The purpose of these analyses was to determine the associations of HIV infection and related immune dysfunction with a glucose homeostasis in the population of antiretroviral-naïve HIV-infected and uninfected Rwandan women. We hypothesise that insulin resistance and its consequences in the developing countries may be further elevated with HIV infection itself regardless of antiretroviral therapy.
Cross-sectional analysis of a longitudinal cohort.
Community-based women's associations.
In 2005, 710 HIV-infected (HIV positive) antiretroviral naïve and 226 HIV-uninfected (HIV negative) women were enrolled in the Rwanda Women's Interassociation Study and Assessment (RWISA). Clinical and demographic parameters, CD4 count, fasting insulin and glucose levels, anthropometric measurements and Bioelectrical Impedance Analysis (BIA) were obtained. Linear models were fit to log-transformed Homeostasis Model Assessment (HOMA) with results exponentiated back to a multiplicative effect on the original scale.
Primary outcome measures
The outcome, insulin resistance, was measured by the HOMA, calculated as fasting insulin (μU/mL)×fasting glucose (mmol/L)⁄22.5.
In adjusted models, HIV-positive women were less insulin resistant than HIV-negative; an HIV-positive woman tended to have 0.728 times as much (95% CI 0.681 to 0.861) HOMA than a comparable HIV-negative woman. Among the HIV-positive women, those with CD4 <200 cells/µL tended to have 0.741 times as much HOMA (95% CI 0.601 to 0.912) as did comparable women with CD4 >350 cells/µL. The older age was independently associated with a lower HOMA insulin resistance. After adjusting for body mass index, fat and fat-free mass were not independently associated with HOMA.
This study found that HIV infection and more advanced HIV infection (CD4 counts <200 cells/µL) were associated with greater insulin sensitivity in antiretroviral naïve African women. These findings provide baseline information for the interpretation of future studies on the effect of antiretroviral therapy on metabolic insulin sensitivity derangements in African population.
Diabetes & Endocrinology; Epidemiology
Men who have sex with men (MSM) accounted for 61% of new HIV diagnoses in the United States in 2010. Recent analyses indicate that socio-structural factors are important correlates of HIV infection. NYCM2M was a cross-sectional study designed to identify neighborhood-level characteristics within the urban environment that influence sexual risk behaviors, substance use and depression among MSM living in New York City. The sample was recruited using a modified venue-based time-space sampling methodology and through select websites and mobile applications.
This paper describes novel methodological approaches used to improve the quality of data collected for analysis of the impact of neighborhoods on MSM health. Previous research has focused predominately on residential neighborhoods and used pre-determined administrative boundaries (e.g., census tracts) that often do not reflect authentic and meaningful neighborhoods. This study included the definition and assessment of multiple neighborhoods of influence including where men live (home neighborhood), socialize (social neighborhood) and have sex (sexual neighborhood). Furthermore, making use of technological advances in mapping, we collected geo-points of reference for each type of neighborhood and identified and constructed self-identified neighborhood boundary definitions. Finally, this study collected both perceived neighborhood characteristics and objective neighborhood conditions to create a comprehensive, flexible and rich neighborhood-level set of covariates. This research revealed that men perceived their home, social and sexual neighborhoods in different ways. Few men (15%) had the same home, social and sexual neighborhoods; for 31%, none of the neighborhoods was the same. Of the three types of neighborhoods, the number of unique social neighborhoods was the lowest; the size of sexual neighborhoods was the smallest. The resultant dataset offers the opportunity to conduct analyses that will yield context-specific and nuanced understandings of the relations among neighborhood space, and the well-being and health of urban MSM.
The objectives of this cross-sectional study were to compare sociodemographic and risk behavior characteristics between black men who have sex with both men and women (MSMW) and those who have sex with men only (MSMO) and assess factors associated with having any unprotected vaginal and/or anal intercourse (UVAI) with women in the last 3 months. Data from 326 black men who reported recent unprotected anal intercourse (UAI) with a man in an HIV behavioral intervention study in New York City were analyzed. Baseline characteristics were compared between MSMW and MSMO, and factors associated with having any UVAI in the past 3 months with women among MSMW were evaluated. In total, 26.8% reported having sex with both men and women in the last 3 months. MSMW were less likely to be HIV-infected, use amyl nitrates, and have unprotected receptive anal sex with most recent male partner. MSMW were more likely to be over 40 years old and use heroin. 55.6% of MSMW reported having UVAI with women in the last 3 months. Compared to MSMW having only protected sex, MSMW having any UVAI with women were less likely to be HIV-infected and to disclose having sex with men to female partners; they were more likely to have greater than 4 male sex partners in the last 3 months. In conclusion, HIV prevention interventions among black MSMW should directly address the risk of HIV transmission to both their female and male partners. Disclosure of bisexuality to female partners may be an important component of future prevention efforts.
