HIV Testing Preferences and Characteristics of Those Who Have Never Tested for HIV in the United States.

BACKGROUND: The initial phase of the federal Ending the HIV Epidemic in the U.S. (EHE) initiative prioritized efforts in 57 geographic areas. The US Centers for Disease Control and Prevention recommends persons aged 13 to 64 years be tested for HIV at least once as part of routine health care; however, it is unclear how effectively these testing recommendations have been implemented in EHE priority areas. METHODS: In 2021 to 2022, we analyzed data from a Web-based, nationally representative survey of adults fielded in 2021. HIV testing preferences were compared by testing history, demographic characteristics, behaviors, and geography. RESULTS: An estimated 72.5% of US adults had never tested for HIV. Never testing was most prevalent among those aged 18 to 29 or those 50 years or older, non-Hispanic White persons, and those living in the Midwest. Among persons living in EHE priority areas and persons reporting at least one behavior that increases risk of HIV transmission, 69.1% and 48.0%, respectively, had never tested for HIV. The top 3 HIV testing preferences among never testers were as follows: testing for HIV during a routine health care visit (41.2%), testing at an urgent care or walk-in clinic (9.6%), and self-testing (8.1%). CONCLUSIONS: Most adults had not been tested for HIV, confirming that US Centers for Disease Control and Prevention recommendations are not being fully implemented, even in EHE priority areas. Moreover, most adults who never tested preferred testing in clinical settings, highlighting missed opportunities. As the EHE initiative continues to advance, it is critical to leverage preferred HIV testing modalities, such as routine testing in clinical settings or HIV self-testing.

Alcohol Use, Screening, and Brief Intervention Among Pregnant Persons - 24 U.S. Jurisdictions, 2017 and 2019.

Alcohol use during pregnancy is a major preventable cause of adverse alcohol-related outcomes, including birth defects and developmental disabilities.* Alcohol screening and brief intervention (ASBI) is an evidence-based primary care tool that has been shown to prevent or reduce alcohol consumption during pregnancy; interventions have resulted in an increase in the proportion of pregnant women reporting abstinence (odds ratio = 2.26; 95% CI = 1.43-3.56) (1). Previous national estimates have not characterized ASBI in populations of pregnant persons. Using 2017 and 2019 Behavioral Risk Factor Surveillance System (BRFSS) data, CDC examined prevalence of ASBI and characteristics of pregnant persons and nonpregnant women aged 18-49 years (reproductive-aged women) residing in jurisdictions that participated in the BRFSS ASBI module. During their most recent health care visit within the past 2 years, approximately 80% of pregnant persons reported being asked about their alcohol use; however, only 16% of pregnant persons who self-reported current drinking at the time of the survey (at least one alcoholic beverage in the past 30 days) were advised by a health care provider to quit drinking or reduce their alcohol use. Further, the prevalence of screening among pregnant persons who did not graduate from high school was lower than that among those who did graduate from high school or had at least some college education. This gap between screening and brief intervention, along with disparities in screening based on educational level, indicate missed opportunities to reduce alcohol use during pregnancy. Strategies to enhance ASBI during pregnancy include integrating screenings into electronic health records, increasing reimbursement for ASBI services, developing additional tools, including electronic ASBI, that can be implemented in a variety of settings (2,3).

Prioritization of Evidence-Based and Evidence-Informed Interventions for Retention in Medical Care for Persons with HIV.

