Community-Based Point-of-Diagnosis Hepatitis C Treatment for Marginalized Populations: A Nonrandomized Controlled Trial.

Importance: Disparities persist in testing and treatment for hepatitis C virus (HCV), leaving socially marginalized populations less likely to benefit from curative treatment. Linkage services are often insufficient to overcome barriers to navigating the medical system and contextual factors. Objective: To determine the feasibility, acceptability, and safety of HCV treatment at the point of HCV infection diagnosis disclosure in a nonclinical community setting. Design, Setting, and Participants: In this single-arm nonrandomized controlled trial conducted between July 1, 2020, and October 31, 2021, street-outreach recruitment targeted people experiencing homelessness and injecting drugs in an urban US community who were eligible for simplified HCV treatment. Interventions: Study procedures were designed to reflect the community environment and services needed to provide HCV testing, disclosure, and treatment in a nonclinical site. The test-and-treat No One Waits (NOW) model of care provided a 2-week starter pack of 400 mg of sofosbuvir and 100 mg of velpatasvir at time of HCV RNA results disclosure. Participants were transitioned to insurance-provided sofosbuvir-velpatasvir when feasible to complete a 12-week treatment course. Main Outcomes and Measures: The primary end point was sustained virologic response at posttreatment week 12 or later (SVR12). Acceptability end points were treatment initiation and completion. Safety end points were treatment discontinuation because of a late exclusion criterion and adverse events. Results: Of the 492 people (median [IQR] age, 48 [37-58] years; 62 [71%] male) who underwent anti-HCV testing, 246 (50%) tested anti-HCV positive, and 111 (23%) tested HCV RNA positive and were eligible for simplified HCV treatment. Eighty-nine of the 111 eligible participants (80%) returned for confirmatory RNA results, and 87 (98%) accepted and initiated HCV treatment. Seventy (80%) were currently injecting drugs, 83 (97%) had an income below the poverty line, and 53 (61%) were currently unsheltered. Most had HCV genotype 1a (45 [52%]) or 3 (20 [23%]). Sixty-nine (79%) completed 12 weeks of sofosbuvir-velpatasvir treatment, 2 stopped treatment because of low adherence, and 16 were lost to follow-up. Of the 66 participants who completed treatment and had a successful blood draw, 61 (92%) had undetectable HCV RNA at treatment completion. Of the 87 treated patients, 58 achieved SVR12, leading to a treatment response of 67% (95% CI, 56%-76%) among the intention-to-treat group and 84% (95% CI, 73%-92%) among the per-protocol group. There were no adverse events, late exclusions, or deaths. Conclusions and Relevance: In this nonrandomized controlled trial of HCV treatment at the point of diagnosis, the NOW model of care reduced steps between HCV testing and treatment initiation and resulted in high levels of treatment initiation, completion, and cure. The NOW model of care can expand the current HCV test-and-treat toolkit by reaching a broader population of marginalized communities and expediting curative therapy. Trial Registration: ClinicalTrials.gov Identifier: NCT03987503.

Evaluating Demographic Representation in Clinical Trials: Use of the Adaptive Coronavirus Disease 2019 Treatment Trial (ACTT) as a Test Case.

Background: Clinical trials initiated during emerging infectious disease outbreaks must quickly enroll participants to identify treatments to reduce morbidity and mortality. This may be at odds with enrolling a representative study population, especially when the population affected is undefined. Methods: We evaluated the utility of the Centers for Disease Control and Prevention's COVID-19-Associated Hospitalization Surveillance Network (COVID-NET), the COVID-19 Case Surveillance System (CCSS), and 2020 United States (US) Census data to determine demographic representation in the 4 stages of the Adaptive COVID-19 Treatment Trial (ACTT). We compared the cumulative proportion of participants by sex, race, ethnicity, and age enrolled at US ACTT sites, with respective 95% confidence intervals, to the reference data in forest plots. Results: US ACTT sites enrolled 3509 adults hospitalized with COVID-19. When compared with COVID-NET, ACTT enrolled a similar or higher proportion of Hispanic/Latino and White participants depending on the stage, and a similar proportion of African American participants in all stages. In contrast, ACTT enrolled a higher proportion of these groups when compared with US Census and CCSS. The proportion of participants aged ≥65 years was either similar or lower than COVID-NET and higher than CCSS and the US Census. The proportion of females enrolled in ACTT was lower than the proportion of females in the reference datasets. Conclusions: Although surveillance data of hospitalized cases may not be available early in an outbreak, they are a better comparator than US Census data and surveillance of all cases, which may not reflect the population affected and at higher risk of severe disease.

