Improving child tuberculosis contact identification and screening in Lesotho: Results from a mixed-methods cluster-randomized implementation science study.

BACKGROUND: Child tuberculosis (TB) contact management is recommended for preventing TB in children but its implementation is suboptimal in high TB/HIV-burden settings. The PREVENT Study was a mixed-methods, clustered-randomized implementation study that evaluated the effectiveness and acceptability of a community-based intervention (CBI) to improve child TB contact management in Lesotho, a high TB burden country. METHODS: Ten health facilities were randomized to CBI or standard of care (SOC). CBI holistically addressed the complex provider-, patient-, and caregiver-related barriers to prevention of childhood TB. Routine TB program data were abstracted from TB registers and cards for all adult TB patients aged >18 years registered during the study period, and their child contacts. Primary outcome was yield (number) of child contacts identified and screened per adult TB patient. Generalized linear mixed models tested for differences between study arms. CBI acceptability was assessed via semi-structured in-depth interviews with a purposively selected sample of 20 healthcare providers and 28 caregivers. Qualitative data were used to explain and confirm quantitative results. We used thematic analysis to analyze the data. RESULTS: From 01/2017-06/2018, 973 adult TB patients were recorded, 490 at CBI and 483 at SOC health facilities; 64% male, 68% HIV-positive. At CBI and SOC health facilities, 216 and 164 child contacts were identified, respectively (p = 0.16). Screening proportions (94% vs. 62%, p = 0.13) were similar; contact yield per TB case (0.40 vs. 0.20, p = 0.08) was higher at CBI than SOC health facilities, respectively. CBI was acceptable to caregivers and healthcare providers. CONCLUSION: Identification and screening for TB child contacts were similar across study arms but yield was marginally higher at CBI compared with SOC health facilities. CBI scale-up may enhance the ability to reach and engage child TB contacts, contributing to efforts to improve TB prevention among children.

Monitoring quality at scale: implementing quality assurance in a diverse, multicountry HIV program.

The centrality of quality as a strategy to achieve impact within the U.S. President's Emergency Plan for AIDS Relief (PEPFAR) has been widely recognized. However, monitoring program quality remains a challenge for many HIV programs, particularly those in resource-limited settings, where human resource constraints and weaker health systems can pose formidable barriers to data collection and interpretation. We describe the practicalities of monitoring quality at scale within a very large multicountry PEPFAR-funded program, based largely at health facilities. The key elements include the following: supporting national programs and strategies; developing a conceptual framework and programmatic model to define quality and guide the provision of high-quality services; attending to program context, as well as program outcomes; leveraging existing and routinely collected data whenever possible; developing additional indicators for judicious use in targeted, in-depth assessments; providing hands-on support for data collection and use at the facility, sub-national, and national levels; utilizing web-based databases for data entry, analysis, and dissemination; and multidisciplinary support from a large team of clinical and strategic information advisors.

Implementation and Operational Research: Evaluation of Loss-to-Follow-up and Postoperative Adverse Events in a Voluntary Medical Male Circumcision Program in Nyanza Province, Kenya.

BACKGROUND: More than 4.7 million voluntary medical male circumcisions (VMMCs) had been provided by HIV prevention programs in sub-Saharan Africa through 2013. All VMMC clients are recommended to return to the clinic for postoperative follow-up, although adherence is variable. The clinical status of clients who do not return is largely unknown. METHODS: VMMC clients from Nyanza Province, Kenya, aged older than or equal to 13 years, were recruited immediately after surgery from April to October 2012 from high-volume sites. Medical record reviews at 13-14 days after surgery indicated which clients had been adherent with recommended follow-up (ADFU) and which were lost-to-follow-up (LTFU). Clients in the LTFU group received clinical evaluations at home approximately 2 weeks postsurgery. Adverse events (AEs) and AE rates were compared between the ADFU and LTFU groups. RESULTS: Of 4504 males approached in 50 VMMC sites, 1699 (37.7%) were eligible and enrolled and 1600 of 1699 (94.2%) contributed to follow-up and AE data. Medical record review indicated 897 of 1600 (56.1%) were LTFU, and 762 (84.9%) of these received home-based clinical evaluations. The rate of moderate or severe AE diagnosis was 6.8% in the LTFU group vs. 3.3% in the ADFU group (relative risk = 2.1, 95% confidence interval: 1.3 to 3.4). CONCLUSIONS: The moderate or severe AE diagnosis rate was approximately 2 times higher in the LTFU group. National programs should consider instituting surveillance systems to detect AEs that might otherwise go unnoticed. Providers should emphasize the importance of follow-up and actively contact LTFU clients to ensure care is provided throughout the entire postoperative course for all.

