Gerald B. Sharp

The Women's Interagency HIV Study: an Observational Cohort Brings Clinical Sciences to the Bench

The Womens Interagency HIV Study (WIHS) is an ongoing long-term observational study of 3,772 women who are either infected with human immunodeficiency virus (HIV) or considered to be at risk for acquiring HIV. Since 1994, the WIHS (pronounced like “wise”) has developed a large database and specimen repository that serve as resources for WIHS investigators as well as for nonaffiliated researchers working on HIV-related or HIV coinfection issues. The purpose of this report is to update researchers on the progress of the WIHS and to provide information on WIHS resources, the methods by which they were obtained, and background for any new potential researchers interested in conducting collaborative research through shared use of these resources.

Prevalence and predictors of HIV infection among female sex workers in Kaiyuan City, Yunnan Province, China

BACKGROUND Sexual transmission is the fastest growing route of HIV transmission in China. We undertook this study to describe the risk factors for HIV infection in female sex workers (FSWs), and to determine the commercial sex venues where FSWs are most at risk of being infected with or infecting others with HIV. METHODS This was a cross-sectional study of 737 FSWs in Kaiyuan City, Yunnan Province in southern China, which took place from March to May 2006. RESULTS The overall HIV prevalence was 10.3%, but prevalence varied with sex venue with 25.8% of FSWs working on the streets being HIV-positive and none of the FSWs working in nightclubs. Adjusted odds ratios (OR) of HIV infection were 9.1 (95% confidence interval (CI) 4.67-17.55) for injection drug use, 3.3 (95% CI 1.46-7.37) for non-injection illegal drug use, 2.7 (95% CI 1.25-5.93) for duration of sex work > or = 5 years, 2.2 (95% CI 1.05-4.70) for infection with herpes simplex virus type 2, and 2.0 (95% CI 1.12-3.47) for working at a higher risk entertainment venue. Although condom use was not a significant risk factor in the overall model, FSWs in lower risk venues who reported consistent use with clients had a 70% reduction in HIV infections (OR 0.30, 95% CI 0.12-0.90). CONCLUSIONS Illegal drug use, particularly with injection drugs, is the single greatest risk factor for HIV infection among FSWs in Kaiyuan City, China. FSWs working on the street or in temporary sub-lets, beauty salons, or saunas are at particularly high risk for transmitting and being infected with HIV. HIV prevention efforts among FSWs should target illegal drug users and these other subgroups.

Atazanavir Concentration in Hair Is the Strongest Predictor of Outcomes on Antiretroviral Therapy

BACKGROUND Adequate exposure to antiretrovirals is important to maintain durable responses, but methods to assess exposure (eg, querying adherence and single plasma drug level measurements) are limited. Hair concentrations of antiretrovirals can integrate adherence and pharmacokinetics into a single assay. METHODS Small hair samples were collected from participants in the Womens Interagency HIV Study (WIHS), a large cohort of human immunodeficiency virus (HIV)-infected (and at-risk noninfected) women. From 2003 through 2008, we analyzed atazanavir hair concentrations longitudinally for women reporting receipt of atazanavir-based therapy. Multivariate random effects logistic regression models for repeated measures were used to estimate the association of hair drug levels with the primary outcome of virologic suppression (HIV RNA level, <80 copies/mL). RESULTS 424 WIHS participants (51% African-American, 31% Hispanic) contributed 1443 person-visits to the analysis. After adjusting for age, race, treatment experience, pretreatment viral load, CD4 count and AIDS status, and self-reported adherence, hair levels were the strongest predictor of suppression. Categorized hair antiretroviral levels revealed a monotonic relationship to suppression; women with atazanavir levels in the highest quintile had odds ratios (ORs) of 59.8 (95% confidence ratio, 29.0-123.2) for virologic suppression. Hair atazanavir concentrations were even more strongly associated with resuppression of viral loads in subgroups in which there had been previous lapses in adherence (OR, 210.2 [95% CI, 46.0-961.1]), low hair levels (OR, 132.8 [95% CI, 26.5-666.0]), or detectable viremia (OR, 400.7 [95% CI, 52.3-3069.7]). CONCLUSIONS Antiretroviral hair levels surpassed any other predictor of virologic outcomes to HIV treatment in a large cohort. Low antiretroviral exposure in hair may trigger interventions prior to failure or herald virologic failure in settings where measurement of viral loads is unavailable. Monitoring hair antiretroviral concentrations may be useful for prolonging regimen durability.

