Bacterial pneumonia risk is disproportionately high among those infected with Human Immunodeficiency Virus (HIV). This risk is present across all CD4+ T cell levels (TCL), suggesting additional factors govern susceptibility. This study examines CD8+ TCL and risk for HIV-associated bacterial pneumonia and all-cause mortality.
Demographic, clinical, and laboratory data were obtained for 885 HIV-infected (HIV+) women enrolled in the HIV Epidemiologic Research Study (HERS). Bacterial pneumonia cases were identified using clinical, microbiologic, and radiographic criteria. CD8+ TCLs were assessed at 6-month intervals. Statistical methods included Cox proportional hazards regression modeling and covariate-adjusted survival estimates.
Relative to a referent CD8+ TCL 401–800 cells/mm3, risk for bacterial pneumonia was significantly higher when CD8+ TCLs were ≤ 400 (hazard ratio 1.65, p=0.017, 95% CI 1.10–2.49), 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/mm3 (hazard ratio 1.45, p=0.04, 95% CI 1.02–2.06). Covariate-adjusted survival estimates revealed shorter time to pneumonia and death in this CD8+ TCL category and the overall association of the categorized CD8+TCL with bacterial pneumonia and all-cause mortality were each statistically significant (p=0.017 and p<0.0001, respectively).
CD8+ TCL ≤ 400 cells/mm3 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.
Pneumonia; CD8+ T cell; Human Immunodeficiency Virus (HIV); Mortality
HIV infection has been associated with development of prediabetes and diabetes. Optimum screening practices for these disorders in HIV-infected populations remain unclear.
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.
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/m2. Neither HIV infection nor highly active antiretroviral therapy (HAART) use were associated with increased risk of diabetes.
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 may be the preferred screening strategy in HIV-infected individuals at high risk for developing hyperglycaemia.
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.
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.
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 (−.009 gm/cm2 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 (.013 gm/cm2 per year, p=.008.)
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.
osteopenia; osteoporosis; bone mineral density; HIV; women
We evaluated the association of alcohol consumption and depression, and their effects on HIV disease progression among women with HIV. The study included 871 women with HIV who were recruited from 1993–1995 in four US cities. The participants had physical examination, medical record extraction, and venipuncture, CD4+ T-cell counts determination, measurement of depression symptoms (using the self-report Center for Epidemiological Studies-Depression Scale), and alcohol use assessment at enrollment, and semiannually until March 2000. Multilevel random coefficient ordinal models as well as multilevel models with joint responses were used in the analysis. There was no significant association between level of alcohol use and CD4+ T-cell counts. When participants were stratified by antiretroviral therapy (ART) use, the association between alcohol and CD4+ T-cell did not reach statistical significance. The association between alcohol consumption and depression was significant (p<0.001). Depression had a significant negative effect on CD4+ T-cell counts over time regardless of ART use. Our findings suggest that alcohol consumption has a direct association with depression. Moreover, depression is associated with HIV disease progression. Our findings have implications for the provision of alcohol use interventions and psychological resources to improve the health of women with HIV.
alcohol use; HIV/AIDS; multilevel longitudinal models; CD4+T-cells; depression
The insulin-like growth factor (IGF) axis has been hypothesized to influence the rate of human immunodeficiency virus (HIV) disease progression. This premise is based largely on laboratory models showing that IGF-I stimulates thymic growth and increases lymphocyte numbers and that IGF-binding protein (IGFBP)–3 has an opposing effect, inhibiting hematopoietic stem cell development.
We studied 1422 HIV-infected women enrolled in a large cohort that entailed semiannual follow-up (initiated in 1994). Baseline serum samples were tested for IGF-I and IGFBP-3 to determine their associations with incident clinical acquired immunodeficiency syndrome (AIDS) and CD4+ T cell count decline prior to April 1996 (before the era of highly active antiretroviral therapy [HAART]).
Low IGF-I levels (Ptrend = .02) and high IGFBP-3 levels (Ptrend = .02) were associated with rapid CD4+ T cell count decline. Only IGFBP-3, however, was significantly associated with AIDS incidence (hazard ratio for highest vs. lowest quartile, 2.65 [95% confidence interval, 1.30–5.42]; Ptrend = .02) in multivariable models.
These findings suggest that serum levels of IGFBP-3 (and possibly IGF-I) are associated with the rate of HIV disease progression in women and, more broadly, that interindividual heterogeneity in the IGF axis may influence HIV pathogenesis. If correct, the IGF axis could be a target for interventions to slow HIV disease progression and extend the time before use of HAART becomes necessary.
