Kimberly Page-Shafer

SEXUAL TRANSMISSION AND THE NATURAL HISTORY OF HUMAN HERPESVIRUS 8 INFECTION

BACKGROUND Although human herpesvirus 8 (HHV-8) has been suspected to be the etiologic agent of Kaposis sarcoma, little is known about its seroprevalence in the population, its modes of transmission, and its natural history. METHODS The San Francisco Mens Health Study, begun in 1984, is a study of a population-based sample of men in an area with a high incidence of human immunodeficiency virus (HIV) infection. We studied all 400 men infected at base line with HIV and a sample of 400 uninfected men. Base-line serum samples were assayed for antibodies to HHV-8 latency-associated nuclear antigen (anti-LANA). In addition to the seroprevalence and risk factors for anti-LANA seropositivity, we analyzed the time to the development of Kaposis sarcoma. RESULTS Anti-LANA antibodies were found in 223 of 593 men (37.6 percent) who reported any homosexual activity in the previous five years and in none of 195 exclusively heterosexual men. Anti-LANA seropositivity correlated with a history of sexually transmitted diseases and had a linear association with the number of male sexual-intercourse partners. Among the men who were infected with both HIV and HHV-8 at base line, the 10-year probability of Kaposis sarcoma was 49.6 percent. Base-line anti-LANA seropositivity preceded and was independently associated with subsequent Kaposis sarcoma, even after adjustment for CD4 cell counts and the number of homosexual partners. CONCLUSIONS The prevalence of HHV-8 infection is high among homosexual men, correlates with the number of homosexual partners, and is temporally and independently associated with Kaposis sarcoma. These observations are further evidence that HHV-8 has an etiologic role in Kaposis sarcoma and is sexually transmitted among men.

Relationship between T Cell Activation and CD4+ T Cell Count in HIV-Seropositive Individuals with Undetectable Plasma HIV RNA Levels in the Absence of Therapy

BACKGROUND Although untreated human immunodeficiency virus (HIV)-infected patients maintaining undetectable plasma HIV RNA levels (elite controllers) have high HIV-specific immune responses, it is unclear whether they experience abnormal levels of T cell activation, potentially contributing to immunodeficiency. METHODS We compared percentages of activated (CD38(+)HLA-DR(+)) T cells between 30 elite controllers, 47 HIV-uninfected individuals, 187 HIV-infected individuals with undetectable viremia receiving antiretroviral therapy (antiretroviral therapy suppressed), and 66 untreated HIV-infected individuals with detectable viremia. Because mucosal translocation of bacterial products may contribute to T cell activation in HIV infection, we also measured plasma lipopolysaccharide (LPS) levels. RESULTS Although the median CD4(+) cell count in controllers was 727 cells/mm(3), 3 (10%) had CD4(+) cell counts <350 cells/mm(3) and 2 (7%) had acquired immunodeficiency syndrome. Controllers had higher CD4(+) and CD8(+) cell activation levels (P < .001 for both) than HIV-negative subjects and higher CD8(+) cell activation levels than the antiretroviral therapy suppressed (P = .048). In controllers, higher CD4(+) and CD8(+) T cell activation was associated with lower CD4(+) cell counts (P = .009 and P = .047). Controllers had higher LPS levels than HIV-negative subjects (P < .001), and in controllers higher LPS level was associated with higher CD8(+) T cell activation (P = .039). CONCLUSION HIV controllers have abnormally high T cell activation levels, which may contribute to progressive CD4(+) T cell loss even without measurable viremia.

Hepatitis C Virus Seroconversion among Young Injection Drug Users: Relationships and Risks

The present study examined reasons for the high incidence of hepatitis C virus (HCV) infection among young injection drug users (IDUs). IDUs <30 years old who tested negative for HCV antibody were enrolled in a prospective cohort. Risk factors for seroconversion were examined using time-dependent regression analyses: 48 of 195 IDUs seroconverted to HCV, for an incidence rate of 25.1/100 person-years (95% confidence interval, 18.7-32.9/100 person-years). Independent risk factors included sharing needles with an HCV-infected sex partner (borderline statistical significance, P=.11) or a person who was not a sex partner, sharing nonsterile drug-preparation equipment, pooling money with another IDU to buy drugs, and exchanging sex for money. Ubiquitous behaviors among young IDUs, such as the forming of injecting or sexual partnerships and consequent sharing of needles and drug preparation equipment, are risk factors for HCV. Interventions to reduce HCV transmission must recognize the importance of relationships on injecting risk.

Gender differences in sexual and injection risk behavior among active young injection drug users in San Francisco (the UFO Study).

