Racial differences in bone loss and relation to menopause among HIV-infected and uninfected women.

OBJECTIVE: To characterize changes in bone mineral density (BMD) according to race among HIV-infected and uninfected women, and to evaluate the relationship between race and menopause-related bone loss. METHODS: Dual X-ray absorptiometry measured BMD on study entry and a minimum of 18 months later in 246 HIV-infected and 219 HIV-uninfected women in the Menopause Study. Linear regression analyses determined percent annual BMD change at the total hip (TH), femoral neck (FN), and lumbar spine (LS) after adjusting for potential confounders. Race-stratified and HIV-infected subgroup analyses were performed. RESULTS: At baseline, mean age was 45 years, 19% of women were postmenopausal. HIV-infected women were more likely to be black (58% vs. 38%), and had lower BMI and less cigarette exposure when compared to HIV-uninfected women. Women who were perimenopausal at baseline and postmenopausal at follow-up had the greatest TH bone loss (-1.68%/yr, p < .0001) followed by those postmenopausal throughout (-1.02%/yr, p = .007). We found a significant interaction between HIV status and race in multivariate analyses of BMD change at the FN and TH. In race-stratified analyses, HIV infection was associated with TH BMD loss in non-black women. Black women experienced greater menopause-associated decline in TH BMD compared with non-black women. CONCLUSIONS: The association of HIV and BMD differs strikingly by race, as do the effects of the menopausal transition on bone. Determining the extent to which the effect of HIV on fracture risk varies by race will be crucial to identify HIV-infected women at greatest risk for osteoporotic fracture, particularly as they enter menopause.

CD8+ T cells and risk for bacterial pneumonia and all-cause mortality among HIV-infected women.

BACKGROUND: Bacterial pneumonia risk is disproportionately high among those infected with HIV. This risk is present across all CD4(+) T-cell levels (TCLs), suggesting that additional factors govern susceptibility. This study examines CD8(+) TCLs and risk for HIV-associated bacterial pneumonia and all-cause mortality. METHODS: Demographic, clinical, and laboratory data were obtained for 885 HIV-infected women enrolled in the HIV Epidemiologic Research Study (HERS). Bacterial pneumonia cases were identified using clinical, microbiological, and radiographic criteria. CD8(+) TCLs were assessed at 6-month intervals. Statistical methods included Cox proportional hazards regression modeling and covariate-adjusted survival estimates. RESULTS: Relative to a referent CD8(+) TCL of 401-800 cells per cubic millimeter, risk for bacterial pneumonia was significantly higher when CD8(+) TCLs were <400 (hazard ratio 1.65, P = 0.017, 95% confidence interval 1.10 to 2.49), after adjusting for age, CD4(+) TCL, viral load, and antiretroviral use. There was also a significantly higher risk of death when CD8(+) TCLs were ≤400 cells per cubic millimeter (hazard ratio 1.45, P = 0.04, 95% confidence interval 1.02 to 2.06). Covariate-adjusted survival estimates revealed shorter time to pneumonia and death in this CD8(+) TCL category, and the overall associations of the categorized CD8(+) TCL with bacterial pneumonia and all-cause mortality were each statistically significant (P = 0.017 and P < 0.0001, respectively). CONCLUSIONS: CD8(+) TCL ≤400 cells per cubic millimeter was associated with increased risk for pneumonia and all-cause mortality in HIV-infected women in the HERS cohort, suggesting that CD8(+) TCL could serve as an adjunctive biomarker of pneumonia risk and mortality in HIV-infected individuals.

Prospective evaluation of bone mineral density among middle-aged HIV-infected and uninfected women: Association between methadone use and bone loss.

