Mirjam-Colette Kempf

HIV infection and obesity: Where did all the wasting go?

BACKGROUND The success of antiretroviral therapy (ART) has led to dramatic changes in causes of morbidity and mortality in HIV-infected individuals. As chronic diseases rates have increased in HIV+ populations, modifiable risk factors such as obesity have increased in importance. Our objective was to evaluate factors associated with weight change among patients receiving ART. METHODS ART-naïve patients initiating therapy at the University of Alabama - Birmingham 1917 HIV/AIDS Clinic from 2000- 2008 were included. Body Mass Index (BMI) was categorized as: underweight (<18.5), normal weight (18.5-24.9), overweight (25-29.9) and obese (≥30). Linear regression models were used to evaluate overall change in BMI and factors associated with increased BMI category 24 months following ART initiation. RESULTS Among 681 patients, the mean baseline BMI was 25.4 ± 6.1; 44% of patients were overweight/obese. At 24 months, 20% of patients moved from normal to overweight/obese or overweight to obese BMI categories. Greater increases in BMI were observed in patients with baseline CD4 count < 50 cells/µl (3.4 ± 4.1, P<0.01) and boosted protease inhibitor use (2.5±4.1 P=0.01), but did not account for all of the variation observed in weight change. CONCLUSIONS The findings that almost half of patients were overweight or obese at ART initiation, and 1 in 5 patients moved to a deleterious BMI category within 2 years of ART initiation are alarming. ART therapy provides only a modest contribution to weight gain in patients. Obesity represents a highly prevalent condition in patients with HIV infection and an important target for intervention.

Gender differences in discontinuation of antiretroviral treatment regimens.

Background:Reported reasons for change or discontinuation of antiretroviral therapy (δART) include adverse events, intolerability, and nonadherence. Little is known how reasons for δART differ by gender. Methods:In a retrospective cohort study, rates and reasons for δART alterations in a large University-based HIV clinic cohort were evaluated. Logistic regression analyses were used to evaluate the relationship between reasons for δART and gender. Cox proportional hazard models were used to investigate time to δART. Results:In total, 631 HIV-positive individuals were analyzed. Women (n = 164) and men (n = 467) were equally likely (53.0% and 54.4%, respectively) to discontinue treatment within 12 month of initiating a new regimen. Reasons for δART, however, were different based on gender-women were more likely to δART due to poor adherence [adjusted odds ratio (OR), 1.44; 95% confidence interval (CI): 0.85 to 2.42], dermatologic symptoms (adjusted OR, 2.88; 95% CI: 1.01 to 8.18), neurological reasons (adjusted OR, 1.82; 95% CI: 0.98 to 3.39), constitutional symptoms (adjusted OR, 2.23; 95% CI: 1.10 to 4.51), and concurrent medical conditions (adjusted OR, 2.03; 95% CI: 1.00 to 4.12). Conclusions:Although the rates of δART are similar among men and women in clinical practice, the reasons for treatment changes are different based on gender. The potential for unique patterns of adverse events and poor adherence among women requires further investigation.

Perceived Barriers to HIV Care Among HIV-Infected Women in the Deep South

Despite the wide availability of effective treatments for HIV disease, many HIV-infected individuals are not in care, and HIV-infected women, particularly those residing in resource-poor areas, may have greater difficulty accessing HIV care than men. The purpose of this research was to explore perceived barriers to care experienced by HIV-infected women living in the Deep South region of the United States. Qualitative research methods were used to generate in-depth descriptions of womens experiences in accessing HIV care. Participants (N = 40) were recruited from 4 community-based HIV service organizations to participate in focus groups. Sessions lasted approximately 2 hours and were audio recorded. Verbatim transcripts, demographic data, and observational notes were subjected to content analysis strategies that coded the data into categories. Five categories of barriers to HIV care were identified as follows: personal, social, financial, geographic/transportation, and health system barriers. Implications of the findings for future research and practice are discussed in this study.

Enrollment and retention of HIV discordant couples in Lusaka, Zambia.