Black MSMW; men who have sex with men and women; bisexuality; HIV/AIDS
First-line antiretroviral treatment regimens in resource-limited settings used in breastfeeding mothers often include stavudine (d4T). Limited data describing d4T concentrations in breast milk are available. We analyzed d4T concentrations in 52 mother-infant pairs using ultra-performance liquid chromatography-tandem mass spectrometry (lower limit of quantification: 5 ng/ml in plasma, 20 ng/ml in breast milk). Median (interquartile range) d4T concentrations were 86 (36–191) ng/ml in maternal plasma, 151 (48–259) ng/ml in whole milk, 190 (58–296) ng/ml in skim milk, and <5 (<5-<5) ng/ml in infant plasma. While d4T is concentrated in breast milk relative to maternal plasma, the infant d4T dose received from breast milk is very small and not clinically significant.
stavudine concentrations; breast milk; mother-to-child transmission; HIV
Highly active antiretroviral therapy (HAART) rapidly suppresses human immunodeficiency virus (HIV) viral replication and reduces circulating viral load, but the long-term effects of HAART on viral load remain unclear.
We evaluated HIV viral load trajectories over 8 years following HAART initiation in the Multicenter AIDS Cohort Study and the Women’s Interagency HIV Study. The study included 157 HIV-infected men and 199 HIV-infected women who were antiretroviral naïve and contributed 1311 and 1837 semiannual person-visits post-HAART, respectively. To account for within-subject correlation and the high proportion of left-censored viral loads, we used a segmental Bernoulli/lognormal random effects model.
Approximately 3 months (0.30 years for men and 0.22 years for women) after HAART initiation, HIV viral loads were optimally suppressed (ie, with very low HIV RNA) for 44% (95% confidence interval = 39%–49%) of men and 43% (38%–47%) of women, whereas the other 56% of men and 57% of women had on average 2.1 (1.5–2.6) and 3.0 (2.7–3.2) log10 copies/mL, respectively.
After 8 years on HAART, 75% of men and 80% of women had optimal suppression, whereas the rest of the men and women had suboptimal suppression with a median HIV RNA of 3.1 and 3.7 log10 copies/mL, respectively.
The Post-exposure Prophylaxis in Infants (PEPI)-Malawi trial evaluated infant antiretroviral regimens for prevention of post-natal HIV transmission. A multi-assay algorithm (MAA) that includes the BED capture immunoassay, an avidity assay, CD4 cell count, and viral load was used to identify women who were vs. were not recently infected at the time of enrollment (MAA recent, N = 73; MAA non-recent, N = 2,488); a subset of the women in the MAA non-recent group known to have been HIV infected for at least 2 years before enrollment (known non-recent, N = 54). Antibody maturation and viral diversification were examined in these women.
Samples collected at enrollment (N = 2,561) and 12–24 months later (N = 1,306) were available for serologic analysis using the BED and avidity assays. A subset of those samples was used for analysis of viral diversity, which was performed using a high resolution melting (HRM) diversity assay. Viral diversity analysis was performed using all available samples from women in the MAA recent group (61 enrollment samples, 38 follow-up samples) and the known non-recent group (43 enrollment samples, 22 follow-up samples). Diversity data from PEPI-Malawi were also compared to similar data from 169 adults in the United States (US) with known recent infection (N = 102) and known non-recent infection (N = 67).
In PEPI-Malawi, results from the BED and avidity assays increased over time in the MAA recent group, but did not change significantly in the MAA non-recent group. At enrollment, HIV diversity was lower in the MAA recent group than in the known non-recent group. HRM diversity assay results from women in PEPI-Malawi were similar to those from adults in the US with known duration of HIV infection.
Antibody maturation and HIV diversification patterns in African women provide additional support for use of the MAA to identify populations with recent HIV infection.
Contraception can reduce the dual burden of high fertility and high HIV prevalence in sub-Sahara Africa, but significant barriers remain regarding access and use. We describe factors associated with nonuse of contraception and with use of specific contraceptive methods in HIV positive and HIV negative Rwandan women. Data from 395 HIV-positive and 76 HIV-negative women who desired no pregnancy in the previous 6 months were analyzed using univariate and multivariate logistic regression models to identify clinical and demographic characteristics that predict contraceptive use. Differences in contraceptive methods used were dependent on marital/partner status, partner's knowledge of a woman's HIV status, and age. Overall, condoms, abstinence, and hormonal methods were the most used, though differences existed by HIV status. Less than 10% of women both HIV+ and HIV− used no contraception. Important differences exist between HIV-positive and HIV-negative women with regard to contraceptive method use that should be addressed by interventions seeking to improve contraceptive prevalence.
