The feasibility of HIV-1 vaccine efficacy trials among gay/bisexual men in New York City: Project ACHIEVE. AIDS Community Health Initiative Enroute to the Vaccine EFfort.

OBJECTIVE: Candidate populations for HIV-1 vaccine efficacy trials need to be at high risk of infection, adhere to study protocols and be willing to participate. The goal of Project ACHIEVE is to collect baseline data needed in order to prepare for vaccine efficacy trials among gay/bisexual men in New York City. DESIGN AND METHODS: HIV-1 antibody-negative men were recruited into a cohort study with follow-up visits every 3 months (n = 622). Frequency of high-risk behaviors and incidence of HIV-1 seroconversion were measured. RESULTS: Of 544 men reporting having had at least one partner in the previous 3 months who was HIV-1 antibody-positive or of unknown status at baseline, 49% reported receptive anal sex encounters. Thirty-two per cent of these men reported the highest risk behavior, unprotected receptive anal sex. The follow-up rate at 12 months was 81%. The incidence rate of infection was 2.9 per 100 person-years (95% confidence interval: 1.7, 4.9). During follow-up, declines were observed in the proportion of men with an HIV-1 antibody-positive partner and the proportion reporting unprotected receptive or insertive anal sex. HIV-1 infection rates declined from 4.3 per 100 person-years in the first 6 months to 1.6 per 100 person-years by the 12-month visit. CONCLUSIONS: Gay/bisexual men in New York City are still placing themselves at risk of HIV-1 infection and may be a suitable population for future vaccine trials. Continued follow-up is needed to further define the incidence over time, especially for the period after the initial 3 to 6 months when vaccines are most likely to be effective. Immediate prevention efforts need to target this population more effectively.

High prevalence of HIV infection among young men who have sex with men in New York City.

OBJECTIVE: To determine the prevalence of HIV infection and risk behaviors among young men who have sex with men (MSM) aged 15-22 years in New York City. DESIGN: An anonymous cross-sectional survey. METHODS: The 1998 Young Men's Survey in New York City (YMS-NYC), was a multistage probability survey of 541 MSM aged 15-22 years who attend public venues. After identification of venues and their associated high attendance time periods, random samples of venues and time periods were selected on a monthly basis. At each sampling event, potential participants were approached to determine eligibility. Eligible and willing men were interviewed, counselled and had a blood specimen drawn. RESULTS: Between December 1997 and September 1998, 115 sampling events were conducted. Of 612 men enrolled, 541 reported ever having had sex with a male partner. The HIV seroprevalence among the 541 MSM sampled was 12.1%. The HIV seroprevalence was 18.4% among African-Americans, 16.7% among persons of mixed race, 8.8% among Latino individuals and 3.1% among white men. HIV seroprevalence was 5.0% among 15-18 year olds and 16.4% among 19-22 year olds. A total of 65.5% of MSM were susceptible to hepatitis B virus infection (HBV). Almost half (46.1%) of the men reported unprotected anal sex in the previous 6 months and 16.3% reported ever having had an STD. Multiple regression analyses found that being older, of mixed race, black or ever having had an STD was associated with being HIV antibody positive. CONCLUSION: These data identify a large subgroup of MSM in need of effective HIV and HBV primary and secondary prevention programs.

Readiness of high-risk populations in the HIV Network for Prevention Trials to participate in HIV vaccine efficacy trials in the United States.

