Faculty Bibliography

BACKGROUND: Douching may interfere with determination of microbicide safety and effectiveness. This practice has not been adequately studied among women at risk of HIV infection. GOAL: This study assessed douching practices among women at risk of HIV infection in the United States. STUDY DESIGN: Data were collected on douching practices, sexually transmitted diseases, birth control, use of spermicidal products, and sexual risk behaviors among HIV antibody-negative women. RESULTS: Of 623 women, 70.2% had recently douched. Most women had been told that douching was not healthy. No associations were found between recent douching and measures of risk behaviors, except number of male partners. Recent douching was associated with being aged 26 to 30 years, compared with being 18 to 25 years of age (odds ratio [OR] = 2.2), black (OR = 3.0), or sterilized (OR = 2.0); having 5 or more male partners (OR = 4.4); and being told that douching is unhealthy (OR = 0.4). CONCLUSIONS: Recent douching was very common. The high prevalence of douching has implications for the design of microbicide trials and prevention interventions

PURPOSE: To compare optic disc topography and nerve fiber layer thickness in ocular hypertensive eyes and normal subjects. DESIGN: Prospective, case-controlled study. PARTICIPANTS AND CONTROLS: One eye in each of 20 normal and 27 ocular hypertensive patients was enrolled. METHODS: Consecutive normal and ocular hypertensive patients were enrolled. Each patient underwent complete ophthalmic examination, achromatic automated perimetry, short-wavelength automated perimetry, confocal scanning laser ophthalmoscopy, confocal scanning laser polarimetry, and optical coherence tomography. The intraocular pressure was 21 mmHg or less for normal subjects and at least 25 mmHg on two separate occasions in ocular hypertensive eyes. Structural parameters were compared between the two groups. Eyes with evidence of glaucomatous optic neuropathy, achromatic visual field loss, or evidence of focal visual field injury during short-wavelength automated perimetry were excluded. MAIN OUTCOME MEASURES: Optic nerve head topography and nerve fiber layer thickness. RESULTS: The three imaging technologies could not detect differences in optic disc or nerve fiber layer anatomy between the two groups. Ocular hypertensive eyes had a greater corrected pattern standard deviation than normal eyes during short-wavelength automated perimetry (P = 0.04). CONCLUSIONS: Ocular hypertensive eyes with normal achromatic automated perimetry and short-wavelength automated perimetry could not be distinguished from normal subjects with confocal scanning laser ophthalmoscopy, confocal scanning laser polarimetry, and optical coherence tomography

OBJECTIVE: To investigate evidence for resistance to HIV-1 infection associated with the heterozygous genotype CCR5-+/Delta32 and with the homozygous genotype CCR5-Delta32/Delta32, which results in a nonfunctional CCR5 receptor. DESIGN: Cohort study of initially HIV-seronegative high-risk individuals from eight different cities. Enrollment data were analyzed to investigate the association of demographic factors and risk behaviors with CCR5 genotypes on the assumption that increased genotype prevalence among persons with histories of longer or more intensive exposure to HIV would indicate HIV resistance associated with that genotype. Longitudinal data were analyzed to investigate the association of HIV seroincidence with CCR5 genotypes. The cohort of 2996 individuals included 1892 men who have sex with men (MSM), 474 male injection drug users (IDUs), 347 women at heterosexual risk, and 283 female IDUs. MEASUREMENTS: CCR5 genotype, HIV serostatus, demographic factors, and risk behaviors during the 6 months before enrollment, followed by measurement of HIV seroincidence during the subsequent 18 months (for men) and 24 months (for women). RESULTS: Forty (1.3%) subjects were homozygous CCR5-Delta32/Delta32 and 387 (12.9%) were heterozygous CCR5-+/Delta32. All but 1 CCR5-Delta32/Delta32 individuals and 51 CCR5-+/Delta32 individuals were Caucasian. Among 1531 Caucasian MSM, CCR5-+/Delta32 individuals were present more frequently (22.3%) among those reporting unprotected receptive anal intercourse than among those not reporting this risk (15.9%) (p =.002), suggesting a selective advantage of the heterozygous genotype. CCR5-+/Delta32 individuals also had a significantly reduced relative risk of HIV seroconversion adjusted for unprotected receptive anal intercourse compared with CCR5-/+ individuals (relative risk = 0.30, 95% confidence interval [CI]: 0.08-0.97). CCR5-Delta32/Delta32 prevalence among Caucasian MSM was significantly associated with age among subjects recruited from high HIV seroprevalence cities (New York City and San Francisco) (odds ratio [OR] for each decade increase in age = 2.57, CI: 1.56-4.21) but not among those recruited from lower HIV prevalence sites (Boston, Chicago, Philadelphia, Seattle, and Providence/Pawtucket, Rhode Island) (OR = 1.20, CI: 0.75-1.89). CONCLUSIONS: Cross-sectional and longitudinal analyses indicated that among high-risk HIV seronegative MSM, CCR5-+/Delta32 and CCR5-Delta32/Delta32 are associated with protection against HIV infection. These findings imply that strategies aimed at reducing susceptibility to HIV infection by blocking CCR5 receptor sites need not seek blockage of all receptor sites to achieve an imperfect but substantial degree of protection