Although haematological abnormalities are common manifestations of HIV infection, few studies on haematological parameters in HIV-infected persons have been undertaken in sub-Saharan Africa. The authors assessed factors associated with haematological parameters in HIV-infected antiretroviral-naïve and HIV-uninfected Rwandan women.
Cross-sectional analysis of a longitudinal cohort.
Community-based women's associations.
710 HIV-infected (HIV+) antiretroviral-naïve and 226 HIV-uninfected (HIV−) women from the Rwanda Women's Interassociation Study Assessment. Haematological parameters categorised as (abnormal vs normal) were compared by HIV status and among HIV+ women by CD4 count category using proportions. Multivariate logistic regression models using forward selection were fit.
Prevalence of anaemia (haemoglobin (Hb) <12.0 g/dl) was higher in the HIV+ group (20.5% vs 6.3%; p<0.001), and increased with lower CD4 counts: ≥350 (7.6%), 200–349 (16%) and <200 cells/mm3 (32.2%). Marked anaemia (Hb <10.0 g/dl) was found in 4.2% of HIV+ and none of the HIV− women (p<0.001), and was highest in HIV+ women with CD4 <200 cells/mm3 (8.4%). The HIV+ were more likely than HIV− women (4.2 vs 0.5%, respectively, p=0.002) to have moderate neutropenia with white blood cells <2.0×103 cells/mm3 and 8.4% of HIV+ women with CD4 <200 cells/mm3 had moderate neutropenia. In multivariate logistic regression analysis, BMI (OR 0.87/kg/m2, 95% CI 0.82 to 0.93; p<0.001), CD4 200–350 vs HIV− (OR 3.59, 95% CI 1.89 to 6.83; p<0.001) and CD4 <200 cells/mm3 vs HIV− (OR 8.09, 95% CI 4.37 to 14.97; <0.001) had large independent associations with anaemia. There were large independent associations of CD4 <200 cells/mm3 vs HIV− (OR 7.18, 95% CI 0.78 to 65.82; p=0.081) and co-trimoxazole and/or dapsone use (OR 5.69, 95% CI 0.63 to 51.45; p=0.122) with moderate neutropenia.
Anaemia was more common than neutropenia or thrombocytopenia in the HIV-infected Rwandan women. Future comparisons of haematological parameters in HIV-infected patients before and after antiretroviral therapy initiation are warranted.
Objectives. To examine associations between having bone density tests and level of education among white elderly women in managed Medicare. Method. Data from the ninth through twelfth cohort (2006–2009) of the Medicare Health Outcome Survey (HOS) of managed Medicare plans were analyzed; 239331 white elderly women were included. Respondents were grouped by education level and the percentages of respondents who had lifetime bone density testing done among each group were analyzed. Results. 62.7% of respondents with less than a high school education reported previously taking a bone density test. This was lower than the 73.8% for respondents who completed high school and the 81.0% for respondents with more than a high school education. When potential confounding factors such as age, body mass index, marital status, smoking history, year of HOS survey, and region were factored in, the odds ratios of having a bone density test when compared to respondents with less than a high school education were 1.61 and 2.39, respectively, for those with just a high school education and more than a high school education (P < 0.001). Conclusion. Higher education was independently associated with greater use of bone density test in these elderly white women.
Depression and posttraumatic stress disorder (PTSD) are common in developing and postconflict countries. The purpose of this study is to examine longitudinal changes in PTSD in HIV-infected and uninfected Rwandan women who experienced the 1994 genocide.
Five hundred thirty-five HIV-positive and 163 HIV-negative Rwandan women in an observational cohort study were followed for 18 months. Data on PTSD symptoms were collected longitudinally by the Harvard Trauma Questionnaire (HTQ) and analyzed in relationship to demographics, HIV status, antiretroviral treatment (ART), and depression. PTSD was defined as a score on the HTQ of ≥2.
There was a continuing reduction in HTQ scores at each follow-up visit. The prevalence of PTSD symptoms changed significantly, with 61% of the cohort having PTSD at baseline vs. 24% after 18 months. Women with higher HTQ score were most likely to have improvement in PTSD symptoms (p<0.0001). Higher rate of baseline depressive symptoms (p<0.0001) was associated with less improvement in PTSD symptoms. HIV infection and ART were not found to be consistently related to PTSD improvement.
HIV care settings can become an important venue for the identification and treatment of psychiatric problems affecting women with HIV in postconflict and developing countries. Providing opportunities for women with PTSD symptoms to share their history of trauma to trained counselors and addressing depression, poverty, and ongoing violence may contribute to reducing symptoms.
HIV-exposed, uninfected infants who do not breastfeed compared to those who breastfeed between 6 and 15 months experience substantially higher acute morbidity and cumulative mortality. Adequate monitoring of infant health and prolonged breastfeeding should be encouraged.
