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Hepatitis B vaccination is the most effective measure to prevent hepatitis B virus (HBV) infection and its consequences, including cirrhosis of the liver, liver cancer, liver failure, and death. In adults, ongoing HBV transmission occurs primarily among unvaccinated persons with behavioral risks for HBV transmission (e.g., heterosexuals with multiple sex partners, injection-drug users [IDUs], and men who have sex with men [MSM]) and among household contacts and sex partners of persons with chronic HBV infection.This report, the second of a two-part statement from the Advisory Committee on Immunization Practices (ACIP), provides updated recommendations to increase hepatitis B vaccination of adults at risk for HBV infection. The first part of the ACIP statement, which provided recommendations for immunization of infants, children, and adolescents, was published previously (CDC. A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immunization Practices [ACIP]. Part 1: immunization of infants, children, and adolescents. MMWR 2005;54[No. RR-16]:1--33).In settings in which a high proportion of adults have risks for HBV infection (e.g., sexually transmitted disease/human immunodeficiency virus testing and treatment facilities, drug-abuse treatment and prevention settings, health-care settings targeting services to IDUs, health-care settings targeting services to MSM, and correctional facilities), ACIP recommends universal hepatitis B vaccination for all unvaccinated adults. In other primary care and specialty medical settings in which adults at risk for HBV infection receive care, health-care providers should inform all patients about the health benefits of vaccination, including risks for HBV infection and persons for whom vaccination is recommended, and vaccinate adults who report risks for HBV infection and any adults requesting protection from HBV infection. To promote vaccination in all settings, health-care providers should implement standing orders to identify adults recommended for hepatitis B vaccination and administer vaccination as part of routine clinical services, not require acknowledgment of an HBV infection risk factor for adults to receive vaccine, and use available reimbursement mechanisms to remove financial barriers to hepatitis B vaccination. [ABSTRACT FROM AUTHOR]

These recommendations for human immunodeficiency virus (HIV) testing are intended for all health-care providers in the public and private sectors, including those working in hospital emergency departments, urgent care clinics, inpatient services, substance abuse treatment clinics, public health clinics, community clinics, correctional health-care facilities, and primary care settings. The recommendations address HIV testing in health-care settings only. They do not modify existing guidelines concerning HIV counseling, testing, and referral for persons at high risk for HIV who seek or receive HIV testing in nonclinical settings (e.g., community-based organizations, outreach settings, or mobile vans). The objectives of these recommendations are to increase HIV screening of patients, including pregnant women, in health-care settings; foster earlier detection of HIV infection; identify and counsel persons with unrecognized HIV infection and link them to clinical and prevention services; and further reduce perinatal transmission of HIV in the United States. These revised recommendations update previous recommendations for HIV testing in health-care settings and for screening of pregnant women (CDC. Recommendations for HIV testing services for inpatients and outpatients in acute-care hospital settings. MMWR 1993;42[No. RR-2]:1--10; CDC. Revised guidelines for HIV counseling, testing, and referral. MMWR 2001;50[No. RR-19]:1--62; and CDC. Revised recommendations for HIV screening of pregnant women. MMWR 2001;50[No. RR-19]:63--85).Major revisions from previously published guidelines are as follows:For patients in all health-care settingsHIV screening is recommended for patients in all health-care settings after the patient is notified that testing will be performed unless the patient declines (opt-out screening).Persons at high risk for HIV infection should be screened for HIV at least annually.Separate written consent for HIV testing should not be required; general consent for medical care should be considered sufficient to encompass consent for HIV testing.Prevention counseling should not be required with HIV diagnostic testing or as part of HIV screening programs in health-care settings.For pregnant womenHIV screening should be included in the routine panel of prenatal screening tests for all pregnant women.HIV screening is recommended after the patient is notified that testing will be performed unless the patient declines (opt-out screening).Separate written consent for HIV testing should not be required; general consent for medical care should be considered sufficient to encompass consent for HIV testing.Repeat screening in the third trimester is recommended in certain jurisdictions with elevated rates of HIV infection among pregnant women. [ABSTRACT FROM AUTHOR]

Reducing new HIV infections in the United States requires allocating public resources to interventions that will have the greatest impact on reducing the number of new infections. We report on the organizational experience of a federal agency's efforts to align its HIV prevention resources to reflect the specific priorities of a five-year strategic plan that has as its goal a fifty percent reduction in the number of annual HIV infections nationwide. Structural and other impediments encountered during the alignment process, and the steps taken to minimize their impact are described, adding to the empirical data base of strategic planning experiences in the public sector. [ABSTRACT FROM AUTHOR]

Risk behavior information is essential for allocating resources and developing effective HIV prevention strategies. Over time, transmission risk information on HIV/AIDS cases has been less likely to be reported to the national surveillance system. The Centers for Disease Control and Prevention (CDC) invited approximately 30 experts in HIV/AIDS and behavioral research from state and local health departments, academia, community-based organizations, and the CDC to participate in a consultation in December 2001 to generate ideas on how best to deal with the lack of risk data. The group was charged with providing recommendations on methods for classifying and reporting risk information and for identifying methods and sources for improving ascertainment of transmission risk behaviors for individuals infected with HIV. This report describes the recommendations and the effects of implementing such recommended procedures on the national HIV/AIDS surveillance database. [ABSTRACT FROM AUTHOR]

In the United States, HIV prevention programs have historically tailored activities for specific groups primarily on the basis of behavioral risk factors and demographic characteristics. Through the Serostatus Approach to Fighting the Epidemic (SAFE), the Centers for Disease Control and Prevention is now expanding prevention programs, especially for individuals with HIV, to reduce the risk of transmission as a supplement to current programs that primarily focus on reducing the risk of acquisition of the virus. For individuals with HIV, SAFE comprises action steps that focus on diagnosing all HIV-infected persons, linking them to appropriate high-quality care and prevention services, helping them adhere to treatment regimens, and supporting them in adopting and sustaining HIV risk reduction behavior. SAFE couple a traditional infectious disease control focus on the infected person with behavioral interventions that have been standard for HIV prevention programs. [ABSTRACT FROM AUTHOR]