Live attenuated viral vectors that express human immunodeficiency virus (HIV) antigens are being developed as potential vaccines to prevent HIV infection. The first phase 2 trial with a canarypox vector (vCP205, which expresses gp120, p55, and protease) was conducted in 435 volunteers with and without gp120 boosting, to expand the safety database and to compare the immunogenicity of the vector in volunteers who were at higher risk with that in volunteers at lower risk for HIV infection. Neutralizing antibodies to the MN strain were stimulated in 94% of volunteers given vCP205 plus gp120 and in 56% of volunteers given vCP205 alone. CD8(+) cytotoxic T lymphocyte cells developed at some time point in 33% of volunteers given vCP205, with or without gp120. Phase 3 field trials with these or similar vaccines are needed, to determine whether efficacy in preventing HIV infection or in slowing disease progression among vaccinees who become infected is associated with the level and types of immune responses that were induced by the vaccines in this 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

Risk behaviors, symptoms, and virologic characteristics were studied among 103 human immunodeficiency virus (HIV) seroconverters in vaccine preparedness cohorts during 1995-1998. Overall, 83% of subjects were men who had sex with men; most reported multiple risk episodes and symptoms (84%, > or =1 symptom) during seroconversion. Acute HIV was diagnosed in only 8 of 50 who sought medical care. Median initial pretreatment plasma virus load was 25,800 copies/mL (range, undetectable-262,000 copies/mL) a mean of 4 months after seroconversion, and 9.7% had nucleoside-associated mutations; none had multidrug resistance. Semen virus load was more variable, 1.3 log(10) lower and modestly correlated (r=.28; 95% confidence interval, 0.16-0.42) with plasma among untreated men. When the plasma RNA level was <5000 copies/mL, 32% of untreated men, 13% on nucleoside regimens, and 7% on protease inhibitor-containing regimens had detectable seminal RNA. Acute HIV was seldom diagnosed, representing missed opportunities for early treatment and prevention. Most subjects had several relatively stable virus loads before initiation of antiretrovirals, indicating feasibility of assessing HIV vaccines on virus set point in efficacy trials

BACKGROUND: Home specimen collection and telephone counseling (HSCTC) may be a convenient new method for detection of HIV infection among cohorts at high-risk for HIV. GOAL: To evaluate attitudes about HSCTC among participants, HIV counselors, and community advisory board members associated with a national multisite study of persons at high risk for HIV. STUDY DESIGN: Twelve focus groups and surveys were conducted at six sites among 126 counselors, community advisory board members, and cohort participants. RESULTS: Staff and community advisory board members raised concerns about the acceptability, feasibility, safety, and effectiveness of HSCTC. In contrast, participants (92%) reported a willingness to collect blood and oral samples on a frequent basis, and preferred telephone (73%) to office-based counseling. CONCLUSION: Home specimen collection and telephone counseling appear to be preferred by study participants at high risk of HIV infection. Staff and community advisory board members had stronger reservations than prospective users

Objectives included (1) to develop methods for identifying injection drug users with accelerating injection habits so they might be referred to counseling and treatment and (2) to investigate behavioral correlates of accelerating injection habits, including syringe-exchange program utilization. Data on drug use, enrollment in methadone maintenance, and demographic variables were obtained from 328 subjects who were seronegative for human immunodeficiency virus (HIV) who attended anywhere from 4 to 11 quarterly study visits for interview, HIV pretest counseling and risk reduction counseling, and blood donation for HIV antibody testing. Subjects were recalled 2 weeks after each study visit to receive their results and post-test counseling. We characterized subjects according to their patterns of drug injection as accelerating, decelerating, or stable, using intraindividual regression analyses and categorization rules, and by syringe-exchange use as consistent users, sporadic users, or nonusers. The present subjects included 52% with decelerating, 29% with stable, and 19% with accelerating rates of drug injection. There were 128 subjects (39%) who were categorized as consistent users of syringe-exchange programs, 84 (25%) were categorized as sporadic users, and 116 (35%) were categorized as nonusers. All syringe-exchange groups showed significantly decelerating drug injection. Rates of decline were significantly less, however, among consistent syringe-exchange users than sporadic or nonusers of syringe exchanges. Categorical analysis also showed significant differences among groups, with 30% of consistent syringe-exchange program users having accelerating rates of drug injection compared to 9% of nonusers and 17% of sporadic users. That consistent syringe-exchange users included a larger proportion of individuals whose drug habits were accelerating than did sporadic users or nonusers of syringe exchanges suggests a need for improved identification and counseling of such subjects by syringe-exchange program staff. The present statistical approaches may be of value in targeting such efforts. The ability of a syringe-exchange program to attract a disproportionate share of drug users with accelerating rates of drug injection underscores the importance of these programs to HIV prevention efforts

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 </=35 years of age, with no formal education beyond high school, who had had a diagnosed sexually transmitted disease in the previous year, a primary male sex partner, and a male sex partner with a history of injecting use. Women were more likely to report anal sex by A-CASI than during interviewer-administered risk assessments (odds ratio [OR], 9.00; 95% confidence interval [CI], 1.14-71.0). A less biased method of ascertainment may account for the large proportion of women reporting anal sex. Given increased vaginal risk among women reporting anal sex, the relative importance of anal sex in heterosexual transmission merits further study. Behavioral and biomedical prevention strategies effective for anal as well as vaginal sex are needed