Background. We assessed morbidity rates during short intervals that accompanied weaning and cumulative mortality among HIV-exposed, uninfected infants enrolled in the postexposure prophylaxis of infants in Malawi (PEPI-Malawi) trial.
Methods. Women were counseled to stop breastfeeding (BF) by 6 months in the PEPI-Malawi trial. HIV-uninfected infants were included in this analysis starting at age 6 months. Breastfeeding and morbidity (illness and/or hospital admission and malnutrition [weight-for-age Z-score, ≤2]) were assessed during age intervals of 6–9, 9–12, and 12–15 months. BF was defined as any BF at the start and end of the interval and no breastfeeding (NBF) was defined as NBF at any time during the interval. The association of NBF with morbidity at each mutually exclusive interval was assessed using Poisson regression models controlling for other factors. Cumulative mortality among infants aged 6–15 months with BF and NBF was assessed using an extended Kaplan–Meier method.
Results. At age 6 months, 1761 HIV-uninfected infants were included in the study. The adjusted rate ratios for illnesses and/or hospital admission for NBF, compared with BF, was 1.7 (P < .0001) at 6–9 months, 1.66 (P = .0001) at 9–12 months, and 1.75 (P = .0008) at 12–15 months. The rates of morbidity were consistently higher among NBF infants during each age interval, compared with BF infants. The 15 months cumulative mortality among BF and NBF children was 3.5% and 6.4% (P = .03), respectively.
Conclusions. Cessation of BF is associated with acute morbidity events and cumulative mortality. Prolonged BF should be encouraged, in addition to close monitoring of infant health and provision of support services.
We previously developed a multi-assay algorithm (MAA) to identify recent HIV infection that includes the BED-Capture Enzyme Immunoassay, an avidity assay based on the Genetic Systems HIV-1/HIV-2+O Enzyme Immunoassay, CD4 cell count, and HIV viral load. We used this MAA to evaluate the association between recent maternal HIV infection and in utero transmission of HIV.
Plasma samples were collected at delivery from 2,561 HIV-infected women in the PEPI-Malawi trial. The MAA described above was used to identify women with recent HIV infection. Logistic regression models assessed association between recent HIV infection and in utero HIV transmission (defined as a positive infant HIV DNA test at birth).
Seventy-three women were identified as recently infected using the MAA. Those women were younger and had lower parity than women who were identified as not recently infected using the MAA (P<0.0001 for age and parity). The frequency of in utero HIV transmission was 17.8% among women identified as recently infected, compared to 6.7% among women identified as not recently infected (13/73 vs. 166/2488, P=0.001). In a multivariate model, three factors were independently associated with in utero HIV transmission: recent infection (adjusted odds ratio [AOR]: 2.49, 95% CI: 1.30–4.78, P=0.006), log10 HIV viral load at delivery (AOR: 2.01, 95% CI: 1.60–2.51, P<0.0001), and younger age (per 10 year increase, AOR: 0.66, 95% CI: 0.43–0.93, P=0.02).
Results obtained using a MAA suggest that recent maternal HIV acquisition is strongly associated with in utero HIV transmission, independent of HIV viral load at delivery.
HIV; incidence; multiassay algorithm; mother-to-child transmission; Malawi
To examine the associations between comorbid mental illness and length of hospital stays (LOS) among Medicaid beneficiaries with AIDS.
Data Source and Collection/Study Setting
Merged 1992–1998 Medicaid claims and AIDS surveillance data obtained from the State of New Jersey for adults with ≥1 inpatient stay after an AIDS diagnosis from 1992 to 1996.
Observational study of 6,247 AIDS patients with 24,975 inpatient visits. Severe mental illness (SMI) and other less severe mental illness (OMI) diagnoses at visits were ascertained from ICD–9 Codes. About 4 percent of visits had an SMI diagnosis; 5 percent had an OMI diagnosis; 43 percent did not have a mental illness diagnosis, but were patients who had been identified as having an SMI or OMI history; and 48 percent were from patients with no identified history of mental illness.
The overall mean hospital LOS was 12.7 days. After adjusting for measures of HIV disease severity and health care access in multivariate models, patients presenting with primary and secondary severe mental illness (SMI) diagnoses had ∼32 percent and ∼11 percent longer LOS, respectively, than did similar patients without a mental illness history (p<0.001 for each). But in these adjusted models of length of stay: (1) diagnosis of OMI was not related to LOS, and (2) in the absence of a mental illness diagnosed at the visit, an identified history of either SMI or OMI was also not related to LOS. In adjusted models of time to readmission for a new visit, current diagnosis of SMI or OMI and in the absences of a current diagnosis, history of SMI or OMI all tended to be associated with quicker readmission.