OBJECTIVE: To determine the willingness of populations at high risk of HIV-1 infection to participate in HIV vaccine efficacy trials, determine factors influencing decision-making, and evaluate knowledge levels of vaccine trial concepts. DESIGN: Cross-sectional study. METHODS: HIV-1-negative homosexual men, male and female injecting drug users and non-injecting women at heterosexual risk were recruited in eight cities in the United States (n=4892). RESULTS: A substantial proportion of the study population (77%) would definitely (27%) or probably (50%) be willing to participate in a randomized vaccine efficacy trial. Increased willingness was associated with high-risk behaviors, lower education level, being uninsured or covered by public insurance, and not having been in a previous vaccine preparedness study. Altruism and a desire for protection from the vaccine were major motivators for participation. Major concerns included positive HIV-1 antibody test due to vaccine, safety of the vaccine, and possible problems with insurance or foreign travel. Baseline knowledge of vaccine trial concepts was low. CONCLUSIONS: It is likely that high-risk volunteers will be willing to enroll in HIV vaccine efficacy trials. A variety of participant and community educational strategies are needed to address participant concerns, and to ensure understanding of key concepts prior to giving consent for participation.

Differences in antibody response to whole-cell pertussis vaccines.

It has been assumed that whole-cell pertussis vaccines (WCVs) commercially distributed in the United States are of comparable immunogenicity, as all must comply with established standards for licensure. However, we have recently noted significant differences in antibody responses between groups of infants receiving the two WCVs commercially available in the United States. In separate studies performed concurrently under similar protocols at Vanderbilt and Johns Hopkins universities, infants were randomized to receive either an acellular pertussis vaccine or WCV. The acellular pertussis vaccine used at the two sites was identical, but the WCVs were from different manufacturers. Antibody responses to acellular pertussis vaccine did not differ between the two studies; responses to WCV differed dramatically, with infants receiving the Lederle WCV producing a 46-fold increase in antibody to pertussis toxin, compared with a 2.4-fold increase for infants receiving the Connaught WCV (P = .00003). Evaluation of other comparative data sets that were available provided further support for the conclusion that the two commercially available WCVs consistently differed in their ability to induce antibody to pertussis toxin. These findings have important implications for the design and interpretation of clinical trials comparing acellular and WCV products.

Response of preterm infants to diphtheria-tetanus-pertussis vaccine.

The American Academy of Pediatrics recommendation that immunization of preterm infants with diphtheria-tetanus-pertussis (DTP) vaccine should begin at 2 months after birth, regardless of gestational age, is based on limited data. A prospective study was conducted to determine the immunogenicity and safety of DTP vaccine in preterm infants. One hundred ten preterm and 146 full term infants received doses of DTP at 2, 4 and 6 months after birth. Adjusted analysis of the antibody responses indicated that after three doses mean titers among preterm infants to each vaccine component were comparable to those of full term infants. Adjusted analysis of the incidence of adverse events indicated that the risk of adverse events in preterm infants was not significantly higher than that in full term infants. DTP vaccine is immunogenic and safe in preterm infants when the series is initiated at 2 months after birth, and this study supports the current recommendation of the American Academy of Pediatrics.

Non-injection substance use correlates with risky sex among men having sex with men: data from HIVNET.

Associations between substance use and sexual behavior were examined among 3220 seronegative men who have sex with men (MSM) in a HIV vaccine preparedness study. Relationships between current and past substance use and current sexual risk were evaluated using crude odds ratios and logistic regression to adjust for confounding variables. Heroin and injection drug use were uncommon (< 2%). Substances most often used were alcohol (89%), marijuana (49%), nitrite inhalants (29%), amphetamines or similarly acting stimulants (21%), cocaine 14% and hallucinogens (14%). Increased adjusted odds for unprotected sex were significantly associated with current heavy alcohol use (OR 1.66; CI 1.18, 2.33), past alcohol problems (OR 1.25; CI 1.05, 1.48), and current drug use (OR 1.26; CI 1.08, 1.48). When associations with specific drugs and nitrite inhalants were examined separately, current use of cocaine and other stimulants (OR 1.25; CI 1.01, 1.55), hallucinogens (OR 1.40; CI 1.10, 1.77), and nitrite inhalants (some (OR 1.61; CI 1.35, 1.92); heavy (OR 2.18; CI 1.48, 3.20)), were independently associated with unprotected sex. Those with past drug use or past heavy alcohol use but not currently using demonstrated no increase in sexual risk, suggesting an important role for substance-focused interventions in risk reduction efforts among MSM.

