Group observed structured encounter (GOSCE) for third-year medical students improves self-assessment of clinical communication.

OBJECTIVES: This study assesses the effectiveness of a GOSCE in teaching medical students clinical communication, as well as group collaboration and peer feedback. METHODS: The GOSCE was administered during the Internal Medicine clerkship. Groups consisted of 4-6 students and one faculty member. Students completed pre- and post-GOSCE surveys to assess confidence in clinical communication and a GOSCE evaluation to rate the overall experience. Pre- and post-GOSCE program survey scores were compared, and the mean score and standard deviation of the GOSCE evaluation was calculated. RESULTS: Students perceived improvement in their general (Mean 4.49-4.57, p < .0001), case-specific (3.61-3.84, p < .0001) and group clinical communication (3.75-4.09, p < .0001) skills. Students agreed or strongly agreed that the GOSCE taught them something new (91.20%), made them more comfortable in giving (64.31%) and receiving (66.57%) feedback and working with a group (64.22%). Students found the GOSCE to be as effective as an OSCE (70.97%). CONCLUSIONS: A GOSCE is a valuable resource for use in formative assessment of clinical communication, and it offers the benefit of group collaboration and peer feedback. These findings support the broader use of GOSCEs in undergraduate medical education.

Importance of substance use and violence in psychosocial syndemics among women with and at-risk for HIV.

Women in the US continue to be affected by HIV through heterosexual contact. Sexual risk behaviors among women have been associated with a syndemic, or a mutually reinforcing set of conditions, including childhood sexual abuse (CSA), depression, substance use, violence, and financial hardship. Baseline data from a cohort of women with and at-risk for HIV (N = 620; 52% HIV+) were analyzed with Poisson regression to assess evidence for additive, independent and interactive effects among syndemic conditions in relation to reported sexual risk behaviors (e.g., unprotected and transactional sex) over the past 6 months, controlling for age and HIV status. The number of syndemic conditions was incrementally associated with more types of sexual risk behaviors. For example, women with all five syndemic conditions reported 72% more types of risk behaviors over 6 months, as compared to women without any syndemic conditions. Compared to women with no syndemic conditions, women with three syndemic conditions reported 34% more and women with one syndemic condition reported 13% more types of risk behaviors. Endorsing substance use in the past 6 months, reporting CSA, and experiencing violence as an adult were independently associated with 49%, 12%, and 8% more types of risk behaviors, respectively compared to women without these conditions. Endorsing both substance use and violence was associated with 27% more types of risk behaviors. These associations were not moderated by HIV status. Understanding specific relationships and interactions are needed to more effectively prioritize limited resources in addressing the psychosocial syndemic associated with sexual risk behavior among women with and at-risk for HIV. Our results identify interrelated psychosocial factors that could be targeted by intervention studies aiming to reduce high-risk sex in this population.

HIV prevalence, risk behavior, knowledge, and beliefs among women seeking care at a sexually transmitted infection clinic in Mumbai, India.

Three hundred women presenting to a sexually transmitted infection (STI) clinic in Mumbai, India were surveyed and HIV tested. Thirty-nine percent were HIV infected; 80% were current sex workers, and HIV infection was not significantly associated with past-year sex work. Only 44% always used condoms with their noncommercial sex partners. Most believed that condom preparation is a male responsibility (58%); that condom use is a sign that partner trust is lacking (84%); and that if a woman asks her partner to use a condom, he will lose respect for her (65%). All women at STI clinics in India need HIV testing and culturally sensitive risk interventions.

Discordance between spermatozoa detection and self-reported semen exposure.

An analysis of data from a prospective study of 1257 high-risk women revealed 7 predictors of discordance between self-reported lack of recent exposure to semen and detection of spermatozoa on Gram stain, suggesting that inaccuracies in the reporting of sexual behaviors cannot be assumed to be distributed randomly.

Implementation of Electronic Decision Support for Diabetic Care in a Student-Run Clinic.