This study finds greater (adjusted) LOS for AIDS patients diagnosed with severe mental illness (but not for those diagnosed with less severe mental comorbidity) at a visit. The effect of acute severe mental illness on hospitalization time may be comparable to that of an acute AIDS opportunistic illness. While previous research raises concerns that mental illness increases LOS by interfering with treatment of HIV conditions, the associations here may simply indicate that extra time is needed to treat severe mental illnesses or arrange for discharge of afflicted patients.
AIDS; HIV disease; hospitalization; length of stay; mental illness
The objectives of this study are to address if and how albumin can be used as an indication of malnutrition in HIV infected and uninfected Africans.
In 2005, 710 HIV-infected and 226 HIV-uninfected women enrolled in a cohort study. Clinical/demographic parameters, CD4 count, albumin, liver transaminases; anthropometric measurements and Bioelectrical Impedance Analysis (BIA) were performed. Malnutrition outcomes were defined as body mass index (BMI), Fat-free mass index (FFMI) and Fat mass index (FMI). Separate linear predictive models including albumin were fit to these outcomes in HIV negative and HIV positive women by CD4 strata (CD4>350,200–350 and <200 cells/µl).
In unadjusted models for each outcome in HIV-negative and HIV positive women with CD4>350 cells/µl, serum albumin was not significantly associated with BMI, FFMI or FMI. Albumin was significantly associated with all three outcomes (p<0.05) in HIV+ women with CD4 200–350 cells/µl, and highly significant in HIV+ women with CD4<200 cells/µl (P<0.001). In multivariable linear regression, albumin remained associated with FFMI in women with CD4 count<200 cells/µl (p<0.01) but not in HIV+ women with CD4>200.
While serum albumin is widely used to indicate nutritional status it did not consistently predict malnutrition outcomes in HIV- women or HIV+ women with higher CD4. This result suggests that albumin may measure end stage disease as well as malnutrition and should not be used as a proxy for nutritional status without further study of its association with validated measures.
HIV-infected breastfeeding infants acquired multi-class drug resistance (MCR) after their mothers started highly active antiretroviral therapy (HAART). MCR was more frequent in infants whose mothers started HAART by 6 months post-partum or were exclusively breastfeeding when they reported HAART use.
Background. The World Health Organization currently recommends initiation of highly active antiretroviral therapy (HAART) for human immunodeficiency virus (HIV)–infected lactating women with CD4+ cell counts <350 cells/μL or stage 3 or 4 disease. We analyzed antiretroviral drug resistance in HIV-infected infants in the Post Exposure Prophylaxis of Infants trial whose mothers initiated HAART postpartum (with a regimen of nevirapine [NVP], stavudine, and lamivudine). Infants in the trial received single-dose NVP and a week of zidovudine (ZDV) at birth; some infants also received extended daily NVP prophylaxis, with or without extended ZDV prophylaxis.
Methods. We analyzed drug resistance in plasma samples collected from all HIV-infected infants whose mothers started HAART in the first postpartum year. Resistance testing was performed using the first plasma sample collected within 6 months after maternal HAART initiation. Categorical variables were compared by exact or trend tests; continuous variables were compared using rank-sum tests.
Results. Multiclass resistance (MCR) was detected in HIV from 11 (29.7%) of 37 infants. Infants were more likely to develop MCR infection if their mothers initiated HAART earlier in the postpartum period (by 14 weeks vs after 14 weeks and up to 6 months vs after 6 months, P = .0009), or if the mother was exclusively breastfeeding at the time of HAART initiation (exclusive breastfeeding vs mixed feeding vs no breastfeeding, P = .003).
Conclusions. postpartum maternal HAART initiation was associated with acquisition of MCR in HIV-infected breastfeeding infants. The risk was higher among infants whose mothers initiated HAART closer to the time of delivery or were still exclusively breastfeeding when they first reported HAART use.
