HIV infection and low CD4+ T-cell count are associated with an increased risk of persistent oncogenic HPV infection – the major risk factor for cervical cancer. Few reported prospective cohort studies have characterized the incidence of invasive cervical cancer (ICC) in HIV-infected women.
Data were obtained from HIV-infected and -uninfected female participants in the NA-ACCORD with no history of ICC at enrollment. Participants were followed from study entry or January, 1996 through ICC, loss-to follow-up or December, 2010. The relationship of HIV infection and CD4+ T-cell count with risk of ICC was assessed using age-adjusted Poisson regression models and standardized incidence ratios (SIR). All cases were confirmed by cancer registry records and/or pathology reports. Cervical cytology screening history was assessed through medical record abstraction.
A total of 13,690 HIV-infected and 12,021 HIV-uninfected women contributed 66,249 and 70,815 person-years (pys) of observation, respectively. Incident ICC was diagnosed in 17 HIV-infected and 4 HIV-uninfected women (incidence rate of 26 and 6 per 100,000 pys, respectively). HIV-infected women with baseline CD4+ T-cells of ≥ 350, 200–349 and <200 cells/uL had a 2.3-times, 3.0-times and 7.7-times increase in ICC incidence, respectively, compared with HIV-uninfected women (Ptrend =0.001). Of the 17 HIV-infected cases, medical records for the 5 years prior to diagnosis showed that 6 had no documented screening, 5 had screening with low grade or normal results, and 6 had high-grade results.
This study found elevated incidence of ICC in HIV-infected compared to -uninfected women, and these rates increased with immunosuppression.
Human papilloma virus; HIV-infection; Invasive Cervical Cancer; Immunosuppression
By comparing younger to older participants enrolled in a HIV vaccine efficacy trial, we aimed to gain insights into the inclusion of adolescents in future trials. This was a sub-analysis of a multisite HIV vaccine randomized clinical trial in South Africa, conducted January-September, 2007. Motivations for trial enrollment, social harms, adverse events, and loss to follow-up were compared between younger (18-20 years old) and older participants (21-35 years old). Both younger (n=238) and older participants (n=563) were equally likely to report enrolling for altruistic reasons. Younger females were less likely than older participants to join for trial reimbursement (p=0.005), while younger males were more likely to enroll because the vaccine may provide protection from HIV-acquisition (p<0.001). There were no significant differences in the number of social harms reported. Compared to males over 20 years-old, 18-20-year-old females were less likely to experience adverse events (OR=0.1, CI 0.01-0.80) and no more likely to be lost to follow up (OR=0.7, CI 0.39-1.25), while 18-20-year-old males were no more likely to experience adverse events (OR=1.3, CI 0.58-2.83) or loss to follow-up (OR=0.8, CI 0.51-1.41). Our data support the inclusion of younger participants who are at risk for HIV in future HIV vaccine efficacy trials.
HIV; vaccine trials; clinical trials; youth; South Africa
To evaluate the association of diet and physical activity with insulin resistance (IR) in HIV-infected and uninfected women.
Cross sectional analyses of summary dietary measures and physical activity intensity scores obtained from women enrolled in the San Francisco (n=113) and Chicago (n=65) Women’s Interagency HIV Study (WIHS) sites. IR was estimated using the homeostasis model assessment (HOMA-IR). Stepwise regression models assessed the association of diet and physical activity with HOMA-IR after adjustment for demographic, behavioral, and clinical factors.
Compared to HIV-uninfected women, HIV-infected women were older and more likely to have health insurance. In multivariable analysis including all women, being from San Francisco (p=0.005), having a higher mean body mass index (BMI, p<0.001), and a higher percent kilocalories from sweets (p=0.025) were associated with greater HOMA-IR; heavy intensity physical activity (p=0.006) and annual household income <$36,000 (p=0.002) was associated with a lower HOMA-IR. In analysis limited to HIV-infected women, having a higher BMI (p<0.001) and a history of protease inhibitor use (0.002) were significantly associated with higher HOMA-IR; heavy intensity activity (p=0.06) was marginally associated with lower HOMA-IR and being menopausal (p=0.05) was marginally associated with higher HOMA-IR.