OBJECTIVES: This study investigated hepatitis B immunization coverage and the extent of hepatitis B virus (HBV) infection among young men who have sex with men (MSM), a group for whom hepatitis B vaccine has been recommended since 1982. METHODS: We analyzed data from 3432 MSM, aged 15 to 22 years, randomly sampled at 194 gay-identified venues in 7 US metropolitan areas from 1994 through 1998. Participants were interviewed, counseled, and tested for serologic markers of HBV infection. RESULTS: Immunization coverage was 9% and the prevalence of markers of HBV infection was 11%. HBV infection ranged from 2% among 15-year-olds to 17% among 22-year-olds. Among participants susceptible to HBV infection, 96% used a regular source of health care or accessed the health care system for HIV or sexually transmitted disease testing. CONCLUSIONS: Despite the availability of an effective vaccine for nearly 2 decades, our findings suggest that few adolescent and young adult MSM in the United States are vaccinated against hepatitis B. Health care providers should intensify their efforts to identify and vaccinate young MSM who are susceptible to HBV. [ABSTRACT FROM AUTHOR]

Context: Studies conducted in the late 1980s on human immunodeficiency virus (HIV) infection among older men who have sex with men (MSM) suggested the epidemic had peaked; however, more recent studies in younger MSM have suggested continued high HIV incidence.Objective: To investigate the current state of the HIV epidemic among adolescent and young adult MSM in the United States by assessing the prevalence of HIV infection and associated risks in this population in metropolitan areas.Design: The Young Men's Survey, a cross-sectional, multisite, venue-based survey conducted from 1994 through 1998.Setting: One hundred ninety-four public venues frequented by young MSM in Baltimore, Md; Dallas, Tex; Los Angeles, Calif; Miami, Fla; New York, NY; the San Francisco (Calif) Bay Area; and Seattle, Wash.Subjects: A total of 3492 15- to 22-year-old MSM who consented to an interview and HIV testing.Main Outcome Measures: Prevalence of HIV infection and associated characteristics and risk behaviors.Results: Prevalence of HIV infection was high (overall, 7.2%; range for the 7 areas, 2.2%-12. 1%) and increased with age, from 0% among 15-year-olds to 9.7% among 22-year-olds. Multivariate-adjusted HIV infection prevalence was higher among blacks (odds ratio [OR], 6.3; 95% confidence interval [CI], 4.1-9.8), young men of mixed or other race (OR, 4.8; 95% CI, 3. 0-7.6), and Hispanics (OR, 2.3; 95% CI, 1.5-3.4), compared with whites (referent) and Asian Americans and Pacific Islanders (OR, 1. 1; 95% CI, 0.5-2.8). Factors most strongly associated with HIV infection were being black, mixed, or other race; having ever had anal sex with a man (OR, 5.0; 95% CI, 1.8-13.8); or having had sex with 20 or more men (OR, 3.0; 95% CI, 2.0-4.7). Only 46 (18%) of the 249 HIV-positive men knew they were infected before this testing; 37 (15%) were receiving medical care for HIV, and 19 (8%) were receiving medical drug therapy for HIV. Prevalence of unprotected anal sex during the past 6 months was high (overall, 41%; range, 33%-49%).Conclusions: Among these young MSM, HIV prevalence was high, underscoring the need to evaluate and intensify prevention efforts for young MSM, particularly blacks, men of mixed race or ethnicity, Hispanics, and adolescents. JAMA. 2000;284:198-204 [ABSTRACT FROM AUTHOR]

CDC recommends that all states and territories conduct case surveillance for human immunodeficiency virus (HIV) infection as an extension of current acquired immunodeficiency syndrome (AIDS) surveillance activities. The expansion of national surveillance to include both HIV infection and AIDS cases is a necessary response to the impact of advances in antiretroviral therapy, the implementation of new HIV treatment guidelines, and the increased need for epidemiologic data regarding persons at all stages of HIV disease. Expanded surveillance will provide additional data about HIV-infected populations to enhance local, state, and federal efforts to prevent HIV transmission, improve allocation of resources for treatment services, and assist in evaluating the impact of public health interventions. CDC will provide technical assistance to all state and territorial health departments to continue or establish HIV and AIDS case surveillance systems and to evaluate the performance of their surveillance programs. This report includes a revised case definition for HIV infection in adults and children, recommended program practices, and performance and security standards for conducting HIV/AIDS surveillance by local, state, and territorial health departments. The revised surveillance case definition and associated recommendations become effective January 1, 2000. [ABSTRACT FROM AUTHOR]

Objective: To estimate the prevalence of human immunodeficiency virus (HIV) infection and risk behaviors among young homosexual and bisexual men sampled from public venues in San Francisco and Berkeley, Calif.Design: A survey of 425 young homosexual and bisexual men sampled from 26 locations during 1992 and 1993. Participants were interviewed and blood specimens were drawn and tested for HIV, level of CD4+ T lymphocytes, and markers of hepatitis B and syphilis.Setting: Public venues in San Francisco and Berkeley, including street corners and sidewalks, dance clubs, bars, and parks.Population Studied: Homosexual and bisexual men aged 17 to 22 years.Main Outcome Measures: Prevalence of HIV infection and risk behaviors.Results: The HIV seroprevalence was 9.4% (95% confidence interval, 6.8% to 12.6%). The prevalence of markers for hepatitis B was 19.8% (95% confidence interval, 16.1% to 23.9%), and that for syphilis was 1.0% (95% confidence interval, 0.3% to 2.4%). The HIV seroprevalence was significantly higher among African Americans (21.2%) than among other racial/ethnic groups (P = .002). Approximately one third (32.7%) of the participants reported unprotected anal intercourse, and 11.8% reported injecting drug use in the previous 6 months. At the time of interview, 70.0% of the HIV-infected men did not know that they were HIV seropositive, and only 22.5% were receiving medical care for HIV infection.Conclusions: The prevalence of HIV infection is high among this young population of homosexual and bisexual men, particularly among young African-American men. The high rates of HIV-related risk behaviors suggest a considerable risk for HIV transmission in this population. Prevention programs and health services need to be tailored to address the needs of a new generation of homosexual and bisexual men. [ABSTRACT FROM AUTHOR]

The article reports on the changes to HIV/AIDS prevention programs in the United States from 1981-2006. The Centers for Disease Control and Prevention support a range of prevention activities, including data collection on HIV/AIDS patients and risk behaviors, education programs, improving prevention programs, program evaluation and research. The prevention efforts have taken a three-pronged approach: prevention activities directed at high risk populations, HIV counseling and testing services, and prevention and health protection activities for those living with HIV/AIDS.