Acceptability of a stage-matched expert system intervention to increase condom use among women at high risk of HIV infection in New York City.

There is an urgent need to develop and implement effective methods for sexual behavior change to curb the spread of HIV. Condoms remain one of the most effective strategies for achieving this, yet consistent condom use is generally low, especially among those at highest risk. This article describes the acceptability of an interactive computer-based expert system designed to increase condom use in women at high risk of HIV infection. The expert system is based on the transtheoretical stages of change model. Using a computer, participants respond to questions about their attitudes and behavior toward using condoms and receive immediate feedback which is matched to their readiness to use condoms. The women were found to be at all stages of change for condom use, although a large proportion of the women (42%) were at early stages of behavior change because they were considering but not using condoms every time during sex with men. The expert system was found to be acceptable to this high-risk group of women. They almost unanimously agreed that they found the feedback useful, would return to use the system again, and would recommend it to a friend. These findings indicate that traditional intervention strategies which assume individuals are ready to use condoms consistently would be appropriate for only about one third of these women, underscoring the importance and potential utility of stage-matched interventions.

PIP: Condoms remain one of the most effective strategies for achieving sexual behavior change to curb the spread of HIV; yet consistent condom use is generally low, especially among those at highest risk. This article describes the acceptability of an interactive computer-based expert system designed to increase condom use in women at high risk of HIV infection in New York City. The expert system is based on the transtheoretical stages of change model. Using a computer, participants respond to questions about their attitudes and behavior concerning using condoms and receive immediate feedback, which is matched to their readiness to use condoms. The women were found to be at all stages of change for condom use, although a large proportion of the women (42%) were at early stages of behavior change because they were considering but not using condoms every time they have sex with men. The expert system was found to be acceptable to this high-risk group of women. They almost unanimously agreed that they found the feedback useful, would return to use the system again, and would recommend it to a friend. The findings indicate that traditional intervention strategies, which assume individuals are ready to use condoms consistently, would be appropriate for only about one-third of these women, underscoring the importance and potential utility of stage-matched interventions.

Time trends in high-risk injection practices in a multi-site study in Massachusetts: effects of enrollment site and residence.

Time trends in needle sharing and bleach use were examined among needle users enrolled at drug abuse treatment and nontreatment sites in greater Worcester, MA, from 1987 through 1989. Substantial declines in high-risk behavior were found, with different trends at drug treatment versus nontreatment sites. The percentage of individuals sharing needles declined at treatment facilities but not at nontreatment sites. Among those sharing, the proportion using bleach increased at both drug treatment and nontreatment sites. The bleach distribution program in Worcester appears to be associated with increased bleach use among residents. Bleach use was associated with residence in Worcester, after controlling for age, gender, race, enrollment site, time period, and frequency of sharing. Risk reduction in the subpopulation of needle users entering treatment was greater than that among those not in treatment. As avoidance of sharing is likely to be more effective than bleaching for the prevention of human immunodeficiency virus (HIV) transmission, the subpopulation not in treatment should be targeted for prevention programs.

Violence and HIV-related risk among young men who have sex with men.

Limited research has been conducted on threats or violence by family members and sexual partners against young men who have sex with men (MSM). Young MSM, aged 15-22 years, who attended public venues in New York City were enrolled in an anonymous, cross-sectional HIV seroprevalence and risk-behavior study. About two-thirds (68%) of the young MSM reported ever experiencing threats or violence from either family or partners and 25% reported threats or violence by both family and partners. In multivariate analysis, threats or violence by partners was significantly associated with older age, a history of forced sex and a history of running away from home. Recent unprotected anal sex and club drug use were significantly associated with a history of threats or violence by both family and partners. HIV prevention interventions need to include multiple factors that may have an impact on risk, including substance use and abuse, anti-violence and other mental-health issues.

