Are US populations appropriate for trials of human immunodeficiency virus vaccine? The HIVNET Vaccine Preparedness Study.

Questions exist about whether testing of preventive human immunodeficiency virus (HIV)-1 vaccines, which will require rapid recruitment and retention of cohorts with high HIV-1 seroincidence, is feasible in the United States. A prospective cohort study was conducted in 1995-1997 among 4,892 persons at high risk for HIV infection in nine US cities. At 18 months, with an 88% retention rate, 90 incident HIV-1 infections were observed (1.31/100 person-years (PY), 95% confidence interval (CI): 1.06, 1.61). HIV-1 seroincidence rates varied significantly by baseline eligibility criteria--1.55/100 PY among men who had sex with men, 0.38/100 PY among male intravenous drug users, 1.24/100 PY among female intravenous drug users, and 1.13/100 PY among women at heterosexual risk-and by enrollment site, from 0.48/100 PY to 2.18/100 PY. HIV-1 incidence was highest among those men who had sex with men who reported unprotected anal intercourse (2.01/100 PY, 95% CI: 1.54, 2.63), participants who were definitely willing to enroll in an HIV vaccine trial (1.96/100 PY, 95% CI: 1.41, 2.73), and women who used crack cocaine (1.62/100 PY, 95% CI: 0.92, 2.85). Therefore, cohorts with HIV-1 seroincidence rates appropriate for HIV-1 vaccine trials can be recruited, enrolled, and retained.

Randomized controlled trial of audio computer-assisted self-interviewing: utility and acceptability in longitudinal studies. HIVNET Vaccine Preparedness Study Protocol Team.

Recent studies have reported on the utility of audio computer-assisted self-interviewing (ACASI) in surveys of human immunodeficiency virus (HIV) risk behaviors that involve a single assessment. This paper reports the results of a test of ACASI within a longitudinal study of HIV risk behavior and infection. Study participants (gay men (n = 1,974) and injection drug users (n = 903)) were randomly assigned to either ACASI or interviewer-administered assessment at their second follow-up visit 12 months after baseline. Significantly more of the sexually active gay men assessed via ACASI reported having sexual partners who were HIV antibody positive (odds ratio = 1.36, 95% confidence interval: 1.08, 1.72), and a higher proportion reported unprotected receptive anal intercourse. Among injection drug users (IDUs), our hypothesis was partially supported. Significantly more IDUs assessed via ACASI reported using a needle after another person without cleaning it (odds ratio = 2.40, 95% confidence interval: 1.34, 4.30). ACASI-assessed IDUs reported similar rates of needle sharing and needle exchange use but a lower frequency of injection. Participants reported few problems using ACASI, and it was well accepted among members of both risk groups. Sixty percent of the participants felt that the ACASI elicited more honest responses than did interviewer-administered questionnaires. Together, these data are consistent with prior research findings and suggest that ACASI can enhance the quality of behavioral assessment and provide an acceptable method for collecting self-reports of HIV risk behavior in longitudinal studies and clinical trials of prevention interventions.

Preventing discrimination against volunteers in prophylactic HIV vaccine trials: lessons from a phase II trial.

CONTEXT: Preventive HIV vaccines can temporarily cause uninfected individuals to have positive results on HIV testing. As preparations are underway to mount larger efficacy trials, the social risks of trial participation should be studied. OBJECTIVE: To describe frequency of HIV testing and discrimination among participants in a preventive phase II HIV vaccine trial. PARTICIPANTS: 266 vaccine trial volunteers were eligible; 247 participated in a confidential survey. RESULTS: 63 volunteers (26% of respondents) reported 185 HIV tests during the prior 12 to 24 months; most tests were for other research studies, health care, insurance, incarceration, or employment. Only 5 volunteers reported having positive HIV test results. Volunteers reported 99 adverse social incidents or problems, 53 of which were related to the trial. The most common type of event occurred when volunteers disclosed their trial participation and were mistakenly presumed to be infected with HIV. Few reported difficulty obtaining insurance, job loss, and inadvertent disclosure of their participation in the trial. CONCLUSION: In this vaccine trial, few serious social harms were reported. Those who conduct HIV tests for insurance, employment, health care, or other reasons should be made aware that HIV vaccines can cause false-positive HIV test results. Those planning future trials must continue to provide needed support to volunteers. Social harms should be monitored with the same vigilance accorded to physical harms.

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.

A factorial survey study to assess the acceptability of HIV vaccine trial designs.

To aid in the design of human immunodeficiency virus (HIV) vaccine trials that maximize volunteer participation, factorial surveys were administered to 73 gay men who were participants in a larger study assessing HIV vaccine trial feasibility. Factorial surveys are "vignettes" that are randomly constructed through the combination of descriptive statements (dimensions) that reflect essential features. In this study, the dimensions define components of clinical trials to assess the efficacy of hypothetical HIV vaccines. Regression analysis shows that anticipated participation was decreased by a sustained vaccine-induced antibody response lasting 3 years, absence of gay men as research subjects in earlier phase trials for the products being tested, and rectal vaccine administration. Three years of scientific experience with the vaccine encouraged participation. We conclude that willingness to participate in vaccine trials varies systematically with some of their characteristics. Where there are design alternatives for identified negative components, these should be considered. If this is not possible, options for decreasing aversion to such features will need to be evaluated, including appropriate education regarding both the benefits and the risks associated with negatively evaluated features.