Performance of symptom-based tuberculosis screening among people living with HIV: not as great as hoped.

OBJECTIVE: The objective of the present study was to determine the diagnostic performance of the symptom-based tuberculosis (TB) screening questionnaire recommended by WHO for people living with HIV (PLWH) in resource-limited settings, among adults off and on antiretroviral therapy (ART). DESIGN: Cross-sectional study at two HIV clinics in South Africa. METHODS: A total of 825 PLWH completed the screening questionnaire and underwent investigations [chest radiography (CXR) and microbiologic testing of sputa]. A positive screen was defined as presence of cough, fever, night sweats, or weight loss. Pulmonary tuberculosis (PTB) was defined as sputum smear positive for acid-fast bacilli or growth of Mycobacterium tuberculosis. RESULTS: Of 737 participants with at least one diagnostic sputum specimen, PTB was diagnosed in 31 of 522 (5.9%) on ART, and 34 of 215 (15.8%) not on ART. The questionnaire missed 15 of 31 (48.4%) PTB cases on ART, and three of 34 (8.8%) not on ART. Among participants on ART, post-test probability of PTB diagnosis (95% confidence interval) was 6.8% (4.0-10.9%) if screening positive, and 5.2% (2.9-8.4%) if screening negative, whereas among participants not on ART, post-test probabilities were 20.3% (14.2-27.5%) and 4.8% (1.0-13.5%), respectively. Among participants diagnosed with PTB, those on ART were significantly less likely to screen positive (adjusted odds ratio 0.04, 95% confidence interval: 0.01-0.39). In both groups (ART and no ART), screening was more sensitive when CXR was incorporated. CONCLUSION: For case detection and exclusion of PTB, the WHO-recommended questionnaire performed adequately among PLWH not on ART, and poorly among those on ART. Further research is needed to identify feasible and effective TB screening strategies for PLWH in resource-limited settings.

Alcohol consumption trajectory patterns in adult women with HIV infection.

HIV-infected women with excessive alcohol consumption are at risk for adverse health outcomes, but little is known about their long-term drinking trajectories. This analysis included longitudinal data, obtained from 1996 to 2006, from 2,791 women with HIV from the Women's Interagency HIV Study. Among these women, the proportion in each of five distinct drinking trajectories was: continued heavy drinking (3 %), reduction from heavy to non-heavy drinking (4 %), increase from non-heavy to heavy drinking (8 %), continued non-heavy drinking (36 %), and continued non-drinking (49 %). Depressive symptoms, other substance use (crack/cocaine, marijuana, and tobacco), co-infection with hepatitis C virus (HCV), and heavy drinking prior to enrollment were associated with trajectories involving future heavy drinking. In conclusion, many women with HIV change their drinking patterns over time. Clinicians and those providing alcohol-related interventions might target those with depression, current use of tobacco or illicit drugs, HCV infection, or a previous history of drinking problems.

PEPFAR support for the scaling up of collaborative TB/HIV activities.