This phase 1 trial assessed the safety and immunogenicity of an investigational tetanus/diphtheria/acellular pertussis vaccine combined with CpG 1018 adjuvant 1500 μg (Tdap-1018 1500 μg) or 3000 μg (Tdap-1018 3000 μg) in adults and adolescents. In this randomized, active-controlled, multicenter, dose-escalation trial, healthy participants aged 10 to 22 years received 1 dose of Tdap-1018 1500 μg, Tdap-1018 3000 μg, or Boostrix. Geometric mean concentrations (GMCs) and booster response rates (BRRs) for antibodies against pertussis (pertussis toxin, filamentous hemagglutinin, pertactin), tetanus, and diphtheria antigens, and neutralizing antibodies against pertussis toxin were assessed 4 weeks after vaccination. Safety and tolerability were assessed for solicited post-injection reactions within 7 days after vaccination and unsolicited adverse events up to 12 weeks after vaccination. Of 117 enrolled participants, 80 adults (92%) and 30 adolescents (100%) completed the study. Both Tdap-1018 formulations were generally well tolerated, with no vaccine-related serious adverse events. Frequency and severity in post-injection reactions after Tdap-1018 administration were similar to Boostrix except for higher proportions of moderate pain for Tdap-1018. In adults at week 4, ratio of GMCs and BRRs for all antigens in the 3000-μg group were similar to or higher than Boostrix, with significantly higher GMC ratios for anti-pertussis toxin (2.1 [1.5-3.0]) and anti-tetanus (1.8 [1.1-2.9]) and significantly higher BRRs for anti-pertussis toxin (difference [95% CI]: 34.5% [13.4-54.6]), anti-pertactin (19.2% [4.4-38.1]), and anti-tetanus (30.0% [3.6-52.7]) antibodies. For adolescents, in the 3000-μg group, ratio of GMCs and BRRs were similar to or higher than Boostrix for all antigens. Both Tdap-1018 formulations showed acceptable safety and tolerability profiles. Tdap-1018 3000 μg induced similar or higher immune responses than Boostrix. ACTRN12620001177943 (Australian New Zealand Clinical Trials Registry; https://anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=ACTRN12620001177943p)., Competing Interests: Declaration of competing interest F.X. and O.G. are consultants for Dynavax Technologies Corporation. J.D.C., O.H., and R.S.J. are employees of Dynavax Technologies Corporation and may hold company stock. P.R. has served on pertussis vaccine scientific advisory boards on behalf of his institution for GlaxoSmithKline and Sanofi outside the submitted work. T.N. has served on vaccine scientific advisory boards for GSK, Sanofi, Pfizer, CSL Seqirus, MSD, Moderna, and AstraZeneca, and on clinical trial data and safety monitoring boards for GSK, CSL Seqirus, Statens Serum Institute, SK Bioscience Korea, Zeria Pharmaceuticals, Clover, Novavax, Serum Institute of India, and Moderna. A.M., F.N-F., J.K., A.L., and N.W. report no potential conflicts., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Hepatitis B virus (HBV) infection remains a significant global burden, especially for patients with chronic kidney disease (CKD) receiving hemodialysis. Three doses of HepB-CpG (HEPLISAV-B® vaccine) induced a superior immune response compared with 4 double doses of HepB-Eng (Engerix-B®) in a phase 3 trial (HBV-17) in adults with CKD. Here we report the long-term immunogenicity and safety of HepB-CpG and HepB-Eng in eligible participants of HBV-17 who enrolled in this optional 34-month follow-up trial (HBV-19)., Methods: HBV-19 is a multicenter, open-label, phase 3b trial of adults with CKD who previously received a complete series of HepB-CpG or HepB-Eng in the HBV-17 trial. Participants were assigned to seroprotection categories at enrollment on the basis of their antibody response to hepatitis B surface antigen (anti-HBs) in HBV-17. The objective was to evaluate the durability of seroprotection (defined as an anti-HBs concentration ≥ 10mIU/mL) induced by HepB-CpG and HepB-Eng. Participants whose anti-HBs concentration was below 10mIU/mL received additional HepB-CpG or HepB-Eng doses., Results: 147 participants were enrolled; 66.7 % were men, median age was 65.0 years, and 83.7 % were white. The durability of seroprotection in participants with CKD was similar in those who received HepB-CpG and those who received HepB-Eng. Antibody concentrations ≥ 100mIU/mL persisted for longer in HepB-CpG than HepB-Eng recipients, among those with anti-HBs ≥ 100mIU/mL post vaccination. The geometric mean anti-HBs concentration in the HepB-CpG group was significantly higher than in the HepB-Eng group over time (P ≤ 0.0001). The safety profiles were similar between the vaccine groups., Conclusions: Due to the higher antibody levels induced by HepB-CpG in participants with CKD, seroprotection against HBV may be expected to persist longer than that induced by HepB-Eng., Clinicaltrials: gov: NCT01282762., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: M.G. received speaker's honoraria from Astellas, Daiichi Sankyo, Novartis, Sanofi, Vifor, and GlaxoSmithKline unrelated to the topic of this work. F.X. is a consultant for and R.S.J. is an employee of Dynavax Technologies Corporation. No other conflicts were reported., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