Limited data exist on the prevalence of inadequate glycemic control and rates of meeting American Diabetic Association (ADA) management guidelines in HIV-infected adults with diabetes mellitus. We conducted a retrospective cross-sectional study of 142 HIV-infected adults with type 2 diabetes at an urban academic HIV clinic during 2008. We estimated the prevalence of and assessed associations with inadequate glycemic control, defined as hemoglobin A1c ≥7.5% for ≥50% of quarters over the year, and determined rates of meeting ADA clinical goals. Ninety-two percent of patients received antiretroviral therapy. The prevalence of inadequate glycemic control was 33% (95% confidence interval [CI] 25%–42%). Compared to patients with adequate control, those with inadequate control had fewer years since HIV diagnosis (12.7 versus 15.1, p = 0.01), increased use of insulin (60% versus 20%, p < 0.001) or any diabetic medication (98% versus 85%, p = 0.02), and higher triglyceride levels (238 versus 168 mg/dL, p = 0.008). Rates of achieving ADA goals were 42% for blood pressure, 66% for low-density lipoprotein cholesterol (LDL-C), 33% for high-density lipoprotein cholesterol, and 31% for triglycerides. Thirty-six percent of patients who did not meet the LDL-C goal received statin therapy. Forty-seven percent of patients were screened for retinopathy and 19% of patients without preexisting renal disease were screened for nephropathy. In conclusion, the prevalence of inadequate glycemic control in HIV-infected patients with diabetes is similar to published data from the general population. Suboptimal rates of meeting ADA blood pressure and lipid goals and adherence to screening guidelines demonstrate need for further clinician and patient education.
We previously reported an increased risk of all-cause and AIDS mortality among HIV-infected women with albuminuria (proteinuria or microalbuminuria) enrolled in the Women’s Interagency HIV Study (WIHS) prior to the introduction of highly active antiretroviral therapy (HAART).
The current analysis includes 1,073 WIHS participants who subsequently initiated HAART. Urinalysis for proteinuria and semi-quantitative testing for microalbuminuria from two consecutive study visits prior to HAART initiation were categorized as follows: confirmed proteinuria (both specimens positive for protein), confirmed microalbuminuria (both specimens positive with at least one microalbuminuria), unconfirmed albuminuria (one specimen positive for proteinuria or microalbuminuria), or negative (both specimens negative). Time from HAART initiation to death was modeled using proportional hazards analysis.
Compared to the reference group of women with two negative specimens, the hazard ratio (HR) for all-cause mortality was significantly elevated for women with confirmed microalbuminuria (HR 1.9; 95% CI 1.2–2.9). Confirmed microalbuminuria was also independently associated with AIDS death (HR 2.3; 95% CI 1.3–4.3), while women with confirmed proteinuria were at increased risk for non-AIDS death (HR 2.4; 95% CI 1.2–4.6).
In women initiating HAART, pre-existing microalbuminuria independently predicted increased AIDS mortality, while pre-existing proteinuria predicted increased risk of non-AIDS death. Urine testing may identify HIV-infected individuals at increased risk for mortality even after the initiation of HAART. Future studies should consider whether these widely available tests can identify individuals who would benefit from more aggressive management of HIV infection and comorbid conditions associated with mortality in this population.
HIV; microalbuminuria; proteinuria; mortality; non-AIDS death
People with severe mental illness (SMI) may be at increased risk for several adverse health conditions, including HIV/AIDS. This disproportionate disease burden has been studied primarily at the individual rather than community level, in part due to the rarity of data sources linking individual information on medical and mental health characteristics with community-level data. We demonstrated the potential of Medicaid data to address this gap.
We analyzed data on Medicaid beneficiaries with schizophrenia from eight states that account for 66% of cumulative AIDS cases nationally.
Across 44 metropolitan statistical areas (MSAs), the treated prevalence of HIV among adult Medicaid beneficiaries diagnosed with schizophrenia was 1.56% (standard deviation = 1.31%). To explore possible causes of variation, we linked claims files with a range of MSA social and contextual variables including local AIDS prevalence rates, area-based economic measures, crime rates, substance abuse treatment resources, and estimates of injection drug users (IDUs) and HIV infection among IDUs, which strongly predicted community infection rates among people with schizophrenia.
Effective strategies for HIV prevention among people with SMI may include targeting prevention efforts to areas where risk is greatest; examining social network links between IDU and SMI groups; and implementing harm reduction, drug treatment, and other interventions to reduce HIV spread among IDUs. Our findings also suggest the need for research on HIV among people with SMI that examines geographical variation and demonstrates the potential use of health-care claims data to provide epidemiologic insights into small-area variations and trends in physical health among those with SMI.
Body mass index (BMI) independently predicts mortality in studies of HIV infected patients initiating antiretroviral therapy (ART). We hypothesized that poorer nutritional status would be associated with smaller gains in CD4 count in Rwandan women initiating ART.
Methods and Findings
The Rwandan Women's Interassociation Study and Assessment, enrolled 710 ART-naïve HIV-positive and 226 HIV-negative women in 2005 with follow-up every 6 months. The outcome assessed in this study was change in CD4 count at 6, 12, and 24 months after ART initiation. Nutritional status measures taken prior to ART initiation were BMI; height adjusted fat free mass (FFMI); height adjusted fat mass (FMI), and sum of skinfold measurements. 475 women initiated ART. Mean (within 6 months) pre-ART CD4 count was 216 cells/µL. Prior to ART initiation, the mean (±SD) BMI was 21.6 (±3.78) kg/m2 (18.3% malnourished with BMI<18.5); and among women for whom the following were measured, mean FFMI was 17.10 (±1.76) kg/m2; FMI 4.7 (±3.5) kg/m2 and sum of skinfold measurements 4.9 (±2.7) cm. FFMI was significantly associated with a smaller change in CD4 count at 6 months in univariate analysis (−6.7 cells/uL per kg/m2, p = 0.03) only. In multivariate analysis after adjustment for covariates, no nutritional variable was associated with change in CD4 count at any follow up visit.