The US President's Emergency Plan for AIDS Relief (PEPFAR) has supported a comprehensive package of care in which interventions to address HIV-related tuberculosis (TB) have received increased funding and support in recent years. PEPFAR's TB/HIV programming is based on the World Health Organization's 12-point policy for collaborative TB/HIV activities, which are integrated into PEPFAR annual guidance. PEPFAR implementing partners have provided crucial support to TB/HIV collaboration, and as a result, PEPFAR-supported countries in sub-Saharan Africa have made significant gains in HIV testing and counseling of TB patients and linkages to HIV care and treatment, intensified TB case finding, and TB infection control. PEPFAR's support of TB/HIV integration has also included significant investment in health systems, including improved laboratory services and educating and enlarging the workforce. The scale-up of antiretroviral therapy along with support of programs to increase HIV counseling and testing and improve linkage and retention in HIV care may have considerable impact on TB morbidity and mortality, if used synergistically with isoniazid preventive therapy, intensified case finding, and infection control. Issues to be addressed by future programming include accelerating implementation of isoniazid preventive therapy, increasing access and ensuring appropriate use of new TB diagnostics, supporting early initiation of antiretroviral therapy for HIV-infected TB patients, and strengthening systems to monitor and evaluate program implementation.

Alcohol consumption and diabetes risk in the Diabetes Prevention Program.

BACKGROUND: Moderate alcohol consumption is associated with a decreased risk of type 2 diabetes in the general population, but little is known about the effects in individuals at high risk of diabetes. OBJECTIVES: The objectives were to determine associations between alcohol consumption and diabetes risk factors and whether alcohol consumption was a predictor of incident diabetes in individuals enrolled in the Diabetes Prevention Program (DPP). DESIGN: DPP participants (n = 3175) had impaired glucose tolerance (2-h glucose: 7.8-11.1 mmol/L), elevated fasting glucose (5.3-7.0 mmol/L), and a body mass index (in kg/m(2)) > or =24. Participants were randomly assigned to placebo, metformin, or lifestyle modification and were followed for a mean of 3.2 y. Alcohol intake was assessed at baseline and year 1 by using a semiquantitative food-frequency questionnaire. Diabetes was diagnosed by annual oral-glucose-tolerance testing and semiannual fasting plasma glucose measurement. RESULTS: Participants who reported higher alcohol consumption tended to be male, older, white, and less obese and to have a higher calorie intake and a higher HDL-cholesterol concentration. Higher alcohol consumption was associated with lower insulin secretion at any level of insulin sensitivity. We found lower incidence rates of diabetes with higher alcohol consumption in the metformin (P < 0.01 for trend) and lifestyle modification (P = 0.02 for trend) groups, which remained significant after adjustment for multiple baseline covariates. No similar association was observed in the placebo group. CONCLUSIONS: Despite overall low rates of alcohol consumption, there was a reduced risk of incident diabetes in those who reported modest daily alcohol intake and were assigned to metformin or lifestyle modification. Moderate daily alcohol intake is associated with lower insulin secretion-an effect that warrants further investigation. This trial was registered at clinicaltrials.gov as NCT00038727.

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.

Crack cocaine, disease progression, and mortality in a multicenter cohort of HIV-1 positive women.

BACKGROUND: Longitudinal associations between patterns of crack cocaine use and progression of HIV-1 disease are poorly understood, especially among women. This study explores relationships between crack use and HIV-1 disease outcomes in a multicenter cohort of infected women. METHODS: Subjects were 1686 HIV-seropositive women enrolled at six US research centers in the Women's Interagency HIV Study. Approximately 80% were non-white and 29% used crack during the study period. Cox survival and random regression analysis examined biannual observations made April 1996 through September 2004. Outcome measures included death due to AIDS-related causes, CD4 cell count, HIV-1 RNA level, and newly acquired AIDS-defining illnesses. RESULTS: Persistent crack users were over three times as likely as non-users to die from AIDS-related causes, controlling for use of HAART self-reported at 95% or higher adherence, problem drinking, age, race, income, education, illness duration, study site, and baseline virologic and immunologic indicators. Persistent crack users and intermittent users in active and abstinent phases showed greater CD4 cell loss and higher HIV-1 RNA levels controlling for the same covariates. Persistent and intermittent crack users were more likely than non-users to develop new AIDS-defining illnesses controlling for identical confounds. These results persisted when controlling for heroin use, tobacco smoking, depressive symptoms, hepatitis C virus coinfection, and injection drug use. CONCLUSION: Use of crack cocaine independently predicts AIDS-related mortality, immunologic and virologic markers of HIV-1 disease progression, and development of AIDS-defining illnesses among women.

