Hepatitis C Treatment in People With HIV: Potential to Eliminate Disease and Disparity.

Access to direct acting antivirals (DAAs) may be associated with reductions in hepatitis C virus (HCV) viremia prevalence among people with human immunodeficiency virus (PWH). Among 3755 PWH, estimated HCV viremia prevalence decreased by 94.0% from 36% (95% confidence interval [CI], 27%-46%) in 2009 (pre-DAA era) to 2% (95% CI, 0%-4%) in 2021 (DAA era). Male sex, black race, and older age were associated with HCV viremia in 2009 but not in 2021. Injection drug use remained associated with HCV viremia in 2009 and 2021. Targeted interventions are needed to meet the HCV care needs of PWH who use drugs.

Patterns of Polysubstance Use in Young Black and Latinx Sexual Minority Men and Transgender Women and Its Association with Sexual Partnership Factors: The PUSH Study.

Background: Adult studies have demonstrated that polysubstance use increases HIV acquisition risk through increased sexual behaviors, however, few studies have examined polysubstance in young Black and Latinx sexual minority men (SMM) and transgender women (TW). Methods: We used cross-sectional data from 466 young Black and Latinx SMM and TW living in four high HIV-burden US cities enrolled in the PUSH Study, a status-neutral randomized control trial to increase HIV prevention and treatment adherence. We examined data for patterns of polysubstance use comparing age differences of use and explored associations between substance use and sexual partnership factors - inconsistent condom use, pressure to have condomless anal sex, and older partner, using bivariate and multivariate analyses. Results: Most participants described prior substance use with alcohol and cannabis being most common (76% each) and 23% described other illicit drug use, including stimulants, cocaine, hallucinogens, sedatives, opioids, and inhalants. Polysubstance use was common with nearly half (47%) of participants reporting alcohol and cannabis use, 20% reporting alcohol, cannabis, and one other illicit drug use, and 19% reporting alcohol or cannabis use plus one other illicit drug use. Polysubstance use was associated with greater adjusted odds of pressure to have condomless anal sex, older partner (>5 years older), and inconsistent condom use. Conclusions: Associations of polysubstance use with sexual practices and sexual partnerships that are known predictors of HIV acquisition or transmission among Black and Latinx SMM and TW underscore the need for combination interventions that include substance use treatment alongside antiretroviral-based and partner-based HIV prevention and treatment interventions.Trial Registration: ClinicalTrials.gov Identifier: NCT03194477.

Geographic variation in HCV treatment penetration among people who inject drugs in Baltimore, MD.

We evaluated geographic heterogeneity in hepatitis C virus (HCV) treatment penetration among people who inject drug (PWID) across Baltimore, MD since the advent of direct-acting antivirals (DAAs) using space-time clusters of HCV viraemia. Using data from a community-based cohort of PWID, the AIDS Linked to the IntraVenous Experience (ALIVE) study, we identified space-time clusters with higher-than-expected rates of HCV viraemia between 2015 and 2019 using scan statistics. We used Poisson regression to identify covariates associated with HCV viraemia and used the regression-fitted values to detect adjusted space-time clusters of HCV viraemia in Baltimore city. Overall, in the cohort, HCV viraemia fell from 77% in 2015 to 64%, 49%, 39% and 36% from 2016 to 2019. In Baltimore city, the percentage of census tracts where prevalence of HCV viraemia was ≥85% dropped from 57% to 34%, 25%, 22% and 10% from 2015 to 2019. We identified two clusters of higher-than-expected HCV viraemia in the unadjusted analysis that lasted from 2015 to 2017 in East and West Baltimore and one adjusted cluster of HCV viraemia in West Baltimore from 2015 to 2016. Neither differences in age, sex, race, HIV status, nor neighbourhood deprivation were able to explain the significant space-time clusters. However, residing in a cluster with higher-than-expected viraemia was associated with age, sex, educational attainment and higher levels of neighbourhood deprivation. Nearly 4 years after DAAs became available, HCV treatment has penetrated all PWID communities across Baltimore city. While nearly all census tracts experienced improvements, change was more gradual in areas with higher levels of poverty.

Hepatitis C in Black Individuals in the US: A Review.

