Hepatitis C treatment uptake among people who inject drugs in the oral direct-acting antiviral era.

BACKGROUND: Increased uptake of hepatitis C virus (HCV) treatment among people who inject drugs (PWID) will be critical to achieve HCV elimination goals. There are limited data on HCV treatment uptake among PWID recruited from community-based settings in the HCV direct-acting antiviral (DAA) era. METHODS: We analysed data from PWID with HCV newly recruited into the Baltimore, Maryland-based AIDS Linked to the IntraVenous Experience (ALIVE) cohort between 2015 and 2018. We characterized the HCV care continuum and evaluated factors associated with HCV treatment uptake. RESULTS: Of the 418 PWID with HCV, the median age was 49 years and most (88%) reported recent injection drug use (IDU). Overall, 23% had ever been evaluated by a provider for HCV treatment, 17% ever initiated DAA treatment and 13% were cured of HCV infection. Treatment uptake approximately doubled between 2015 and 2018 (13% to 26%, P = .01). In multivariable analyses, HIV infection (adjusted Odds Ratio [aOR] 2.5 [95% Confidence Interval (CI) 1.3, 4.8]), current employment (aOR 4.1 [CI 1.2, 14.4]), having a primary care provider (aOR 4.3 [CI 1.2, 14.9) and longer duration of IDU (aOR 1.3 [CI 1.1, 1.6]) were positively associated with HCV treatment. PWID with a lower annual income (≤$5000) were less likely to have initiated HCV treatment (aOR 0.5 [CI 0.3, 0.98]). CONCLUSIONS: Although HCV treatment uptake among PWID in this community-based setting in the DAA era remains suboptimal, it is encouraging that treatment uptake has increased in recent years. Innovative strategies are needed to reach all PWID infected with HCV.

Reduced Forced Vital Capacity Among Human Immunodeficiency Virus-Infected Middle-Aged Individuals.

BACKGROUND: Pulmonary function impairments are more common among people living with HIV (PLWH), as are contributing risk behaviors. To understand the effects of human immunodeficiency virus (HIV) infection independent of risk behaviors, pulmonary function was evaluated in lifestyle-comparable HIV-infected and -uninfected AGEhIV cohort participants. METHODS: Prevalence of obstructive lung disease in 544 HIV-infected and 529 HIV-uninfected participants was determined using spirometry. Logistic regression was used to assess HIV as a determinant of obstructive lung disease. Additional explanatory models were constructed to explain observed differences. RESULTS: The unadjusted obstructive lung disease prevalence was similar in HIV-infected (23.0%) and -uninfected (23.4%) participants. Multivariable logistic regression analysis showed an effect modification whereby obstructive lung disease prevalence among persons with limited smoking experience was notably lower among HIV-infected compared with HIV-uninfected participants. This resulted from a lower forced vital capacity (FVC) in HIV-infected participants but similar 1-second forced expiratory volume (FEV1), especially in those with limited smoking experience. CONCLUSIONS: The lower FVC in HIV-infected participants could indicate HIV-related restrictive or fibrotic pulmonary changes. Factors that decrease the FVC could obscure emphysematous changes in the lungs of PLWH when using the FEV1/FVC ratio as single diagnostic measure. CLINICAL TRIALS REGISTRATION: NCT01466582.

Hepatitis C virus infection is not an independent risk factor for obstructive lung disease.

Several epidemiological studies have suggested that hepatitis C virus (HCV) infection is associated with the presence of obstructive lung disease (OLD). However, there is a strong link between HCV infection and tobacco abuse, a major risk factor for the development of OLD. In this study we analyzed clinical, laboratory and spirometric data from 1068 study participants to assess whether HCV infection, viremia, or HCV-associated end organ damage were associated with OLD. Demographics, risk behavior, serologic status for HCV and HIV, and spirometric measurements were collected from a cross-sectional analysis of the Acquired Immunodeficiency Syndrome (AIDS) Linked to the IntraVenous Experience (ALIVE) study, an observational cohort of IDUs followed in Baltimore, MD since 1988. Of 1,068 participants, 890 (83%) were HCV positive and 174 (16%) met spirometric criteria for OLD. Factors independently associated with OLD were age and BMI. HCV infection, viral load and HCV-associated end organ damage were similar in participants with and without OLD. In summary, there was no independent association between markers of HCV exposure, chronicity, viremia, or HCV-associated end-organ damage with OLD. Our findings support the strong correlation between HCV status, injection drug use, and smoking. These data suggest that HCV may not be a sole contributor to the increased prevalence of OLD described in previous studies of HCV-infected individuals.

