseline HIV RNA status.

Of 65 individuals included, 83% were at least 3-class antiretroviral-experienced and median time since starting ART was 19 years (IQR 13–22). Median follow-up was 419 days (IQR 286–744). An undetectable HIV RNA was achieved by 62/65 (95%) individuals at any time point on the study regimen. At the end of follow-up 61/65 (94%) individuals remained undetectable, including 48/49 (98%) with an undetectable HIV RNA at baseline (those changing for optimization) and 13/16 (81%) with viraemia at baseline (those changing therapy during virological failure). At the end of follow-up, 55 (85%) individuals were still taking the study regimen. No individuals stopped therapy due to virological failure or intolerance.

In a highly treatment-experienced cohort, boosted darunavir with dolutegravir dual therapy demonstrated high rates of virological success, even in those with detectable HIV RNA prior to initiating the study regimen. Further study of this potent, simple, high-barrier dual-class regimen is warranted.

HBV and HIV infections are highly endemic in sub-Saharan Africa and Nigeria while HBV–HIV coinfection is not uncommon. Antiretroviral (ART)-treatment for HIV can affect HBV whereby antiviral resistance mutations in the HBV genome can be selected. Here, we determined the prevalence of resistance mutations among ART-experienced and ART-naive HIV–HBV-coinfected patients in southwestern Nigeria.

A total of 81 serum samples from HBV–HIV-coinfected patients who were either ART-naive or received lamivudine (3TC)-containing ART-therapy and HBV-monoinfected patients were analysed. Hepatitis B surface antigen (HBsAg) was detected using ELISA. HBV-positive samples were confirmed by PCR amplification of the surface and polymerase regions. Mutations conferring drug resistance to HBV were analysed by direct sequencing. Phylogenetic analysis was performed to identify the HBV genotype.

Of the 81 HBsAg-positive samples, 27 had detectable HBV DNA by real-time PCR with mean viral loads of 6.77 log IU/ml. Phylogenetic analyses showed a predominance of HBV genotype E. A high prevalence (22.2%; 6/27) of HBV resistance mutations among ART-experienced HBV–HIV-coinfected patients was detected. However, a relatively high selection rate of resistance mutations in drug-naive HIV–HBV-coinfected (3.7%; 1/27) and in HBV-monoinfected patients, potential drug resistance mutations (7.4%; 2/27) were also observed. HBV polymerase amino acid substitutions found included rtV173L, rtL180M, rtM204V, rtK212R, rtS213T, rtV214A, rtL229V and rtP237A/S.

Drug resistant mutations were detected frequently in ART-experienced HIV–HBV patients. Well-coordinated antiviral therapy for HIV patients coinfected with HBV should include proper HBV diagnosis and resistance testing to minimize the emergence and spread of antiviral drug resistance.

Tenofovir disoproxil fumarate (TDF), the oral prodrug of tenofovir (TFV), is advocated in pregnancy for prevention of mother-to-child transmission (PMCT) with failure of hepatitis B immunoglobulin and vaccination. The pharmacokinetics of TDF monotherapy for PMCT-HBV is important if deployment is to emulate the success of multiple antiretrovirals (ARVs) for PMCT-HIV in resource-constrained settings.

This systematic review followed a protocol and is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement (PRISMA) guidelines. We included studies that enrolled pregnant women who received oral TDF therapy as mono-therapy or in combination with other ARVs: irrespective of the reason for receiving the drug (for example, HIV, HBV or pre-exposure prophylaxis); and reported pharmacokinetics.

The area under the concentration–time curve (AUC), maximum plasma concentrations (C_max) and last measurable plasma concentration (C_last) of TFV were decreased in the second and third trimester compared with first trimester or post-partum. In none of the manuscripts was the non-pregnant HBV threshold of C_max of 300 ng/ml reached, but the 50% effective concentration (EC₅₀) of TFV is lower for treatment of HBV compared with HIV. The TFV concentration in breastfed infants was 0.03% of the recommended infant dose.

Most knowledge of pharmacokinetics of TFV in pregnancy results from studies on HIV involving multiple ARVs. Increased TFV clearance occurred in the second and third trimester when optimal TFV concentrations are required to maximize suppression of HBV in the window before birth. Dose or duration adjustments will be better conceptualized with concurrent analysis of the pharmacokinetics of TFV monotherapy and hepatitis B pharmacodynamics in pregnancy.

In Western countries, viral rebound on antiretroviral therapy (ART) appears to occur more frequently in migrants. We aimed to assess the respective roles of socioeconomic factors and migration on viral rebound in people living with HIV (PLHIV) in France.

We included PLHIV in France, enrolled from 2004 to 2008 in the French ANRS-COPANA cohort, who started a first ART and achieved undetectability (<50 copies/ml) within 1 year. Determinants of viral rebound were assessed using Cox models including geographical origin, HIV transmission group, and clinicobiological and sociodemographic data.

Of 499 included individuals, 288 were born in France, 158 in sub-Saharan Africa (SSA) and 53 in another country. Kaplan–Meier probabilities of viral rebound-free survival were similar for men having sex with men (MSM) and heterosexuals born in France, and lower in migrants from SSA or other countries (P<0.001). The crude hazard ratio (HR) of viral rebound was 2.49 (95% CI, 1.59, 3.90) in migrants from SSA and 1.78 (0.94, 3.88) in migrants from other countries compared with MSM born in France. Educational level, financial difficulties and HIV status disclosure had the biggest impact on the difference between the crude and adjusted HRs for viral rebound in migrants. In multivariable analysis, viral rebound was no longer associated with geographical origin, but with protease inhibitor-containing ART, a VACS index ≥35 as a potential indicator of frailty, poor financial status (difficulties or debts) and non-disclosure to friend(s).

Socioeconomic factors affect outcomes on ART, even in the context of free access to HIV care and treatment. Patient-centred strategies should be encouraged with the intervention of social workers to address basic needs and promote social support for more socially vulnerable individuals.