Bivalent and Monovalent SARS-CoV-2 Variant Vaccine Boosters Improve coverage of the known Antigenic Landscape: Results of the COVID-19 Variant Immunologic Landscape (COVAIL) Trial.

Vaccine protection against COVID-19 wanes over time and has been impacted by the emergence of new variants with increasing escape of neutralization. The COVID-19 Variant Immunologic Landscape (COVAIL) randomized clinical trial (clinicaltrials.gov NCT05289037) compares the breadth, magnitude and durability of antibody responses induced by a second COVID-19 vaccine boost with mRNA (Moderna mRNA-1273 and Pfizer-BioNTech BNT162b2), or adjuvanted recombinant protein (Sanofi CoV2 preS DTM-AS03) monovalent or bivalent vaccine candidates targeting ancestral and variant SARS-CoV-2 spike antigens (Beta, Delta and Omicron BA.1). We found that boosting with a variant strain is not associated with loss in neutralization against the ancestral strain. However, while variant vaccines compared to the prototype/wildtype vaccines demonstrated higher neutralizing activity against Omicron BA.1 and BA.4/5 subvariants for up to 3 months after vaccination, neutralizing activity was lower for more recent Omicron subvariants. Our study, incorporating both antigenic distances and serologic landscapes, can provide a framework for objectively guiding decisions for future vaccine updates.

Association of Convalescent Plasma Treatment With Clinical Status in Patients Hospitalized With COVID-19: A Meta-analysis.

Importance: COVID-19 convalescent plasma (CCP) is a potentially beneficial treatment for COVID-19 that requires rigorous testing. Objective: To compile individual patient data from randomized clinical trials of CCP and to monitor the data until completion or until accumulated evidence enables reliable conclusions regarding the clinical outcomes associated with CCP. Data Sources: From May to August 2020, a systematic search was performed for trials of CCP in the literature, clinical trial registry sites, and medRxiv. Domain experts at local, national, and international organizations were consulted regularly. Study Selection: Eligible trials enrolled hospitalized patients with confirmed COVID-19, not receiving mechanical ventilation, and randomized them to CCP or control. The administered CCP was required to have measurable antibodies assessed locally. Data Extraction and Synthesis: A minimal data set was submitted regularly via a secure portal, analyzed using a prespecified bayesian statistical plan, and reviewed frequently by a collective data and safety monitoring board. Main Outcomes and Measures: Prespecified coprimary end points-the World Health Organization (WHO) 11-point ordinal scale analyzed using a proportional odds model and a binary indicator of WHO score of 7 or higher capturing the most severe outcomes including mechanical ventilation through death and analyzed using a logistic model-were assessed clinically at 14 days after randomization. Results: Eight international trials collectively enrolled 2369 participants (1138 randomized to control and 1231 randomized to CCP). A total of 2341 participants (median [IQR] age, 60 [50-72] years; 845 women [35.7%]) had primary outcome data as of April 2021. The median (IQR) of the ordinal WHO scale was 3 (3-6); the cumulative OR was 0.94 (95% credible interval [CrI], 0.74-1.19; posterior probability of OR <1 of 71%). A total of 352 patients (15%) had WHO score greater than or equal to 7; the OR was 0.94 (95% CrI, 0.69-1.30; posterior probability of OR <1 of 65%). Adjusted for baseline covariates, the ORs for mortality were 0.88 at day 14 (95% CrI, 0.61-1.26; posterior probability of OR <1 of 77%) and 0.85 at day 28 (95% CrI, 0.62-1.18; posterior probability of OR <1 of 84%). Heterogeneity of treatment effect sizes was observed across an array of baseline characteristics. Conclusions and Relevance: This meta-analysis found no association of CCP with better clinical outcomes for the typical patient. These findings suggest that real-time individual patient data pooling and meta-analysis during a pandemic are feasible, offering a model for future research and providing a rich data resource.

Remdesivir for the Treatment of Covid-19 - Final Report.