This study compared the immunogenicity and safety of a booster dose of HepB-CpG (HEPLISAV-B® vaccine) with HepB-Eng (Engerix-B®) and HepB-AS04 (Fendrix®) in patients receiving chronic hemodialysis. This was a multicenter, randomized, open-label, phase 3 study of adults receiving hemodialysis with antibodies to HBsAg (anti-HBs) <10 mIU/mL at study entry. The objective was to compare the seroprotection rate (SPR) induced by HepB-CpG with HepB-Eng or HepB-AS04. The SPR was defined as the percentage of patients with anti-HBs ≥10 mIU/mL post-vaccination. At 20 sites in Germany, 155 participants were randomized: HepB-CpG = 54; HepB-Eng = 50; and HepB-AS04 = 51. Of the 149 participants in the modified intention-to-treat population, 76.5% had not previously responded to at least one series of hepatitis B vaccine. Based on a post hoc analysis, the SPR in HepB-CpG recipients (52.8%; 95% confidence interval [CI]: 38.6%, 66.7%) was significantly higher than in HepB-Eng recipients (32.6%; 95% CI: 19.5%, 48.0%), and non-inferior to that in HepB-AS04 recipients (43.1%; 95% CI: 29.3%, 57.8%). Local post-injection reactions occurred in significantly fewer HepB-CpG (9.3%) than HepB-AS04 recipients (31.4%; p = .007) and at a similar rate to HepB-Eng recipients (8.2%). Systemic post-injection reactions in HepB-CpG recipients (18.5%) were similar to the HepB-AS04 group (19.6%) and higher than in the HepB-Eng group (12.2%). In this difficult-to-immunize population, a booster dose of HepB-CpG induced significantly higher levels of seroprotection than HepB-Eng with a similar safety profile. The higher levels of immunogenicity were not accompanied by higher levels of local post-injection reactions compared with HepB-AS04.

Background: In the absence of field efficacy studies, estimating the real-world effectiveness of vaccines may consider immunogenicity from randomized controlled clinical trials and real-world adherence. Combining seroprotection rates (SPRs) with regimen completion rates gives an estimate of an effective vaccine protection rate (eVPR), which can be leveraged to evaluate real-world cost-effectiveness by linking it with vaccine costs to estimate the cost-per-protected patient (CPP)., Methods: This study evaluated eVPR and CPP as estimates of vaccine clinical- and cost-effectiveness of two-dose (HepB-CpG) and three-dose (HepB-Alum) hepatitis B virus (HBV) vaccines in the general adult population and a subpopulation with diabetes mellitus. eVPR was calculated from head-to-head SPR data from phase 3 clinical trials directly comparing HepB-CpG and HepB-Alum vaccine regimens and real-world head-to-head adherence data. CPP was calculated as the average cost of each regimen divided by eVPR., Results: Higher eVPR in the adult population was achieved with HepB-CpG (68.0%) versus HepB-Alum (41.6%), reflecting the combination of higher SPR and vaccine regimen completion. The CPP for HepB-CpG ($331.31) was $45.67 (95% CI: $36.66, $55.19) less than HepB-Alum ($377.09). Greater savings were observed among persons with diabetes, with CPP $149.60 (95% CI: $80.29, $195.63) lower with HepB-CpG ($367.57) than HepB-Alum ($517.37)., Conclusions: Metrics estimating vaccine real-world effectiveness and value may guide informed decisions in vaccine selection. For example, using eVPR and CPP, HepB-CpG represents a more effective, value-advantaged approach than HepB-Alum toward reducing HBV infection., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [RJ and CD are current employees and RH is a former employee of Dynavax Technologies. KB has received research funding from Dynavax Technologies during the conduct of the study and has received research funding from GlaxoSmithKline, Seqirus, Pfizer, and Gilead outside the submitted work. JS has received research funding from Dynavax Technologies during the conduct of the study, and has received research funding from GlaxoSmithKline and Novavax outside the submitted work. SJJ has received research funding from Dynavax Technologies. GAP is the chair of a Safety Evaluation Committee for novel investigational vaccine trials being conducted by Merck Research Laboratories; offers consultative advice on vaccine development to Merck & Co, Medicago, GlaxoSmithKline, Sanofi Pasteur, Emergent Biosolutions, Dynavax Technologies, Genentech, Eli Lilly and Company, Janssen Global Services LLC, Kentucky Bioprocessing, AstraZeneca, and Genevant Sciences, Inc; holds patents related to vaccinia and measles peptide vaccines; and has received grant funding from ICW Ventures for preclinical studies on a peptide-based COVID-19 vaccine; these activities have been reviewed by the Mayo Clinic Conflict of Interest Review Board and are conducted in compliance with Mayo Clinic Conflict of Interest policies.]., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The hepatitis B virus is highly infectious and can cause incurable liver disease, leading to high morbidity rates, increased healthcare utilization, and high mortality. Multiple preventative hepatitis B vaccine options have been available for decades, but adherence to the traditional 6-month vaccine schedule for the approved 3-dose series remains low in adult populations at risk of hepatitis B exposure. A 2-dose hepatitis B vaccine (HEPLISAV-B) approved by the US Food and Drug Administration in 2017 induces rapid seroprotection within 1 month and has a safety profile comparable to a commonly used 3-dose vaccine. In a previous cost-effectiveness study, HEPLISAV-B had a favorable cost-effectiveness profile for multiple at-risk populations. The goal of the current analysis was to update and extend previous findings by evaluating cost-effectiveness of HEPLISAV-B compared with a 3-dose vaccine (Engerix-B) in selected adult populations, including patients with diabetes, chronic liver or kidney disease, end-stage renal disease, healthcare personnel, travelers to countries with endemic hepatitis B, and a public health population. Cost-effectiveness was measured as incremental cost-effectiveness ratios using a health economics Markov model that accounts for adherence rates, seroprotection rates, healthcare costs, and current pricing considerations. Patients progressed between a series of health states, and the difference in lifetime spending and survival for individuals receiving either HEPLISAV-B or Engerix-B was estimated from the perspective of a US managed care payer, HEPLISAV-B had favorable cost-effectiveness profiles for patients with diabetes, healthcare personnel, travelers, and patients with chronic liver disease and dominant incremental cost-effectiveness ratios for patients with chronic kidney disease and end-stage renal disease. A probabilistic sensitivity analysis supported the robustness of the cost-effectiveness profiles, and an additional analysis indicated that HEPLISAV-B was cost-effective in the general adult population. Overall, HEPLISAV-B was cost-effective in multiple adult populations recommended for HBV vaccination in the United States., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [AH is a former employee of ICON plc, which received funding from Dynavax Technologies Corporation to conduct health economics modeling; RNH is a former employee and RSJ is an employee of Dynavax Technologies Corporation.]., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Hemodialysis patients are at increased risk of hepatitis B virus (HBV) infection and are poorly responsive to HBV vaccines. Current vaccine recommendations for hemodialysis patients utilize more than twice the amount of hepatitis B surface antigen (HBsAg) used for healthy adults and achieve lower immune responses., Methods: An open-label, single-arm, multicenter trial was conducted among adults 18 years of age and older who were initiating or undergoing hemodialysis who had not previously received hepatitis B vaccine. Participants received four doses of HepB-CpG (HEPLISAV-B®) (20 mcg rHBsAg + 3000 mcg CpG 1018, a Toll-like receptor 9 agonist) administered at 0, 4, 8, and 16 weeks. Participants are being followed for 68 weeks. This paper reports the final immunogenicity analysis of the primary endpoint at study week 20 and an interim safety analysis., Results: We enrolled 119 participants receiving hemodialysis who were followed for a median of 47.4 weeks. Of the 119 participants, 75 were in the per-protocol population. At week 20, the seroprotection rate (% with antibodies to hepatitis B surface antigen [anti-HBs] ≥ 10 mIU/mL) was 89.3% and the percentage of participants with anti-HBs ≥ 100 mIU/mL was 81.3%. The anti-HBs geometric mean concentration was 1061.8 mIU/mL. HepB-CpG was well tolerated with no observed safety concerns., Conclusion: In patients receiving hemodialysis, HepB-CpG given as four doses was well tolerated and induced very high anti-HBs concentrations and seroprotection in a very high proportion of recipients., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Randall Hyer, Fang Xie, Kimberly Erby, and Robert Janssen were employed by Dynavax Technologies Corporation at the time of study conduct. No other author reported competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Hepatitis B virus (HBV) remains a major public health issue, although it is a vaccine-preventable disease. Adults with diabetes are at greater risk of contracting HBV than the general population. Commonly used 3-dose HBV vaccines have reduced immunogenicity in older individuals and in those with diabetes mellitus., Methods: In this post hoc analysis of a phase 3 clinical trial, participants with type 2 diabetes mellitus aged 60-70 years received either 2-dose HBsAg/CpG 1018 (HEPLISAV-B®, n = 327) at 0 and 4 weeks and placebo at 24 weeks or 3-dose HBsAg/alum (Engerix-B®, n = 153) at 0, 4, and 24 weeks. Immunogenicity, including seroprotection rate (SPR) at week 28, and safety were assessed by subgroup (sex, body mass index, and smoking status). SPR was defined as antibody against hepatitis B surface antigen serum concentration ≥10 mIU/mL., Results: The SPR at week 28 was significantly higher with HBsAg/CpG 1018 (85.8% [235/274]) than with HBsAg/alum (58.5% [76/130]) in the per-protocol analysis, for an overall difference of 27.3% (95% CI, 18.0-36.8). SPRs with HBsAg/CpG 1018 were consistently markedly higher compared with HBsAg/alum, regardless of sex, body mass index, or smoking status. Adverse events and deaths were comparable between groups., Conclusions: Two-dose HBsAg/CpG 1018 provides a higher level of seroprotection against HBV than does a 3-dose vaccine (HBsAg/alum) with a similar safety profile in patients aged 60-70 years with type 2 diabetes mellitus. Study identifier: NCT02117934., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

