Andrea A. Howard

Antiretroviral therapy adherence and viral suppression in HIV-infected drug users: Comparison of self-report and electronic monitoring

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.

A prospective study of adherence and viral load in a large multi-center cohort of HIV-infected women

Objectives: To examine the relationship between antiretroviral adherence and viral load, and to determine the predictors of adherence over time in HIV-infected women. Design: Prospective observational study. Methods: One-hundred sixty-one HIV-infected women who were taking antiretroviral therapy for a median of 3.0 years were recruited from the HIV Epidemiology Research Study, a multicenter cohort study of HIV infection in women. Antiretroviral adherence (percent of doses taken as prescribed) was measured over a 6-month period using MEMS caps. At baseline and follow-up, CD4 lymphocyte count and viral load were measured, and a standardized interview was administered to elicit medication history and drug use behaviors. To examine changes in adherence over time, the mean adherence to all antiretroviral agents was calculated for each monitored month. Results: Adherence varied significantly over time (P < 0.001), ranging from a mean of 64% in month 1 to 45% in month 6. Nearly one-fourth of the participants had a 10% or greater decrease in adherence between consecutive months. Virologic failure occurred in 17% of women with adherence of ⩾ 88%, 28% of those with 45–87% adherence, 43% of those with 13–44% adherence, and 71% of those with ⩽ 12% adherence. In multivariate analysis, factors predicting lower adherence included active drug use, alcohol use, more frequent antiretroviral dosing, shorter duration of antiretroviral use, younger age, and lower initial CD4 lymphocyte count. Conclusions: Antiretroviral adherence is not stable over time. Interventions aimed at monitoring and improving long-term adherence in women are urgently needed.

Decreased bone mineral density and increased fracture risk in aging men with or at risk for HIV infection.

Background:Osteopenia has been described in HIV-infected persons, but most studies have not focused on aging men, have not included an HIV-negative comparison group with similar risks to those of the HIV-infected men, or lacked data on fracture rates. Methods:We analyzed bone mineral density (BMD) and incident fractures in 559 men who were ≥ 49 years old with or at-risk for HIV, including 328 with and 231 without HIV infection. Results:Median age was 55 years, 56% were black and 89% had used illicit drugs. In unadjusted analysis, BMD was lower in HIV-infected compared with HIV-uninfected men at the femoral neck (0.97 ± 0.14 versus 1.00 ± 0.15 g/cm2; P < 0.05) and lumbar spine (1.17 ± 0.20 versus 1.20 ± 0.21 g/cm2; P = 0.06); both differences were significant (P < 0.05) after adjusting for age, weight, race, testosterone level, and prednisone and illicit drug use. Non-black race and body weight were independently associated with BMD at both measurement sites and methadone therapy was independently associated with spine BMD. Among HIV-infected men, 87% had taken antiretrovirals and 74% had taken protease inhibitors, but their use was not associated with BMD. Among men who had at least one subsequent study visit (94%), incident fracture rates per 100 person-years differed among men with normal BMD, osteopenia and osteoporosis (1.4 versus 3.6 versus 6.5; P < 0.01). A 38% increase in fracture rate among HIV-infected men was not statistically significant. Conclusions:HIV infection is independently associated with modestly reduced BMD in aging men, and decreased BMD is associated with increased fracture risk.

Gender differences in factors associated with adherence to antiretroviral therapy

OBJECTIVE: To identify gender differences in social and behavioral factors associated with antiretroviral adherence.DESIGN: Prospective cohort study.SETTING: Methadone maintenance program.PARTICIPANTS: 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).CONCLUSIONS: 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.

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 Womens 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.

HIV infection and bone mineral density in middle-aged women

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

Bacterial Pneumonia, HIV Therapy, and Disease Progression among HIV-Infected Women in the HIV Epidemiologic Research (HER) Study

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

HIV infection, 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 Organizations 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.

Integration of Tuberculosis and HIV Services in Sub-Saharan Africa: Lessons Learned

Promoting linkages between tuberculosis (TB) and human immunodeficiency virus (HIV) treatment and prevention programs in resource-constrained environments where both diseases are prevalent is essential to improve the diagnosis, treatment, and outcomes for patients affected by both diseases. In this article, we share insights based on our experiences supporting integrated TB and HIV service delivery programs, including intensified TB case finding, isoniazid preventive therapy, infection control, and initiation of antiretroviral therapy. Our experience indicates that successful integration of TB and HIV services in resource-constrained environments is feasible, although programmatic, infrastructural, and staffing challenges remain. Successful implementation of TB and HIV collaborative activities requires consideration of the realities that exist on the ground and the importance of tailoring interventions in a manner that enables their seamless introduction into existing programs that are often overwhelmed with large numbers of patients and a paucity of human and other resources.

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.