Association of the IFNL4-ΔG Allele With Impaired Spontaneous Clearance of Hepatitis C Virus

Interferon lambda 4 protein can be generated in IFNL4-ΔG carriers but not IFNL4-TT homozygotes. We studied 890 anti-hepatitis C virus (HCV)-positive participants in the Womens Interagency HIV Study. Among blacks (n = 555), HCV was more often cleared for those with genotype IFNL4-TT/TT (32.6%; odds ratio [OR], 3.59; P = 3.3 × 10(-5)) than IFNL4-TT/ΔG (11.3%; OR, 0.95; P = .86) or IFNL4-ΔG/ΔG (11.9%; referent). Pooling these data with published results in blacks (n = 1678), ORs were 3.84 (P = 8.6 × 10(-14)) for IFNL4-TT/TT and 1.44 (P = .03) IFNL4-TT/ΔG, and the area under the curve was 0.64 for IFNL4-ΔG genotype and 0.61 for rs12979860 (IL28B). IFNL4-ΔG is strongly associated with impaired spontaneous HCV clearance.

Assessing mortality in women with hepatitis C virus and HIV using indirect markers of fibrosis.

Objective:Co-infection with hepatitis C virus (HCV) is a major cause of morbidity and mortality in HIV-infected individuals. However, predictors of mortality are poorly defined and most studies have focused predominantly on co-infection in men. We evaluated whether two indirect markers of hepatic fibrosis, aspartate aminotransferase-to-platelet ratio index (APRI) and FIB-4 scores, were predictive of mortality in a well defined longitudinal cohort of HCV/HIV-co-infected women on HAART. Methods:HCV/HIV-co-infected women on antiretroviral therapy enrolled in Womens Interagency HIV Study (WIHS), a National Institutes of Health-funded prospective, multicenter, cohort study of women with and at risk for HIV infection were included. Using Cox regression analysis, associations between APRI and FIB-4 with all-cause mortality were assessed. Results:Four hundred and fifty HCV/HIV-co-infected women, of whom 191 women died, had a median follow-up of 6.6 years and 5739 WIHS visits. Compared with women with low APRI or FIB-4 levels, severe fibrosis was significantly associated with an increased risk of all-cause mortality {APRI: hazard ratio 2.78 [95% confidence interval (CI) 1.87, 4.12]; FIB-4: hazard ratio 2.58 (95% CI 1.68, 3.95)}. Crude death rates per 1000 patient-years increased with increasing liver fibrosis: 34.8 for mild, 51.3 for moderate and 167.9 for severe fibrosis as measured by FIB-4. Importantly, both APRI and FIB-4 increased during the 5 years prior to death for all women: the slope of increase was greater for women dying a liver-related death compared with nonliver-related death. Conclusion:Both APRI and FIB-4 are independently associated with all-cause mortality in HCV/HIV-co-infected women and may have clinical prognostic utility among women with HIV and HCV.

Disclosure of complementary and alternative medicine use to health care providers among HIV-infected women.

To determine prevalence and predictors of complementary and alternative medicine (CAM) use disclosure to health care providers and whether CAM use disclosure is associated with highly active antiretroviral therapy (HAART) adherence among HIV-infected women, we analyzed longitudinal data collected between October 1994 and March 2002 from HIV-infected CAM-using women enrolled in the Womens Interagency HIV Study. Repeated measures Poisson regression models were constructed to evaluate associations of selected predictors with CAM use disclosure and association between CAM use disclosure and HAART adherence. A total of 1,377 HIV-infected women reported CAM use during study follow-up and contributed a total of 4,689 CAM-using person visits. The overall prevalence of CAM use disclosure to health care providers was 36% across study visits. Women over 45 years old, with a college education, or with health insurance coverage were more likely to disclose their CAM use to health care providers, whereas women identified as non-Hispanic Black or other ethnicities were less likely to communicate their CAM usage. More health care provider visits, more CAM domains used, and higher health care satisfaction scores had significant relationships with increased levels of CAM use disclosure. Restricting analysis to use of herbal or nonherbal medications only, similar results were obtained. Compared to other CAM domains, mind-body practice had the lowest prevalence of CAM use disclosure. Additionally, CAM use disclosure was significantly associated with higher HAART adherence. From this study, we showed that a high percentage of HIV-infected women did not discuss their CAM use with health care providers. Interventions targeted towards both physicians and patients may enhance communication of CAM use, avoid potential adverse events and drug interactions, and enhance HAART adherence.

Relationship of hepatocellular carcinoma to soya food consumption: A cohort-based, case-control study in Japan

To determine if the risk of hepatocellular carcinoma (HCC) is reduced by consumption of soya foods, we conducted a case‐control study within a cohort of Japanese A‐bomb survivors. We compared the prediagnosis consumption of isoflavone‐rich miso soup and tofu to HCC risk, adjusting for hepatitis B (HBV) and C (HCV) viral infections, the major HCC risk factors in this population. The study included 176 pathologist‐confirmed cases of HCC diagnosed in 1964–1988 and 560 controls who died of diseases other than liver cancer. We examined dietary information collected at least 2 years before diagnosis or death and tissue‐based measures of viral hepatitis. Using logistic regression, crude ORs were 0.5 (95% CI 0.29–0.95) and 0.5 (95% CI 0.20–0.99) for high vs. low miso soup and tofu intake, respectively. Adjusting for year of birth, sex, HBV, HCV and other factors, the OR for miso soup was unchanged at 0.5 (95% CI 0.14–1.55), and miso results were similar when ORs were recalculated separately for earlier and later birth cohorts to assess consistency of results. The adjusted OR for tofu was 0.9 (95% CI 0.20–3.51). We also found a statistically significant (p < 0.0001) interaction between sex and HCV, with risk of HCC being substantially higher for women. We conclude that consumption of miso soup and other soya foods may reduce HCC risk.