OBJECTIVE: We undertook a prospective study to assess the impact of HIV infection on BMD in a cohort of HIV-infected and uninfected women that included illicit drug users, and to measure the contribution of traditional risk factors as well as HIV-related factors to loss of BMD over time. METHODS: We analyzed BMD at baseline and after ≥18 months in 245 middle-aged HIV-infected and 219 uninfected women, and conducted linear regression analysis to determine factors associated with annual BMD change at the femoral neck, total hip and lumbar spine. RESULTS: HIV-infected women had lower baseline BMD at the femoral neck and total hip compared with controls; unadjusted rates of BMD change did not differ by HIV status at any site. In multivariable analyses, we found that HIV seropositivity without protease inhibitor (PI) use was associated with BMD decline at the lumbar spine (-.009g/cm(2) per year, p=.03). Additional factors associated with BMD decline were: postmenopausal status, lower BMI, and methadone use at the lumbar spine; postmenopausal status and hepatitis C seropositivity at the femoral neck; and postmenopausal status, age, smoking, and lower BMI at the total hip (all p<.05). Among HIV-infected women, ≥3 years of PI use was associated with an increase in lumbar spine BMD (.013g/cm(2) per year, p=.008). CONCLUSIONS: Bone loss among HIV-infected middle-aged women was modest, and possibly mitigated by PI use. Methadone use was associated with BMD decline, and should be considered when evaluating women for osteoporosis risk.

Incident hyperglycaemia among older adults with or at-risk for HIV infection.

BACKGROUND: HIV infection has been associated with development of prediabetes and diabetes. Optimum screening practices for these disorders in HIV-infected populations remain unclear. METHODS: We screened 377 adults, with or at-risk for HIV infection, for incident hyperglycaemia (prediabetes or diabetes) using two oral glucose tolerance tests (OGTTs) a median of 18.6 months apart. We determined proportion of incident cases detected by fasting and 120-min plasma glucose levels. Independent predictors of incident hyperglycaemia were identified using logistic regression. RESULTS: The baseline OGTT was consistent with diabetes in 7% of participants and with prediabetes in 31%. Among 352 normoglycaemic and prediabetic participants at baseline, 19 (5%) developed diabetes on follow-up. Among participants normoglycaemic at baseline, an additional 38 (16%) developed prediabetes. Overall 52% of incident hyperglycaemia cases were detected by fasting plasma glucose alone, 33% by a 120-min glucose level alone and 15% by both. Factors independently associated with incident hyperglycaemia included age ≥50 years and body mass index ≥30 kg/m(2). Neither HIV infection nor highly active antiretroviral therapy (HAART) use were associated with increased risk of diabetes. CONCLUSIONS: Incident hyperglycaemia is common among older adults with or at-risk for HIV infection. HIV-infected individuals with classic diabetes risk factors should be screened for hyperglycaemia regardless of HAART use. OGTTs might be the preferred screening strategy in HIV-infected individuals at high risk for developing hyperglycaemia.

Defining translational research: implications for training.

Because translational research is not clearly defined, developers of translational research programs are struggling to articulate specific program objectives, delineate the knowledge and skills (competencies) that trainees are expected to develop, create an appropriate curriculum, and track outcomes to assess whether program objectives and competency requirements are being met. Members of the Evaluation Committee of the Association for Clinical Research Training (ACRT) reviewed current definitions of translational research and proposed an operational definition to use in the educational framework. In this article, the authors posit that translational research fosters the multidirectional and multidisciplinary integration of basic research, patient-oriented research, and population-based research, with the long-term aim of improving the health of the public. The authors argue that the approach to designing and evaluating the success of translational training programs must therefore be flexible enough to accommodate the needs of individual institutions and individual trainees within the institutions but that it must also be rigorous enough to document that the program is meeting its short-, intermediate-, and long-term objectives and that its trainees are meeting preestablished competency requirements. A logic model is proposed for the evaluation of translational research programs.

Association of HIV viral load with monocyte chemoattractant protein-1 and atherosclerosis burden measured by magnetic resonance imaging.