Importance: In the US, the prevalence of hepatitis C virus (HCV) is 1.8% among people who are Black and 0.8% among people who are not Black. Mortality rates due to HCV are 5.01/100 000 among people who are Black and 2.98/100 000 among people who are White. Observations: While people of all races and ethnicities experienced increased rates of incident HCV between 2015 and 2021, Black individuals experienced the largest percentage increase of 0.3 to 1.4/100 000 (367%) compared with 1.8 to 2.7/100 000 among American Indian/Alaska Native (50%), 0.3 to 0.9/100 000 among Hispanic (200%), and 0.9 to 1.6/100 000 among White (78%) populations. Among 47 687 persons diagnosed with HCV in 2019-2020, including 37 877 (79%) covered by Medicaid (7666 Black and 24 374 White individuals), 23.5% of Black people and 23.7% of White people with Medicaid insurance initiated HCV treatment. Strategies to increase HCV screening include electronic health record prompts for universal HCV screening, which increased screening tests from 2052/month to 4169/month in an outpatient setting. Awareness of HCV status can be increased through point-of-care testing in community-based settings, which was associated with increased likelihood of receiving HCV test results compared with referral for testing off-site (69% on-site vs 19% off-site, P < .001). Access to HCV care can be facilitated by patient navigation, in which an individual is assigned to work with a patient to help them access care and treatments; this was associated with greater likelihood of HCV care access (odds ratio, 3.7 [95% CI, 2.9-4.8]) and treatment initiation within 6 months (odds ratio, 3.2 [95% CI, 2.3-4.2]) in a public health system providing health care to individuals regardless of their insurance status or ability to pay compared with usual care. Eliminating Medicaid's HCV treatment restrictions, including removal of a requirement for advanced fibrosis or a specialist prescriber, was associated with increased treatment rates from 2.4 persons per month to 72.3 persons per month in a retrospective study of 10 336 adults with HCV with no significant difference by race (526/1388 [37.8%] for Black vs 2706/8277 [32.6%] for White patients; adjusted odds ratio, 1.02 [95% CI, 0.8-1.3]). Conclusions and Relevance: In the US, the prevalence of HCV is higher in people who are Black than in people who are not Black. Point-of-care HCV tests, patient navigation, electronic health record prompts, and unrestricted access to HCV treatment in community-based settings have potential to increase diagnosis and treatment of HCV and improve outcomes in people who are Black.

Nonadherence to Ledipasvir/Sofosbuvir Did Not Predict Sustained Virologic Response in a Randomized Controlled Trial of Human Immunodeficiency Virus/Hepatitis C Virus Coinfected Persons Who Use Drugs.

BACKGROUND: Eliminating hepatitis C virus (HCV) will require effective treatment delivery to persons with substance use disorders (SUDs). We evaluated the relationship between ledipasvir/sofosbuvir treatment persistence (receiving 84 tablets), adherence, and sustained virologic response (SVR) in persons with human immunodeficiency virus (HIV)/HCV coinfection. METHODS: Of the 144 participants with HIV/HCV and SUDs, 110 initiated a 12-week treatment course under 1 of 3 conditions (usual care, peer mentors, and cash incentives). We used self-report, pharmacy pill counts, and expected date of refill to examine adherence. Persistent participants were categorized as high adherence (taking ≥90% of doses) or low adherence (taking <90% of doses). RESULTS: Most participants persisted on treatment after initiation (n = 105), with 95% (n = 100) achieving SVR. One third (34%) of participants had moderate/heavy alcohol use by the biomarker phosphatidylethanol ([Peth] ≥50 ng/mL), and 44% had urine toxicology positive for cocaine or heroin at enrollment. The proportion of persons with high adherence was 72% (n = 76), and the proportion of persons with low adherence was 28%. Although low adherence was associated with moderate/heavy alcohol use by PEth (relative risk = 2.77; 95% confidence interval, 1.50-5.12), SVR did not vary according to adherence (P = .702), and most participants (97%) with low adherence achieved SVR. CONCLUSIONS: Treatment persistence led to high SVR rates among persons with HIV/HCV, despite imperfect adherence and SUDs.

The Influence of PrEP-Related Stigma and Social Support on PrEP-Use Disclosure among Women Who Inject Drugs and Social Network Members.