BACKGROUND: Although several therapeutic agents have been evaluated for the treatment of coronavirus disease 2019 (Covid-19), no antiviral agents have yet been shown to be efficacious. METHODS: We conducted a double-blind, randomized, placebo-controlled trial of intravenous remdesivir in adults who were hospitalized with Covid-19 and had evidence of lower respiratory tract infection. Patients were randomly assigned to receive either remdesivir (200 mg loading dose on day 1, followed by 100 mg daily for up to 9 additional days) or placebo for up to 10 days. The primary outcome was the time to recovery, defined by either discharge from the hospital or hospitalization for infection-control purposes only. RESULTS: A total of 1062 patients underwent randomization (with 541 assigned to remdesivir and 521 to placebo). Those who received remdesivir had a median recovery time of 10 days (95% confidence interval [CI], 9 to 11), as compared with 15 days (95% CI, 13 to 18) among those who received placebo (rate ratio for recovery, 1.29; 95% CI, 1.12 to 1.49; P<0.001, by a log-rank test). In an analysis that used a proportional-odds model with an eight-category ordinal scale, the patients who received remdesivir were found to be more likely than those who received placebo to have clinical improvement at day 15 (odds ratio, 1.5; 95% CI, 1.2 to 1.9, after adjustment for actual disease severity). The Kaplan-Meier estimates of mortality were 6.7% with remdesivir and 11.9% with placebo by day 15 and 11.4% with remdesivir and 15.2% with placebo by day 29 (hazard ratio, 0.73; 95% CI, 0.52 to 1.03). Serious adverse events were reported in 131 of the 532 patients who received remdesivir (24.6%) and in 163 of the 516 patients who received placebo (31.6%). CONCLUSIONS: Our data show that remdesivir was superior to placebo in shortening the time to recovery in adults who were hospitalized with Covid-19 and had evidence of lower respiratory tract infection. (Funded by the National Institute of Allergy and Infectious Diseases and others; ACTT-1 ClinicalTrials.gov number, NCT04280705.).

Impact of a digital medicine programme on hepatitis C treatment adherence and efficacy in adults at high risk for non-adherence.

BACKGROUND: Direct-acting anti-virals (DAA) are highly effective for hepatitis C virus (HCV) treatment, but perceived risks of medication non-adherence may restrict access to care. Digital medicine programme (DMP) has improved adherence and outcomes for some conditions. AIMS: To conduct a prospective, single-arm, open-label study across the United States to assess the impact of DMP on adherence and efficacy in adults with chronic HCV infection at high risk for non-adherence. METHODS: Eligible participants were placed on the DMP to evaluate real-time adherence; primary outcome was sustained virological response (SVR) at ≥10 weeks post-treatment. RESULTS: Between August 2017 and April 2019, 288 participants (Medicaid, 64.9%; psychiatric disorders, 61.1%; homeless, 9.4%) received DAAs for 8-12 weeks (sofosbuvir/velpatasvir or ledipasvir, 45%; glecaprevir/pibrentasvir, 55%). SVR was achieved in 99.1% of 218 participants who had HCV RNA assessed at ≥10 weeks post-treatment; of the 70 participants who did not have SVR assessed, 17 had SVR4 with HCV RNA assessed at a median (IQR; interquartile range) 5.6 weeks (4.1, 7.9) post-treatment; one completed treatment but did not have HCV RNA assessed, and 52 discontinued treatment early without assessment. Overall, the primary analysed participants (n = 218) actively used the DMP for median (range) 92.9% (12.5%, 100%) of their prescribed treatment time, and overall pill-taking adherence was 95.0% (57.1%, 100%). Participants reported the programme was useful and easy to use through satisfaction surveys. CONCLUSIONS: HCV treatment with DMP was accepted by patients and clinicians and may support HCV treatment outcomes among patients at high risk for treatment non-adherence (Clinical trials.gov NCT03164902).

Ledipasvir/Sofosbuvir for 8 Weeks to Treat Acute Hepatitis C Virus Infections in Men With Human Immunodeficiency Virus Infections: Sofosbuvir-Containing Regimens Without Interferon for Treatment of Acute HCV in HIV-1 Infected Individuals.