Natural history of somatic growth in infants born to women infected by human immunodeficiency virus. Women and Infants Transmission Study Group.

OBJECTIVE: To evaluate the nature and magnitude of the effect of congenitally or perinatally acquired human immunodeficiency virus (HIV) infection on somatic growth from birth through 18 months of age. STUDY DESIGN: Anthropometry was performed serially in 282 term infants born to HIV-infected women in a multicenter prospective natural history cohort study. Repeated measures analysis was used to compare z-score anthropometric indexes of weight-for-age, length-for-age, weight-for-length, and head circumference-for-age between infected and uninfected infants, with adjustment for covariates including infant gender; maternal education; prenatal alcohol, tobacco, and/or illicit drug exposure; and mean prenatal CD4+ T-lymphocyte count. A separate repeated measures model was used to assess the effect of infant zidovudine treatment on growth. RESULTS: Infants infected with HIV were an estimated average 0.28 kg lighter and 1.64 cm shorter than uninfected infants at birth, were 0.71 kg lighter and 2.25 cm shorter by 18 months of age, and had a sustained estimated average decrement of 0.70 to 0.75 cm in head circumference. Patterns of growth were similar in male and female infants. Infected infants had a progressive decrement in body mass index from birth through 6 months of age. Infection with HIV was associated with significant decrements across all standardized growth outcome measures after adjustment for covariates. Mean z scores were lower for weight by 0.612 (p < 0.001), for length by 0.735 (p < 0.001), for weight-for-length by 0.255 (p = 0.02), and for head circumference by 0.563 (p < 0.001) SD units compared with uninfected infants. Zidovudine treatment was not associated with improved growth. CONCLUSION: The effect of congenitally or perinatally acquired HIV infection on infant growth is one of early and progressive decrements in attained linear growth and growth in mass, early and sustained decrements in head growth, and marked early decrements in body mass index.

Will preventive HIV vaccine efficacy trials be possible with female injection drug users?

This article examines whether preventive HIV vaccines trials will be viable among female injection drug users (IDUs). Of the 137 women who completed baseline serologic and behavioral assessments, 121 (88%) were seronegative; all enrolled in Project Jumpstart in Philadelphia (PA, U.S.A.), a vaccine preparedness initiative cosponsored by NIAID and NIDA. Subjects were seen every 3 months for risk and vaccine opinion assessment, risk reduction counseling, and HIV antibody testing. The baseline prevalence rate of HIV infection was 12% (16 of 137) with an annual incidence rate of 3.5% (4 of 114) during the first year. Of the 121 baseline seronegative women, 28% shared needles and 52% engaged in unprotected intercourse. Sixty percent of the baseline seronegative women reported being willing to be one of the first people to try an HIV vaccine. According to logistic regression, needle sharers were 12.8 times more likely, women who engaged in sex for drugs or money 6.6 times more likely, out-of-treatment women 3.5 times more likely, and those who believed that vaccines can prevent disease acquisition 3 times more likely to report willingness to try an HIV vaccine than their respective counterparts. At 1-year postbaseline assessment, 98% of the women had behavioral data collected and 95% had serologic specimens collected. Given that seroconversions occur and that these women engage in risk behaviors, report willingness to try an HIV vaccine, and can be retained for longitudinal assessment, they appear to be suitable participants for preventive HIV vaccine efficacy trials. Nonetheless, work is required to insure that these women make informed and knowledgeable decisions regarding trial enrollment.

Misdiagnosed HIV infection in pregnant women: implications for clinical care.

Out of nearly 900 women in a research study of human immunodeficiency virus infection in pregnancy, 8 were subsequently found not to be infected. Misdiagnoses could have resulted from (a) laboratory errors or specimen mixups; (b) failure to follow the testing algorithm recommended by the Centers for Disease Control and Prevention to confirm results; (c) women perceiving they were infected by high-risk behavior in the absence of testing, despite the receipt of negative test results, or based on screening results only; or (d) factitious disorder, HIV Munchausen syndrome, or malingering. Because of the potentially devastating impact of an HIV diagnosis and the toxicity of HIV therapies, health care providers should obtain independent confirmation of the diagnosis before initiating treatment or followup for HIV based on patient report or provider referral. Quality test interpretation and counseling must be ensured. Therapeutic interventions may be indicated for persons intentionally and falsely presenting themselves as HIV-infected.

Behavioral studies relevant to vaccine trial preparation: an introduction.