Pre-exposure prophylaxis (PrEP) is a promising but underutilized HIV prevention strategy for Women who Inject Drugs (WWID). Stigma and disclosure concerns have been key barriers to PrEP use among women in PrEP efficacy trials. Social support has been found to buffer against some PrEP stigma, though these factors have been largely unexplored among WWID. Investigating how WWID disclose PrEP use is important given evidence that disclosure is associated with higher adherence. We aimed to identify the impact of stigma and support on PrEP disclosure within social networks of WWID participating in a PrEP demonstration project in Philadelphia, PA, USA. PrEP-using WWID ≥ 18 years completed social network surveys. Generalized estimating equations were used to account for the correlation of network structure. Thirty-nine WWID (i.e. egos) named an average of 9.5 ± 3.3 network members (i.e. alters), for a total sample of 371 unique relationships. Egos disclosed their PrEP use to an average of 4.0 alters (SD = 2.8). Related to PrEP stigma, participants had 0.4 times decreased odds of PrEP disclosure with alters who would disapprove of them taking PrEP (95% CI: 0.1-0.9). Related to support, participants had 2.5 times higher odds of disclosure among peers who could provide PrEP advice (95% CI: 1.0-6.0). Interventions that increase social support and decrease stigma are pivotal for increasing PrEP use disclosure among WWID.

Hepatitis C Virus Treatment: Simplifying the Simple and Optimizing the Difficult.

The availability of safe, efficacious, oral direct-acting antivirals (DAAs) have ushered in a new era of hepatitis C treatment with potential to eliminate hepatitis C as a public health threat. To achieve population-level effectiveness of these oral DAAs, hepatitis C treatment by a wide range of providers in different settings will be essential to increase the number of persons treated. We provide a clinical review of hepatitis C treatment with a focus on practical tools for management of hepatitis C in majority of currently infected individuals who can be easily cured and optimization of treatment for those in whom treatment may not be as simple.

Network-based recruitment of people who inject drugs for hepatitis C testing and linkage to care.

Although oral direct-acting agent (DAA) therapies have the potential to reduce the burden of hepatitis C virus (HCV) infection, treatment uptake remains low, particularly among people who inject drugs (PWID). This study examined the feasibility of an innovative peer-based recruitment strategy to engage PWID in HCV testing and treatment. We interviewed an initial set of HCV antibody-positive PWID as 'primary indexes' to gather demographic, drug use, health information and drug network characteristics. Primary indexes were then briefly educated on HCV and its treatment and encouraged to recruit their injection drug 'network members' for HCV testing and linkage to care. Eligible network members were enrolled as 'secondary indexes' and completed the same index study procedures. In sum, 17 of 36 primary indexes initiated the recruitment of 64 network members who were HCV antibody positive and eligible to become indexes. In multivariable analysis, successful recruitment of at least one network member was positively associated with prior HCV treatment (OR 2.80; CI [1.01, 7.72]), daily or more injection drug use (OR 2.38; CI [1.04, 5.47]), and a higher number of injection drug network members (OR 1.20; CI [1.01, 1.42]). Among the 69 participants with chronic HCV not previously linked to HCV care at enrolment, 91% (n = 63) completed a linkage to HCV care appointment, 45% (n = 31) scheduled an appointment with an HCV provider, and 20% (n = 14) initiated HCV therapy. These findings suggest a potential benefit for peer-driven, network-based interventions focused on HCV treatment-experienced PWID as a mechanism to increase HCV linkage to care.

Sharing the cure: Building primary care and public health infrastructure to improve the hepatitis C care continuum in Maryland.

In 2014, trained healthcare provider capacity was insufficient to deliver care to an estimated 70 000 persons in Maryland with chronic hepatitis C virus (HCV) infection. The goal of Maryland Community Based Programs to Test and Cure Hepatitis C, a public health implementation project, was to improve HCV treatment access by expanding the workforce. Sharing the Cure (STC) was a package of services deployed 10/1/14-9/30/18 that included enhanced information technology and public health infrastructure, primary care provider training and practice transformation. Nine primary care sites enrolled. HCV clinical outcomes were documented among individuals who presented for care at sites and met criteria for HCV testing including risk factor or birth cohort (born between 1945 and 1965) based testing. Fifty-three providers completed the STC training. STC providers identified 3237 HCV antibody-positive patients of which 2624 (81%) were RNA+. Of those HCV RNA+, 1739 (66%) were staged, 932 (36%) were prescribed treatment, 838 (32%) started treatment, 721 (27%) completed treatment and 543 (21%) achieved cure. Among 1739 patients staged, 693 (40%) patients had a liver fibrosis assessment score < F2, rendering them ineligible for treatment under Maryland Medicaid guidelines. HCV RNA testing among HCV antibody-positive people increased from 40% (baseline) to 95% among STC providers. Of 554 patients with virologic data reported, 543 (98%) achieved cure. Primary care practices can effectively serve as HCV treatment centers to expand treatment access. However, criteria by insurance providers in Maryland were a major barrier to treatment.