PD-1 inhibitors are approved for treating advanced melanoma, but resistance has been observed. This phase Ib trial evaluated intratumoral SD-101, a synthetic CpG oligonucleotide that stimulates Toll-like receptor 9 (TLR9), in combination with pembrolizumab in patients with unresectable or metastatic malignant melanoma. The most common adverse events related to SD-101 were injection-site reactions and transient, mild-to-moderate "flu-like" symptoms. Among the 9 patients naïve to anti-PD-1 therapy, the overall response rate (ORR) was 78%. The estimated 12-month progression-free survival rate was 88%, and the overall survival rate was 89%. Among 13 patients having prior anti-PD-1 therapy, the ORR was 15%. RNA profiling of tumor biopsies demonstrated increased CD8 + T cells, natural killer cells, cytotoxic cells, dendritic cells, and B cells. The combination of intratumoral SD-101 and pembrolizumab was well tolerated and induced broad immune activation in the tumor microenvironment with durable tumor responses in both peripheral and visceral lesions. Significance: These early data demonstrate that the combination of pembrolizumab with intratumoral SD-101 is well tolerated and can induce immune activation at the tumor site. Combining an intratumoral TLR9 innate immune stimulant with PD-1 blockade can potentially increase clinical efficacy with minimal additional toxicity relative to PD-1 blockade alone. Cancer Discov; 8(10); 1250-7. ©2018 AACR. This article is highlighted in the In This Issue feature, p. 1195 ., (©2018 American Association for Cancer Research.)