Up to 50% of those diagnosed with HIV in the U.S. are not retained in medical care. Care retention provides opportunity to monitor benefits of HIV therapy and enable viral suppression. To increase retention, there is a need to prioritize best practices appropriate for translation and dissemination for real-world implementation. Eighteen interventions from CDC's Compendium of Evidence-Based Interventions were scored using the RE-AIM framework to determine those most suitable for dissemination. A CDC Division of HIV Prevention workgroup developed a RE-AIM scale with emphasis on the Implementation and Maintenance dimensions and less emphasis on the Efficacy dimension since all 18 interventions were already identified as evidence-based or evidence-informed. Raters referenced primary efficacy publications and scores were averaged for a ranked RE-AIM score for interventions. Of 18 interventions, four included care linkage and 7 included viral suppression outcomes. Interventions received between 20.6 and 35.3 points (45 maximum). Scores were converted into a percentage of the total possible with ranges between 45.8 and 78.4%. Top four interventions were ARTAS (78.4%); Routine Screening for HIV (RUSH) (73.2%); Optn4Life (67.4%) and Virology Fast Track (65.9%). All four scored high on Implementation and Maintenance dimensions. Select items within the scale were applicable to health equity, covering topics such as reaching under-served focus populations and acceptability to that population. Navigation-enhanced Case Management (NAV) scored highest on the health equity subscale. RE-AIM prioritization scores will inform dissemination and translation efforts, help clinical staff select feasible interventions for implementation, and support sustainability for those interventions.

RESUMEN: Hasta el 50% de las personas diagnosticadas con VIH en USA no son retenidos en cuidados médicos impactando su monitoreo y supresión viral. Dieciocho intervenciones de retención fueron evaluadas utilizando el marco RE-AIM para determinar su adecuación para la difusión. Evaluadores promediaron las intervenciones. Cuatro intervenciones incluyeron enlace de atención y 7 supresión viral. Las cuatro intervenciones principales fueron ARTAS, detección de rutina para el VIH, Optn4Life y Vía rápida de virología. Elementos del marco fueron usados para evaluar equidad en salud y cubrieron temas de cómo llegar a las poblaciones desatendidas y la aceptabilidad de esa población. La intervención gestión de casos para mejorar con navegación (NAV) obtuvo la puntuación más alta en la subescala de equidad. RE-AIM y los puntajes de priorización de equidad informarán los esfuerzos de difusión y traducción, ayudarán al personal clínico a seleccionar las intervenciones para la implementación y apoyarán la sostenibilidad.

HIV Testing Before and During the COVID-19 Pandemic - United States, 2019-2020.

HIV testing is a core strategy for the Ending the HIV Epidemic in the U.S. (EHE) initiative, which has the aim of reducing new HIV infections by at least 90% by 2030.* During 2016-2017, jurisdictions with the highest HIV diagnosis rates were those with higher prevalences of HIV testing; past-year HIV testing was higher among persons who reported recent HIV risk behaviors compared with those who did not report these risks (1). During 2020-2021, the COVID-19 pandemic disrupted health care delivery, including HIV testing in part because many persons avoided services to comply with COVID-19 risk mitigation efforts (2). In addition, public health departments redirected some sexual health services to COVID-19-related activities.† CDC analyzed data from four national data collection systems to assess the numbers of HIV tests performed and HIV infections diagnosed in the United States in the years before (2019) and during (2020) the COVID-19 pandemic. In 2020, HIV diagnoses reported to CDC decreased by 17% compared with those reported in 2019. This decrease was preceded by decreases in HIV testing during the same period, particularly among priority populations including Black or African American (Black) gay men, Hispanic or Latino (Hispanic) gay men, bisexual men, other men who have sex with men (MSM), and transgender persons in CDC-funded jurisdictions. To compensate for testing and diagnoses missed during the COVID-19 pandemic and to accelerate the EHE initiative, CDC encourages partnerships among federal organizations, state and local health departments, community-based organizations, and health care systems to increase access to HIV testing services, including strategies such as self-testing and routine opt-out screening in health care settings.

Vital Signs: HIV Infection, Diagnosis, Treatment, and Prevention Among Gay, Bisexual, and Other Men Who Have Sex with Men - United States, 2010-2019.