Background and objectives Type 2 diabetes mellitus (T2DM) is a complex disease that can lead to complications. Electronic decision support in the electronic medical record (EMR) aids management. There is no study demonstrating the effectiveness of electronic decision support in assisting medical student providers in student-run free clinics. Methods There were 71 T2DM patients seen by medical students. Twenty-three encounters used a Diabetes Progress Note (DPN) that was created from consensus, opinion-based guidelines. Each note received a total composite score based on an eight-point scale for adherence to guidelines. Statistical comparisons between mean composite scores were performed using independent t-tests. Results The mean total composite score of DPN users was significantly greater than DPN non-users (5.35 vs. 4.23, p = 0.008), with a significant difference in the physical exam component (1.70 vs. 1.31, p = 0.002). Conclusions In this exploratory study, medical student providers at an attending-supervised, student-run free clinic that used electronic decision support during T2DM patient visits improved adherence to screening for diabetic complications and standard of care.

Alpha Omega Alpha Honor Medical Society: A Commitment to Inclusion, Diversity, Equity, and Service in the Profession of Medicine.

With a motto of "Be Worthy to Serve the Suffering," Alpha Omega Alpha Honor Medical Society (AΩA) supports the importance, inclusion, and development of a culturally and ethnically diverse medical profession with equitable access for all. The underrepresentation of minorities in medical schools and medicine continues to be a challenge for the medical profession, medical education, and AΩA. AΩA has worked, and continues to work, to ensure the development of diverse leaders, fostering within them the objectivity and equity to be inclusive servant leaders who understand and embrace diversity in all its forms.Inclusion of talented individuals from different backgrounds benefits patient care, population health, education, and scientific discovery. AΩA values an inclusive, diverse, fair, and equitable work and learning environment for all and supports the medical profession in its work to achieve a welcoming, inclusive environment in teaching, learning, caring for patients, and collaboration.The diversity of medical schools is changing and will continue to change. AΩA is committed to continuing to work with its members, medical school deans, and AΩA chapters to assure that AΩA elections are unbiased and based on the values of AΩA and the profession of medicine in service to patients and the profession.Progress toward diversity, inclusion, and equity is more than simply checking off a box or responding to criticism-it is about being and developing diverse excellent physicians. AΩA and all those in the medical profession must continue to guide medicine to be unbiased, open, accepting, inclusive, and culturally aware in order to "Be Worthy to Serve the Suffering."

Longitudinal association of alcohol use with HIV disease progression and psychological health of women with HIV.

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.

Prevalence, Risk Factors, and Treatment for Overactive Bladder in a Racially Diverse Population.

OBJECTIVE: To evaluate differences in prevalence, overactive bladder (OAB) risk factors, and OAB treatment in a diverse population of underrepresented racial/ethnic groups. METHODS: This is a retrospective cohort study of women ≥ 18 years who had an OAB diagnosis code from June 1, 2013 to June 30, 2016. Women who had neurogenic bladder or pelvic cancer were excluded. OAB risk factors included age, body mass index, socioeconomic status, diabetes, and smoking. OAB treatment included consultation with a specialist, diagnostic testing, medication, and third-line therapy (neuromodulation or chemodennervation). ANOVA and Chi-square were used to compare continuous and categorical variables. Multivariable logistic regression models were developed to examine the association between racial/ethnic groups and OAB management while controlling for risk factors. RESULTS: OAB prevalence was 4.41% (5407/122,606) and was highest in Hispanic women. Black and Hispanic women were significantly younger, had a higher median body mass index, higher rate of diabetes, and lower socioeconomic status compared to White women. There was no racial difference in OAB prescriptions. Black women were less likely to consult with a specialist in multivariable analysis. CONCLUSION: OAB prevalence and presence of OAB risk factors was highest in Hispanic and Black women. Black women were less likely to consult with a specialist suggesting that Black women receive initial therapy from primary care physicians. Future studies will evaluate if racial differences in OAB treatment are due to patient preference or provider practices.

Enhancing Medical Student-Interpreter Collaboration in an Urban Free Clinic.