BACKGROUND: HIV-infected individuals may be at increased risk for atherosclerosis. Although this is partially attributable to metabolic factors, HIV-associated inflammation may play a role. OBJECTIVE: To investigate associations of HIV disease with serum monocyte chemoattractant protein-1/chemokine (C-C motif) ligand 2 (MCP-1/CCL2) levels and atherosclerosis burden. DESIGN: A cross-sectional analysis. METHODS: : Serum MCP-1/CCL2, fasting lipids, and glucose tolerance were measured in 98 HIV-infected and 79 demographically similar uninfected adults. Eighty-four participants had MRI of the carotid arteries and thoracic aorta to measure atherosclerosis burden. Multivariate analyses were performed using linear regression. RESULTS: Mean MCP-1/CCL2 levels did not differ between HIV-infected and uninfected participants (P = 0.65). Among HIV-infected participants, after adjusting for age, BMI, and cigarette smoking, HIV-1 viral load was positively associated with MCP-1/CCL2 (P = 0.02). Multivariate analyses adjusting for sex, low-density lipoprotein cholesterol, total cholesterol:high-density lipoprotein cholesterol ratio, cigarette smoking, MCP-1/CCL2, and protease inhibitor use found that HIV infection was associated with greater mean thoracic aorta vessel wall area (VWA, P < 0.01) and vessel wall thickness (VWT, P = 0.03), but not with carotid artery parameters. Compared with being uninfected, having detectable HIV-1 viremia was associated with greater mean thoracic aorta VWA (P < 0.01) and VWT (P = 0.03), whereas being HIV-infected with undetectable viral load was associated with greater thoracic aorta VWA (P = 0.02) but not VWT (P = 0.15). There was an independent positive association of MCP-1/CCL2 with thoracic aorta VWA (P = 0.01) and VWT (P = 0.01). CONCLUSION: HIV-1 viral burden is associated with higher serum levels of MCP-1/CCL2 and with atherosclerosis burden, as assessed by thoracic aorta VWA and VWT.

Effects of hepatitis C virus infection on menopause status and symptoms.

OBJECTIVE: To examine the relationship between hepatitis C virus (HCV) infection with menopause status and vasomotor symptoms among middle-aged, impoverished women. METHODS: The baseline interview and laboratory data from a study on menopause were used for a cross-sectional analysis of HCV antibody and HCV-RNA levels and their relationship to menopause status and symptoms, using logistic regression. For HCV-infected and HCV-uninfected women, menopause status was defined according to the World Health Organization criteria. RESULTS: Of 559 participants, 48% were black, 38.6% were Hispanic, and 267 (47.8%) were HCV seropositive; of these, 189 (72.1%) had detectable HCV-RNA levels. The median age was 43 years [interquartile range (IQR), 40-46 years]; 50.2% of the women were premenopausal, 31.8% were perimenopausal, and 18% were postmenopausal. Median age at natural menopause was 46 years (IQR, 42.25-49 years) in HCV-infected women compared with 47 years (IQR, 40.25-48 years) in uninfected controls. Women infected with HCV were more likely to be postmenopausal than were uninfected women (adjusted odds ratio [ORadj], 1.68; 95% CI, 1.02-2.77). Human immunodeficiency virus status (ORadj, 1.69; 95% CI, 1.04-2.75), drug use (ORadj, 2.34; 95% CI, 1.42-3.86), and nulliparity (ORadj, 2.74; 95% CI, 1.42-5.29) were independently associated with natural menopause, whereas being more physically active (ORadj, 0.90; 95% CI, 0.85-0.95) was inversely associated with menopause. Women infected with HCV were more likely than uninfected women to report vasomotor symptoms (ORadj, 1.52; 95% CI, 1.06-2.18). CONCLUSIONS: Hepatitis C virus infection is independently associated with natural menopause, controlling for age. In addition, HCV was associated with vasomotor symptoms. Further studies are warranted to better understand the menopausal transition in HCV-infected women.

Attitudes toward menopause in HIV-infected and at-risk women.

OBJECTIVE: To study attitudes toward menopause in women with or at risk of human immunodeficiency virus (HIV) aged 35 to 60 in New York City, NY, USA. DESIGN: Data were obtained at the baseline interview in a cohort study of menopause. Of 502 participating women, 92 were postmenopausal and 162 were perimenopausal. RESULTS: Overall, 37.5% of women had a relatively favorable attitude toward menopause. African Americans had a 72% greater odds of a positive attitude (OR = 1.72, 95% CI 1.16-2.57) than all other groups after adjusting for covariates. Hispanic women had the least favorable view of menopause. Experience of > 3 menopausal symptoms and negative life events-being a witness to a murder, and the death ofa child-were significantly associated with negative attitudes towards menopause (OR = 0.62, 95% CI 0.42-0.93 and OR = 0.64, 95% CI 0.43-0.93, respectively). Depressive symptoms, street drug use, and having a domestic partner, which is significant in single variable analyses, did not remain independent predictors in multivariate results. HIV status, menopause status, and age at interview were not associated with menopause attitudes. CONCLUSIONS: HIV-infected, drug-using, low-income women showed generally unfavorable attitudes towards menopause. High stress life events coupled with a high prevalence of depressive symptoms indicate this population has special needs marked by the menopause transition into older age.