BACKGROUND: Men who have sex with men (MSM) accounted for two thirds of new HIV infections in the United States in 2019 despite representing approximately 2% of the adult population. METHODS: CDC analyzed surveillance data to determine trends in estimated new HIV infections and to assess measures of undiagnosed infection and HIV prevention and treatment services including HIV testing, preexposure prophylaxis (PrEP) use, antiretroviral therapy (ART) adherence, and viral suppression, as well as HIV-related stigma. RESULTS: The estimated number of new HIV infections among MSM was 25,100 in 2010 and 23,100 in 2019. New infections decreased significantly among White MSM but did not decrease among Black or African American (Black) MSM and Hispanic/Latino MSM. New infections increased among MSM aged 25-34 years. During 2019, approximately 83% of Black MSM and 80% of Hispanic/Latino MSM compared with 90% of White MSM with HIV had received an HIV diagnosis. The lowest percentage of diagnosed infection was among MSM aged 13-24 years (55%). Among MSM with a likely PrEP indication, discussions about PrEP with a provider and PrEP use were lower among Black MSM (47% and 27%, respectively) and Hispanic/Latino MSM (45% and 31%) than among White MSM (59% and 42%). Among MSM with an HIV diagnosis, adherence to ART and viral suppression were lower among Black MSM (48% and 62%, respectively) and Hispanic/Latino MSM (59% and 67%) compared with White MSM (64% and 74%). Experiences of HIV-related stigma among those with an HIV diagnosis were higher among Black MSM (median = 33; scale = 0-100) and Hispanic/Latino MSM (32) compared with White MSM (26). MSM aged 18-24 years had the lowest adherence to ART (45%) and the highest median stigma score (39). CONCLUSION: Improving access to and use of HIV services for MSM, especially Black MSM, Hispanic/Latino MSM, and younger MSM, and addressing social determinants of health, such as HIV-related stigma, that contribute to unequal outcomes will be essential to end the HIV epidemic in the United States.

HIV Testing Trends at Visits to Physician Offices, Community Health Centers, and Emergency Departments - United States, 2009-2017.

In 2019, the U.S. Department of Health and Human Services launched the Ending the HIV Epidemic: A Plan for America (EHE) initiative to end the U.S. human immunodeficiency virus (HIV) epidemic by 2030. A critical component of the EHE initiative involves early diagnosis of HIV infection, along with prevention of new transmissions, treatment of infections, and response to HIV outbreaks (1). HIV testing is the first step in identifying persons with HIV infection who need to be engaged in treatment and care as well as persons with a negative HIV test result and who are at high risk for infection and can benefit from HIV preexposure prophylaxis (PrEP) and other prevention services. These opportunities are often missed for persons receiving clinical services in ambulatory care settings (2). Data from the 2009-2016 National Ambulatory Medical Care Survey (NAMCS) and 2009-2017 National Hospital Ambulatory Medical Care Survey (NHAMCS) were analyzed to estimate trends in HIV testing at visits by males and nonpregnant females to physician offices, community health centers (CHCs), and emergency departments (EDs) in the United States. HIV tests were performed at 0.63% of 516 million visits to physician offices, 2.65% of 37 million visits to CHCs, and 0.55% of 87 million visits to EDs. The percentage of visits with an HIV test did not increase at visits to physician offices during 2009-2016, increased at visits to CHC physicians during 2009-2014, and increased slightly at visits to EDs during 2009-2017. All adolescents and adults should have at least one HIV test in their lifetime (3). Strategies that reduce clinical barriers to HIV testing (e.g., clinical decision supports that use information in electronic health records [EHRs] to order an HIV test for persons who require one or standing orders for routine opt-out testing) are needed to increase HIV testing at ambulatory care visits.

Self-Reported Prevalence of HIV Testing Among Those Reporting Having Been Diagnosed With Selected STIs or HCV, United States, 2005-2016.