Among urban women with or at risk for HIV-infection, heavy intensity physical activity was associated with lower HOMA-IR while higher percent kilocalories from sweets were associated with higher HOMA-IR. Given the overall health benefits of physical activity and a diet low on sugar, these behaviors should be encouraged whenever possible.
HIV; HOMA-IR; insulin resistance; macronutrients; physical activity; women
U.S. state AIDS Drug Assistance Programs (ADAPs) are federally funded to provide antiretroviral therapy (ART) as the payer of last resort to eligible persons with HIV infection. States differ regarding their financial contributions to and ways of implementing these programs, and it remains unclear how this interstate variability affects HIV treatment outcomes.
We analyzed data from HIV-infected individuals who were clinically-eligible for ART between 2001 and 2009 (i.e., a first reported CD4+ <350 cells/uL or AIDS-defining illness) from 14 U.S. cohorts of the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD). Using propensity score matching and Cox regression, we assessed ART initiation (within 6 months following eligibility) and virologic suppression (within 1 year) based on differences in two state ADAP features: the amount of state funding in annual ADAP budgets and the implementation of waiting lists. We performed an a priori subgroup analysis in persons with a history of injection drug use (IDU).
Among 8,874 persons, 56% initiated ART within six months following eligibility. Persons living in states with no additional state contribution to the ADAP budget initiated ART on a less timely basis (hazard ratio [HR] 0.73, 95% CI 0.60–0.88). Living in a state with an ADAP waiting list was not associated with less timely initiation (HR 1.12, 95% CI 0.87–1.45). Neither additional state contributions nor waiting lists were significantly associated with virologic suppression. Persons with an IDU history initiated ART on a less timely basis (HR 0.67, 95% CI 0.47–0.95).
We found that living in states that did not contribute additionally to the ADAP budget was associated with delayed ART initiation when treatment was clinically indicated. Given the changing healthcare environment, continued assessment of the role of ADAPs and their features that facilitate prompt treatment is needed.
To estimate the accuracy of Pap testing for women who are human immunodeficiency virus (HIV)-seropositive, with a focus on negative predictive value.
Participants in the Women’s Interagency HIV Study were followed with conventional Pap smears every 6 months. After excluding those with abnormal Pap tests before study, cervical disease, or hysterectomy, women with negative enrollment Pap results were followed for development within 15 or within 39 months of precancer, defined as a Pap read as high grade squamous intraepithelial lesion, atypical glandular cells favor neoplasia, or adenocarcinoma in situ, or a cervical biopsy read as cervical intraepithelial neoplasia 2+. Correlations between one or more consecutive negative Pap results and subsequent precancer were assessed using Cox proportional hazards models.
Among 942 HIV infected women with negative baseline Pap tests, 8 (1%) developed precancer within 15 months and 40 (4%) within 39 months. After three consecutive negative Pap tests, precancer was rare, with no cases within 15 months and 10/539 (2%) within 39 months. No women developed precancer or cancer within 39 months after 10 consecutive negative Pap tests. Risks for precancer within 15 months after negative Pap included current smoking (aHR 1.5, 95% CI 1.2, 2.0 vs nonsmokers), younger age (aHR=1.5, 95% CI 1.1, 2.1 for women aged younger than 31 years vs older than 45 years) and lower CD4 count (aHR 11.8, 95% CI 1.3, 2.3 for CD4 200–500, aHR 2.2, 95% CI 1.6, 2.9 for CD4 <200/cmm, vs CD4 >500/cmm).
Annual Pap testing appears safe for women infected with HIV; for those with serial negative tests, longer intervals are appropriate.
To assess the impact of knowledge of cervical cancer biology and prevention as well as noncognitive measures on compliance with colposcopy referral in a high risk population.
Participants in a U.S. cohort of women with human immunodeficiency virus (HIV) and at risk comparison women completed behavior questionnaires and instruments measuring knowledge of cervical cancer prevention, depressive symptoms, trust in doctors, and perceived stress. Examinations including Pap tests also were conducted. Associations with compliance with resulting indicated colposcopy were assessed in multivariable models.