Background: Hepatitis B virus infection remains an important public health problem in the United States. Currently approved alum-adjuvanted vaccines require three doses and have reduced immunogenicity in adults, particularly in those who have diabetes mellitus, or are older, male, obese, or who smoke., Methods: Phase 3 observer-blinded, randomized (2:1 HBsAg-1018 [HEPLISAV-B™]:HBsAg-Eng [Engerix-B®]), active-controlled trial in adults 18-70 years of age. HBsAg-1018 was administered intramuscularly at weeks 0 and 4 and placebo at week 24 and HBsAg-Eng at weeks 0, 4, and 24. The primary immunogenicity endpoint assessed the noninferiority of the seroprotection rate at week 28 in participants with type 2 diabetes mellitus. Secondary endpoints included seroprotection rates in the total trial population and by age, sex, body mass index, and smoking status., Results: Among 8374 participants randomized, 961 participants in the per-protocol population had type 2 diabetes mellitus. In diabetes participants, the seroprotection rate in the HBsAg-1018 group at week 28 was 90.0%, compared with 65.1% in the HBsAg-Eng group, with a difference of 24.9% (95% CI: 19.3%, 30.7%), which met the prospectively-defined criteria for noninferiority and statistical significance. In the total study per-protocol population (N = 6826) and each pre-specified subpopulation, the seroprotection rate in the HBsAg-1018 group was statistically significantly higher than in the HBsAg-Eng group., Conclusion: Two doses of HBsAg-1018, administered over 4 weeks, induced significantly higher seroprotection rates than three doses of HBsAg-Eng, given over 24 weeks, in adults with factors known to reduce the immune response to hepatitis B vaccines as well as in those without those factors. With fewer doses in a shorter time, and greater immunogenicity, HBsAg-1018 has the potential to significantly improve protection against hepatitis B in adults at risk for hepatitis B infection. Trial Registration clinicaltrials.gov Identifier: NCT02117934., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Immunologic response to a complete vaccine regimen of currently licensed alum-adjuvanted hepatitis B vaccines is reduced in several subpopulations, including older adults, men, obese persons, and smokers. Two phase 3 trials in healthy adults demonstrated that 2 doses over 1 month of an investigational hepatitis B vaccine (HBsAg-1018) induced superior seroprotection rates (SPRs) to 3 doses over 6 months of the licensed vaccine Engerix-B (HBsAg-Eng)., Methods: An exploratory analysis of immunogenicity was conducted in subpopulations from pooled data for the 2 phase 3 trials., Results: In each subpopulation, the peak SPR in the HBsAg-1018 group was statistically significantly higher than the peak SPR in the HBsAg-Eng group. Peak HBsAg-1018 SPRs ranged from 91.6% to 99.7%, while peak HBsAg-Eng SPRs ranged from 67.7% to 92.9%., Conclusion: In these exploratory analyses, 2 doses of HBsAg-1018 induced statistically significantly higher rates of seroprotection than 3 doses of HBsAg-Eng across all subpopulations., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Many patients with chronic kidney disease (CKD) are hyporesponsive to currently licensed alum-adjuvanted hepatitis B vaccines, including Engerix-B(®) (HBsAg-Eng). Seroprotection rates (SPRs) are further reduced in CKD patients with diabetes mellitus. Three doses of an investigational hepatitis B vaccine (HBsAg-1018) that uses a Toll-like receptor 9 agonist demonstrated superior SPRs to 4 double doses of HBsAg-Eng in a large phase 3 trial of CKD patients., Methods: A prespecified subgroup analysis of immunogenicity was conducted in CKD participants with type 2 diabetes in the phase 3 trial., Results: In 328 participants, the peak SPR in the HBsAg-1018 group met criteria for noninferiority and superiority to the peak SPR in the HBsAg-Eng group. The peak geometric mean concentration of antibody against hepatitis B surface antigen in the HBsAg-1018 group was statistically significantly higher than in the HBsAg-Eng group., Conclusion: HBsAg-1018 induced significantly higher seroprotection than HBsAg-Eng in CKD patients with diabetes., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Hemodialysis patients are at increased risk of hepatitis B virus (HBV) infection and patients with chronic kidney disease (CKD) are commonly hyporesponsive to HBV vaccines. Current recommendations for CKD patients are to utilize 4 double-doses (2×20 mcg HBsAg) of a licensed hepatitis B vaccine (HBsAg-Eng)., Methods: An observer-blind, randomized, active-controlled, parallel group, multicenter trial was conducted among 521 patients 18-75 years of age with CKD, comparing 3 single doses of an investigational hepatitis B vaccine (20 mcg rHBsAg+3000 mcg 1018, a toll-like receptor 9 agonist) given at 0, 4, and 24 weeks to 4 double-doses of HBsAg-Eng (2×20 mcg rHBsAg+500 mcg alum) given at 0, 4, 8, and 24 weeks (total of 8 injections). Participants were followed for 1 year., Results: Among 467 participants in the modified intent-to-treat population, at the primary endpoint at week 28, the seroprotection rate (SPR: % with anti-HBs≥10mIU/mL) in the HBsAg-1018 group (89.9%) met criteria for noninferiority and superiority to the SPR in the HBsAg-Eng group (81.8%). At week 28, the percentage of participants with anti-HBs≥100mIU/mL in the HBsAg-1018 group (73.6%) was significantly higher than in the HBsAg-Eng group (63.2%). In addition, the geometric mean concentration of anti-HBs in the HBsAg-1018 group (587.1mIU/mL) was significantly higher than in the HBsAg-Eng group (156.5mIU/mL). At weeks 8 and 12 after the first study injection, SPRs in the HBsAg-1018 group were significantly higher than in the HBsAg-Eng group. At 52 weeks, the immune response to HBsAg-1018 remained higher than to HBsAg-Eng. HBsAg-1018 was generally well tolerated and had a similar safety profile to HBsAg-Eng., Conclusion: In CKD patients, 3 doses of HBsAg-1018 induced significantly higher seroprotection, earlier seroprotection, and more durable seroprotection than 4 double doses of HBsAg-Eng., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: The currently licensed hepatitis B vaccines have limitations including hyporesponsiveness in older adults, poor compliance, and the extended time for most persons to develop seroprotection (e.g. >6months). A vaccine containing HBsAg combined with a Toll-like receptor 9 agonist adjuvant (HBsAg-1018) has been developed to overcome these limitations., Methods: A Phase 3, multicenter, randomized, subject- and observer-blinded, active-controlled trial was conducted among healthy subjects 40-70years of age comparing the immunogenicity and safety of two doses of HBsAg-1018 at 0 and 4weeks to three doses of licensed hepatitis B vaccine, HBsAg-Eng, at 0, 4, and 24weeks. The primary immunogenicity endpoint was noninferiority of the seroprotection rate (SPR; % with anti-HBs≥10mIU/mL) of HBsAg-1018 compared to the SPR of HBsAg-Eng at 8 weeks following the last dose of vaccine. Conditional upon meeting noninferiority, superiority of HBsAg-1018 over HBsAg-Eng was assessed. Safety was compared between the two vaccines., Results: At the primary endpoint, the SPR for the HBsAg-1018 group (90.0%) was superior to the SPR for the HBsAg-Eng group (70.5%) with an SPR difference of 19.5% (95% CI, 14.7%, 24.7%). At week 28 when the SPR peaked in the HBsAg-Eng group (72.8%), the SPR in the HBsAg-1018 group (94.8%) was significantly higher than in the HBsAg-Eng group. The SPR in the HBsAg-1018 group was significantly higher than in the HBsAg-Eng group at each study visit from week 4 through week 52. The safety profiles for the two vaccines were similar., Conclusion: When compared to the HBsAg-Eng three-dose regimen given at 0, 1, and 6months, HBsAg-1018 demonstrated superior seroprotection with only two doses at 0 and 1month. The safety profile of HBsAg-1018 was comparable to that of the licensed vaccine, HBsAg-Eng. HBsAg-1018 would provide a significant public health contribution toward the prevention of hepatitis B infection., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Purpose: To determine the status of the HIV epidemic in the United States and Canada., Methods: We used data on AIDS and HIV diagnoses for 1996-2005 reported to the United States and Canadian national surveillance systems to determine trends in AIDS and HIV (33 US states only) diagnoses and to identify population groups most affected by HIV. HIV incidence for Canada was determined using back-calculation methods. We also determined the proportion of persons diagnosed late (HIV diagnosis within 12 months before AIDS diagnosis)., Results: AIDS diagnosis rates were higher in 2005 among blacks (54.1 per 100,000) and Hispanics (18.0) compared with whites (5.9) in the United States and among blacks (4.7) and aboriginal peoples (4.9) compared with whites (0.7) in Canada. Since 2001, HIV diagnoses increased among men who have sex with men in both countries and in Canada, increased among persons from HIV-endemic countries and where heterosexual contact was the only identified risk of transmission. Overall, HIV incidence remained relatively stable in Canada during that period. A large proportion of persons were diagnosed late in the disease process (United States, 54.3%; Canada, 64.2%)., Conclusions: Rates of HIV transmission remain a challenge in both the United States and Canada as overall diagnosis rates have not decreased in recent years. Renewed prevention efforts are needed to further reduce the high HIV diagnosis rates among racial/ethnic minorities and to decrease HIV transmission among men who have sex with men.