Use of complementary and alternative medicine in inner-city persons with or at risk for HIV infection.

Previous studies have shown that use of complementary and alternative medicine (CAM) is prevalent among HIV-infected persons, but have focused primarily on men who have sex with men. To determine factors associated with CAM use in an inner city population, individuals (n = 93) recruited from two established cohort studies were interviewed between October and November 2004. The interview assessed the use of dietary supplements and other CAM therapies, reasons for CAM use, and use of prescription medications. Study participants were 52% male and 47% HIV infected. Median age was 50 years, and 60% reported illicit drug use ever. CAM use during the prior 6 months was reported by 94%, with 48% reporting daily use of a dietary supplement. Vitamin C, vitamin E, and soy were used more often by HIV-infected than uninfected persons (p < 0.05). Prevention of illness was the most common reason for dietary supplement use (27%). HIV-infected persons were more likely than uninfected persons (95% versus 67%) to report use of both dietary supplements and prescription medications within the past 6 months (p < 0.001). In multivariate analysis, HIV infection (odds ratio [OR] 3.1, CI 1.3, 7.7) was the only factor associated with daily dietary supplement use whereas gender, race/ethnicity, working in the last year, homelessness, and financial comfort were not associated. CAM use among persons with or at risk for HIV infection due to drug use or high-risk heterosexual behaviors is common, and is used almost exclusively as an adjunct and not an alternative to conventional health care.

Attribution of menopause symptoms in human immunodeficiency virus-infected or at-risk drug-using women.

OBJECTIVE: To examine the relationship of human immunodeficiency virus (HIV) and attribution of menopausal symptoms. DESIGN: Peri- and postmenopausal women participating in a prospective study of HIV-infected and at-risk midlife women (the Ms. Study) were interviewed to determine whether they experienced hot flashes and/or vaginal dryness and to what they attributed these symptoms. RESULTS: Of 278 women, 70% were perimenopausal; 54% were HIV-infected; and 52% had used crack, cocaine, heroin, and/or methadone within the past 5 years. Hot flashes were reported by 189 women and vaginal dryness was reported by 101 women. Overall, 69.8% attributed hot flashes to menopause and 28.7% attributed vaginal dryness to menopause. In bivariate analyses, age 45 years and older was associated with attributing hot flashes and vaginal dryness to menopause, and postmenopausal status and at least 12 years of education were associated with attributing vaginal dryness to menopause, but HIV status was not associated with attribution to menopause. In multivariate analysis, significant interactions between age and menopause status were found for both attribution of hot flashes (P=0.019) and vaginal dryness (P=0.029). Among perimenopausal women, older age was independently associated with attribution to menopause for hot flashes (adjusted odds ratio=1.2, 95% CI: 1.1-1.4, P=0.001) and vaginal dryness (adjusted odds ratio=1.3, 95% CI: 1.1-1.6, P=0.011). None of the tested factors were independently associated with attribution to menopause among postmenopausal women. CONCLUSION: Tailored health education programs may be beneficial in increasing the knowledge about menopause among HIV-infected and drug-using women, particularly those who are perimenopausal.

Hepatitis C infection is associated with lower lipids and high-sensitivity C-reactive protein in HIV-infected men.

