Sten H. Vermund

A Prospective Study of the Risk of Tuberculosis among Intravenous Drug Users with Human Immunodeficiency Virus Infection

To determine the risk of active tuberculosis associated with human immunodeficiency virus (HIV) infection, we prospectively studied 520 intravenous drug users enrolled in a methadone-maintenance program. Tuberculin skin testing and testing for HIV antibody were performed in all subjects. Forty-nine of 217 HIV-seropositive subjects (23 percent) and 62 of 303 HIV-seronegative subjects (20 percent) had a positive response to skin testing with purified protein derivative (PPD) tuberculin before entry into the study. The rates of conversion from a negative to a positive PPD test were similar for seropositive subjects (15 of 131; 11 percent) and seronegative subjects (26 of 202; 13 percent) who were retested during the follow-up period (mean, 22 months). Active tuberculosis developed in eight of the HIV-seropositive subjects (4 percent) and none of the seronegative subjects during the study period (P less than 0.002). Seven of the eight cases of tuberculosis occurred in HIV-seropositive subjects with a prior positive PPD test (7.9 cases per 100 person-years, as compared with 0.3 case per 100 person-years among seropositive subjects without a prior positive PPD test; rate ratio, 24.0; P less than 0.0001). We conclude that, although the prevalence and incidence of tuberculous infection were similar for both HIV-seropositive and HIV-seronegative intravenous drug users, the risk of active tuberculosis was elevated only for seropositive subjects. These data also suggest that in HIV-infected persons tuberculosis most often results from the reactivation of latent tuberculous infection; our results lend support to recommendations for the aggressive use of chemoprophylaxis against tuberculosis in patients with HIV infection and a positive PPD test.

Virologic and Immunologic Determinants of Heterosexual Transmission of Human Immunodeficiency Virus Type 1 in Africa

More than 80% of the worlds HIV-infected adults live in sub-Saharan Africa, where heterosexual transmission is the predominant mode of spread. The virologic and immunologic correlates of female-to-male (FTM) and male-to-female (MTF) transmission are not well understood. A total of 1022 heterosexual couples with discordant HIV-1 serology results (one partner HIV infected, the other HIV uninfected) were enrolled in a prospective study in Lusaka, Zambia and monitored at 3-month intervals. A nested case-control design was used to compare 109 transmitters and 208 nontransmitting controls with respect to plasma HIV-1 RNA (viral load, VL), virus isolation, and CD4(+) cell levels. Median plasma VL was significantly higher in transmitters than nontransmitters (123,507 vs. 51,310 copies/ml, p < 0.001). In stratified multivariate Cox regression analyses, the risk ratio (RR) for FTM transmission was 7.6 (95% CI: 2.3, 25.5) for VL > or = 100,000 copies/ml and 4.1 (95% CI: 1.2, 14.1) for VL between 10,000 and 100,000 copies/ml compared with the reference group of <10,000 copies/ml. Corresponding RRs for MTF transmission were 2.1 and 1.2, respectively, with 95% CI both bounding 1. Only 3 of 41 (7%) female transmitters had VL < 10,000 copies/ml compared with 32 of 93 (34%) of female nontransmitters (p < 0.001). The transmission rate within couples was 7.7/100 person-years and did not differ from FTM (61/862 person-years) and MTF (81/978 person-years) transmission. We conclude that the association between increasing plasma viral load was strong for female to male transmission, but was only weakly predictive of male to female transmission in Zambian heterosexual couples. FTM and MTF transmission rates were similar. These data suggest gender-specific differences in the biology of heterosexual transmission.

High risk of human papillomavirus infection and cervical squamous intraepithelial lesions among women with symptomatic human immunodeficiency virus infection

We investigated the relationship of human papillomavirus (by cervicovaginal lavage and Southern blot), human immunodeficiency virus, and squamous intraepithelial lesions in 96 high-risk women in the Bronx, New York. Antibodies for human immunodeficiency virus were detected in 51 (53%) women. Of the 33 women with symptomatic human immunodeficiency virus infection, 23 (70%) had human papillomavirus infection compared with 4 of 18 (22%) asymptomatic women who were human immunodeficiency virus seropositive and 10 of 45 (22%) uninfected women (p less than 0.0001). The rate of squamous intraepithelial lesions was 52% (14 of 27) for women with both viruses detected, 18% (6 of 34) for women with either virus detected, and 9% (3 of 35) for uninfected women. Among symptomatic human immunodeficiency virus-infected women, a strong association between human papillomavirus infection and squamous intraepithelial lesions was demonstrated (odds ratio, 12; 95% confidence interval, 1.3 to 108). Risk was highest for younger women from ethnic or racial minority groups. Advanced human immunodeficiency virus-related disease, with its associated immunosuppression, seems to exacerbate human papillomavirus-mediated cervical cytologic abnormalities. Public health measures are needed to provide Papanicolaou smear screening and appropriate clinical follow-up and treatment for women at high risk for human immunodeficiency virus infection.