Immunity to diphtheria and tetanus in inner-city women of childbearing age.

This study was conducted to determine immunity to diphtheria and tetanus in 232 inner-city women experiencing a recent birth. Forty-three (18.5 percent) of the women had levels of diphtheria antitoxin below the protective level (less than 0.01 unit/ml), whereas only 10 (4.3 percent) had insufficient levels of tetanus antitoxin. The percent of women susceptible increased with age, with 33 percent and 25 percent of women over the age of 30 years susceptible to diphtheria and tetanus, respectively.

Readiness for HIV vaccine trials: changes in willingness and knowledge among high-risk populations in the HIV network for prevention trials. The HIVNET Vaccine Preparedness Study Protocol Team.

Longitudinal data were analyzed to determine changes in willingness to participate in HIV vaccine efficacy trials and knowledge of vaccine trial concepts among populations at high risk of HIV-1 infection. Gay men (MSM), male and female injection drug users, and non-injecting women at heterosexual risk were recruited (n = 4892). Follow-up visits occurred every 6 months up to 18 months. Willingness was significantly lower at follow-up visits compared with at baseline. Knowledge levels increased for all study populations. Problematic concepts were possible effects of the vaccine on the immune system and lack of knowledge about efficacy of a vaccine before the start of a trial. For concepts concerning safety, blinding, and guarantees of future participation in trials, MSM men had significant increases in knowledge, but little to no change occurred for the other populations. An increase in knowledge was associated with becoming not willing, particularly among MSM with low knowledge levels. At least half of high-risk participants were consistently willing to participate in future vaccine efficacy trials and with basic vaccine education, knowledge levels increased. Continued educational efforts at the community and individual level are needed to address certain vaccine trial concepts and to increase knowledge levels in all potential study populations.

Lysozyme activity in cystic fibrosis.

The activity of lysozyme in saliva and serum was determined in 51 patients with cystic fibrosis. Measurements were made on two occasions at least 1 month apart and compared to those of 25 normal healthy individuals of the same ages, sex, and race. The mean serum lysozyme activity of normal individuals was 5.8 micrograms/ml (S.E. = 0.4), whereas that of cystic fibrosis patients was 10.8 micrograms/ml (S.E. = 0.5). The difference is significant (P less than 0.05). Initial mean values compared to those of repeated samples from the cystic fibrosis group were similar, whereas individual fluctuations occurred between test periods. The mean lysozyme activity of the saliva sample of normal individuals was 63.5 micrograms/ml (S.E. = 9.3) and the mean value from cystic fibrosis patients was 82.7 (S.E. = 6.9). This difference was not significant (P greater than 0.1). Mean values from specimens obtained a month or longer after the initial saliva samples were similar for the two episodes. There was no correlation between the serum and salivary values and the age, sex or race of the subjects, the Shwachman-Kulczycki scores, colonization with Pseudomonas aeruginosa, Staphylococcus aureus or Haemophilus influenzae or absolute white blood cell counts. In vitro studies failed to demonstrate bactericidal activity for mucoid and nonmucoid strains of P. aeruginosa or for S. aureus. Elevated lysozyme activity in cystic fibrosis may be related to either an increased granulocyte turnover because of chronic bacterial infection of the respiratory tract or to a basic defect in the lysosomal membrane allowing an increased release of the enzyme, or a combination of both.

Effect of duration of hepatitis B virus infection on the association between human immunodeficiency virus type-1 and hepatitis B viral replication.