The relationship between cocaine use and human papillomavirus infections in HIV-seropositive and HIV-seronegative women.

OBJECTIVE: Animal data suggest that cocaine has an immunosuppressive effect, but no human studies have been conducted to assess the relation of cocaine use with human papillomavirus (HPV) infection, the viral cause of cervical cancer. Since both cocaine use and HPV infection are common among HIV-positive women, we sought to determine whether use of cocaine and/or crack influences the natural history of HPV among women with or at high risk of HIV. METHODS: Women enrolled in the Women's Interagency HIV Study (2278 HIV-seropositive and 826 high-risk seronegative women) were examined every six months for up to 9.5 years with Pap smear, collection of cervicovaginal lavage (CVL) samples, and detailed questionnaires regarding health and behavior, including use of crack and cocaine (crack/cocaine). CVLs were tested for HPV DNA by PCR, with genotyping for over forty HPV types. RESULTS: In multivariate logistic regression models, censoring women treated for cervical neoplasia, crack/cocaine use within the last six months was associated with prevalent detection of oncogenic HPV DNA (odds ratio [OR] = 1.30 (1.09-1.55)), and with oncogenic HPV-positive squamous intraepithelial lesions (SIL) (OR = 1.70 (1.27-2.27)), following adjustment for age, race, HIV-serostatus, and CD4+ T-cell count, the number of sexual partners in the past six months, and smoking. In multivariate Cox models crack/cocaine use was also associated with a trend that approached significance in regard to incident detection of oncogenic HPV-positive SIL (HR = 1.51, 95% CI 0.99-2.30), and while the rate of oncogenic HPV clearance was not related to cocaine use, the clearance of any SIL was significantly lower in those with versus those without recent crack/cocaine use (HR = 0.57, 95% CI 0.34-0.97). CONCLUSIONS: Cocaine use is associated with an increased risk of detection of both prevalent and incident oncogenic HPV infection, as well as an increased risk of HPV-positive SIL over time.

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.

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.

Impact of street drug use, HIV infection, and highly active antiretroviral therapy on reproductive hormones in middle-aged women.

OBJECTIVE: To assess the impact of street drug use and HIV infection on reproductive hormones in 82 women aged 28?56 and 15 HIV-uninfected, regularly cycling premenopausal historical controls. METHODS: Prospective, pilot cohort study. Baseline blood samples were assayed for follicle stimulating hormone (FSH), human chorionic gonadotropin (hCG), prolactin (PRL), thyroid stimulating hormone (TSH), and estradiol (E(2)). Menopausal status was defined as premenopause: age<40, not amenorrheic; perimenopause: age>40, not amenorrheic; menopause: age>40, with> or =12 months' amenorrhea. Kruskal-Wallis testing was used to compare groups of women sorted by menopausal status and separated by drug use and HIV serostatus. Controls were regularly cycling premenopausal women. RESULTS: Thirty-eight of the 82 women (46%) reported substance abuse, and 47 of the 82 (57%) were HIV infected. TSH did not differ by HIV serostatus or drug use. PRL was elevated in drug users compared with nonusers and healthy volunteers (10.3, 5.9 vs. 6.2 ng/ml, respectively, p = 0.002), with no effect of HIV serostatus. FSH was reduced in each menstrual category related to drug use and in postmenopausal women associated with positive HIV serostatus. Highly active antiretroviral therapy (HAART) use was not related to PRL or E(2) but was associated with higher FSH. FSH was greater in cohort participants compared with controls. CONCLUSIONS: Drug use, not HIV, relates to increased PRL. Both drug use and HIV infection are associated with decreased FSH. Women in this socioeconomic stratum at high risk for HIV may be at risk for early menopause. Increased PRL may falsely reduce FSH, necessitating a more careful hormonal characterization of menopausal status in this sample of women.