Of 326 women with indicated colposcopy, 222 (68%) were compliant with colposcopy referral and 104 (32%) noncompliant. In multivariable analysis, better colposcopy compliance was associated with less education (O.R. for compliance 2.24, 95% C.I. 1.12–4.51 vs more than high school), prior abnormal Pap (O.R. per prior abnormal Pap 1.08 95% C.I. 1.01–1.15), study site (O.R. for site with best vs worst compliance 16.1, 95% C.I. 2.91–88.6), and higher stress (O.R. for Perceived Stress Scale-10 score >16 vs lower 3.25, 95% C.I. 1.45–7.26).
Noncognitive factors and how sites manage abnormal Pap testing affect colposcopy compliance. Educational interventions alone are unlikely to improve colposcopy compliance in similar high-risk populations.
HPV; cervical cancer prevention; Pap test; health education; perceived stress; HIV in women
In a large North American cohort study, anal cancer incidence rates were substantially higher for HIV-infected men who have sex with men, other men, and women compared with HIV-uninfected individuals. Rates increased from 1996–1999 to 2000–2003 but plateaued by 2004–2007.
Background. Anal cancer is one of the most common cancers affecting individuals infected with human immunodeficiency virus (HIV), although few have evaluated rates separately for men who have sex with men (MSM), other men, and women. There are also conflicting data regarding calendar trends.
Methods. In a study involving 13 cohorts from North America with follow-up between 1996 and 2007, we compared anal cancer incidence rates among 34 189 HIV-infected (55% MSM, 19% other men, 26% women) and 114 260 HIV-uninfected individuals (90% men).
Results. Among men, the unadjusted anal cancer incidence rates per 100 000 person-years were 131 for HIV-infected MSM, 46 for other HIV-infected men, and 2 for HIV-uninfected men, corresponding to demographically adjusted rate ratios (RRs) of 80.3 (95% confidence interval [CI], 42.7–151.1) for HIV-infected MSM and 26.7 (95% CI, 11.5–61.7) for other HIV-infected men compared with HIV-uninfected men. HIV-infected women had an anal cancer rate of 30/100 000 person-years, and no cases were observed for HIV-uninfected women. In a multivariable Poisson regression model, among HIV-infected individuals, the risk was higher for MSM compared with other men (RR, 3.3; 95% CI, 1.8–6.0), but no difference was observed comparing women with other men (RR, 1.0; 95% CI, 0.5–2.2). In comparison with the period 2000–2003, HIV-infected individuals had an adjusted RR of 0.5 (95% CI, .3–.9) in 1996–1999 and 0.9 (95% CI, .6–1.2) in 2004–2007.
Conclusions. Anal cancer rates were substantially higher for HIV-infected MSM, other men, and women compared with HIV-uninfected individuals, suggesting a need for universal prevention efforts. Rates increased after the early antiretroviral therapy era and then plateaued.
To review the incidence of respiratory conditions and their effect on mortality in HIV-infected and uninfected individuals prior to and during the era of highly active antiretroviral therapy (HAART).
Two large observational cohorts of HIV-infected and HIV-uninfected men (Multicenter AIDS Cohort Study [MACS]) and women (Women’s Interagency HIV Study [WIHS]), followed since 1984 and 1994, respectively.
Adjusted odds or hazards ratios for incident respiratory infections or non-infectious respiratory diagnoses, respectively, in HIV-infected compared to HIV-uninfected individuals in both the pre-HAART (MACS only) and HAART eras; and adjusted Cox proportional hazard ratios for mortality in HIV-infected persons with lung disease during the HAART era.
Compared to HIV-uninfected participants, HIV-infected individuals had more incident respiratory infections both pre-HAART (MACS, odds ratio [adjusted-OR], 2.4; 95% confidence interval [CI], 2.2–2.7; p<0.001) and after HAART availability (MACS, adjusted-OR, 1.5; 95%CI 1.3–1.7; p<0.001; WIHS adjusted-OR, 2.2; 95%CI 1.8–2.7; p<0.001). Chronic obstructive pulmonary disease was more common in MACS HIV-infected vs. HIV-uninfected participants pre-HAART (hazard ratio [adjusted-HR] 2.9; 95%CI, 1.02–8.4; p = 0.046). After HAART availability, non-infectious lung diseases were not significantly more common in HIV-infected participants in either MACS or WIHS participants. HIV-infected participants in the HAART era with respiratory infections had an increased risk of death compared to those without infections (MACS adjusted-HR, 1.5; 95%CI, 1.3–1.7; p<0.001; WIHS adjusted-HR, 1.9; 95%CI, 1.5–2.4; p<0.001).