Missing data on the estimation of the prevalence of accumulated human immunodeficiency virus drug resistance in patients treated with antiretroviral drugs in north america.

Determination of the prevalence of accumulated antiretroviral drug resistance among persons infected with human immunodeficiency virus (HIV) is complicated by the lack of routine measurement in clinical care. By using data from 8 clinic-based cohorts from the North American AIDS Cohort Collaboration on Research and Design, drug-resistance mutations from those with genotype tests were determined and scored using the Genotypic Resistance Interpretation Algorithm developed at Stanford University. For each year from 2000 through 2005, the prevalence was calculated using data from the tested subset, assumptions that incorporated clinical knowledge, and multiple imputation methods to yield a complete data set. A total of 9,289 patients contributed data to the analysis; 3,959 had at least 1 viral load above 1,000 copies/mL, of whom 2,962 (75%) had undergone at least 1 genotype test. Using these methods, the authors estimated that the prevalence of accumulated resistance to 2 or more antiretroviral drug classes had increased from 14% in 2000 to 17% in 2005 (P < 0.001). In contrast, the prevalence of resistance in the tested subset declined from 57% to 36% for 2 or more classes. The authors' use of clinical knowledge and multiple imputation methods revealed trends in HIV drug resistance among patients in care that were markedly different from those observed using only data from patients who had undergone genotype tests.

Individual and network factors associated with HCV treatment uptake among people who inject drugs.

BACKGROUND: Hepatitis C virus (HCV) treatment uptake among people who inject drugs (PWID), a population with disproportionately high rates of HCV, remains low. Peers have been shown to positively impact a broad range of health outcomes for PWID. There is, however, limited data on the impact of PWID social network members on HCV treatment. METHODS: HCV-infected PWID enrolled in an ongoing community-based cohort were recruited as "indexes" to complete an egocentric social network survey. The survey elicited from the index PWID a list of their network members and the index's perception of network member characteristics. Logistic regression analyses were conducted to compare individual and network factors associated with HCV treatment in the index PWID. RESULTS: Among 540 HCV-infected PWID, the mean age was 55.7 years and the majority were black (87.2%) and male (69.8%). PWID reported a mean of 4.4 (standard deviation [SD] 3.2) network members, most of whom were relatives (mean 2.2 [SD 1.5]). In multivariable analysis, increasing index age and HIV infection were positively associated with HCV treatment, while drug use and homelessness in the preceding 6 months were negatively associated with HCV treatment. From a network perspective, having at least one network member who regularly talked with the index about seeing their doctor for HIV care was associated with HCV treatment (Adjusted Odds Ratio [AOR] 2.7; 95% Confidence Interval (CI) [1.3, 5.6]). Conversely, PWID who had at least one network member who helped them understand their HCV care were less likely to have been HCV treated (AOR 0.2; CI [0.1, 0.6). CONCLUSION: HCV treatment uptake in this group of PWID appeared to be positively influenced by discussions with network members living with HIV who were in care and negatively influenced by HCV information sharing within PWID networks. These findings underscore the influence of peers on health seeking behaviors of their network members and emphasizes the importance of well-informed peers.

Persistence of HIV transmission clusters among people who inject drugs.