In this cohort of African women initiating ART, no measure of malnutrition prior to ART was consistently associated with change in CD4 count at 6, 12, and 24 months of follow up, suggesting that poorer pre-treatment nutritional status does not prevent an excellent response to ART.
Scale-up of highly active antiretroviral treatment therapy (HAART) programs in Rwanda has been highly successful but data on adherence is limited. We examined HAART adherence in a large cohort of HIV+ Rwandan women.
The Rwanda Women's Interassociation Study Assessment (RWISA) was a prospective cohort study that assessed effectiveness and toxicity of ART. We analyzed patient data 12±3 months after HAART initiation to determine adherence rates in HIV+ women who had initiated HAART.
Of the 710 HIV+ women at baseline, 490 (87.2%) initiated HAART. Of these, 6 (1.2%) died within 12 months, 15 others (3.0%) discontinued the study and 80 others (19.0%) remained in RWISA but did not have a post-HAART initiation visit that fell within the 12±3 month time points leaving 389 subjects for analysis. Of these 389, 15 women stopped their medications without being advised to do so by their doctors. Of the remaining 374 persons who reported current HAART use 354 completed the adherence assessment. All women, 354/354, reported 100% adherence to HAART at the post-HAART visit. The high self-reported level of adherence is supported by changes in laboratory measures that are influenced by HAART. The median (interquartile range) CD4 cell count measured within 6 months prior to HAART initiation was 185 (128, 253) compared to 264 (182, 380) cells/mm3 at the post-HAART visit. Similarly, the median (interquartile range) MCV within 6 months prior to HAART initiation was 88 (83, 93) fL compared to 104 (98, 110) fL at the 12±3 month visit.
Self-reported adherence to antiretroviral treatment 12±3 months after initiating therapy was 100% in this cohort of HIV-infected Rwandan women. Future studies should explore country-specific factors that may be contributing to high levels of adherence to HAART in this population.
The clinical importance of the association of HIV infection and antiretroviral therapy (ART) with low bone mineral density (BMD) in premenopausal women is uncertain because BMD stabilizes on established ART and fracture data are limited.
We measured time to first new fracture at any site with median follow-up of 5.4 years in 2391 (1728 HIV-infected, 663 HIV-uninfected) participants in the Women’s Interagency HIV Study (WIHS). Self-report of fracture was recorded at semiannual visits. Proportional hazard models assessed predictors of incident fracture.
At baseline, HIV-infected women were older (40 ± 9 vs. 36 ± 10 years, P <0.0001), more likely to report postmenopausal status and be hepatitis C virus-infected, and weighed less than HIV-uninfected women. Among HIV-infected women, mean CD4+ cell count was 482 cells/μl; 66% were taking ART. Unadjusted incidence of fracture did not differ between HIV-infected and uninfected women (1.8 vs. 1.4/100 person-years, respectively, P = 0.18). In multivariate models, white (vs. African-American) race, hepatitis C virus infection, and higher serum creatinine, but not HIV serostatus, were statistically significant predictors of incident fracture. Among HIV-infected women, older age, white race, current cigarette use, and history of AIDS-defining illness were associated with incidence of new fracture.
Among predominantly premenopausal women, there was little difference in fracture incidence rates by HIV status, rather traditional risk factors were important predictors. Further research is necessary to characterize fracture risk in HIV-infected women during and after the menopausal transition.
fracture; fragility fracture; HIV-infected women; premenopausal
Prevalence of microalbuminuria is increased in patients with HIV. Microalbuminuria is associated with increased mortality in other populations, including diabetics, for whom microalbuminuria testing is standard of care. We investigated whether microalbuminuria is associated with mortality in HIV-infected women not receiving antiretroviral therapy.
Urinalysis for proteinuria and semi-quantitative testing for microalbuminuria were performed in specimens from two consecutive visits in 1,547 HIV-infected women enrolled in the Women’s Interagency HIV Study in 1994–1995. Time to death was modeled using proportional hazards analysis.