BACKGROUND: Persons with STIs or HCV infection often have indicators of HIV risk. We used weighted data from 6 cycles of the National Health and Nutrition Examination Survey (NHANES) to assess the proportion of persons who reported ever being diagnosed as having a selected STI or HCV infection and who reported that they were ever tested for HIV. METHODS: Persons aged 20 to 59 years with prior knowledge of HCV infection before receiving NHANES HCV RNA-positive results (2005-2012) or reporting ever being told by a doctor that they had HCV infection (2013-2016), or ever had genital herpes, or had chlamydia or gonorrhea in the past 12 months were categorized as having had a selected STI or HCV infection. Weighted proportions and 95% confidence intervals were estimated for reporting ever being tested for HIV for those who did and did not report a selected STI or HCV infection. RESULTS: A total of 19,102 respondents had nonmissing data for STI and HCV diagnoses and HIV testing history; 44.4% reported ever having been tested for HIV, and 5.2% reported being diagnosed as having a selected STI or HCV infection. The proportion reporting an HIV test was higher for the group that reported an STI or HCV infection than for the group that did not. CONCLUSION: Self-reported HIV testing remains low in the United States, even among those who reported a previous selected STI or HCV infection. Ensuring HIV tests are conducted routinely for those with overlapping risk factors can help facilitate the diagnosis of HIV infections.

HIV Testing and Linkage to Care Among Transgender Women Who Have Sex with Men: 23 U.S. Cities.

Transgender women face unique barriers to HIV testing and linkage to care. This article describes the results of a national testing initiative conducted by 36 community-based and other organizations using a variety of recruitment and linkage-to-care strategies. A total of 2191 HIV tests were conducted with an estimated 1877 unique transgender women, and 4.6% of the transgender women had confirmed positive results. Two thirds (66.3%) were linked to care within approximately three months of follow-up, and the median time to linkage was 7 days. Transgender women tested at clinical sites were linked to care faster than those tested at non-clinical sites (median: 0 vs. 12 days; P = .003). Despite the use of a variety of linkage-to-care strategies, the proportion of transgender women successfully linked to care was below national goals. Tailored programs and interventions are needed to increase HIV testing and improve timely linkage to care in this population.

Performance of an Alternative Laboratory-Based HIV Diagnostic Testing Algorithm Using HIV-1 RNA Viral Load.

BACKGROUND: Since 2014, the recommended algorithm for laboratory diagnosis of HIV infection in the United States has consisted of an HIV-1/2 antigen/antibody (Ag/Ab) test followed by an HIV-1/2 antibody (Ab) differentiation test and, if necessary, a diagnostic HIV-1 nucleic acid test to resolve discordant or indeterminate results. METHODS: Using stored specimens from persons seeking HIV testing who had not received a previous diagnosis or treatment, we compared the performance of a 3-step alternative algorithm consisting of an Ag/Ab test followed by a quantitative HIV-1 RNA viral load assay and, if viral load is not detected, an Ab differentiation test, to that of the recommended algorithm. We calculated the sensitivity and specificity of 5 Ag/Ab tests and the proportion of specimens correctly classified by the alternative algorithm compared with the recommended algorithm. Results were examined separately for specimens classified as early infection, established infection, and false-reactive screening. RESULTS: Sensitivity and specificity were similar among all Ag/Ab tests. Viral load quantification correctly classified all specimens from early infection, all false-reactive screening specimens, and the majority of specimens from established infection. CONCLUSIONS: Although cost, regulatory barriers, test availability, and the ability to differentiate early from established infection must be considered, this alternative algorithm can potentially decrease the total number of tests performed and reduce turnaround time, thereby streamlining HIV diagnosis and initiation of treatment.

HIV Testing in 50 Local Jurisdictions Accounting for the Majority of New HIV Diagnoses and Seven States with Disproportionate Occurrence of HIV in Rural Areas, 2016-2017.