BACKGROUND AND OBJECTIVES: Cultural barriers and patient-provider language discordance exert deleterious effects on patient care. One solution has been the integration of medical interpreters into the care of patients with limited English proficiency. While medical schools and residency programs have started developing training programs on how to work with medical interpreters, no similar endeavor has been reported by student-run free clinics. METHODS: Over 1 year, 76 third-year medical students (MS3s) were enrolled in control and intervention groups, and evaluated by in-person interpreters during interpreted real-patient encounters. MS3s in the intervention group received a lesson- and reminder-based training program on how to work with in-person interpreters. RESULTS: MS3s who received the intervention were more likely to ask the patient one question at a time (odds ratio [OR] 3.54, P=.0079), listen to the interpreter without unnecessary interruption (OR 3.30, P=.022), and speak in short, simple sentences with pauses for interpretation (OR 3.08, P=.017). CONCLUSIONS: Our lesson- and reminder-based training program on provider-interpreter collaboration can improve the performance of MS3s within a select skill set with minimal cost and time investment.

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

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

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

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

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.

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

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

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

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

Two-step tuberculin skin testing in drug users.

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

Psychological resources protect health: 5-year survival and immune function among HIV-infected women from four US cities.

OBJECTIVE: Guided by Cognitive Adaptation Theory, the aim was to determine whether psychological resources (positive affect, positive expectancy regarding health outcomes, finding meaning in challenging circumstances) protect against HIV-related mortality and decline in CD4 lymphocyte counts among women with HIV. DESIGN: The HIV Epidemiologic Research Study, a longitudinal prospective cohort study, with semi-annual interview, physical examination and laboratory assays. METHODS: A total of 773 HIV-seropositive women aged 16 to 55 years were recruited from four academic medical centers in Baltimore, Maryland; Bronx, New York; Providence, Rhode Island; and Detroit, Michigan. Semi-annually for up to 5 years, the women were interviewed, underwent physical examination, medical record abstraction, and venipuncture. Primary outcomes for these analyses included HIV-related mortality and CD4 cell count slope decline over 5 years. RESULTS: Psychological resources were inversely associated with HIV-related mortality and time to death, beyond the effects of potential confounding variables such as clinical status (e.g., HIV viral load, symptoms, antiretroviral therapy), sociodemographic characteristics (e.g. age, race), and depression at study entry (P < 0.05). Psychological resources also were inversely associated with CD4+ cell count decline (P < 0.01), serving as a possible mechanism linking resources to mortality. CONCLUSIONS: Psychological resources may protect against HIV-related mortality and immune system decline. Findings have implications for understanding individual variability in HIV disease progression. Moreover, because psychological resources are potentially amenable to change, results can be applied to clinical interventions aimed at improving the health of women with HIV.

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

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

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.

Combination of Antiretroviral Drugs and Radioimmunotherapy Specifically Kills Infected Cells from HIV-Infected Individuals.

Eliminating virally infected cells is an essential component of any HIV eradication strategy. Radioimmunotherapy (RIT), a clinically established method for killing cells using radiolabeled antibodies, was recently applied to target HIV-1 gp41 antigen expressed on the surface of infected cells. Since gp41 expression by infected cells is likely downregulated in patients on antiretroviral therapy (ART), we evaluated the ability of RIT to kill ART-treated infected cells using both in vitro models and lymphocytes isolated from HIV-infected subjects. Human peripheral blood mononuclear cells (PBMCs) were infected with HIV and cultured in the presence of two clinically relevant ART combinations. Scatchard analysis of the 2556 human monoclonal antibody to HIV gp41 binding to the infected and ART-treated cells demonstrated sufficient residual expression of gp41 on the cell surface to warrant subsequent RIT. This is the first time the quantification of gp41 post-ART is being reported. Cells were then treated with Bismuth-213-labeled 2556 antibody. Cell survival was quantified by Trypan blue and residual viremia by p24 ELISA. Cell surface gp41 expression was assessed by Scatchard analysis. The experiments were repeated using PBMCs isolated from blood specimens obtained from 15 HIV-infected individuals: 10 on ART and 5 ART-naïve. We found that 213Bi-2556 killed ART-treated infected PBMCs and reduced viral production to undetectable levels. ART and RIT co-treatment was more effective at reducing viral load in vitro than either therapy alone, indicating that gp41 expression under ART was sufficient to allow 213Bi-2556 to deliver cytocidal doses of radiation to infected cells. This study provides proof of concept that 213Bi-2556 may represent an innovative and effective targeting method for killing HIV-infected cells treated with ART and supports continued development of 213Bi-2556 for co-administration with ART toward an HIV eradication strategy.