Compared to women without albuminuria, the hazard ratio (HR) for all-cause mortality was increased in women with one (HR 3.4; 95% CI 2.2–5.2) or two specimens positive for either proteinuria or microalbuminuria (HR 3.9; 95% CI 2.1–7.0). The highest risk was observed in women with both specimens positive for proteinuria (HR 5.8; 95% CI 3.4–9.8). The association between albuminuria and all-cause mortality risk remained significant after adjustment for demographics, HIV disease severity, and related comorbidities. Similar results were obtained for AIDS death.
We identified a graded relationship between albuminuria and the risk of all-cause and AIDS mortality.
HIV; microalbuminuria; proteinuria; mortality
Virologic response to highly active antiretroviral therapy (HAART) typically results in a substantial rise in CD4 cell counts. We investigated factors associated with poor CD4 response among HIV-infected women followed at 6-monthly intervals in the Women’s Interagency HIV Study. Women with nadir CD4 counts <350 cells/mm3 who achieved at least 6 months of plasma HIV RNA < 400 copies/ml were studied. Demographic, clinical, and treatment factors were compared between immunologic nonresponders, defined as the lower quartile of CD4 count change after two visits with virologic suppression (<56 cell/mm3; n = 38), and the remaining group of responders (n = 115). Immunologic nonresponders had lower baseline HIV RNA levels and higher CD4 counts, more frequently used HAART 6 months prior to achieving consistent viral suppression, and more commonly had HIV RNA levels >80 but <400 copies/mL at both suppressive visits (21 vs. 7.8%, p = 0.024). In multivariate analysis, higher CD4 count and lower HIV RNA level at the last presuppressive visit were associated with immune nonresponse. We conclude that higher baseline CD4 count and lower HIV RNA level were associated with poor immunologic response to HAART in women with virologic suppression for at least 6 months. Persistent low level viremia may also contribute.
Opiate use is common in HIV- and hepatitis C virus (HCV)-infected individuals, however its contribution to the risk of diabetes mellitus is not well understood.
Prospective study of 1,713 HIV-infected and 652 uninfected participants from the Women’s Interagency HIV Study between October 2000 and March 2006. Diabetes defined as fasting glucose ≥126 mg/dl, or self-report of diabetes medication use or confirmed diabetes diagnosis. Opiate use determined using an interviewer-administered questionnaire. Detectable plasma HCV RNA confirmed HCV infection.
Current opiate users had a higher prevalence of diabetes (15%) than non-users (10%, p=.03), as well as a higher risk of incident diabetes (adjusted relative hazard [RHadj] 1.58, 95% CI 1.01, 2.46), after controlling for HCV infection, HIV/antiretroviral therapy status and diabetes risk factors including age, race/ethnicity, family history of diabetes and body mass index. HCV infection was also an independent risk factor for diabetes (RHadj 1.61, 95% CI 1.02, 2.52). HCV-infected women reporting current opiate use had the highest diabetes incidence (4.83 cases/100 person-years).
Among women with or at-risk for HIV, opiate use is associated with increased diabetes risk independently of HCV infection. Diabetic screening should be part of care for opiate users, and those infected with HCV.
opiate use; diabetes mellitus; fasting glucose; Hepatitis C virus; HIV; women
Obesity is a major risk factor for endometrial cancer, a relationship thought to be largely explained by the prevalence of high estrogen levels in obese women. Obesity is also associated with high levels of insulin, a known mitogen. However, no prospective studies have directly assessed whether insulin and/or insulin-like growth factor-I (IGF-I), a related hormone, are associated with endometrial cancer while accounting for estrogen levels. We therefore conducted a case-cohort study of incident endometrial cancer in the Women’s Health Initiative Observational Study, a prospective cohort of 93,676 postmenopausal women. The study involved all 250 incident cases and a random subcohort of 465 subjects for comparison. Insulin, total IGF-I, free IGF-I, IGF-binding protein-3, glucose, and estradiol levels were measured in fasting baseline serum specimens. Cox models were used to estimate associations with endometrial cancer, particularly endometrioid adenocarcinomas, the main histologic type (n = 205). Our data showed that insulin levels were positively associated with endometrioid adenocarcinoma [hazard ratio contrasting highest versus lowest quartile (HRq4-q1), 2.33; 95% confidence interval (95% CI), 1.13–4.82] among women not using hormone therapy after adjustment for age and estradiol. Free IGF-I was inversely associated with endometrioid adenocarcinoma (HRq4-q1, 0.53; 95% CI, 0.31–0.90) after adjustment for age, hormone therapy use, and estradiol. Both of these associations were stronger among overweight/obese women, especially the association between insulin and endometrioid adenocarcinoma (HRq4-q1, 4.30; 95% CI, 1.62–11.43). These data indicate that hyperinsulinemia may represent a risk factor for endometrioid adenocarcinoma that is independent of estradiol. Free IGF-I levels were inversely associated with endometrioid adenocarcinoma, consistent with prior cross-sectional data.