BACKGROUND: Current guidelines for the management of hepatitis C virus (HCV) infections provide varying recommendations for the optimal treatment of acute HCV infections. There are limited data from small cohort studies to provide guidance on the best approach to treatment of this important patient population. METHODS: Sofosbuvir-Containing Regimens Without Interferon for Treatment of Acute HCV in HIV-1 Infected Individuals is an open-label, 2-cohort, Phase 1 clinical trial in which the second cohort assessed the safety and efficacy of 8 weeks of ledipasvir/sofosbuvir for the treatment of acute HCV infections in participants with chronic human immunodeficiency virus (HIV)-1 infections. This final analysis of the second cohort had a planned accrual of 27 participants, based on non-inferiority criteria, compared to the study-defined, historical, sustained virologic response (SVR) of 60% with pegylated-interferon/ribavirin. RESULTS: We enrolled 27 men (9 Hispanic; 11 White, non-Hispanic; 5 Black, non-Hispanic; 2 Asian or Pacific Islander; median age 46 years). Most (96%) had HCV genotype-1 infection and 59% had the favorable interleukin 28B CC genotype. The median baseline HCV RNA load was 6.17 log10 IU/mL (interquartile range 4.51 - 6.55). All participants (100%) achieved the primary outcome of a sustained virologic response 12 weeks after the date of the last dose of study treatment (90% confidence interval 90-100%), achieving non-inferiority versus the 60% historic benchmark. No treatment discontinuations occurred. CONCLUSIONS: This multicenter clinical trial, investigating 8 weeks of ledipasvir/sofosbuvir for acute HCV infections in men with HIV infections, reports a 100% SVR. This study provides the rationale for larger studies of shortened courses of direct-acting antiviral therapies in persons with HIV infections, including those with high baseline HCV RNA loads. CLINICAL TRIALS REGISTRATION: NCT02128217.

A pilot metabolomics study of tuberculosis immune reconstitution inflammatory syndrome.

BACKGROUND: Diagnosis of paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is challenging and new tools are needed for early diagnosis as well as to understand the biochemical events that underlie the pathology in TB-IRIS. METHODS: Plasma samples were obtained from participants from a randomized HIV/TB treatment strategy study (AIDS Clinical Trials Group [ACTG] A5221) with (n = 26) and without TB-IRIS (n = 22) for an untargeted metabolomics pilot study by liquid-chromatography mass spectrometry. The metabolic profile of these participants was compared at the study entry and as close to the diagnosis of TB-IRIS as possible (TB-IRIS window). Molecular features with p < 0.05 and log2 fold change ≥0.58 were submitted for pathway analysis through MetaboAnalyst. We also elucidated potential metabolic signatures for TB-IRIS using a LASSO regression model. RESULTS: At the study entry, we showed that the arachidonic acid and glycerophospholipid metabolism were altered in the TB-IRIS group. Sphingolipid and linoleic acid metabolism were the most affected pathways during the TB-IRIS window. LASSO modeling selected a set of 8 and 7 molecular features with the potential to predict TB-IRIS at study entry and during the TB-IRIS window, respectively. CONCLUSION: This study suggests that the use of plasma metabolites may distinguish HIV-TB patients with and without TB-IRIS.

Localized US Efforts to Eliminate Hepatitis C.

The United States has national plans for the elimination of hepatitis C virus but much of US health care is organized on the state level and requires local solutions. This article describes the plans developed by New York, Massachusetts, and the city/county of San Francisco for hepatitis C virus elimination. Coalitions capitalize on existing resources and advocate for new resources to address barriers in hepatitis C virus care. Although each coalition has distinct plans, all share a commitment to groups that are disproportionately affected and are at risk for being excluded from advances in hepatitis C virus treatment and cure.

Grazoprevir, ruzasvir, and uprifosbuvir for hepatitis C virus after NS5A treatment failure.