Female injection drug users (IDUs) represent a large proportion of persons infected with HIV in the United States, and women who inject drugs have a high incidence of hepatitis B virus (HBV) and hepatitis C virus (HCV) injection. Therefore, it is important to understand the role of gender in injection risk behavior and the transmission of blood-borne virus. In 2000–2002, 844 young (<30 years old) IDUs were surveyed in San Francisco. We compared self-reported risk behavior between 584 males and 260 female participants from cross-sectional baseline data. We used logistic regression to determine whether demographic, structural, and relationship variables explained increased needle borrowing, drug preparation equipment sharing, and being injected by another IDU among females compared to males. Females were significantly younger than males and were more likely to engage in needle borrowing, ancillary equipment sharing, and being injected by someone else. Females were more likely than males to report recent sexual intercourse and to have IDU sex partners. Females and males were not different with respect to education, race/ethnicity, or housing status. In logistic regression models for borrowing a used needle and sharing drug preparation equipment, increased risk in females was explained by having an injection partner who was also a sexual partner. Injecting risk was greater in the young female compared to male IDUs despite equivalent frequency of injecting. Overlapping sexual and injection partnerships were a key factor in explaining increased injection risk in females. Females were more likely to be injected by another IDU even after adjusting for years injecting, being in a relationship with another IDU, and other potential confounders. Interventions to reduce sexual and injection practices that put women at risk of contracting hepatitis and HIV are needed.

Correlates of heavy substance use among young gay and bisexual men: The San Francisco Young Men's Health Study

Correlates of heavy substance use among a household-based sample of young gay and bisexual men (n=428) were identified and the odds ratio (OR) was calculated. A total of 13.6% reported frequent, heavy alcohol use and 43% reported polydrug use. Compared with men employed in professional occupations, men in service positions (OR=3.77) and sales positions (OR=2.51) were more likely to be heavy alcohol consumers. Frequent gay bar attendance and multiple sex partners were related to heavy alcohol use, as well as to polydrug use. Polydrug users were more likely to be HIV seropositive (OR=2.05) or of unknown HIV serostatus (OR=2.78). HIV serostatus was similarly related to frequent drug use. These correlates of heavier substance use among young gay and bisexual men could be used to identify and intervene early with members of this population who are at risk of substance misuse, as well as HIV/AIDS risk.

Comorbidity and survival in HIV-Infected men in the San Francisco Men's Health Survey☆

The course of disease associated with infection with the human immunodeficiency virus varies widely. Some patients deteriorate rapidly, while others live for years, even after an illness that defines the acquired immunodeficiency syndrome (AIDS). In this study, comorbidity, or the presence of concurrent health problems, was investigated prospectively as a possible co-factor for different rates of decline in 395 homosexual/bisexual men in the San Francisco Mens Health Study (SFMHS) who were infected with the human immunodeficiency virus (HIV). Comorbidity data obtained from baseline interviews included both chronic and infectious diseases as well as depression. Smoking, alcohol, and drug use were also examined. The most prevalent comorbid conditions were sexually transmitted diseases (90%) and hepatitis B infection (76%). Most chronic and acute concurrent health conditions were not significant discrete predictors of survival to AIDS or death after controlling for immune status and markers of disease progression. Significantly, other risk factors (e.g., depression and smoking) were found to be associated with more rapid progression. Men with symptoms of depression had a higher risk of progression of AIDS diagnosis; the relative hazard (RH) was 1.4 (95% confidence interval [CI], 1.00-2.08); smoking was associated with higher risk of death (RH, 1.6; 95% CI, 1.20-2.17). Older age was marginally associated with poorer survival to death. No associations were found between survival and alcohol and drug use.

Risk of prevalent HIV infection associated with incarceration among injecting drug users in Bangkok, Thailand: case-control study