HIV infection remained a significant risk for infectious respiratory diseases after the introduction of HAART, and infectious respiratory diseases were associated with an increased risk of mortality.
Depression is common in people with cardiovascular diseases (CVD) and those with HIV, and is a risk factor for CVD-related mortality. However, little is known about whether HIV influences the relationship between depression and cardiovascular risk. 526 HIV-infected and 132 uninfected women from the Women’s Interagency HIV Study were included in an analysis of women who completed twice-yearly study visits over 9.5 years. CVD risk was calculated at baseline and approximately 9.5 years later using the Framingham Risk Score (FRS). Chronic depressive symptoms were defined as Center for Epidemiologic Studies Depression Scale scores of 16 or greater at ≥75% of study visits. Over the follow-up period, 22.8% of HIV-infected women and 15.9% of HIV-uninfected women had chronic depressive symptoms (p=0.08). Baseline FRS were similar between HIV infected and uninfected women (M=−5.70±SE=0.30 vs. M=−6.90± SE=0.60, p=0.07) as was follow-up FRS (M=0.82±SE=0.30 vs. M=−0.44± SE=0.73, p=0.11). Among HIV-infected and uninfected women, together, follow-up FRS were higher among women with chronic depressive symptoms as compared to those without (M=1.3± SE=0.6 vs. M=−0.3± SE=0.40, p<0.01), after adjusting for baseline FRS and other covariates. HIV status did not modify the relationship between chronic depressive symptoms and FRS. Chronic depressive symptoms accelerated CVD risk scores to a similar extent in both HIV infected and uninfected women. This implies that the diagnosis and treatment of depression may be an important consideration in CV risk reduction in the setting of HIV-infection. The determination of factors that mediate the depression/CVD relationship merits further study.
To evaluate the association between enrollment into an AIDS Drug Assistance Program (ADAP) and use of highly active antiretroviral therapy (HAART) and antihypertensive therapy.
Cross-sectional analyses of data were performed on HAART-eligible women enrolled in the California (n=439), Illinois (n=168), and New York (n=487) Women’s Interagency HIV Study (WIHS) sites. A subset of HIV-infected women with hypertension (n=395) was also analyzed. Unadjusted and adjusted backward stepwise elimination logistic regression measured the association between demographic, behavioral, and health service factors and non-use of HAART or antihypertensive medication.
In adjusted analysis of HAART non-use, women without ADAP were significantly more likely not to use HAART (odds ratio [OR] = 2.4, 95% confidence interval [CI] = 1.5–3.7) than women with ADAP. In adjusted analysis of antihypertensive medication non-use, women without ADAP had an increased but not significant odds of antihypertensive medication non-use (OR = 2.4, 95% CI = 0.93–6.0) than women with ADAP.
Government-funded programs for prescription drug coverage, such as ADAP, may play an important role in how HIV-positive women to access and use essential medications for chronic diseases.
AIDS; antiretroviral therapy; hypertension; women; healthcare disparity; prescription insurance
To assess the impact of HAART use on AIDS-defining KS and NHL among adults with AIDS.
Registry linkage study.
Adults diagnosed with AIDS from 1990 to 2000 in the San Francisco AIDS case registry were matched with cancer cases diagnosed from 1985 to 2002 in the California Cancer Registry. Multivariate Cox proportional hazards models were used to evaluate the risk and survival of AIDS- related KS, systemic NHL, and primary CNS lymphoma.
Of the 14,183 adults with AIDS, 3028 were diagnosed with KS, 776 with systemic NHL, and 254 with CNS NHL. After adjustment for potential confounders, more recent calendar period and use of HAART were significantly associated with a decreased risk of KS while HAART use but not calendar period were significantly associated with systemic and CNS NHL. In adjusted analysis of KS survival time, there was strong evidence of a reduced risk of death associated with HAART use and more recent calendar period. In contrast, in adjusted analyses of systemic NHL survival time, HAART use was not associated with improved survival time; however, calendar period was associated with longer survival. In adjusted analysis of CNS NHL survival time, only cancer treatment was associated with a longer survival time.