People with hepatitis C virus (HCV) infection who have failed treatment with an all-oral regimen represent a challenging treatment population. The present studies evaluated the safety and efficacy of grazoprevir, ruzasvir, and uprifosbuvir, with or without ribavirin, in participants who had failed an NS5A inhibitor-containing regimen. C-SURGE (PN-3682-021) and C-CREST Part C (PN-3682-011 and -012) were open-label, multicenter studies. Participants who had previously relapsed following an NS5A inhibitor-containing all-oral regimen were retreated with grazoprevir 100 mg, ruzasvir 60 mg, and uprifosbuvir 450 mg alone for 24 weeks or with ribavirin for 16 weeks. The primary efficacy endpoint was sustained virologic response (HCV RNA below the limit of quantitation [<15 IU/mL]) 12 weeks after treatment completion (SVR12). In C-SURGE, SVR12 was achieved by 49/49 (100%) and 43/44 (98%) genotype (GT)1 participants in the 24-week no ribavirin arm and the 16-week plus ribavirin arm (lost to follow-up, n = 1), respectively. In C-CREST Part C, SVR12 was achieved by 23/24 (96%) participants treated for 16 weeks with ribavirin (GT1, 2/2 [100%]; GT2, 13/14 [93%]; GT3, 8/8 [100%]). One participant with GT2 infection discontinued study medication after a single dose of grazoprevir, ruzasvir, and uprifosbuvir plus ribavirin due to serious adverse events of vomiting and tachycardia. The presence of baseline resistance-associated substitutions had no impact on SVR12. No participant who completed treatment in either study experienced virologic failure. CONCLUSION: Grazoprevir, ruzasvir, and uprifosbuvir, with or without ribavirin, for 16 or 24 weeks was safe and highly effective in participants with HCV infection who had previously failed NS5A inhibitor-containing therapy. (Hepatology 2017;66:1794-1804).

Safety and Efficacy of Pegylated Interferon Lambda, Ribavirin, and Daclatasvir in HCV and HIV-Coinfected Patients.

To evaluate the efficacy and safety of pegylated interferon-lambda-1a (Lambda)/ribavirin (RBV)/daclatasvir (DCV) for treatment of patients coinfected with chronic hepatitis C virus (HCV) and human immunodeficiency virus (HIV). Treatment-naive patients were assigned to cohort A [HCV genotype (GT)-2 or -3] or cohort B [HCV GT-1(a or b) or -4]. All patients received Lambda/RBV/DCV for the first 12 weeks; cohort A received Lambda/RBV for an additional 12 weeks, followed by 24 weeks of follow-up, and cohort B received response-guided therapy. The primary endpoint was the proportion of patients who achieved a sustained virologic response at post-treatment week 12 (SVR12). In cohort A (n = 104), 84.6% achieved SVR12 (95.0% in GT-2; 83.1% in GT-3). In cohort B (n = 196), 76.0% achieved SVR12 (71.7% in GT-1a; 86.0% in GT-1b; 70.7% in GT-4). Rates of discontinuation due to adverse events (AEs) (3.8% and 6.1%) and serious AEs (5.8% and 6.1%) were low in cohorts A and B, respectively. In addition, treatment with Lambda/RBV/DCV had little impact on CD4 counts. SVR12 rates with Lambda/RBV/DCV in an HCV/HIV-coinfected population ranged from 71.7% to 95.0%. Treatment was generally well tolerated, with a low proportion of patients discontinuing due to AEs. Clinical trial registration NCT01866930.

Pilot study of pioglitazone before HCV retreatment in HIV/HCV genotype 1-infected subjects with insulin resistance and previous nonresponse to peginterferon and ribavirin therapy: A5239.

: Insulin resistance is associated with nonresponse to hepatitis C virus (HCV) treatment. In this multicenter, single-arm pilot study, adult, HIV/HCV genotype 1-coinfected previous nonresponders to peginterferon/ribavirin (PegIFN/RBV) with homeostatic model assessment of insulin resistance >2.5 were treated with pioglitazone (PIO) for 24 weeks followed by PegIFN/RBV/PIO. Three of 19 subjects (15.8%) achieved undetectable HCV RNA at week 24 of PegIFN/RBV/PIO, which was not significantly different than the historical null rate of 10% (P = 0.29, lower limit of the exact 1-sided 90% confidence interval 5.9%). Over the 24 weeks of PIO monotherapy, alanine aminotransferase and aspartate aminotransferase declined significantly and correlated with improved metabolic parameters.

CDC/NIH Workshop. Tuberculosis biomarker and surrogate endpoint research roadmap.

The Centers for Disease Control and Prevention and National Institutes of Health convened a multidisciplinary meeting to discuss surrogate markers of treatment response in tuberculosis. The goals were to assess recent surrogate marker research and to provide specific recommendations for (1) the qualification and validation of biomarkers of treatment outcome; (2) the standardization of specimen and data collection for future clinical trials, including a minimum set of samples and collection time points; and (3) the creation ofa specimen repository to support biomarker testing. This article summarizes these recommendations and provides a roadmap for their implementation.

Tuberculosis as part of the natural history of HIV infection in developing countries.

