Human herpesvirus 8 infection among adolescents in the REACH cohort.

OBJECTIVE: Human herpesvirus 8 (HHV-8) infection is common among children in areas where Kaposi sarcoma is endemic. Human herpesvirus 8 is uncommon in children but prevalent in adults at risk for human immunodeficiency virus (HIV) infection in the United States, including men who have sex with men (MSM) and women who engage in high-risk sexual behavior. We examined the prevalence and predictors of HHV-8 infection among adolescents with or at high risk for acquiring HIV infection. DESIGN: Cross-sectional analysis. SETTING: National study of HIV infection among adolescents in primary care. PARTICIPANTS: A total of 537 young adults practicing high-risk sexual behavior, of which 403 were women and 134 were men; among the 134 men, 75% were MSM. INTERVENTIONS: Detailed questionnaires and testing for serum antibodies to HHV-8. OUTCOME MEASURE: Detection of serum antibodies to HHV-8. RESULTS: Sixty (11.2%) of 537 young adults were HHV-8 seropositive, including 20 MSM (19.6%), 2 male heterosexuals (6.5%), and 27 female heterosexuals (8.2%). The prevalence of HHV-8 in HIV-positive MSM (17/74 [23.0%]) was twice as high as that in HIV-negative MSM (3/28 [10.7%]) (P = .18), but no characteristic predicted HHV-8 infection among MSM. In multivariate analysis, history of gonorrhea (odds ratio [OR], 2.8; 95% confidence interval [CI], 1.4-5.7; P<.01), history of having sex with women (OR, 2.4; 95% CI, 1.1-5.3; P = .03), and African American race (OR, 3.4; 95% CI, 1.1-10.0; P = .03) were associated with HHV-8 infection among women. CONCLUSIONS: Human herpesvirus 8 is common among US adolescents practicing high-risk sexual behaviors. Sexual identity, race, and sexual behavior may influence the risk of infection with HHV-8 in women.

Independent association of hygiene, socioeconomic status, and circumcision with reduced risk of HIV infection among Kenyan men.

Among Kenyan men recruited as sex partners of women with genital symptoms, 22 of 150 were HIV seropositive. Because male HIV infection and male hygiene were unexpectedly found to be associated with each other, we examined the relationship of 5 hygiene variables with HIV infection in the men in a principal components analysis, controlling for socioeconomic status and other potential confounders. By multivariate analyses, HIV infection in men was not only independently associated with previous illness (odds ratio [OR], 5.1; 95% confidence interval [CI], 1.4-19.1) and inversely associated with being circumcised (OR, 0.12; 95% CI, 0.02-0.91), but also independently associated with a combined measure of hygiene (OR, 0.41; 95% CI, 0.19-0.90).

Bacterial vaginosis: risk factors among Kenyan women and their male partners.

OBJECTIVES: To simultaneously examine associations of bacterial vaginosis (BV) with potential risk factors in both the female and her male partner. STUDY DESIGN: We recruited women 18-45 years of age and their male partners from clinics in Nairobi, Kenya. All underwent face-to-face standardized interview physical examination, human immunodeficiency virus (HIV)-1 and syphilis serologic testing, endocervical cultures for Neisseria gonorrhoeae, and vaginal swabs for diagnosis of BV by Gram stain and trichomoniasis by culture. RESULTS: Of 219 women, 97 (44%) had BV. BV was significantly associated by univariate analyses with women's own risk factors (young age, being unmarried, early sexual debut, more than 1 sexual partner, lifetime, rectal sex, trichomoniasis, HIV infection, and by principal components analysis, with low socioeconomic status [SES]) and also with male partners' characteristics (HIV infection, and by principal components analysis, low SES, and poor hygiene). In multivariate analysis including risk factors from both genders, the odds of having BV was 5.7 times higher if either partner was HIV seropositive, 13.2 times higher if the female had trichomoniasis, 2.5 times higher if the female had more than 1 sex partner ever, and decreased with increasing age of the female. CONCLUSION: In this population, characteristics of males and of females were independently associated with BV. Close association of male hygiene and male HIV status precluded distinguishing the influence of male hygiene on partner's BV.

Accuracy and precision of estimating intervention efficacy when the timing of observed events differ by treatment arm.

Randomization in clinical trials minimizes differences between treatment arms, allowing observed treatment differences to be attributable to an intervention. For prospective clinical trials, we examine the effects on inference when other specified treatment arm differences are also present. These differences are imposed using three measures: time between the unobserved failure event (e.g., HIV infection) and its detection, visit schedule adherence and dropout. Our context of interest is trials with non-recurrent time-to-event outcomes and fixed visit intervals, where treatment efficacy is measured either by a hazard ratio or by a ratio of cumulative incidence functions. Moderate treatment differences in visit adherence, either through missed visits or additional unscheduled visits, were not found to cause substantial bias or to reduce power. However, both differential loss to follow-up (when coincidentally dependent on risk of failure) and differential time between event and detection should be of concern in designing clinical trials. Efforts to re-capture subjects at the end of study for failure assessment are helpful in some contexts, and may be considered in study planning.

Immunoepidemiologic profile of Chlamydia trachomatis infection: importance of heat-shock protein 60 and interferon- gamma.

Epidemiological, animal, and in vitro investigations suggest that Chlamydia trachomatis infection engenders acquired immunity, the basis for which is incompletely defined, especially in humans. In a prospective cohort study of women at high risk for C. trachomatis infection, we found that, at baseline and after adjustment for age and other potential confounding variables, production of interferon- gamma by peripheral-blood mononuclear cells (PBMCs) stimulated with chlamydia heat-shock protein 60 strongly correlated with protection against incident C. trachomatis infection. This investigation supports a direct role for C. trachomatis-specific immune responses in altering the risk of infection and suggests immune correlates of protection that are potentially useful in vaccine development.