Declining prevalence of cervicovaginal human papillomavirus infection with age is independent of other risk factors.

Background and Objectives: Human papillomavirus (HPV) infection of the female genital tract is the most common sexually transmitted disease. Although the prevalence of HPV in women without detectable cervical disease has been shown to decline with increasing age, the relationship to sexual behavior has not been investigated. Goal: To identify risk factors for, and associated with the age‐dependent decline in, genital HPV infection in women. Study Design: The prevalence of HPV was determined in a cohort of 439 sexually active inner‐city women between the ages of 18 and 50 years recruited in Brooklyn, New York. Cervicovaginal cells were collected by lavage, and HPV was detected by low‐stringent Southern blot hybridization. Results: The prevalence of HPV infection ranged from 36% in women younger than 25 years of age to 2.8% in women 45 years or older. Logistic regression analysis identified an increased risk for cervical HPV infection to be independently associated with number of sex partners in the past year (odds ratio [OR], 1.04 per yearly increase in age; 95% confidence interval [CI], 1.00 to 1.08), younger age (OR, 0.92 per year increase in age; 95% CI, 0.88 to 0.95), and not living with partner (OR, 2.28; 95% CI, 1.40 to 4.22). Conclusions: The lower prevalence of HPV infection in older women compared to younger women was found to be independent of sexual behavior. These results suggest that a biologic effect, such as HPV immunity acquired over time and with multiple exposures, may mediate the inverse relationship between age and HPV prevalence.

Combination HIV Prevention: Significance, Challenges, and Opportunities

No single HIV prevention strategy will be sufficient to control the HIV pandemic. However, a growing number of interventions have shown promise in partially protecting against HIV transmission and acquisition, including knowledge of HIV serostatus, behavioral risk reduction, condoms, male circumcision, needle exchange, treatment of curable sexually transmitted infections, and use of systemic and topical antiretroviral medications by both HIV-infected and uninfected persons. Designing the optimal package of interventions that matches the epidemiologic profile of a target population, delivering that package at the population level, and evaluating safety, acceptability, coverage, and effectiveness, all involve methodological challenges. Nonetheless, there is an unprecedented opportunity to develop “prevention packages” that combine various arrays of evidence-based strategies, tailored to the needs of diverse subgroups and targeted to achieve high coverage for a measurable reduction in population-level HIV transmission. HIV prevention strategies that combine partially effective interventions should be scaled up and evaluated.

Hepatitis B and hepatitis C in Pakistan: prevalence and risk factors §

BACKGROUND Pakistan carries one of the worlds highest burdens of chronic hepatitis and mortality due to liver failure and hepatocellular carcinomas. However, national level estimates of the prevalence of and risk factors for hepatitis B and hepatitis C are currently not available. METHODS We reviewed the medical and public health literature over a 13-year period (January 1994-September 2007) to estimate the prevalence of active hepatitis B and chronic hepatitis C in Pakistan, analyzing data separately for the general and high-risk populations and for each of the four provinces. We included 84 publications with 139 studies (42 studies had two or more sub-studies). RESULTS Methodological differences in studies made it inappropriate to conduct a formal meta-analysis to determine accurate national prevalence estimates, but we estimated the likely range of prevalence in different population sub-groups. A weighted average of hepatitis B antigen prevalence in pediatric populations was 2.4% (range 1.7-5.5%) and for hepatitis C antibody was 2.1% (range 0.4-5.4%). A weighted average of hepatitis B antigen prevalence among healthy adults (blood donors and non-donors) was 2.4% (range 1.4-11.0%) and for hepatitis C antibody was 3.0% (range 0.3-31.9%). Rates in the high-risk subgroups were far higher. CONCLUSIONS Data suggest a moderate to high prevalence of hepatitis B and hepatitis C in different areas of Pakistan. The published literature on the modes of transmission of hepatitis B and hepatitis C in Pakistan implicate contaminated needle use in medical care and drug abuse and unsafe blood and blood product transfusion as the major causal factors.

