2023

25th January Chaudron et al., HIV-1 superinfection screen in the SHCS


A systematic molecular epidemiology screen reveals numerous HIV-1 superinfections in the Swiss HIV Cohort Study.    Journal of Infectious Diseases

Chaudron et al. aimed to study immunodeficiency virus type 1 (HIV-1) superinfection in the Swiss HIV Cohort Study (SHCS). Superinfection is the acquisition of another HIV-1 strain among individuals with an already established HIV-1 infection.

The authors used a phylogeny built from 22’243 HIV-1 partial polymerase sequences to identify potential superinfections among 4’575 SHCS participants with longitudinal sequences. A subset of potential superinfections was tested by near-full-length viral genome sequencing (NFVGS) of biobanked plasma samples.

Based on phylogenetic and distance criteria, 325 potential HIV-1 superinfections were identified and categorized by their likelihood of being detected as superinfections due to sample misidentification. NFVGS was performed for 128 potential superinfections; of these, 52 were confirmed by NFVGS, 15 were not confirmed, and for 61 sampling did not allow confirming or rejecting superinfection because the sequenced samples did not include the relevant time points causing the superinfection signal in the original screen. Thus, NFVGS could support 52 of 67 adequately sampled potential superinfections.

In conclusion, the study confirms that superinfections are rare but not negligible events, with an estimated prevalence of 1% to 7%, most likely an underestimation since detection is challenging. Nevertheless, this work paves the way for follow-up studies to benefit from the sample size and the NGS data generated to molecularly characterize HIV-1 superinfection and investigate other risk factors associated. Better molecular characterization and risk factors understanding could provide further insights into HIV transmission and pathogenesis, benefit HIV vaccine research, and enable preventive measures to raise awareness on HIV-1 superinfection in the community.

PubMed

19th January Hofmann et al., HBV replication during tenofovir therapy


Hepatitis B virus replication during tenofovir therapy is frequent in HIV/HBV coinfection.    Clinical Infectious Diseases

Hofmann et al. analyzed rates of hepatitis B virus (HBV) suppression with tenofovir-containing antiretroviral therapy (ART), and assessed determinants for ongoing HBV replication despite treatment among people living with HIV and HBV in the Swiss HIV Cohort Study (SHCS).

The present study included all cohort participants with chronic HBV infection. The authors evaluated HBV replication at 2 years and at the latest available follow-up (categorized as suppression if HBV DNA was <20 IU/mL, low-level viremia if HBV DNA was 20-2000 IU/mL, and high-level viremia if HBV DNA was >2000 IU/mL). Risk factors for persistent viral replication (HBV DNA >20 IU/mL) were assessed using multivariable logistic regression.

The study population consisted of 222 individuals with HIV/HBV coinfection on tenofovir-containing ART. The median age was 41 years (IQR 36-47), 19% were female, 21% were of African origin, and 59% had been previously treated with lamivudine- or emtricitabine-containing ART. After 2 years of tenofovir, 61/222 (27%) had persistent HBV replication. Persistent HBV replication was more common among individuals with high HBV-DNA at tenofovir start (adjusted odds ratio [aOR] 1.38, 95% CI 1.20-1.57), and less likely among patients with a CD4 cell count >350cells/μL (aOR 0.41, 0.19-0.90), among people with hepatitis D coinfection (aOR 0.07, 0.01-0.59) and those with good self-reported ART adherence (aOR 0.04, 0.01-0.33). Of the 61 individuals with a replicating HBV infection at 2 years, 14 (23%) had persistent replication at the latest follow-up visit (median 8.4 years after starting tenofovir).

In summary, this work shows that ongoing HBV replication is frequent after 2 years of tenofovir-containing ART, especially in individuals with a high HBV viral load at tenofovir start and suboptimal ART adherence. In contrast, HDV coinfection was associated with higher rates of HBV suppression. As 77% of individuals eventually achieved HBV viral suppression during follow-up, replication after 2 years does not necessarily imply treatment failure. As ongoing viral replication contributes to liver fibrosis and to the development of hepatocellular carcinoma, these findings highlight the importance of continued follow-up of individuals with HIV/HBV coinfection.

PubMed

11th January Isfordink et al., DAAs in people with HIV/HCV from sub-Saharan Africa or Southeastern Asia


Low risk of failing direct-acting antivirals in people with HIV/HCV from Sub-Saharan Africa or Southeastern Asia: a European cross-sectional study.    Open Forum Infectious Diseases

Isfordink et al. for EuroSIDA, the Swiss HIV Cohort Study, and the ATHENA Observational Cohort aimed to investigate the real-world efficacy of direct-acting antivirals (DAA) treatment in individuals with HIV/hepatitis C virus (HCV) originating from low- and middle-income countries (LMICs), namely for sub-Saharan Africa (SSA) and Southeastern Asia (SEA) in multiple European cohorts of people with HIV (PWH).

The author group retrospectively analyzed data from the above-mentioned cohorts of PWH. The primary outcome was HCV cure defined as sustained virological response at least 12 weeks after the end of treatment (SVR12).

Of the 3’293 individuals with HIV/HCV treated with DAA and with available SVR12 data, 142 were from SSA (n=64) and SEA (n=78). SVR12 was achieved by 60 (94% [95% confidence interval {CI}, 86%–98%]) individuals from SSA and 76 (97% [95% CI, 92%–99%]) from SEA. The genotypes of the 6 individuals failing DAA treatment were 2, 3a, 3h, 4a, 4c, and 6j. For 2 of the 4 unsuccessfully treated individuals with available sequence data at treatment failure, NS5A resistance-associated substitutions were present (30R/93S in an individual with genotype 4c and 31M in an individual with genotype 6j).

In conclusion, the study shows that DAA efficacy in people with HIV/HCV originating from SSA or SEA and living in Europe is high. Although the limited number of participants with genotypes of concern and the lack of data on location of HCV acquisition limit conclusions on DAA efficacy for individuals with HIV/HCV residing in SSA or SEA, it seems unlikely that suboptimal response to DAAs specific to these individuals could become a complicating factor for overall HCV elimination in Europe in the near future.

PubMed