A population-based study of primary human herpesvirus 6 infection.

BACKGROUND: Serologic studies indicate that human herpesvirus 6 (HHV-6) infects 90 percent of children by two years of age. Little is known about the acquisition, virologic course, and clinical manifestations of HHV-6 infection. METHODS: We prospectively studied a cohort of 277 children from birth through the first two years of life to define the pattern of acquisition of HHV-6. The children's saliva was tested weekly for HHV-6 DNA with the use of the polymerase chain reaction. Parents maintained a daily log of signs and symptoms of illness in their children. RESULTS: Primary HHV-6 infection occurred in 130 children, with cumulative percentages of 40 percent by the age of 12 months and 77 percent by the age of 24 months. The peak age of acquisition was between 9 and 21 months. The acquisition of HHV-6 was associated with female sex (adjusted hazard ratio, 1.7; 95 percent confidence interval, 1.2 to 2.4) and having older siblings (adjusted hazard ratio, 2.1; 95 percent confidence interval, 1.4 to 2.9). Among 81 children with a well-defined time of acquisition of HHV-6, 93 percent had symptoms, and 38 percent were seen by a physician. None had seizures. As compared with children who had other illnesses, those with primary HHV-6 infection were more likely to have fever (P=0.003), fussiness (P=0.02), diarrhea (P=0.03), rash (P=0.003), and roseola (P=0.002) and were more likely to visit a physician (P=0.003). CONCLUSIONS: The acquisition of HHV-6 in infancy is usually symptomatic and often results in medical evaluation. Roseola occurs in a minority of patients, and febrile seizures are infrequently associated with primary HHV-6 infection. Older siblings appear to serve as a source of HHV-6 transmission.

Association of hormonal contraception and HIV-seroprevalence in Nairobi, Kenya.

Among women attending family planning clinics in Nairobi, Kenya, the HIV-seroprevalence rates for different contraceptive methods were: depomedroxyprogesterone acetate (DMPA) 431/3279 (13.1%), combination oral contraceptive pill 114/1073 (10.6%), and progesterone-only contraceptive pill (POCP) 45/741 (6.1%). After adjusting for age, marital status, and parity, women using the POCP had a lower HIV seroprevalence (adjusted odds ratio 0.5, 95% confidence interval 0.3-0.7) than women using DMPA. This association was most pronounced among POCP users of lower parity.

Risk factors for pneumonia in urban-dwelling HIV-infected women: a case-control study in Nairobi, Kenya.

In sub-Saharan Africa, respiratory tract infections (RTI) are the leading cause of serious morbidity and mortality in HIV-infected persons. This study sought to investigate demographic, socioeconomic, and environmental risk factors for pneumonia in a cohort of HIV-infected women. The authors performed a nested case-control study in a cohort of HIV-1-infected adults followed in Nairobi, Kenya. Thirty-nine women who developed pneumonia during the follow-up period were selected as cases, and 66 women who did not develop pneumonia were randomly chosen to serve as control subjects. A questionnaire was administered in subjects' homes that assessed demographics, home environment, and socioeconomic status. Women were followed in the cohort for a median of 36.8 months (range, 27.3-39.3). Adjusting for length of follow-up period, factors associated with lower socioeconomic status (lower monthly spending [OR = 3.2; 95% CI, 1.2-8.4 per 10,000 Kenyan shilling decrease], having no savings [OR = 4.1; 95% CI, 1.4-11.9], less sturdy home construction material such as mud or cement walls [OR = 2.6; 95% CI, 1.1-5.9] or dirt floors [OR = 2.8; 95% CI, 1.0-7.6], and lack of a window in the home [OR = 5.5; 95% CI, 0.9-32.2]) and being widowed (OR = 4.3; 95% CI, 1.2-15.1) or single (OR = 3.3; 95% CI, 1.0-11.2) were associated with an increased risk of pneumonia. In multivariate analysis, widowed (AOR = 5.9; 95% CI, 1.3-26.3), single (AOR = 7.7; 95% CI, 1.6-36.4), and divorced (AOR = 4.5; 95% CI, 1.0-20.1) women, those without savings (AOR = 3.7; 95% CI, 1.2-11.7), and those living in more crowded and contagious conditions (AOR = 1.5; 95% CI, 1.1-2.1) remained at increased risk of pneumonia. If confirmed by prospective investigation, these findings could help identify persons and subpopulations of HIV-infected women with the greatest risk of pneumonia.

Discrete proportional hazards models for mismeasured outcomes.

Outcome mismeasurement can lead to biased estimation in several contexts. Magder and Hughes (1997, American Journal of Epidemiology 146, 195-203) showed that failure to adjust for imperfect outcome measures in logistic regression analysis can conservatively bias estimation of covariate effects, even when the mismeasurement rate is the same across levels of the covariate. Other authors have addressed the need to account for mismeasurement in survival analysis in selected cases (Snapinn, 1998, Biometrics 54, 209-218; Gelfand and Wang, 2000, Statistics in Medicine 19, 1865-1879; Balasubramanian and Lagakos, 2001, Biometrics 57, 1048-1058, 2003, Biometrika 90, 171-182). We provide a general, more widely applicable, adjusted proportional hazards (APH) method for estimation of cumulative survival and hazard ratios in discrete time when the outcome is measured with error. We show that mismeasured failure status in a standard proportional hazards (PH) model can conservatively bias estimation of hazard ratios and that inference, in most practical situations, is more severely affected by poor specificity than by poor sensitivity. However, in simulations over a wide range of conditions, the APH method with correctly specified mismeasurement rates performs very well.