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.

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).

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.

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.

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.

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.

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.