This study examined the effect of duration of hepatitis B virus infection on the association between human immunodeficiency virus type-1 infection and hepatitis B viral replication. Twenty-five chronic HBsAg carriers were studied. Presence of hepatitis B virus DNA and expression of HBeAg were more frequent among 20 chronic HBsAg carriers positive for human immunodeficiency virus type-1 antibody compared with five chronic HBsAg carriers negative for human immunodeficiency virus type-1 antibody, but the associations were not statistically significant. Hepatitis B virus DNA and HBeAg were inversely related to duration of hepatitis B virus infection (p less than 0.001). Stratifying for duration of hepatitis B virus infection, the presence of viral replication was similar among patients negative and positive for antibody to human immunodeficiency virus type-1. Hepatitis B virus DNA levels did not increase with the decline of cellular immunity over time. In conclusion, hepatitis B virus replication among chronic carriers may be a function of duration of hepatitis B virus infection rather than of an effect of human immunodeficiency virus type-1.

Willingness to participate in HIV-1 vaccine efficacy trials and the effect of media events among gay and bisexual men in New York City: Project ACHIEVE.

Efficacy trials of candidate HIV-1 vaccines require study populations at high risk of infection who adhere to study protocols and who are willing to participate. Data from HIV-1 antibody-negative men (n = 698) enrolled in Project ACHIEVE in New York City were analyzed to assess willingness to participate in efficacy trials, factors influencing willingness, and the effect on willingness of the June 1994 media events about the decision not to proceed with phase III trials and about breakthrough infections during phase I and II vaccine trials. Sixty-eight percent indicated they would definitely or probably be willing to participate. Men enrolled during the time of media events were significantly less willing compared with men enrolled during other periods. These men were also more likely to mention safety of the vaccine, fear or mistrust of research or government, and social risks as important factors in their decision compared with men enrolled during other periods. The most frequently cited motivator for participation was altruism (57%); the most frequently cited barriers were vaccine safety (36%) and vaccine-induced seropositivity (19%). A substantial proportion of this cohort was willing to participate in future vaccine efficacy trials. However, because willingness may be affected by issues of vaccine safety, vaccine-induced seropositivity, and media coverage of these issues, significant efforts are needed for participant and community education, and specific concerns must be addressed in the design and implementation of trials.

Involving women in HIV vaccine efficacy trials: lessons learned from a vaccine preparedness study in New York City.

This paper identifies the recruitment strategies and human immunodeficiency virus (HIV) risk behaviors of at-risk women in an HIV vaccine preparedness study in New York City, assesses how these behaviors changed over time, and draws implications for women's involvement in HIV vaccine efficacy trials. Noninjecting HIV-1 negative women (N = 89) were recruited into an HIV vaccine preparedness study. An observational cohort study design was used. Women were recruited from clinics and community-based organizations (40%), through other study participants (24%), through newspaper advertisements (20%), and through street outreach (16%). Most women who refused (72%) also came from clinics and agencies. Retention after 12 months was 67%; after 18 months, it was 62%. The proportion of women reporting unprotected vaginal sex in the previous 3 months was 85% at baseline and declined to 70% after 12 months (P < .05). There have been no seroconversions detected. Recruitment efforts to include at-risk women in HIV vaccine efficacy trials must be diverse and actively involve community agencies. Successfully retaining these cohorts over time and detecting a high enough HIV seroincidence rate present ongoing challenges that will need to be addressed to ensure women's involvement in future trials in the US.

Racial/ethnic differences in HIV-1 seroprevalence and risky behaviors among intravenous drug users in a multisite study.

Differences in human immunodeficiency virus type 1 (HIV-1) seroprevalence and patterns of drug-use and sexual behaviors were examined among Hispanic, black, and white intravenous drug users recruited at multiple sites in Worcester, Massachusetts. A total of 1,092 (786 males, 306 females) intravenous drug users were interviewed, and HIV-1 antibody test results were available for 874 (80.0%). After adjustment for demographic differences, black males were significantly less likely to report risky drug-use behaviors (ever sharing needles and recently visiting shooting galleries) compared with white males. In contrast, Hispanic males were significantly more likely to report recent risky drug-use behaviors (sharing needles in New York City, daily needle-sharing, and visiting shooting galleries). Both groups were less likely to report risky sexual behaviors compared with whites. The odds ratios for HIV-1 seropositivity remained significantly greater than 1 for Hispanics compared with whites (odds ratio = 4.5) and maintained marginal significance for blacks compared with whites (odds ratio = 2.1) when adjusted for risky behaviors and demographic variables. The different patterns of drug-use and sexual behaviors by race/ethnicity indicate the need for interventions targeted to specific populations.