Unreported alcohol use was common but did not impact hepatitis C cure in HIV-infected persons who use drugs.

We investigated the prevalence and impact of heavy alcohol use on the hepatitis C virus (HCV) care continuum amongst HIV/HCV co-infected persons who use drugs. In the CHAMPS study, 144 HIV/HCV co-infected persons were randomized to contingent cash incentives, peer mentors and usual care to evaluate the impact on HCV care. Alcohol use was ascertained using the 10-item AUDIT (hazardous: male ≥8, female ≥4) and phosphatidylethanol (PEth) (heavy: ≥50 ng/mL), an alcohol biomarker. Log binomial regression was used to evaluate the association between heavy alcohol use and failure to initiate treatment and to achieve sustained virologic response (SVR). Of the 135 participants with PEth data, median age was 55 years, 59% were male, 92% were Black, 91% reported a history of drug use, and 97% were on antiretroviral therapy. Hazardous drinking was reported on AUDIT by 28% of participants, and 35% had heavy alcohol use by PEth. Of the 47 individuals with a PEth ≥50 ng/mL, 23 (49%) reported no or minimal alcohol use by AUDIT. HCV treatment was initiated in 103 of 135 participants, and SVR was achieved in 92%. PEth ≥50 ng/mL (Relative Risk [RR] 0.72, 95% CI 0.35-1.48) was not significantly associated with failure to initiate HCV treatment or failure to achieve SVR (RR 0.85, 95% CI 0.46-1.57).In conclusion, alcohol use was common and frequently not detected by self-report. However, heavy alcohol use, even when measured objectively, was not associated with failure to initiate HCV treatment or to achieve cure.

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.

Factors associated with phylogenetic clustering of hepatitis C among people who inject drugs in Baltimore.

BACKGROUND: The availability of effective, oral direct acting antivirals (DAAs) for hepatitis C virus (HCV) treatment has put elimination of HCV as a public health challenge within reach. However, little is known about the characteristics of transmission networks of people who inject drugs (PWID). METHODS: Sequencing of a segment of the HCV genome was performed on samples collected from a community-based cohort of PWID between August 2005 and December 2016. Phylogenetic trees were inferred, and clusters were identified (70% bootstrap threshold; 0.04 maximum genetic distance threshold). We describe sex, race, age difference, and HIV infection status of potential transmission partners. Logistic regression was used to assess factors associated with being in an HCV cluster. RESULTS: Of 508 HCV genotype 1 viremic PWID, 8% (n = 41) were grouped into 20 clusters, consisting of 19 pairs and 1 triad. In adjusted analyses, female sex (odds ratio [OR] 2.3 [95% confidence interval (CI) 1.2-4.5]) and HIV infection (OR 5.7 [CI 2.7-11.9]) remained independently associated with being in an HCV infection cluster. CONCLUSIONS: Molecular epidemiological analysis reveals that, in this cohort of PWID in Baltimore, HIV infection and female sex were associated with HCV clustering. Combination HCV prevention interventions targeting HIV infected PWID and addressing HCV infection prevention needs of women have potential to advance HCV elimination efforts.

Staying hepatitis C negative: A systematic review and meta-analysis of cure and reinfection in people who inject drugs.