Since 2006, CDC has recommended universal screening for human immunodeficiency virus (HIV) infection at least once in health care settings and at least annual rescreening of persons at increased risk for infection (1,2), but data from national surveys and HIV surveillance demonstrate that these recommendations have not been fully implemented (3,4). The national Ending the HIV Epidemic initiative* is intended to reduce the number of new infections by 90% from 2020 to 2030. The initiative focuses first on 50 local jurisdictions (48 counties, the District of Columbia, and San Juan, Puerto Rico) where the majority of new diagnoses of HIV infection in 2016 and 2017 were concentrated and seven states with a disproportionate occurrence of HIV in rural areas relative to other states (i.e., states with at least 75 reported HIV diagnoses in rural areas that accounted for ≥10% of all diagnoses in the state).† This initial geographic focus will be followed by wider implementation of the initiative within the United States. An important goal of the initiative is the timely identification of all persons with HIV infection as soon as possible after infection (5). CDC analyzed data from the Behavioral Risk Factor Surveillance System (BRFSS)§ to assess the percentage of adults tested for HIV in the United States nationwide (38.9%), in the 50 local jurisdictions (46.9%), and in the seven states (35.5%). Testing percentages varied widely by jurisdiction but were suboptimal and generally low in jurisdictions with low rates of diagnosis of HIV infection. To achieve national goals and end the HIV epidemic in the United States, strategies must be tailored to meet local needs. Novel screening approaches might be needed to reach segments of the population that have never been tested for HIV.

Men Who Have Sex with Men (MSM) Who Have Not Previously Tested for HIV: Results from the MSM Testing Initiative, United States (2012-2015).

The Centers for Disease Control and Prevention recommends annual HIV tests for men who have sex with men (MSM), yet some have never tested. We analyzed data from the MSM Testing Initiative. Of 68,185 HIV tests, 8% were with MSM who never previously tested ("first-time testers"). Among tests with first-time testers, 70.7% were with MSM from racial or ethnic minorities; 66.5% were with MSM younger than 30 years. Tests with MSM who reported female partners only during the past year (compared to male partners only) or were recruited for at-home testing (compared to venue-based recruitment) were 4 times (prevalence ratio [PR] 3.62, 95% CI 3.15-4.15) and 5 times as likely (PR 4.69, 95% CI 4.22-5.21) to be associated with first-time testing. At-home testing and focusing on MSM who have sex with women may be effective methods for reaching MSM who are first-time testers.

Chlamydia, Gonorrhea, and Human Immunodeficiency Virus Infection Among Transgender Women and Transgender Men Attending Clinics that Provide Sexually Transmitted Disease Services in Six US Cities: Results From the Sexually Transmitted Disease Surveillance Network.

BACKGROUND: Transgender women and transgender men are disproportionately affected by human immunodeficiency virus (HIV) infection and may be vulnerable to other sexually transmitted diseases (STDs), but the lack of surveillance data inclusive of gender identity hinders prevention and intervention strategies. METHODS: We analyzed data from 506 transgender women (1045 total visits) and 120 transgender men (209 total visits) who attended 26 publicly funded clinics that provide STD services in 6 US cities during a 3.5-year observation period. We used clinical and laboratory data to examine the proportion of transgender women and transgender men who tested positive for urogenital and extragenital chlamydial or gonococcal infections and who self-reported or tested positive for HIV infection during the observation period. RESULTS: Of the transgender women tested, 13.1% tested positive for chlamydia and 12.6% tested positive for gonorrhea at 1 or more anatomic sites, and 14.2% were HIV-infected. Of transgender men tested, 7.7% and 10.5% tested positive for chlamydia and gonorrhea at 1 or more anatomic sites, and 8.3% were HIV-infected. Most transgender women (86.0% and 80.9%, respectively) and more than a quarter of transgender men (28.6% and 28.6%, respectively) with an extragenital chlamydial or gonococcal infection had a negative urogenital test at the same visit. CONCLUSIONS: Publicly funded clinics providing STD services are likely an important source of STD care for transgender persons. More data are needed to understand the most effective screening approaches for urogenital, rectal, and pharyngeal Chlamydia trachomatis and Neisseria gonorrhoeae infections in transgender populations.