After controlling for calendar period and other confounders, use of HAART decreased the risk of KS, systemic NHL, and CNS NHL. Use of HAART also increased KS survival time but not NHL survival time.
AIDS; HAART; KS; NHL; risk factors; survival
To estimate changes in high risk women’s knowledge of cervical cancer prevention, human papillomavirus (HPV), and HPV vaccination since introduction and marketing of HPV vaccines.
At study visits in 2006 and 2008, women with the human immunodeficiency virus (HIV) and at-risk comparison women in a multicenter U.S. cohort study completed 44-item self-report questionnaires exploring their knowledge of cervical cancer prevention, HPV, and HPV vaccination. Results from 2006 were compared to those obtained in 2008. Knowledge scores were correlated with demographic variables, measures of education and attention, and medical factors. Significant associations were assessed in multivariable models.
HIV-seropositive women had higher knowledge scores than seronegative women at baseline (13.2 +/− 5.7 vs 11.8 +/− 6.0, P = 0.0002) and follow-up (14.1 +/− 5.3 vs 13.2 +/− 5.5, P = 0.01), but the change in scores was similar (0.9 +/− 5.3 vs 1.5 +/− 5.5, P = 0.13). Knowledge that cervical cancer is caused by a virus rose significantly (P = 0.005), but only to 24%. Belief that cervical cancer is preventable only rose from 52% to 55% (P = 0.04), but more than 90% of women in both periods believed regular Pap testing was important. In ANCOVA models, higher baseline score, younger age, higher education level, higher income, and former- as opposed to never-drug users, but not HIV status, were associated with improved knowledge.
High-risk women’s understanding of cervical cancer and HPV has improved, but gaps remain. Improvement has been weakest for less-educated and lower-income women.
The lifespan of people with human immunodeficiency virus (HIV) infection has increased as a result of effective antiretroviral therapy, and the incidences of the AIDS-defining cancers, non-Hodgkin's lymphoma and Kaposi sarcoma, have declined. Even so, HIV-infected individuals are now at greater risk of other cancers, including Hodgkin's lymphoma (HL). To identify candidate biomarkers for the early detection of HL, we undertook an accurate mass and elution time tag proteomics analysis of individual plasma samples from either HIV-infected patients without HL (controls; n = 14) and from HIV-infected patient samples with HL (n = 22). This analysis identified 60 proteins that were statistically (p<0.05) altered and at least 1.5-fold different between the two groups. At least three of these proteins have previously been reported to be altered in the blood of HL patients that were not known to be HIV positive, suggesting that these markers may be broadly useful for detecting HL. Ingenuity Pathway Analysis software identified “inflammatory response” and “cancer” as the top two biological functions associated with these proteins. Overall, this study validated three plasma proteins as candidate biomarkers for detecting HL, and identified 57 novel candidate biomarkers that remain to be validated. The relationship of these novel candidate biomarkers with cancer and inflammation suggests that they are truly associated with HL and therefore may be useful for the early detection of this cancer in susceptible populations.
Relationships between non-use of highly active anti-retroviral therapy (HAART), race/ethnicity, violence, drug use and other risk factors are investigated using qualitative profiles of five risk factors (unprotected sex, multiple male partners, heavy drinking, crack, cocaine or heroin use, and exposure to physical violence) and association of the profiles and race/ethnicity with non-use of HAART over time.
A Hidden Markov Model (HMM) was used to summarize risk factor profiles and changes in profiles over time in a longitudinal sample of HIV-infected women enrolled in the Women's Interagency HIV Study (WIHS) with follow-up from 2002 to 2005 (N=802).
Four risk factor profiles corresponding to four distinct latent states were identified from the five risk factors. Trajectory analysis indicated that states characterized by high probabilities of all risk factors or by low probabilities of all risk factors were both relatively stable over time. Being in the highest risk state did not significantly elevate the odds of HAART non-use (OR: 1.05; 95% CI: 0.6-1.8). However, being in a latent state characterized by elevated probabilities of heavy drinking and exposure to physical violence, along with slight elevations in three other risk factors, significantly increased odds of HAART non-use (OR: 1.4; 95% CI: 1.1-1.9).