BACKGROUND AND AIMS: Direct-acting antivirals (DAAs) are highly effective in treating hepatitis C. However, there is concern that cure rates may be lower, and reinfection rates higher, among people who inject drugs. We conducted a systematic review of treatment outcomes achieved with DAAs in  people who inject drugs (PWID). METHODS: A search strategy was used to identify studies that reported sustained viral response (SVR), treatment discontinuation, adherence or reinfection in recent PWID and/or opioid substitution therapy (OST) recipients. Study quality was assessed using the Newcastle-Ottawa Scale. Meta-analysis of proportions was used to estimate pooled SVR and treatment discontinuation rates. The pooled relative risk of achieving SVR and pooled reinfection rate were calculated using generalized mixed effects linear models. RESULTS: The search identified 8075 references; 26 were eligible for inclusion. The pooled SVR for recent PWID was 88% (95% CI, 83%-92%) and 91% (95% CI 88%-95%) for OST recipients. The relative risk of achieving SVR for recent PWID compared to non-recent PWID was 0.99 (95% CI, 0.94-1.06). The pooled treatment discontinuation was 2% (95% CI, 1%-4%) for both recent PWID and OST recipients. Amongst recent PWID, the pooled incidence of reinfection was 1.94 per 100 person years (95% CI, 0.87-4.32). In OST recipients, the incidence of reinfection was 0.55 per 100 person years (95% CI, 0.17-1.76). CONCLUSIONS: Treatment outcomes were similar in recent PWID compared to non-PWID treated with DAAs. People who report recent injecting or OST recipients should not be excluded from hepatitis C treatment.

High hepatitis C cure rates among black and nonblack human immunodeficiency virus-infected adults in an urban center.

Hepatitis C virus (HCV) cure rates have been similar in patients with and without human immunodeficiency virus (HIV) coinfection; however, in the ION-4 study, black patients treated with ledipasvir/sofosbuvir (LDV/SOF) were significantly less likely to achieve cure (90%) compared to nonblack patients (99%). There are limited real-world data on the effectiveness of oral direct-acting antivirals (DAAs) in predominantly minority HIV/HCV coinfected populations. We analyzed HCV treatment outcomes among 255 HCV coinfected patients initiating DAAs between February 2014 and March 2016 in an urban clinic in Baltimore, Maryland. To facilitate adherence, patients received standardized HIV nurse/pharmacist support, which included nurse visits and telephone calls. Median age was 43 years, 88% were black, 73% male, 69% had a history of injection drug use, 45% a history of hazardous alcohol use, and 57% a comorbid psychiatric diagnosis. Median CD4 count was 577 (interquartile range, 397-820) cells/mm3 ; most (97%) were on antiretroviral therapy, had HIV RNA <20 copies/mL (87%), and were infected with HCV genotype 1 (98%). Over 60% had significant fibrosis (Fibrosis-4 Index score 1.45-3.25 [44%] and >3.25 [17%, cirrhosis]) and 30% were HCV treatment experienced. The majority of patients received LDV/SOF with or without ribavirin (91%) and were treated for 12 weeks. Overall, the sustained virological response rate was 97% (95% confidence interval [CI], 93-98) and did not vary by race (black, 96% [95% CI, 93-98]; nonblack, 97%, [95% CI, 83-99]), history of injection drug use, alcohol use, or psychiatric diagnosis. CONCLUSION: HCV treatment was highly effective among HIV-infected patients who received care within an integrated nurse/pharmacist adherence support program. These results suggest that race and psychosocial comorbidity may not be barriers to HCV elimination. (Hepatology 2017;66:1402-1412).

Oral Direct-Acting Agent Therapy for Hepatitis C Virus Infection: A Systematic Review.

BACKGROUND: Rapid improvements in hepatitis C virus (HCV) therapy have led to the approval of multiple oral direct-acting antiviral (DAA) regimens by the U.S. Food and Drug Administration (FDA) for treatment of chronic HCV infection. PURPOSE: To summarize published literature on the efficacy and safety of oral DAAs for treatment of persons with chronic HCV infection. DATA SOURCES: MEDLINE and EMBASE from inception through 1 November 2016. STUDY SELECTION: 42 English-language studies from controlled and single-group registered clinical trials of adults with HCV infection that evaluated at least 8 weeks of an FDA-approved interferon-free HCV regimen that included at least 2 DAAs. DATA EXTRACTION: Two investigators abstracted data on study design, patient characteristics, and virologic and safety outcomes sequentially and assessed quality independently. DATA SYNTHESIS: Six DAA regimens showed high sustained virologic response (SVR) rates (>95%) in patients with HCV genotype 1 infection without cirrhosis, including those with HIV co-infection. Effective treatments for HCV genotype 3 infection are limited (2 DAA regimens). Patients with hepatic decompensation, particularly those with Child-Turcotte-Pugh class C disease, had lower SVR rates (78% to 87%) than other populations. The addition of ribavirin was associated with increased SVR rates for certain DAA regimens and patient groups. Overall rates of serious adverse events and treatment discontinuation were low (<10% in the general population); regimens that included ribavirin had more mild or moderate adverse events than those without. LIMITATIONS: Twenty-three studies had moderate risk of bias (10 were open-label single-group trials, 11 had limited information on concealment of the allocation scheme, and 5 had selective outcome reporting). All but 1 of the studies were industry-funded. Heterogeneity of interventions precluded pooling. CONCLUSION: Multiple oral DAA regimens show high rates of safety, tolerability, and efficacy for treatment of HCV genotype 1 infection, particularly among persons without cirrhosis. PRIMARY FUNDING SOURCE: Patient-Centered Outcomes Research Institute. (PROSPERO: CRD42014009711).