OBJECTIVE: We investigated the duration of HIV transmission clusters. DESIGN: Fifty-four individuals newly infected at enrollment in the ALIVE cohort were included, all of whom had sequences at an intake visit (T1) and from a second (T2) and/or a third (T3) follow-up visit, median 2.9 and 5.4 years later, respectively. METHODS: Sequences were generated using the 454 DNA sequencing platform for portions of HIV pol and env (HXB2 positions 2717-3230; 7941-8264). Genetic distances were calculated using tn93 and sequences were clustered over a range of thresholds (1--5%) using HIV-TRACE. Analyses were performed separately for individuals with pol sequences for T1 + T2 (n = 40, 'Set 1') and T1 + T3 (n = 25; 'Set 2'), and env sequences for T1 + T2 (n = 47, 'Set 1'), and T1 + T3 (n = 30; 'Set 2'). RESULTS: For pol, with one exception, a single cluster contained more than 75% of samples at all thresholds, and cluster composition was at least 90% concordant between time points/thresholds. For env, two major clusters (A and B) were observed at T1 and T2/T3, although cluster composition concordance between time points/thresholds was low (<60%) at lower thresholds for both sets 1 and 2. In addition, several individuals were included in clusters at T2/T3, although not at T1. CONCLUSION: Caution should be used in applying a single threshold in population studies where seroconversion dates are unknown. However, the retention of some clusters even after 5 + years is evidence for the robustness of the clustering approach in general.

Short Communication: HIV Controller T Cells Effectively Inhibit Viral Replication in Alveolar Macrophages.

Macrophages are targets of HIV-1 infection, and control of viral replication within these cells may be an important component of a T-cell-based vaccine. Although several studies have analyzed the ability of CD8+ T cells to inhibit viral replication in monocyte-derived macrophages, the effect of T cells on HIV-1-infected tissue macrophages is less clear. We demonstrate here that both CD4+ and CD8+ T-cell effectors from HIV controllers are capable of suppressing viral replication in bronchoalveolar lavage-derived alveolar macrophages. These findings have implications for HIV-1 vaccine and eradication strategies.

Increased levels of aflatoxin-albumin adducts are associated with CYP3A5 polymorphisms in The Gambia, West Africa.

OBJECTIVES: Major risk factors for hepatocellular carcinoma (HCC) are hepatitis viruses and exposure to aflatoxins, including aflatoxin B1 (AFB1). The mutagenic effect of AFB1 results from hepatic bioactivation to AFB1-exo-8,9-epoxide. This is in part catalysed by CYP3A5, an enzyme expressed polymorphically. We investigated the role of CYP3A5 polymorphisms in the formation of AFB1-exo-8,9-epoxide in The Gambia, a population exposed to high aflatoxin levels. METHODS: Common CYP3A5 polymorphisms were identified in an African-American population. Subsequently, 288 Gambian subjects were genotyped and CYP3A5 activity predicted using haplotypes of the three variant loci (CYP3A5*3, *6 and *7) associated with decreases in protein expression. CYP3A5 expression was then compared to aflatoxin-albumin (AF-alb) adduct, a biomarker of AFB1 bioactivation; data were also analysed in relation to expression of other aflatoxin-metabolizing enzymes. RESULTS: CYP3A5 haplotypes reflecting high CYP3A5 protein expression were associated with increased AF-alb. Compared to individuals with predicted low expression those predicted to express CYP3A5 from one allele displayed 16.1% higher AF-alb (95% CI: -2.5, 38.2, P = 0.093) and homozygous expressers displayed 23.2% higher AF-alb levels (95% CI: -0.01, 52.0, P = 0.051). The effect of the CYP3A5 polymorphism was strongest in individuals with low CYP3A4 activity with a 70.1% increase in AF-alb (95% CI: 11.8, 158.7, P < 0.05) in high compared to low expressers. A similar effect was observed for individuals with null alleles of GSTM1, which conjugates the AFB1-exo-8,9-epoxide to reduced glutathione. CONCLUSIONS: The CYP3A5 polymorphism is associated with increased levels of the mutagenic AFB1-exo-8,9-epoxide, particularly in individuals with low CYP3A4, and this may modulate individual risk of HCC.