Preparations for large-scale trials to test the efficacy of candidate HIV vaccines can benefit in several crucial ways from a targeted program of behavioral and social research. Randomized field experiments testing alternative procedures for the recruitment and retention of subjects can help identify research procedures that will ensure adequate sample sizes while minimizing sample attrition over time. Similarly, assuring that subjects accurately comprehend the potential risks of participation will require more than simply presenting scientifically accurate information. Ensuring both the adequacy and appropriateness of risk communications as well as the accuracy of subject perception of risks (across the social and cultural milieux in which vaccine trials will be undertaken) is a critical task. Ethnographic and behavioral studies can help to ensure that our obligation to obtain truly informed consent from our research subjects is fully met and documented. Monitoring risk behaviors over the course of the vaccine trials could also benefit from strategic investments in new technologies developed by social researchers to permit the collection of sensitive personal data while affording complete privacy to subjects. These new measurement technologies include procedures that permit private data collection (without a human interviewer) in any spoken language and without requiring that subjects be literate.

Reproductive preferences of pregnant women under shifting probabilities of vertical HIV transmission.

PIP: Between December 1989 and September 1990 in Baltimore, Maryland, researchers interviewed 363 pregnant women attending the Johns Hopkins Hospital obstetric clinic concerning their perspectives on HIV infection and childbearing. All women who agreed to be tested for HIV infection (91%) tested negative for HIV infection. The women lived in a community with a high prevalence of HIV infection. 90% were African-American. As the stated probability of vertical transmission increased so did the women's stated willingness to undergo an abortion. Specifically, if the stated transmission rate was 30%, 28% said they would have an abortion. If the rate was 50%, 47% would have an abortion. At a 70% transmission rate, 68% would have an abortion. At a 100% transmission rate, 74% would have an abortion. 23% of the women would never have an abortion, even if the vertical transmission rate were 100%. 36% of the women had had at least 1 abortion. They were more likely than the non-abortion group to have an abortion at all stated transmission rates. 74% of the women stated that prayer was important during personal problems. 28% of women had a planned pregnancy. These 2 aforementioned groups were less likely than their counterparts to have an abortion at the 30% transmission rate. 48% reported that HIV infection is the only reason for an abortion. An increase in the stated probability of vertical transmission did not strongly influence the women's willingness to avoid pregnancy. 78% would avoid pregnancy at the 30% transmission rate. At the 50% transmission rate, 97% would avoid pregnancy. 99% would avoid pregnancy at the 70% transmission rate. Only 3 women would not avoid pregnancy at the 100% transmission rate. These findings suggest that HIV-positive pregnant women need access to health care providers who are as comfortable respecting and supporting decisions to continue their pregnancies as they are referring them to abortion facilities.^ieng

HIV and AIDS among adolescents in the United States: increasing risk in the 1990s.

Acquired immunodeficiency syndrome (AIDS) and human immunodeficiency virus (HIV) are growing problems among U.S. adolescents. By examining recent data on AIDS surveillance and HIV seroprevalence, surveys on teenagers' knowledge, beliefs, and behaviors related to HIV/AIDS, key treatment issues, and barriers to prevention, this manuscript reviews the problem and proposes possible ways of combating it. African American youth have the highest rates of AIDS and white youth the lowest. However, the largest number of AIDS cases overall has been recorded in white males, reflecting relatively high case rates in boys with hemophilia and in young male homosexuals. Predominant HIV risk factors for adolescents are unprotected sex and/or sharing injection drug equipment with an infected partner. Relatively high rates of HIV infection in adolescent females may indicate their greater physiological vulnerability than adult females to sexually transmitted diseases (STDs). Data from HIV seroprevalence studies suggest a substantially increased heterosexual epidemic in the 1990s, especially in large east coast cities and southeastern rural areas where drug use and/or STDs are highly prevalent. More comprehensive prevention and treatment services are needed to prevent ongoing expansion of HIV infection and AIDS in the adolescent age group.

Human immunodeficiency virus/acquired immunodeficiency syndrome in pregnant women.

A pregnant woman experiences selective immunosuppression as a physiologic response to the presence of a genetically heterologous fetus. Case reports early in the acquired immunodeficiency syndrome (AIDS) epidemic suggested that adverse human immunodeficiency virus (HIV)-related clinical outcomes might be causally associated with pregnancy. A review of relevant published data indicates that: (1) Adverse clinical outcomes of pregnancy are common among HIV-infected pregnant women, but no studies to date have fully disentangled the many confounding factors. (2) HIV-related complications are common in pregnancy only among immunosuppressed (< 300 CD4+ cells/mm3) women. (3) The distinct effect of pregnancy on the expression of HIV infection cannot be evaluated in the absence of appropriately controlled observations. (4) Cofactors for perinatal transmission are poorly understood. (5) Research into the motives for reproductive decisions and behaviors is of critical importance for improving our health education and outreach efforts for high-risk women. (6) Adequate clinical treatment and prophylactic health care services must be made easily accessible and available to women at high risk of HIV disease. (7) Treatment with available antiviral and anti-Pneumocystis drugs is advisable for HIV-infected pregnant women with fewer than 300 to 350 CD4+ cells/mm3, though data to definitively guide therapeutic decision making are not available. (8) Large multicenter studies are needed to recruit patients and to retain them in sufficient numbers, allowing for better evaluation of the many variables determining clinical outcomes for HIV-infected mothers and their infants. The natural history of HIV in pregnant women must be studied to facilitate clinical decision making, and to design and implement interventions, including prevention (behavior change, vaccines) and treatment (chemotherapy, immunotherapy).