Prevalence and predictors of herpes simplex virus type 2 infection among female sex workers in Yunnan Province, China

Summary: The objective of this study was to determine the seroprevalence of herpes simplex virus type 2 (HSV-2), and to evaluate the relationship between HSV-2 infection and sociodemographic factors and the sexual practices of female sex workers (FSWs) in Kaiyuan city, Yunnan Province, China. This cross-sectional study involved 737 FSWs and was carried out from March to May 2006 with confidential interviews and laboratory tests for HSV-2 and other sexually transmitted infections (STI). HSV-2 was the most common STI (68%), followed by Chlamydia trachomatis (26%), Trichomonas vaginalis (11%), Neisseria gonorrhoeae (8%) and syphilis (7%). Prevalence of HIV-1 was 10.3%. Adjusted odds ratios of HSV-2 seroprevalence were 2.6 (95% CI [confidence interval]: 1.30-5.38) for HIV-1 infection, 2.0 (95% CI: 1.33-3.16) for vaginal douching, 2.0 (95% CI: 0.45-0.86) for condom breaking or falling off during sexual intercourse with the client in the previous week, 1.8 (95% CI: 1.07-3.18) for ≥5 years of commercial sex work, 1.6 (95% CI: 1.08-2.33) for ≥5 clients in the previous week, 0.6 (95% CI: 0.45-0.86) for ≥9 years of education. This study identifies a very high prevalence of HSV-2 infections among FSWs in Yunnan Province, with only a few who reported a prior history of genital herpes. HSV-2 serological screening and suppressive therapy should be considered for study populations. Education on the importance of diagnosis, treatment and prevention may help control the spread of HSV-2 infection.

Mobility, risk behavior and HIV/STI rates among female sex workers in Kaiyuan City, Yunnan Province, China

BackgroundThe mobility of female sex workers (FSWs) is a factor in the geographic spread of human immunodeficiency virus (HIV) and other sexually transmitted infections (STIs). This study describes FSW mobility patterns in a high risk area of China to identify factors associated with increased mobility, and to study the incidence and prevalence of HIV/STIs in this group.Methods270 FSWs recruited from a baseline cross-sectional study were invited to participate in a one-year monthly follow-up cohort study in Kaiyuan City, Yunnan Province, China from 2006 to 2007. Laboratory tests were conducted for HIV/STIs at baseline, 6 and 12 months.ResultsA total of 117 (43.3%) FSWs moved to another city during the year. Risk factors for increased mobility included being from another city within Yunnan (adjusted hazard ratio [AHR] 1.67, 95% confidence interval [CI] 1.09-2.56), being from outside Yunnan (AHR 1.58, 95% CI 1.04-2.54), and working in lower risk entertainment establishments (AHR 1.55, 95% CI 1.03-2.35). HIV-positive subjects, drug users and FSWs in higher risk venue were less likely to change residence, less likely to use condoms with clients, and earned less per client, but had more working locations and more clients each month.ConclusionsThe least mobile FSWs were from Kaiyuan, worked in higher risk venues, were more likely to use drugs and be HIV-infected. Because FSWs characteristics differ according to the venue at which they work, future prevention work should tailor programs according to venue with a particular focus on FSWs in higher risk venues.

Longitudinal Trends in Hazardous Alcohol Consumption Among Women With Human Immunodeficiency Virus Infection, 1995–2006

Hazardous alcohol consumption among women with human immunodeficiency virus (HIV) infection is associated with several adverse health and behavioral outcomes, but the proportion of HIV-positive women who engage in hazardous drinking over time is unclear. The authors sought to determine rates of hazardous alcohol consumption among these women over time and to identify factors associated with this behavior. Subjects were 2,770 HIV-positive women recruited from 6 US cities who participated in semiannual follow-up visits in the Womens Interagency HIV Study from 1995 to 2006. Hazardous alcohol consumption was defined as exceeding daily (> or =4 drinks) or weekly (>7 drinks) consumption recommendations. Over the 11-year follow-up period, 14%-24% of the women reported past-year hazardous drinking, with a slight decrease in hazardous drinking over time. Women were significantly more likely to report hazardous drinking if they were unemployed, were not high school graduates, had been enrolled in the original cohort (1994-1995), had a CD4 cell count of 200-500 cells/mL, were hepatitis C-seropositive, or had symptoms of depression. Approximately 1 in 5 of the women met criteria for hazardous drinking. Interventions to identify and address hazardous drinking among HIV-positive women are urgently needed.