Increased cardiovascular risk has been linked to HIV infection and combination antiretroviral therapy, but the impact of hepatitis C virus (HCV) status on indices of cardiovascular risk has not been routinely assessed in the HIV-infected population. The objective of this study was to analyze associations of HCV, HIV, and combination antiretroviral therapy with lipid levels and C-reactive protein (CRP) among older men. We measured fasting total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride, and high-sensitivity CRP serum levels in a cross-sectional study of 108 HIV-infected and 74 HIV-uninfected at-risk older men. One hundred ten men (60%) had detectable HCV RNA, with no difference by HIV status (p = 0.25). The majority (88%) of men with HCV infection had a history of injection drug use. Among all men, HCV infection was independently associated with lower total cholesterol (p < 0.001), LDL-C (p < 0.001), triglycerides (p = 0.01), and CRP (p = 0.001). Among HIV-infected men, HCV infection was associated with lower total cholesterol (p < 0.001), LDL-C (p < 0.001), and CRP (p = 0.004). HCV infection was associated with lower triglycerides among men on protease inhibitors (PI) (p = 0.02) and non-PI combination antiretroviral therapy (p = 0.02), but not among antiretroviral-naïve men. These findings demonstrate an association of lower serum lipid and CRP levels with HCV infection and suggest that HCV status should be assessed as an important correlate of cardiovascular risk factors in studies of older men with or at risk for HIV.

Two-step tuberculin skin testing in drug users.

To assess the utility of booster testing and to identify factors associated with a positive booster test, two-step tuberculin testing was performed in drug users recruited from methadone treatment. Participants also received a standardized interview on demographics and testing for HIV and CD4+ lymphocyte count. Of 619 enrollees completing the protocol, 174 (28%) had a positive PPD and 24 of the remaining 445 (5%) had a positive booster test. On multivariate analysis, boosting was associated with older age (adjusted odds ratio [ORadj] 2.38/decade, 95% confidence interval [CI] 1.34-4.22), history of using crack cocaine (ORadj 2.61, 95% CI 1.10-6.18) and a history of working as a home health aide (ORadj 4.23, 95% CI 1.39-12.86). Two-step tuberculin skin testing increased the proportion of participants with latent tuberculosis infection from 22% to 25%. Given the effectiveness of chemoprophylaxis, booster testing should be considered when drug users are screened for tuberculosis infection.

Factors affecting reproductive hormones in HIV-infected, substance-using middle-aged women.

OBJECTIVE: To determine whether reproductive hormone levels are affected by human immunodeficiency virus (HIV) and drug use. DESIGN: HIV-infected and uninfected women (N=429), median age 45, were interviewed on menstrual frequency, demographic and psychosocial characteristics, and drug use behaviors. Serum was obtained on cycle days 1 to 5 in women reporting regular menses. Premenopausal-, early menopausal, and late menopausal transition and postmenopausal stages were assigned based on menstrual history. Serum was assayed for follicle-stimulating hormone (FSH), estradiol (E2), luteinizing hormone (LH), prolactin, thyroid-stimulating hormone, and inhibin B. Body mass index, HIV serostatus, and CD4+ counts were measured. Factors associated with hormone concentrations were assessed using uni- and multivariable analyses. Hormone concentrations were compared within menstrual status categories using nonparametric comparisons of means. RESULTS: In this cross-sectional analysis, LH and FSH increased, and E2 and inhibin B were significantly lower in women of older age and more advanced menopausal status. Increased body mass index was strongly associated with decreased LH. Opiate use was significantly associated with lower inhibin B and E2 and increased prolactin. Poorer self-rated health was statistically significantly associated with lower LH and FSH, but increased education was associated with higher LH and FSH. Among HIV-seropositive women, opiate users had detectably lower FSH and LH than nonusers, and use of highly active antiretroviral therapy was significantly related to higher LH, FSH, and E2, whereas cocaine use was associated with lower E2. CONCLUSIONS: Age and menopausal status are strongly related to reproductive hormones. Body mass index and use of opiates, cocaine, and highly active antiretroviral therapy as well as educational attainment and perceived health can significantly modify reproductive hormones during the menopausal transition and need to be considered when interpreting hormone levels in middle-aged women.

Hepatitis C virus infection is associated with insulin resistance among older adults with or at risk of HIV infection.