Mortality trends in a cohort of homosexual men in New York City, 1978-1988.

Trends in mortality related to infection by human immunodeficiency virus type 1 (HIV-1) and to other causes were examined from 1978 to 1988 in a cohort of 8,906 homosexual men who participated in studies of hepatitis B virus infection in the late 1970s in New York City. HIV-related mortality rates increased from 1 per 10,000 person-years in 1980 to 181 per 10,000 person-years in 1986, followed by a plateau from 1986 to 1988. The standardized mortality ratio among white men in the cohort was 3.7 (95% confidence interval (Cl) 3.4-3.9) as compared with white men from across the United States. Higher HIV-related mortality rates were associated with a higher number of sexual partners, a history of gonorrhea and/or syphilis, and serologic markers of infection with hepatitis B virus. After adjustment for demographics and sexual behaviors, the relative risk of mortality for Hispanic men as compared with white men was 1.5 (95% Cl 1.1-1.9). This study illustrates the large excess in mortality among homosexual men over the last decade, with the excess accounted for by deaths from HIV-related diseases. The recent plateau in mortality may be due to the effect of new treatments and/or the decline in new HIV-1 infections among homosexual men. The excess in HIV-related mortality among Hispanic homosexual men was not explained by differences in demographics and factors associated with the sexual transmission of HIV-1.

Anal sex among HIV-seronegative women at high risk of HIV exposure. The HIVNET Vaccine Preparedness Study 2 Protocol Team.

To assess the prevalence and the sociodemographic and behavioral correlates of anal sex in a cohort of HIV-seronegative U.S. women at high risk of HIV exposure, we administered a risk assessment using audio computer-assisted self-interview (A-CASI). Of 1268 sexually active women, 432 (32%) reported anal sex in the previous 6 months. Compared with women who did not report anal sex, those who did had more unprotected vaginal sex (median of 11 versus 7 episodes; p <. 001) and a higher proportion of unprotected sexual (vaginal plus anal) episodes (median of 0.90 versus 0.81; p =.01). Anal sex was reported by higher proportions of women who did not always use condoms, who used crack in the past year, who were

Use of reality "female condoms" for anal sex by US men who have sex with men. HIVNET Vaccine Preparedness Study Protocol Team.

OBJECTIVES: This study assessed use of Reality "female condoms" for anal sex by HIV-seronegative men who have sex with men and are at high risk for HIV infection. METHODS: Self-administered questionnaires were completed by 2277 participants in a 6-city prospective cohort study. RESULTS: Of the 1084 (48%) men who had heard of using the female condom for anal sex, 145 (13%) reported using it in the prior 6 months. Users were at greater risk than nonusers: 47 receptive and 35 insertive users reported problems, including bleeding by the receptive partner (4). CONCLUSIONS: Redesign of the female condom could increase acceptability and use by men who have sex with men and could address possible safety concerns.

Retaining hard-to-reach women in HIV prevention and vaccine trials: Project ACHIEVE.

Project ACHIEVE, which conducts HIV prevention research studies, maintains a women's site in the South Bronx in NewYork City. Owing to a focused retention effort at the South Bronx site, high retention rates were achieved in a vaccine preparedness study for women at high risk of HIV infection. Comparable retention rates have been achieved in HIV vaccine trials with similar cohorts of women at this site. These results suggest that concerns about retaining hard-to-reach populations should not cause these populations to be excluded from HIV vaccine and prevention trials.