Context: Incidence of human immunodeficiency virus (HIV) in the United States has not been directly measured. New assays that differentiate recent vs long-standing HIV infections allow improved estimation of HIV incidence., Objective: To estimate HIV incidence in the United States., Design, Setting, and Patients: Remnant diagnostic serum specimens from patients 13 years or older and newly diagnosed with HIV during 2006 in 22 states were tested with the BED HIV-1 capture enzyme immunoassay to classify infections as recent or long-standing. Information on HIV cases was reported to the Centers for Disease Control and Prevention through June 2007. Incidence of HIV in the 22 states during 2006 was estimated using a statistical approach with adjustment for testing frequency and extrapolated to the United States. Results were corroborated with back-calculation of HIV incidence for 1977-2006 based on HIV diagnoses from 40 states and AIDS incidence from 50 states and the District of Columbia., Main Outcome Measure: Estimated HIV incidence., Results: An estimated 39,400 persons were diagnosed with HIV in 2006 in the 22 states. Of 6864 diagnostic specimens tested using the BED assay, 2133 (31%) were classified as recent infections. Based on extrapolations from these data, the estimated number of new infections for the United States in 2006 was 56,300 (95% confidence interval [CI], 48,200-64,500); the estimated incidence rate was 22.8 per 100,000 population (95% CI, 19.5-26.1). Forty-five percent of infections were among black individuals and 53% among men who have sex with men. The back-calculation (n = 1.230 million HIV/AIDS cases reported by the end of 2006) yielded an estimate of 55,400 (95% CI, 50,000-60,800) new infections per year for 2003-2006 and indicated that HIV incidence increased in the mid-1990s, then slightly declined after 1999 and has been stable thereafter., Conclusions: This study provides the first direct estimates of HIV incidence in the United States using laboratory technologies previously implemented only in clinic-based settings. New HIV infections in the United States remain concentrated among men who have sex with men and among black individuals.

The recommendations for human immunodeficiency virus (HIV) testing in the United States were recently revised. An important goal of these revisions is to reduce the proportion of individuals infected with HIV who are unaware of their infection. In the new guidelines, screening is recommended for all individuals aged 13-64 years in any health care setting, provided that they are notified that testing will be performed and do not decline testing. It was further recommended that individuals at high risk for HIV infection be screened annually. Through wider screening, the identification of persons with unrecognized HIV is expected to facilitate treatment and allow better targeting of HIV prevention strategies.

The need for a new surveillance approach to understand the clinical outcomes and behaviors of people in care for HIV evolved from the new challenges for monitoring clinical outcomes in the HAART era, the impact of the epidemic on an increasing number of areas in the US, and the need for representative data to describe the epidemic and related resource utilization and needs. The Institute of Medicine recommended that the Centers for Disease Control and Prevention and the Heath Resources and Services Administration coordinate efforts to survey a random sample of HIV-infected persons in care, in order to more accurately measure the need for prevention and care services. The Medical Monitoring Project (MMP) was created to meet these needs. This manuscript describes the evolution and design of MMP, a new nationally representative clinical outcomes and behavioral surveillance system, and describes how MMP data will be used locally and nationally to identify care and treatment utilization needs, and to plan for prevention interventions and services.

HIV testing is an important and effective strategy for preventing HIV infection. Infected individuals who know their HIV serostatus are less likely to engage in high-risk sexual behavior, and it is estimated that knowledge of HIV serostatus in unaware persons could reduce new infections by more than 30%. The availability of rapid testing for HIV expands testing opportunities. Expanded routine, voluntary, and opt-out screening in health care settings is needed to reduce the number of persons who are unaware of their HIV-infected status, get newly diagnosed patients into care, and reduce transmission of HIV infection. This article summarizes a presentation on revisions to Centers for Disease Control and Prevention HIV screening recommendations made by Robert S. Janssen, MD, at the 9th Annual Ryan White CARE Act Clinical Update in Washington, DC, in August 2006. The original presentation is available as a Webcast at www.iasusa.org.

Background: New HIV infections stem from people who are aware they are HIV positive (approximately 75% of infected persons in the USA) and those who are unaware of their HIV-positive status (approximately 25%)., Objective: We estimated the relative contribution of these two groups in sexually transmitting new HIV infections to at-risk (HIV-negative or unknown serostatus) partners in the USA., Methods: The parameters in the estimation included: number of people aware and unaware they are infected with HIV; 33% of the aware group are at low risk of transmitting HIV because of low/undetectable viral load; 57% relative reduction in the prevalence of unprotected anal and vaginal intercourse (UAV) with at-risk partners in persons aware (compared to unaware) they have HIV; and assumed differences in the average number of at-risk UAV partners in each awareness group (ranging from equal to twice as many in the unaware group)., Results: The proportion of sexually transmitted HIV from the HIV-positive unaware group was estimated to range from 0.54 (assuming no difference in average number of at-risk UAV partners between groups) to 0.70 (assuming twice as many at-risk UAV partners in the unaware group). Using the lower bounds, the transmission rate from the unaware group was 3.5 times that of the aware group after adjusting for population size differences between groups., Conclusion: The results indicate that the HIV/AIDS epidemic can be lessened substantially by increasing the number of HIV-positive persons who are aware of their status.