The research suggests that HAART use might be improved by interventions aimed at women who are heavy drinkers with recent exposure to physical violence and evidence of other risk factors. More research about the relationship between clustering and patterns of risk factors and use of HAART is needed.
We examined racial/ethnic disparities in highly active antiretroviral therapy (HAART) use and whether differences are moderated by substance use or insurance status, using data from the Women’s Interagency HIV Study (WIHS).
Logistic regression examined HAART use in a longitudinal cohort of women for whom HAART was clinically indicated in 2005 (N=1354).
Approximately 3 of every 10 eligible women reported not taking HAART. African American and Hispanic women were less likely than were White women to use HAART. After we adjusted for potential confounders, the higher likelihood of not using HAART persisted for African American but not for Hispanic women. Uninsured and privately insured women, regardless of race/ethnicity, were less likely than were Medicaid enrollees to use HAART. Although alcohol use was related to HAART nonuse, illicit drug use was not.
These findings suggest that expanding and improving insurance coverage should increase access to antiretroviral therapy across racial/ethnic groups, but it is not likely to eliminate the disparity in use of HAART between African American and White women with HIV/AIDS.
To examine changes in the causes of death and mortality in women with human immunodeficiency virus (HIV) infection in the era of combination antiretroviral therapy.
Among women with, or at risk of, HIV infection, who were enrolled in a national study from 1994 to 1995, we used an algorithm that classified cause of death as due to acquired immunodeficiency syndrome (AIDS) or non-AIDS causes based on data from death certificates and the CD4 count. Poisson regression models were used to estimate death rates and to determine the risk factors for AIDS and non-AIDS deaths.
Of 2059 HIV-infected women and 569 who were at risk of HIV infection, 468 (18%) had died by April 2000 (451 HIV-infected and 17 not infected). Causes of death were available for 428 participants (414 HIV-infected and 14 not infected). Among HIV-infected women, deaths were classified as AIDS (n = 294), non-AIDS (n = 91), or indeterminate (n = 29). The non-AIDS causes included liver failure (n = 19), drug overdose (n = 16), non-AIDS malignancies (n = 12), cardiac disease (n = 10), and murder, suicide, or accident (n = 10). All-cause mortality declined an average of 26% per year (P = 0.03) and AIDS-related mortality declined by 39% per year (P = 0.01), whereas non-AIDS-related mortality remained stable (10% average annual decrease, P = 0.73). Factors that were independently associated with non-AIDS-related mortality included depression, history of injection drug use with hepatitis C infection, cigarette smoking, and age.
A substantial minority (20%) of deaths among women with HIV was due to causes other than AIDS. Our data suggest that to decrease mortality further among HIV-infected women, attention must be paid to treatable conditions, such as hepatitis C, depression, and drug and tobacco use.
Liver disease is a leading cause of death in human immunodeficiency virus (HIV)–infected women; however, risk factors for hepatitis B virus (HBV) infection in this population have not been well studied.
We describe the seroprevalence and predictors of HBV infection in a cross-sectional analysis of 2132 women with and at risk for HIV infection enrolled in the Women’s Interagency HIV Study during the periods 1994–95 and 2001–02. Any test result positive for antibody to hepatitis B core antigen defined infection; those women with serological evidence of vaccine immunity were excluded from analysis. Women were stratified into those with a history of injection drug use (IDU), those with a history of noninjection drug use (non-IDU), and those with no history of illicit drug use.
Of 1606 HIV-infected and 526 HIV-uninfected women, 7% and 12%, respectively, appeared to be vaccine immune. After exclusion of these women, 43% of 1500 HIV-infected and 22% of 461 HIV-uninfected women had HBV infection. HBV infection prevalence differed among the IDU, non-IDU, and no illicit drug use groups (76%, 30%, and 17%, respectively; P < .0001). HBV infection was strongly associated with herpes simplex virus 2 (HSV-2) seropositivity in the IDU group (odds ratio [OR], 2.9; 95% confidence interval [CI], 1.6–5.4) and with a history of syphilis in the non-IDU group (OR, 2.7; 95% CI, 1.4–5.0).