HIV infection, drug use, and onset of natural menopause.

OBJECTIVE: To study the relationship of HIV infection and drug use with the onset of natural menopause. METHODS: Our analyses used the World Health Organization's definition of menopause (i.e., the date of the last menstrual period is confirmed after 12 months of amenorrhea) and baseline data from a prospective study. Semiannual interviews were conducted. Levels of HIV antibody and CD4+ cell counts were obtained. Menopause was identified at baseline or during 12 months of follow-up. Women ingesting reproductive hormones were excluded. Logistic regression analyses were used to assess factors associated with menopause. RESULTS: Of 571 women, 53% were HIV infected, and 52% had used heroin or cocaine in the previous 5 years. The median age was 43 years (interquartile range [IQR], 40-46 years); 48.9% of the women were black, 40.4% were Hispanic, and 10.7% were white. The median body mass index was 29.1 kg/m2, and 90.4% of participants were current or former cigarette smokers. Menopause was identified in 102 women: 62 HIV-infected women (median age, 46 years; interquartile range [IQR], 39-49 years) and 40 uninfected women (median age, 47 years; IQR, 44.5-48 years). Factors independently associated with menopause included HIV infection (adjusted odds ratio [OR], 1.73; 95% confidence interval [CI], 1.075-2.795), drug use (adjusted OR, 2.633; 95% CI, 1.610-4.308), and physical activity (adjusted OR, 0.895; 95% CI, 0.844-0.950). Among HIV-infected women, factors independently associated with menopause included CD4+ cell counts of >500 cells/mm3 (adjusted OR, 0.191; 95% CI, 0.076-0.4848) and 200-500 cells/mm3 (adjusted OR, 0.356; 95% CI, 0.147-0.813). CONCLUSION: Our study shows that HIV infection and immunosuppression are associated with an earlier age at the onset of menopause. Whether early onset of menopause in HIV-infected women increases their risk of osteoporosis and heart disease requires further study.

Disorders of glucose metabolism among HIV-infected women.

BACKGROUND: Abnormal glucose metabolism in HIV-infected patients has largely been attributed to the use of protease inhibitors. However, most studies of glucose metabolism in HIV-infected patients have focused on men or have lacked appropriate control groups. METHODS: We assessed the factors associated with previously diagnosed diabetes among 620 middle-aged women with or at risk for HIV infection. For a subset of 221 women without previously diagnosed diabetes, we performed an oral glucose tolerance test (OGTT) to measure glucose and insulin levels, and we assessed factors associated with abnormal glucose tolerance, insulin resistance, and insulin secretion. RESULTS: Thirteen percent of the women in the present study had previously diagnosed diabetes. Among women without previously diagnosed diabetes who underwent an OGTT, 6% had previously undiagnosed diabetes, and 12% had impaired glucose tolerance (IGT). According to multivariate analysis, factors that were associated with previously diagnosed diabetes included current methadone treatment, body mass index of > or =25, family history of diabetes, and physical inactivity. Factors that were independently associated with an abnormal result of an OGTT (i.e., a result consistent with IGT or diabetes) included age > or =50 years, family history of diabetes, physical inactivity, and a high number of pack-years of smoking. Factors independently associated with insulin resistance included waist circumference, Hispanic ethnicity, physical inactivity, and, among HIV-infected women, use of HAART that did not include protease inhibitors. Factors associated with lower levels of insulin secretion included current opiate use (i.e., methadone or heroin) and older age. CONCLUSIONS: Abnormal glucose metabolism is highly prevalent among middle-aged women with or at risk for HIV infection, particularly women who use opiates. Screening for diabetes in the HIV primary care setting should occur for women who have classic risk factors for diabetes, rather than solely for women who are taking PIs. Interventions that target modifiable risk factors, including obesity and physical inactivity, are also warranted.