The Relationship between Neighborhood Disorder, Social Networks, and Indoor Cigarette Smoking among Impoverished Inner-City Residents.

Impoverished urban neighborhoods tend to have higher rates of smoking and higher rates of exposure to secondhand smoke as compared to more affluent neighborhoods. Contextual factors of neighborhood disorder and social network and household composition may have an impact on indoor smoking behaviors. The TIDE study examined psychosocial factors associated with smoking behaviors among impoverished inner-city smokers in Baltimore, Maryland. Among a community-recruited sample of 413 smokers who lived with others, most (73%) reported that they or others smoked in their residence. Cohabitation with children, elderly, and those with asthma and other respiratory condition was not associated with indoor smoking. Neighborhood disorder, the proportion of social network members who smoked with the study participant, and the proportion of household members who smoked were all independently associated with smoking indoors. The study findings suggest the importance of addressing neighborhood and social network factors when developing programs for promoting indoor smoking bans as well as cessation and prevention programs.

Incident Hepatitis B Virus Infection in HIV-Infected and HIV-Uninfected Men Who Have Sex With Men From Pre-HAART to HAART Periods: A Cohort Study.

BACKGROUND: Men who have sex with men (MSM) are at high risk for hepatitis B virus (HBV) infection. Data on the effect of highly active antiretroviral therapy (HAART) on incident HBV infection in HIV-infected and HIV-uninfected MSM are limited. OBJECTIVE: To determine predictors of incident HBV infection in MSM during pre-HAART and HAART periods. DESIGN: Observational cohort study. SETTING: Cohort of MSM who have, or are at risk for, HIV infection. PATIENTS: 2375 HBV-uninfected MSM in the Multicenter AIDS Cohort Study. MEASUREMENTS: Poisson regression was used to compare incidence rates of HBV infection in the pre-HAART and HAART eras and to identify factors associated with incidence of HBV infection. RESULTS: In 25,322 person-years of follow-up, 244 incident HBV infections occurred. The unadjusted incidence rate was higher in HIV-infected MSM than in HIV-uninfected MSM (incidence rate ratio [IRR], 1.9 [95% CI, 1.5 to 2.4]) and was significantly lower in the HAART era than in the pre-HAART era among HIV-infected (IRR, 0.2 [CI, 0.1 to 0.4]) and HIV-uninfected (IRR, 0.3 [CI, 0.2 to 0.4]) MSM. Age younger than 40 years (IRR, 2.3 [CI, 1.7 to 3.0]), more than 1 recent sexual partner (IRR, 3.1 [CI, 2.3 to 4.2]), and HIV infection (IRR, 2.4 [CI, 1.8 to 3.1]) were independently associated with higher incidence of HBV infection, whereas HBV vaccination was protective (IRR, 0.3 [CI, 0.2 to 0.4]). Highly active antiretroviral therapy with HIV RNA levels less than 400 copies/mL was associated with protection (IRR, 0.2 [CI, 0.1 to 0.5]), but HAART in those with HIV RNA levels of 400 copies/mL or greater was not. LIMITATION: The observational nature limits inferences about causality. CONCLUSION: Effective HAART is associated with lower incidence of HBV infection; however, even in the HAART era, incidence of HBV infection remains high among MSM. PRIMARY FUNDING SOURCE: National Institute of Allergy and Infectious Diseases.