We found a high prevalence of HBV infection in our cohort of women with and at risk for HIV infection. HSV-2 seropositivity and a history of syphilis appeared to be important correlates of HBV infection. Sexual transmission of HBV, particularly in those with a history of genital ulcer disease, should be a major focus of education in all high-risk groups.
To assess knowledge of and attitudes towards human papillomavirus (HPV), Pap testing, and the HPV vaccine.
In a multicenter U.S. cohort study, women with the human immunodeficiency virus (HIV) and at-risk comparison women completed 44-item standardized self-report questionnaires exploring their knowledge of cervical cancer prevention, HPV, and HPV vaccination. Results were correlated with demographic variables, measures of education and attention, and medical factors. Data were clustered using principal component analysis. Significant associations were assessed in multivariable models.
Among 1588 women, HIV seropositive women better understood facts about cervical cancer prevention and HPV than seronegative women, but both had substantial knowledge deficits. Almost all women considered Pap testing important, although 53% of HIV seropositive and 48% of seronegative women considered cervical cancer not preventable (P=0.21). Only 44% of HIV seropositive women knew Paps assess the cervix, versus 42% of HIV seronegative women (P=0.57). Both groups understood that HPV causes genital warts and cervical cancer (67% of HIV seropositive vs. 55% of seronegative women, P=0.002). About half of both groups considered HPV vaccination extremely important for cervical cancer prevention. HIV seronegative women were more likely to report learning of HPV vaccination through advertising than from clinicians (81% vs. 64%, P<0.0001).
High risk women need effective education about cervical cancer prevention, HPV, and HPV vaccination.
HPV; Cervical cancer prevention; Pap test; Health education; HIV in women
Prior reports of an increased risk of lung cancer in HIV-infected individuals have not always included control groups, nor considered other risk factors such as tobacco exposure. We sought to determine the role of HIV infection and highly active antiretroviral therapy (HAART) on lung cancer incidence in 2,651 HIV-infected and 898 HIV-uninfected women from the Women's Interagency HIV Study (WIHS).
A prospective study of the incidence rates of lung cancer was conducted, with cases identified through medical records, death certificates, and state cancer registries. Standardized incidence ratios (SIRs) were calculated to compare lung cancer incidence among HIV-infected and uninfected WIHS participants, with population-based expectations using the Surveillance, Epidemiology, and End Results registry. Behavioral characteristics in the WIHS were compared to US women by age and race adjusting the population-based data from the National Health and Nutritional Examination Survey (NHANES) III.
Incidence rates of lung cancer were similar among HIV-infected and uninfected WIHS women. Lung cancer SIRs were increased in both HIV-infected and -uninfected women compared with population expectations, but did not differ by HIV status. Among HIV-infected women, lung cancer incidence rates were similar in pre-HAART and HAART eras. All WIHS women with lung cancer were smokers; the risk of lung cancer increased with cumulative tobacco exposure. WIHS women were statistically more likely to smoke than US women studied in NHANES III.
HIV infection is strongly associated with smoking behaviors that increase lung cancer risk. The role of HIV itself remains to be clarified.
During the first two decades of the U.S. AIDS epidemic, and unlike some malignancies, breast cancer risk was significantly lower for women with human immunodeficiency virus (HIV) infection compared to the general population. This deficit in HIV-associated breast cancer could not be attributed to differences in survival, immune deficiency, childbearing or other breast cancer risk factors. HIV infects mononuclear immune cells by binding to the CD4 molecule and to CCR5 or CXCR4 chemokine coreceptors. Neoplastic breast cells commonly express CXCR4 but not CCR5. In vitro, binding HIV envelope protein to CXCR4 has been shown to induce apoptosis of neoplastic breast cells. Based on these observations, we hypothesized that breast cancer risk would be lower among women with CXCR4-tropic HIV infection.