Abstract Objectives: To identify risks for HIV infection related to incarceration among injecting drug users in Bangkok, Thailand. Design: Case-control study of sexual and parenteral exposures occurring before, during, and after the most recent incarceration. Setting: Metropolitan Bangkok. Participants: Non-prison based injecting drug users formerly incarcerated for at least six months in the previous five years, with documented HIV serostatus since their most recent release; 175 HIV positive cases and 172 HIV negative controls from methadone clinics. Main outcome measure: Injection of heroin and methamphetamine, sharing of needles, sexual behaviour, and tattooing before, during, and after incarceration. Results: In the month before incarceration cases were more likely than controls to have injected methamphetamine and to have borrowed needles. More cases than controls reported using drugs (60% v 45%; P=0.005) and sharing needles (50% v 31%; P<0.01) in the holding cell before incarceration. Independent risk factors for prevalent HIV infection included injection of methamphetamine before detention (adjusted odds ratio 3.3, 95% confidence interval 1.01 to 10.7), sharing needles in the holding cell (1.9, 1.2 to 3.0), being tattooed while in prison (2.1, 1.3 to 3.4), and borrowing needles after release (2.5, 1.3 to 4.4). Conclusions: Injecting drug users in Bangkok are at significantly increased risk of HIV infection through sharing needles with multiple partners while in holding cells before incarceration. The time spent in holding cells is an important opportunity to provide risk reduction counselling and intervention to reduce the incidence of HIV. What is already known on this topic The incidence of HIV in Thailand is highest among injecting drug users in Bangkok Incarceration is a risk factor for incident HIV infection among Thai injecting drug users What this study adds Injecting drug users are at increased risk of HIV infection from sharing needles with multiple partners while in police holding cells before incarceration Other risk factors include injecting methamphetamine before imprisonment, being tattooed while imprisoned, and sharing needles after release

Hepatitis C Virus Infection among Prisoners in the California State Correctional System

BACKGROUND Incarcerated populations are at high risk for hepatitis C virus (HCV) infection, yet prisoners are not routinely screened or treated for HCV infection. Understanding the risk factors of HCV infection among prisoners could help improve HCV interventions. METHODS Prevalence and risk of HCV infection among 469 prisoners entering California State correctional facilities were assessed using HCV antibody screening, HCV RNA measurement, and structured interviews. Multivariate logistic regression analysis was used to identify independent correlates of HCV infection. RESULTS The prevalence of HCV infection was 34.3% overall (95% confidence interval [CI], 30%-38%) and was 65.7% among those with a history of injection drug use (IDU), compared with 10.2% among those with no history of IDU (odds ratio [OR], 17.24; 95% CI, 10.52-28.25). Significant differences in HCV antibody positivity were found in association with age at first detention but not with the nature of the crime. Independent correlates of HCV infection included age, history of IDU, cumulative time of incarceration, biological sex (OR for females subjects compared with males subjects, 0.35; 95% CI, 0.13-0.96), and a history of having sex with a male IDU (OR, 4.42; 95% CI, 1.46-13.37). We identified significant differences in risk factors between male and female subjects--notably, that the risk of HCV infection was significantly elevated among female non-IDUs who reported having sexual partners with a history of IDU. Among non-IDUs, correlates of HCV infection included history of receipt of blood products and cumulative years of incarceration. CONCLUSIONS HCV infection is pervasive among the California prison population, including prisoners who are non-IDUs and women with high-risk sexual behavior. These results should promote consideration of routine HCV antibody screening and behavioral interventions among incarcerated men and women.

Adverse impact of cigarette smoking on dimensions of health-related quality of life in persons with HIV infection.

Because effects of cigarette smoking on health-related quality of life (HRQL) have not been well described, we carried out a cross-sectional assessment of HRQL using the Medical Outcomes Survey Scale adapted for patients with human immunodeficiency virus (MOS-HIV questionnaire) in 585 HIV-infected homosexual/bisexual men, injection drug users, and female partners enrolled in a multicenter, prospective study of the pulmonary complications of HIV infection. Mean scores for the following dimensions of HRQL were calculated: general health perception, quality of life, physical functioning, bodily pain, social functioning, role functioning, energy, cognitive functioning, and depression. A multivariate model was used to determine the impact on HRQL of the following factors: smoking, CD4 loss, acquired immune deficiency syndrome (AIDS) diagnoses, number of symptoms, study site, education, injection drug use, gender, and age. Current smoking was independently associated with lower scores for general health perception, physical functioning, bodily pain, energy, role functioning, and cognitive functioning (all with p < 0.05). We conclude that patients with HIV infection who smoke have poorer HRQL than nonsmokers. These results support the use of smoking cessation strategies for HIV-infected persons who smoke cigarettes.

Risk of HIV infection attributable to oral sex among men who have sex with men and in the population of men who have sex with men

We examined HIV infection and estimated the population-attributable risk percentage (PAR%) for HIV associated fellatio among men who have sex with other men (MSM). Among 239 MSM who practised exclusively fellatio in the past 6 months, 50% had three partners, 98% unprotected; and 28% had an HIV-positive partner; no HIV was detected. PAR%, based on the number of fellatio partners, ranges from 0.10% for one partner to 0.31% for three partners. The risk of HIV attributable to fellatio is extremely low.