OBJECTIVES: To determine the associations of hepatitis C virus (HCV) infection with insulin resistance and abnormal glucose tolerance in a cohort of older adults with or at risk of HIV infection. DESIGN: A cross-sectional study of 267 HIV-infected and 179 at-risk-uninfected adults without a history of diabetes mellitus. METHODS: HCV antibody assays and RNA levels were performed to assess HCV status. Antiretroviral use, family history of diabetes, sedentary behavior, and sociodemographic data were obtained using standardized interviews. Fasting insulin levels and oral glucose tolerance tests were performed to assess two outcomes, the homeostasis model assessment of insulin resistance and abnormal glucose tolerance [impaired glucose tolerance (IGT) or diabetes]. RESULTS: Of 446 participants, 265 (59%) were HCV seropositive; of these, 199 (75%) had detectable HCV-RNA levels. Insulin resistance was greater among HCV-seropositive compared with seronegative participants, adjusting for body mass index, Hispanic ethnicity, age greater than 55 years, sedentary behavior (watching television > 4 h/day), HIV status, HAART, and protease inhibitor (PI) use. Ninety-eight participants (22%) had abnormal glucose tolerance (69 with IGT and 29 with diabetes). Among HIV-infected participants, 25% were on non-PI HAART and 52% were on PI HAART, but HAART and PI use were not associated with insulin resistance or abnormal glucose tolerance. Among obese participants, abnormal glucose tolerance was more common in HCV-seropositive than seronegative individuals, whereas among non-obese participants there was no association. CONCLUSION: The potential impact of HCV co-infection and obesity on glucose metabolism should be recognized in clinical care, and addressed in future research studies of HIV-infected individuals.

On-site medical care in methadone maintenance: associations with health care use and expenditures.

To evaluate whether long-term drug treatment with on-site medical care is associated with diminished inpatient and outpatient service use and expenditures, we linked prospective interview data to concurrent Medicaid claims of drug users in a methadone program with comprehensive medical services. Patient care was classified as follows: long-term (>/=6 months) drug treatment with on-site usual source of medical care (linked care), long-term drug treatment only, or neither. Multivariate analyses adjusted for visit clustering within patients (n = 423, with 1,161 person-years of observation). After adjustment, linked care participants had more outpatient visits (p < .001), fewer emergency department (ED) visits (24% vs. 33%, p = .02) and fewer hospitalizations (27% vs. 40%, p = .002) than the "neither" group. Ambulatory care expenditures in the linked group were increased, whereas expenditures for other services were similar or reduced. Long-term drug treatment with on-site medical care was associated with increased ambulatory care, less ED and inpatient care, and no net increase in expenditures.

Gender differences in illicit substance use among middle-aged drug users with or at risk for HIV infection.

OBJECTIVE: The objective of the present study was to examine gender differences and other factors associated with current heroin and cocaine use among middle-aged drug users. METHODS: Baseline data were merged from 2 studies of men and of women with or at risk for HIV infection. Analysis was restricted to study participants who had ever used heroin or cocaine and who were 49-60 years of age at the time that they were interviewed. HIV-antibody status, drug-use history, and psychosocial and sociodemographic data were examined. Logistic regression models were used to assess factors independently associated with current heroin and cocaine use. RESULTS: Of 627 persons who ever used heroin and/or cocaine, 250 (39.9%) reported using these drugs within 6 months of the study interview conducted at baseline. Men were more likely to be using drugs currently, compared with women (42.3% vs. 28.2%; P = .007). In multivariate analysis, men, unemployed persons, and HIV-seronegative persons were more likely to be using heroin or cocaine at the time of the interview. In addition, current marijuana users, persons drinking alcohol on a daily basis, and persons who had been homeless in the 6 months before the interview were also more likely to be using these drugs. CONCLUSION: A relatively high proportion of middle-aged substance users with or at risk for HIV infection, especially men, may continue to use illicit drugs into the sixth decade of life. The differences noted between men and women who have used heroin and/or cocaine at some point in their lives suggest that special attention be given to aging and gender issues in framing HIV-prevention and drug-treatment programs.

Aging and HIV infection.

With the advent of highly active antiretroviral therapy (HAART) in mid-1995, the prognosis for HIV-infected individuals has brightened dramatically. However, the conjunction of potent antiviral therapy and longer life expectancy may engender a variety of health risks that, heretofore, HIV specialists have not had to confront. The long-term effects of HIV infection itself and exposure to antiretroviral agents is unknown. Several aspects of aging, including psychiatric disease, neurocognitive impairment, and metabolic and hormonal disorders, may be influenced by chronic exposure to HIV and/or HIV therapeutics. In this paper, we discuss the health issues confronting HIV-infected older adults and areas for future research.