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.
With the advent of highly active antiretroviral agents, women with HIV infection can expect to live longer than ever before. This increased survival has led to concerns about the long-term implications of HIV disease and its treatment. Women with HIV infection appear to lose ovarian function earlier in life than women without HIV infection. They also have evidence of reduced bone mineral density and increased cardiovascular risk. Moreover, many of these increases in risk factors are present even prior to the menopausal transition. All of these risks, present at mid-life, augur poorly for future health and describe a substantially increased burden of disease likely to accrue to HIV infected women as they enter older age groups. Further compounding the adversity faced by the HIV infected, the demographics of women most vulnerable to this disease include adverse social and economic influences, both of which worsen their long term prognosis. For example, drug use and poverty are related to more severe menopausal symptoms and chronic stress is related to worse psychological and cardiovascular risk. An understanding of how menopause interacts with HIV infection is therefore most important to alert the clinician to perform surveillance for common health problems in postmenopausal women, and to address directly and appropriately symptomatology during the menopausal transition.
HIV; menopause; women; diabetes; heart disease; symptoms
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.
To compare electronically monitored (MEMS) with self-reported adherence in drug users, including the impact of adherence on HIV load, we conducted a 6-month observational study of 67 antiretroviral-experienced current and former drug users. Adherence (percentage of doses taken as prescribed) was calculated for both the day and the week preceding each of 6 research visits. Mean self-reported 1-day adherence was 79% (median, 86%), and mean self-reported 1-week adherence was 78% (median, 85%). Mean MEMS 1-day adherence was 57% (median, 52%), and mean MEMS 1-week adherence was 53% (median, 49%). One-day and 1-week estimates were highly correlated (r> .8 for both measures). Both self-reported and MEMS adherence were correlated with concurrent HIV load (r=.43–.60), but the likelihood of achieving virologic suppression was greater if MEMS adherence was high than if self-reported adherence was high. We conclude that self-reported adherence is higher than MEMS adherence, but a strong relationship exists between both measures and virus load. However, electronic monitoring is more sensitive than self-report for the detection of nonadherence and should be used in adherence intervention studies.
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.
Data were obtained at the baseline interview in a cohort study of menopause. Of 502 participating women, 92 were postmenopausal and 162 were perimenopausal.
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 of a 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.
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.
menopause; attitudes; HIV; street drug users
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.
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.
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.
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.
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.
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.
A cross-sectional study of 267 HIV-infected and 179 at-risk-uninfected adults without a history of diabetes mellitus.
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].
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.
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.
Hepatitis C virus; HIV; impaired glucose tolerance; insulin resistance; obesity; type 2 diabetes
Abnormal glucose metabolism in HIV-infected patients has largely been attributed to protease inhibitor use. However most studies of glucose metabolism in HIV-infected patients have focused on men or have lacked appropriate controls.
We assessed factors associated with previously-diagnosed diabetes among 620 midlife women with- or at-risk for HIV infection. In a subset of 221 women without previously-diagnosed diabetes, we performed an oral glucose tolerance test (OGTT) with insulin levels, and assessed factors associated with abnormal glucose tolerance, insulin resistance, and insulin secretion.
Thirteen percent had previously-diagnosed diabetes. Among women without previously diagnosed diabetes who underwent an OGTT, 6% had undiagnosed diabetes and 12% had impaired glucose tolerance (IGT). On multivariate analysis, factors associated with previously-diagnosed diabetes included current methadone treatment, body mass index, family history of diabetes, and physical inactivity. Factors independently associated with abnormal OGTT (IGT or diabetes) included age ≥50 y, family history of diabetes, physical inactivity, and pack-years of smoking. Factors independently associated with insulin resistance included waist circumference, Hispanic ethnicity, physical inactivity, and among HIV-infected women, use of non-PI HAART. Factors associated with lower insulin secretion included current opiate use (methadone or heroin) and older age.
Abnormal glucose metabolism is highly prevalent among midlife women with or at-risk for HIV infection, particularly those who use opiates. Women with classic diabetes risk factors, rather than solely those taking PIs, should be screened for diabetes in the primary care setting. Interventions targeting modifiable risk factors, including obesity and physical inactivity, are also warranted.
human immunodeficiency virus (HIV); diabetes mellitus; antiretroviral therapy; women; drug use
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.