Stigmatizing Attitudes Toward People Living with HIV Among Adults and Adolescents in the United States.

Stigmatizing attitudes toward people living with HIV (PLWH) cause psychological distress for PLWH and hinder HIV prevention efforts. We estimated the prevalence of stigmatizing attitudes among 6809 adults and 885 adolescents who responded to online surveys in 2015. Fear of casual contact with PLWH was reported by 17.5% [95% confidence interval (CI) 16.3-18.6%] of adults and 31.6% (CI 27.8-35.4%) of adolescents. Among adults, 12.5% (CI 11.6-13.5%) endorsed a measure of moral judgment toward PLWH. Stigmatizing attitudes toward PLWH persist in the United States. Continued monitoring of these attitudes and efforts to reduce associated stigma are warranted.

Interval Since Last HIV Test for Men and Women with Recent Risk for HIV Infection - United States, 2006-2016.

Since 2006, CDC has recommended routine screening of all persons aged 13-64 years for human immunodeficiency virus (HIV) and at least annual rescreening of persons at higher risk (1). However, national surveillance data indicate that many persons at higher risk for HIV infection are not screened annually, and delays in diagnosis persist (2). CDC analyzed 2006-2016 data from the General Social Survey (GSS)* and estimated that only 39.6% of noninstitutionalized U.S. adults had ever tested for HIV. Among persons ever tested, the estimated median interval since last test was 1,080 days or almost 3 years. Only 62.2% of persons who reported HIV-related risk behaviors in the past 12 months were ever tested for HIV, and the median interval since last test in this group was 512 days (1.4 years). The percentage of persons ever tested and the interval since last test remained largely unchanged during 2006-2016. More frequent screening of persons with ongoing HIV risk is needed to achieve full implementation of CDC's screening recommendations and to prevent new infections. Integration of routine screening as standard clinical practice through existing strategies, such as electronic medical record prompts (3), or through new, innovative strategies might be needed to increase repeat screening of persons with ongoing risk.

HIV Testing Among Transgender Women and Men - 27 States and Guam, 2014-2015.

Transgender persons are at high risk for human immunodeficiency virus (HIV) infection; in a recent analysis of the results of over nine million CDC funded HIV tests, transgender women* had the highest percentage of confirmed positive results (2.7%) of any gender category (1). Transgender men,† particularly those who have sex with cisgender§ men, are also at high risk for infection (2). HIV testing is critical for detecting and treating persons who are infected and delivering preventive services to those who are uninfected. CDC recommends that persons at high risk for HIV infection be screened for HIV at least annually, although transgender persons are not specified in the current recommendations. CDC analyzed data from the Behavioral Risk Factor Surveillance System (BRFSS) to describe HIV testing among transgender women and men and two cisgender comparison groups in 27 states and Guam. After adjusting for demographic characteristics, transgender women and men had a lower prevalence of ever testing and past year testing for HIV (35.6% and 31.6% ever, and 10.0% and 10.2% past year, respectively) compared with cisgender gay and bisexual men (61.8% ever and 21.6% past year) and instead reported testing at levels comparable to cisgender heterosexual men and women (35.2% ever, and 8.6% past year). This finding suggests that transgender women and men might not be sufficiently reached by current HIV testing measures. Tailoring HIV testing activities to overcome the unique barriers faced by transgender women and men might increase rates of testing among these populations.

Faster entry into HIV care among HIV-infected drug users who had been in drug-use treatment programs.