Methods and Findings
We conducted a breast cancer nested case-control study among women who participated in the WIHS and HERS HIV cohort studies with longitudinally collected risk factor data and plasma. Cases were HIV-infected women (mean age 46 years) who had stored plasma collected within 24 months of breast cancer diagnosis and an HIV viral load ≥500 copies/mL. Three HIV-infected control women, without breast cancer, were matched to each case based on age and plasma collection date. CXCR4-tropism was determined by a phenotypic tropism assay. Odds ratios (OR) and 95% confidence intervals (CI) for breast cancer were estimated by exact conditional logistic regression. Two (9%) of 23 breast cancer cases had CXCR4-tropic HIV, compared to 19 (28%) of 69 matched controls. Breast cancer risk was significantly and independently reduced with CXCR4 tropism (adjusted odds ratio, 0.10, 95% CI 0.002–0.84) and with menopause (adjusted odds ratio, 0.08, 95% CI 0.001–0.83). Adjustment for CD4+ cell count, HIV viral load, and use of antiretroviral therapy did not attenuate the association between infection with CXCR4-tropic HIV and breast cancer.
Low breast cancer risk with HIV is specifically linked to CXCR4-using variants of HIV. These variants are thought to exclusively bind to and signal through a receptor that is commonly expressed on hyperplastic and neoplastic breast duct cells. Additional studies are needed to confirm these observations and to understand how CXCR4 might reduce breast cancer risk.
The objective was to assess study retention and attendance for two recruitment waves of participants in the Women's Interagency HIV Study (WIHS).
The WIHS, a prospective study at six clinical centers in the United States, has experienced two phases of participant recruitment. In phase one, women were screened and enrolled at the same time, and in phase two, women were screened and enrolled at separate visits. Compliance with study follow-up was evaluated by examining semiannual study retention and visit attendance.
After 10 study visits, the retention rate in the original recruits (enrolled in 1994–1995) was 83% for the HIV-infected women and 69% for the HIV-uninfected women compared with 86% and 86%, respectively, in the new recruits (enrolled in 2001–2002). In logistic regression analysis of the HIV-infected women, factors associated with early (visits 2 and 3) nonattendance were temporary housing, moderate alcohol consumption, use of crack/cocaine/heroin, having a primary care provider, WIHS site of enrollment, lower CD4 cell count, and higher viral load. Among HIV-uninfected women, the factors associated with early nonattendance were recruitment into the original cohort, household income ≥$12,000 per year, temporary housing, unemployment, use of crack/cocaine/heroin, and WIHS site of enrollment. Factors associated with nonattendance at later visits (7–10) among HIV-infected participants were younger age, white race, not having a primary care provider, not having health insurance, WIHS site of enrollment, higher viral load, and nonattendance at a previous visit. In HIV-uninfected participants, younger age, white race, WIHS site of enrollment, and nonattendance at a previous visit were significantly associated with nonattendance at later visits.
Preventing early loss to follow-up resulted in better study retention early, but late loss to follow-up may require different retention strategies.
To assess trends in mortality and cause of death for women with HIV, we studied deaths over a 10 year period among participants in the Women’s Interagency HIV Study (WIHS), a representative US cohort.
Deaths were ascertained by National Death Index-Plus match and causes of death determined by death certificate.
From 1995 through 2004, 710 of 2792 HIV-infected participants died. During this interval the standardized mortality ratio (SMR) fell from a high of 24.7 in 1996 to a plateau with a mean of 10.3 from 2001–2004. Over the decade, deaths from non-AIDs causes increased and accounted for the majority of deaths by 2001–2004. The most common non-AIDS causes of death were trauma or overdose, liver disease, cardiovascular disease and malignancy. Independent predictors of mortality besides HIV-associated variables were depressive symptoms, and active hepatitis B or C. Women who were overweight or obese were significantly less likely to die of AIDS than women of normal weight.
In the WIHS, the death rate has plateaued in recent years. While HIV-associated factors predicted AIDS and non-AIDS deaths, other treatable conditions predicted mortality. Further gains in reducing mortality among HIV-infected women may require broader access to therapies for depression, viral hepatitis and HIV itself.
HIV; mortality; women; viral hepatitis; non-AIDs mortality
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 Women's Interagency HIV Study from 1995 to 2006. Hazardous alcohol consumption was defined as exceeding daily (≥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.
alcohol drinking; HIV; longitudinal studies; women