Aging; HIV infection; Substance abuse; HAART
To identify gender differences in social and behavioral factors associated with antiretroviral adherence.
Prospective cohort study.
Methadone maintenance program.
One hundred thirteen HIV-seropositive current or former opioid users.
MEASUREMENTS AND MAIN RESULTS
Participants were surveyed at baseline about social and behavioral characteristics and at monthly research visits about drug and alcohol use and medication side effects. Electronic monitors (MEMS) were used to measure antiretroviral adherence. Median adherence among women was 27% lower than among men (46% vs. 73%; P < .05). In gender-stratified multivariate models, factors associated with worse adherence in men included not belonging to an HIV support group (P < .0001), crack/cocaine use (P < .005), and medication side effects (P = .01). Among women, alcohol use (P = .005), heroin use (P < .05), and significant medication side effects (P < .005) were independently associated with worse adherence. In a model including both men and women, worse adherence was associated with lack of long-term housing (P < .005), not belonging to any HIV support groups (P < .0005), crack or cocaine use (P < .01), and medication side effects (P < .0005). In addition, worse adherence was associated with the interaction between female gender and alcohol use (P ≤ .05).
In this cohort of current and former opioid users, gender-stratified analysis demonstrated that different social and behavioral factors are associated with adherence in men and women. Among both men and women, worse adherence was associated with lack of long-term housing, not belonging to an HIV support group, crack/cocaine use, and medication side effects. Among women only, alcohol use was associated with worse adherence.
adherence; gender; alcohol; antiretroviral therapy; electronic monitors
To define the prevalence of and factors associated with having a negative purified protein derivative (PPD) among persons who self-report a prior positive PPD and to define the safety of repeat testing in such persons.
Observational cohort study.
Methadone maintenance program with onsite primary care.
Current or former drug users enrolled in methadone maintenance treatment.
Structured interview, tuberculin skin testing regardless of self-reported PPD status, and anergy testing.
MEASUREMENTS AND MAIN RESULTS
Nearly one third (31%) of participants who self-reported a prior positive PPD had a negative measured PPD, despite receipt of a “booster” PPD. A single participant (0.5%) blistered in response to the PPD without lasting ill effect. Participants with PPD results discordant from their history were more likely to be HIV-seropositive and nonreactive to the anergy panel. The discordance rate among HIV-infected participants was 43%, and was largely attributable to immune dysfunction. Among HIV-seronegative participants, the discordance rate was 27%. Recent crack-cocaine use was independently associated with discordance in the absence of HIV infection.
We confirmed that planting a PPD in patients who self-report a positive PPD history confers minimal risk. Substantial rates of discordance exist between self-reported history of a positive PPD and measured PPD status. Further research is needed to define the optimal management of PPD-negative patients who self-report a prior positive PPD and who have not received prior treatment for latent tuberculosis.
tuberculin skin testing; PPD; tuberculosis screening; drug users
OBJECTIVE: This study sought to determine whether health outcomes differed by gender in a cohort of African American, Hispanic American, and white drug users. METHODS: The authors studied hospitalization rates and discharge diagnoses in the HERO Study, an ongoing prospective study of drug users that included HIV-positive and HIV-negative opiate users. The data are from 1996-2000, when highly active antiretroviral therapy (HAART) was available. RESULTS: Women had higher rates of hospitalization than men independent of HIV status, and there was no association between ethnicity and hospitalization. Being a woman was an independent risk factor for HIV and non-HIV-related hospitalization. CONCLUSION: Health disparities between men and women extend to HIV.
Despite a burgeoning literature on adherence to HIV therapies, few studies have examined the impact of ongoing drug use on adherence and viral suppression, and none of these have utilized electronic monitors to quantify adherence among drug users. We used 262 electronic monitors to measure adherence with all antiretrovirals in 85 HIV-infected current and former drug users, and found that active cocaine use, female gender, not receiving Social Security benefits, not being married, screening positive for depression, and the tendency to use alcohol or drugs to cope with stress were all significantly associated with poor adherence. The strongest predictor of poor adherence and, in turn, failure to maintain viral suppression, was active cocaine use. Overall adherence among active cocaine users was 27%, compared to 68% among subjects who reported no cocaine use during the 6-month study period. Consequently, 13% of active cocaine users maintained viral suppression, compared to 46% of nonusers. Interventions to improve adherence should focus on reducing cocaine use, developing adaptive coping skills, and identifying and treating depression.
adherence; drug users; antiretroviral therapy; electronic monitors