An enhanced, refocused research agenda is critical to reducing the burden of tuberculosis (TB) in the human immunodeficiency virus (HIV) epidemic in developing countries. TB threatens HIV-infected patients before and after initiation of antiretroviral therapy, is difficult to diagnose, is rapidly fatal when it is drug resistant, and is being spread in clinics and hospitals. Research priorities include improved and point-of-care TB diagnostics; TB treatment and prevention during HIV infection, drug-resistant TB, and childhood TB; and optimization of TB and HIV program integration. With new TB diagnostics and drugs reaching approval, research must focus on effectively deploying these advancements. Research must include evaluations of individual, household, health care, and community approaches. Studies must apply implementation science to determine how to increase and adapt effective interventions to reduce TB burden in the context of HIV infection. Investment in this research will improve the lives of persons infected with HIV and contribute to efforts to reduce the global TB burden.

Comparison of an interferon-gamma release assay with tuberculin skin testing in HIV-infected individuals.

RATIONALE: Although interferon (IFN)-gamma release assays are approved for the diagnosis of latent tuberculosis infection (LTBI), limited data exist regarding their performance in HIV infection. OBJECTIVES: To compare tuberculin skin test (TST) results to the commercial IFN-gamma release assay QuantiFERON-TB Gold In-Tube (QFT) for the diagnosis of LTBI in HIV-infected adults. METHODS: A total of 294 HIV-infected subjects sampled from two San Francisco cohorts underwent TST, using 5 TU of purified protein derivative, and QFT, measuring IFN-gamma response to Mycobacterium tuberculosis-specific RD-1 antigens. MAIN RESULTS: Of 294 participants, 205 (70%) returned for an evaluable TST. Concordance between QFT and TST was 89.3% (kappa=0.37, p=0.007). However, in subjects with positive test results by either TST or QFT, only 28% (8/29) had positive test results by both modalities. TST-positive/QFT-negative discordant results were found in 5.1% of subjects and TST-negative/QFT-positive discordance in 5.6%. Indeterminate QFT results occurred in 5.1%, all due to a failure to respond to the phytohemagglutinin-positive control. Subjects with a CD4(+) count of less than 100 cells/mm(3) had a relative risk of an indeterminate result of 4.24 (95% confidence interval, 1.55-11.61; p=0.003) compared with those with a CD4(+) count of 100 or more. CONCLUSIONS: Overall concordance between QFT and TST in HIV infection was high, but agreement among subjects with positive tests by either modality was low.

Antiretroviral therapy and TB.

With the expansion and convergence of the HIV and TB epidemics worldwide, clinicians will increasingly will be called to manage and treat co-infected patients. TB and HIV medications have overlapping and additive toxicities that can complicate therapy. Additional clinical challenges include choice of optimal first and second line antiretroviral therapy, appropriate timing of antiretroviral initiation, management of immune reconstitution disease, and TB diagnosed after initiation of HIV therapy. Despite the complexities presented by co-infection, many programmes have integrated care and are successfully treating patients with both HIV and TB.

Clinical presentation and course of acute hepatitis C infection in HIV-infected patients.

Hepatitis C virus (HCV) has become a significant source of morbidity and mortality in HIV-infected patients. However, little is known about the clinical presentation and course of acute HCV infection in this population. This study reports the outcomes of acute HCV infection in 9 HIV-infected men. Sex with men was the only reported risk factor for HCV infection in 6 of the subjects. Clinical presentation of acute HCV ranged from incidentally discovered elevated transaminases to severe liver dysfunction requiring hospitalization. At the time of HCV diagnosis, 8 of 9 patients had CD4+ counts >250 cells/mm(3), and 6 had HIV viral loads of < or =5000 copies/mL. Eight patients were receiving antiretroviral therapy. Outcome of these acute HCV infections varied. Five patients experienced virologic clearance, 2 in whom virus cleared spontaneously and 3 who were treated with pegylated interferon and ribavirin. Four patients developed chronic infection, one of whom had a relapse during HCV treatment and 3 of whom were untreated. All 4 patients to whom HCV therapy was administered experienced significant anemia or neutropenia, necessitating dose reduction or support with growth factors. Prompt recognition of acute HCV infection may minimize antiretroviral treatment interruption and will allow early treatment, which may improve virologic clearance. Unexplained transaminase elevations in HIV-infected patients, including men who have sex with men, should trigger an evaluation for acute HCV infection.