The Effects on Survival of Early Treatment of Human Immunodeficiency Virus Infection

BACKGROUND Zidovudine has been shown to prolong survival in patients with the acquired immunodeficiency syndrome (AIDS) and, in persons with human immunodeficiency virus (HIV) infection but not AIDS, to delay the progression to AIDS. However, it is still uncertain whether treatment before the development of AIDS prolongs survival. METHODS We analyzed data from a cohort of 2162 high-risk men who were already seropositive for HIV type 1 (HIV-1) and 406 men who seroconverted from October 1986 through April 1991. There were 306 deaths. The probabilities of death were compared among men at similar stages of disease who began zidovudine therapy before the diagnosis of AIDS and among those who did not. Relative risks of death were calculated for each of five initial disease states on the basis of CD4+ cell counts and clinical symptoms and signs appearing over follow-up periods of 6, 12, 18, and 24 months. Adjustments were also made for the use of prophylaxis against Pneumocystis carinii pneumonia (PCP). RESULTS After we controlled for CD4+ cell count and symptoms, the use of zidovudine with or without PCP prophylaxis before the development of AIDS significantly reduced mortality in all follow-up periods. The relative risks of death were 0.43 (95 percent confidence interval, 0.23 to 0.78) at 6 months, 0.54 (95 percent confidence interval, 0.38 to 0.78) at 12 months, 0.59 (95 percent confidence interval, 0.44 to 0.79) at 18 months, and 0.67 (95 percent confidence interval, 0.52 to 0.86) at 24 months. After we adjusted for the effects of PCP prophylaxis, zidovudine alone significantly reduced mortality at 6, 12, and 18 months (relative risks, 0.45, 0.59, and 0.70, respectively), but not at 24 months (relative risk, 0.81). Among zidovudine users, those who also used PCP prophylaxis before the development of AIDS had significantly lower mortality at 18 and 24 months than those who did not (relative risks, 0.62 and 0.60, respectively). CONCLUSIONS The results of this study support the hypothesis that in HIV-1 infection, early treatment with zidovudine and PCP prophylaxis improves survival in addition to slowing the progression to AIDS.

Prevention of mother-to-child transmission of HIV in Africa: successes and challenges in scaling-up a nevirapine-based program in Lusaka, Zambia

Background: Nearly half of perinatal HIV infection is preventable with nevirapine (NVP), which has transformed the ability to confront this transmission route in resource‐limited settings. Methods: A NVP‐based perinatal HIV prevention program initiated in Lusaka, Zambia in November 2001. Results: The first 12 months cost US

No Change in Health Risk Behaviors Over Time Among HIV Infected Adolescents in Care: Role of Psychological Distress

221 000 and enabled 178 district health employees to be trained in voluntary counseling and testing: 17 263 pregnant women were counseled for HIV, 12 438 (72%) were tested, and 2924 (24%) were found to be infected with HIV. NVP has been taken by 1654 (57%) mothers and 1157 (40%) babies. It is estimated that at least 190 infants have been spared HIV infection (11 per 1000 counseled women or 65 per 1000 identified HIV‐infected women). Conclusions: Prevention of mother‐to‐child HIV transmission is feasible and cost effective in resource‐limited settings. In Lusaka, thousands of women have received voluntary counseling and testing and NVP therapy under the present scheme. Patient attrition and non‐adherence represented a major source of program inefficiency, which requires to be systematically addressed.

Risk of HIV/AIDS in China : subpopulations of special importance

PURPOSE To investigate the association of psychological distress and health risk behaviors among HIV infected adolescents. It was hypothesized that higher levels of distress would be associated with increased sexual risk behaviors, and increased use of alcohol and drugs. METHODS HIV infected adolescents (N = 323) were recruited into an observational study in 15 clinical sites; for the 323 subjects, a total of 1212 visits were used in a repeated measures analysis. Data on depression (using the CES-D), anxiety (manifest anxiety scale), sexual behaviors and alcohol and marijuana use were obtained through computer-assisted self-administered interview. RESULTS Approximately 65% of the sample was sexually active across all six study visits, with approximately 43% consistently reporting having unprotected sex at last intercourse. Higher levels of depression were associated with frequent alcohol use and with unprotected sex at last intercourse, with depressed adolescents significantly more likely to have had unprotected sex than those who were not depressed. Health anxiety was associated with frequent marijuana use and with recent sexual activity, and physiological anxiety was also associated with recent sexual activity. CONCLUSIONS Despite the fact that these HIV infected adolescents are all engaged in primary care, overall the sample is maintaining its high-risk sexual behavior. In addition, these adolescents may be self-medicating to deal with health-related anxiety. Health interventions for HIV infected adolescents should examine whether psychological distress is contributing to maintenance health risk behaviors.