Objectives: To compare the prevalence of high-risk sexual behaviors in HIV persons aware of their serostatus with that in HIV persons unaware of their status in the United States and to discuss implications for HIV prevention programs., Methods: A meta-analysis was conducted on 11 independent findings. Six findings compared HIV(+) aware persons with independent groups of HIV(+) unaware persons (between-group comparisons), and 5 findings compared seroconverting individuals before and after being notified of their HIV status (within-subject comparisons). Outcomes were self-reported unprotected anal or vaginal intercourse (UAV) during specified recall periods., Results: The analysis integrating all 11 findings indicated that the prevalence of UAV with any partner was an average of 53% (95% confidence interval [CI]: 45%-60%) lower in HIV persons aware of their status relative to HIV(+) persons unaware of their status. There was a 68% reduction (95% CI: 59%-76%) after adjusting the data of the primary studies to focus on UAV with partners who were not already HIV(+). The reductions were larger in between-group comparisons than in within-subject comparisons. Findings for men and women were highly similar., Conclusions: The prevalence of high-risk sexual behavior is reduced substantially after people become aware they are HIV(+). Increased emphasis on HIV testing and counseling is needed to reduce exposure to HIV(+) from persons unaware they are infected. Ongoing prevention services are needed for persons who know they are HIV(+) and continue to engage in high-risk behavior.

This study evaluated the magnitude and distribution of unrecognized HIV infection among young men who have sex with men (MSM) and of those with unrecognized infection, the prevalence and correlates of unprotected anal intercourse (UAI), perceived low risk for infection, and delayed HIV testing. MSM aged 15-29 years were approached, interviewed, counseled, and tested for HIV at 263 randomly sampled venues in 6 US cities from 1994-2000. Of 5649 MSM participants, 573 (10%) tested positive for HIV. Of these, 91% of black, 69% of Hispanic, and 60% of white MSM (77% overall) were unaware of their infection. The 439 MSM with unrecognized infection reported a total of 2253 male sex partners in the previous 6 months; 51% had UAI; 59% perceived that they were at low risk for being infected; and 55% had not tested in the previous year. The HIV epidemic among MSM in the United States continues unabated, in part, because many young HIV-infected MSM are unaware of their infection and unknowingly expose their partners to HIV. To advance HIV prevention in the third decade of HIV/AIDS, prevention programs must reduce unrecognized infection among young MSM by increasing the demand for and availability of HIV testing services.

Less sensitive (LS) HIV-1 enzyme immunoassays (EIAs) have significantly improved the quantity and quality of HIV surveillance data. The first LS-HIV-1 EIA, the Abbott 3A11-LS, provided reliable incidence data, but the assay required specialized equipment, and the lack of available reagents made testing difficult. This study evaluated the use of an alternate assay, a modified version of the Vironostika HIV-1 EIA (Vironostika-LS), to be used for LS testing. The Vironostika-LS has similar performance characteristics to the Abbott 3A11-LS with additional advantages. This 96-well formatted assay is commonly found in public health laboratories for routine HIV-1 testing and can be used with both serum and dried blood spot specimens. The estimated mean time from seroconversion (defined using a standardized optical density cutoff of 1.0) with the Vironostika-LS was 170 days (95% CI, 145-200 days). When the Vironostika-LS was applied to a matched serum set previously tested with the Abbott 3A11-LS, the Vironostika-LS accurately identified 97% of specimens with recent or long-standing HIV infection. The paper also reports Vironostika-LS quality control guidelines and the results from 3 rounds of proficiency testing.

The sensitive/less-sensitive (S/LS) enzyme immunoassay (EIA) testing strategy for discriminating "early" from "longstanding" HIV infection has been widely applied for detecting recent seroconverters and estimating HIV incidence rates. The originally developed assay (3A11-LS EIA; Abbott Laboratories, Abbott Park, IL) involved performance of LS EIAs using a bead-based assay that required specialized equipment and reagents of limited availability. In contrast, 96-microwell-based EIAs are more universally applied for HIV serodiagnosis throughout the world. The authors report development and preliminary validation of an LS protocol using an EIA in a 96-well format: the Vironostika HIV-1 MicroElisa System (Vironostika-LS EIA; Bio Merieux, Raleigh, NC). The results with samples from recent HIV-1 seroconverters, persons with longstanding HIV-1 asymptomatic infection, patients on highly active antiretroviral therapy, and AIDS patients show a high degree of correlation between the Vironostika-LS EIA and 3A11-LS EIA. The authors also demonstrate that the Abbott 3A11-LS EIA and Vironostika-LS EIA performed comparably on HIV-1-positive samples from persons infected with non-B HIV-1 subtypes. These results support the potential use of the Vironostika-LS EIA for detection of recent HIV-1 infections for incidence projections and for other epidemiologic, clinical, and molecular surveillance applications.

Although the numbers of newly reported diagnoses of AIDS decreased in the 1990s, it is not clear whether they reflect a decreasing number of new HIV infections. Direct measurement of HIV incidence through follow-up cohort studies is difficult and costly. We estimated HIV incidence and trends in incidence among men who have sex with men (MSM) and heterosexual men and women at clinics for sexually transmitted diseases (STDs) by using a recently developed serologic testing algorithm that requires only a single blood specimen. Cross-sectional anonymous serosurveys were conducted at 13 STD clinics in nine cities in the United States from 1991 through 1997. Before anonymous HIV testing, demographic and clinical information was abstracted. Of 129,774 specimens tested, 362 (0.28%) were from persons estimated to be recently infected. Incidence among MSM was 7.1% (95% confidence interval (CI): 4.8-10.3), 14 times higher than that among heterosexuals, which was 0.5% (CI: 0.4- 0.7). Incidence among MSM and heterosexuals remained unchanged during the time studied. Decreasing rates of new AIDS diagnoses in the 1990s do not reflect stable rates of new HIV infections among MSM and heterosexual patients attending these clinics.