OBJECTIVE: We evaluated whether being in drug use treatment improves linkage to HIV medical care for HIV-infected drug users. We assessed whether an evidence-based intervention for linkage to care ['ARTAS'] works better for HIV-infected drug users who had been in drug use treatment than those who had not. DESIGN: Randomized trial. METHODS: 295 Participants in the Antiretroviral Treatment Access Study ['ARTAS'] trial were followed for time to first HIV medical care. Drug use (injected and non-injected drugs) in the last 30days and being in drug treatment in the last 12 months were assessed by audio-CASI. We used a proportional hazards model of time to care in drug users with and without drug treatment, adjusting for barriers to care, AIDS symptoms, and demographic factors. We tested whether drug treatment modified the intervention effect by using a drug use/drug treatment*intervention interaction term. RESULTS: Ninety-nine participants (30%) reported drug use in the 30days before enrollment. Fifty-three (18%) reported being in a drug treatment program in the last 12 months. Drug users reporting methadone maintenance became engaged in care in less than half the time of drug users without a treatment history [HR 2.97 (1.20, 6.21)]. The ARTAS intervention effect was significantly larger for drug users with a treatment history compared to drug users without a treatment history (AHR 5.40, [95% CI, 2.03-14.38]). CONCLUSIONS: Having been in drug treatment programs facilitated earlier entry into care among drug users diagnosed with HIV infection, and improved their response to the ARTAS linkage intervention.

Hepatitis B virus (HBV) infection, immunity and susceptibility among men who have sex with men (MSM), Los Angeles County, USA.

Men who have sex with men (MSM) bear a disproportionate burden of hepatitis B virus (HBV) infections. We used serologic data from the National HIV Behavioral Surveillance (NHBS) system to determine the prevalence and correlates of HBV infection, immunization, and susceptibility in a sample of Los Angeles County MSM. Approximately 19 % (95 % CI 15-24 %) had serologic evidence of current or past infection, while 35 % (95 % CI 30-40 %) were susceptible. Compared with the youngest age group, MSM ages 40-49 years had a lower prevalence of immunization (aPR 0.28, 95 % CI 0.17-0.45) and a higher prevalence of infection (aPR 8.53, 95 % CI 3.95-18.4) and susceptibility (aPR 2.02, 95 % CI 1.13-3.63). We also observed poor concordance between self-reported and serologic measures of vaccination. Our results indicate the possibility of missed opportunities to vaccinate MSM. Gaps in implementing existing vaccination strategies must be addressed to increase hepatitis B vaccination coverage for MSM, especially in older age groups.

Eradication of hepatitis C virus infection and the development of hepatocellular carcinoma: a meta-analysis of observational studies.

BACKGROUND: Hepatitis C virus (HCV) is a leading cause of hepatocellular carcinoma (HCC). In the United States, this form of cancer occurs in approximately 15 000 persons annually. A systematic review of the evidence is needed to assess the benefits of treatment of HCV-infected persons on development of HCC. PURPOSE: To systematically review observational studies to determine the association between response to HCV therapy and development of HCC among persons at any stage of fibrosis and those with advanced liver disease. DATA SOURCES: MEDLINE, EMBASE, CINAHL, the Cochrane Library, Web of Science, and the Database of Abstracts of Reviews and Effectiveness from inception through February 2012. STUDY SELECTION: English-language observational studies that compared therapy-derived sustained virologic response (SVR) with no response to therapy among HCV-infected persons, targeted an adult population, and had an average follow-up of at least 2 years. DATA EXTRACTION: Two investigators independently extracted data into uniform relative risk measures. The Grading of Recommendations Assessment, Development and Evaluation framework was used to determine the quality of the evidence. DATA SYNTHESIS: Thirty studies fulfilled the inclusion criteria, and 18 provided adjusted effect estimates that were used to calculate pooled relative risks. Among HCV-infected persons, SVR was associated with reduced risk for HCC (relative risk for all persons, 0.24 [95% CI, 0.18 to 0.31], moderate-quality evidence; advanced liver disease hazard ratio, 0.23 [CI, 0.16 to 0.35], moderate-quality evidence). LIMITATION: In the meta-analyses, some variables could not be controlled for because of the observational design of the included studies. CONCLUSION: Sustained virologic response after treatment among HCV-infected persons at any stage of fibrosis is associated with reduced HCC. The evidence was determined to be of moderate quality.