Bacterial pneumonia, HIV therapy, and disease progression among HIV-infected women in the HIV epidemiologic research (HER) study.

BACKGROUND: To determine the rate and predictors of community-acquired bacterial pneumonia and its effect on human immunodeficiency virus (HIV) disease progression in HIV-infected women, we performed a multiple-site, prospective study of HIV-infected women in 4 cities in the United States. METHODS: During the period of 1993-2000, we observed 885 HIV-infected and 425 HIV-uninfected women with a history of injection drug use or high-risk sexual behavior. Participants underwent semiannual interviews, and CD4+ lymphocyte count and viral load were assessed in HIV-infected subjects. Data regarding episodes of bacterial pneumonia were ascertained from medical record reviews. RESULTS: The rate of bacterial pneumonia among 885 HIV-infected women was 8.5 cases per 100 person-years, compared with 0.7 cases per 100 person-years in 425 HIV-uninfected women (P < .001). In analyses limited to follow-up after 1 January 1996, highly active antiretroviral therapy (HAART) and trimethoprim-sulfamethoxazole (TMP-SMX) use were associated with a decreased risk of bacterial pneumonia. Among women who had used TMP-SMX for 12 months, each month of HAART decreased bacterial pneumonia risk by 8% (adjusted hazard ratio [HR(adj)], 0.92; 95% confidence interval [CI], 0.89-0.95). Increments of 50 CD4+ cells/mm3 decreased the risk (HR(adj), 0.88; 95% CI, 0.84-0.93), and smoking doubled the risk (HR(adj), 2.12; 95% CI, 1.26-3.55). Bacterial pneumonia increased mortality risk (HR(adj), 5.02; 95% CI, 2.12-11.87), with adjustment for CD4+ lymphocyte count and duration of HAART and TMP-SMX use. CONCLUSIONS: High rates of bacterial pneumonia persist among HIV-infected women. Although HAART and TMP-SMX treatment decreased the risk, bacterial pneumonia was associated with an accelerated progression to death. Interventions that improve HAART utilization and promote smoking cessation among HIV-infected women are warranted.

HIV infection and bone mineral density in middle-aged women.

BACKGROUND: Osteopenia is prevalent in persons with human immunodeficiency virus (HIV) infection and is part of a normal sequence of aging in women. Most studies of bone mineral density (BMD) and HIV infection have focused on men or have lacked a comparison group of individuals without HIV infection with similar behavioral risk factors. METHODS: We analyzed BMD in 495 middle-aged women (defined as women > or =40 years of age); 263 women had HIV infection, and 232 women were HIV-negative with behavioral risk factors similar to those of the HIV-positive group. RESULTS: The median age of the women in the study was 44 years, 54% were black, and 92% had used illicit drugs. Femoral neck BMD and lumbar spine BMD were reduced in women with HIV infection, compared with women without HIV infection (femoral neck BMD, 1.01+/-0.13 g/cm2 vs. 1.05+/-0.13 g/cm2; P=.001; lumbar spine BMD, 1.21+/-0.17 g/cm2 vs. 1.24+/-0.17 g/cm2; P=.04). In addition to HIV infection, other factors independently associated with lower BMD in both sites were being older, not being black, and having a low body weight. In race-stratified multivariate analyses, HIV infection was associated with BMD only in non-black women. Among HIV-positive women, 84% had taken antiretrovirals, and 62% had taken protease inhibitors, but their use was not associated with BMD. Methadone treatment was also independently associated with reduced lumbar spine BMD. CONCLUSION: Middle-aged women with HIV infection have reduced BMD, compared with women at similar risk for HIV infection, independent of antiretroviral use. Among HIV-positive women, those who are not black, who are underweight, and who use opiates may be at particular risk. Although the prevalence of reduced BMD in this cohort was higher among women with HIV infection than among those without (27% vs. 19%), the overall prevalence of reduced BMD was low, compared with national estimates and with previous studies involving HIV-positive women and men.