Background:Biased enrollment and attrition compromise the power of clinical trials and limit generalizability of findings. We identify predictors of enrollment and retention for HIV-discordant couples enrolled in prospective studies in Zambia. Principal Findings:A total of 1995 discordant couples were invited to enroll. Predictors of nonenrollment, loss to follow-up, and missed appointments were evaluated using multivariate models. M+F− couples were more likely to be eligible and to enroll and less likely to be lost to follow-up than F+M− couples. Substantial losses to follow-up occurred between testing and enrollment (21.3% of M+F− and 28.1% of F+M−) and between enrollment and the first follow-up visit (24.9% of M+F− and 30.5% of F+M−). Among M+F− and F+M− couples, residence far from the clinic, younger age, and womens age at first intercourse ≤17 years were predictive of attrition. No income, ≤2 lifetime sex partners, no history of sexually transmitted infection in women, and recent extramarital contact in their male partners predicted attrition in F+M− couples. Conclusions:Discordant couples are critical to observational studies and clinical trials to prevent male-to-female and female-to-male transmission. Retention biases must be taken into account during analysis. Run-in designs that delay randomization may improve retention in clinical trials.

Antifungal Susceptibilities of Cryptococcus Neoformans Cerebrospinal fluid Isolates from AIDS Patients in Kenya

Poor susceptibility of Cryptococcus neoformans to fluconazole (FLC) is a matter of concern among clinicians in Africa. The emergence of resistance to FLC was recently reported in Kenya, but it is not known whether it is widespread. Thus, there is need for more antifungal drug susceptibility studies in Kenya. The aim of this study was to measure the in vitro antifungal drug susceptibilities of incident C. neoformans isolates from acquired immunodeficiency syndrome patients in Kenya. Antifungal susceptibility testing was performed in 67 C. neoformans isolates by broth microdilution method as outlined in the Clinical and Laboratory Standards Institute document M27‐A3 using FLC, amphotericin B (AMB), voriconazole (VOR), ravuconazole (RAV) and flucytosine (5‐FC). Isolates were grown on l‐canavanine glycine bromothymol blue medium for serotype identification. Six per cent of the isolates were identified as C. neoformans var. gattii serotype B or C and 94% as C. neoformans var. neoformans. All isolates tested were susceptible to AMB, VOR and RAV (100%), and high susceptibilities were seen to FLC (97%), and 5‐FC (90%). Only 3% and 10% of the isolates’ susceptibility to FLC and 5‐FC, respectively, was dose‐dependent or intermediate. These results demonstrate high susceptibilities of incident C. neoformans isolates to FLC and AMB, antifungals used for treatment of cryptococcal meningitis in Kenya.

Adverse Events in a Cohort of HIV Infected Pregnant and Non-Pregnant Women Treated with Nevirapine versus Non-Nevirapine Antiretroviral Medication

Background Predictors of adverse events (AE) associated with nevirapine use are needed to better understand reports of severe rash or liver enzyme elevation (LEE) in HIV+ women. Methodology AE rates following ART initiation were retrospectively assessed in a multi-site cohort of 612 women. Predictors of onset of rash or LEE were determined using univariate and multivariate analyses. Principal Findings Of 612 subjects, 152 (24.8%) initiated NVP-based regimens with 86 (56.6%) pregnant; 460 (75.2%) initiated non-NVP regimens with 67 (14.6%) pregnant. LEE No significant difference was found between regimens in the development of new grade ≥2 LEE (p = 0.885). Multivariate logistic regression demonstrated an increased likelihood of LEE with HCV co-infection (OR 2.502, 95% CI: 1.04 to 6, p = 0.040); pregnancy, NVP-based regimen, and baseline CD4 >250 cells/mm3 were not associated with this toxicity. Rash NVP initiation was associated with rash after controlling for CD4 and pregnancy (OR 2.78; 95%CI: 1.14–6.76), as was baseline CD4 >250 cells/mm3 when controlling for pregnancy and type of regimen (OR 2.68; 95% CI: 1.19–6.02 p = 0.017). Conclusions CD4 at initiation of therapy was a predictor of rash but not LEE with NVP use in HIV+ women. Pregnancy was not an independent risk factor for the development of AEs assessed. The findings from this study have significant implications for women of child-bearing age initiating NVP-based ART particularly in resource limited settings. This study sheds more confidence on the lack of LEE risk and the need to monitor rash with the use of this medication.

Toll-like receptor gene variants associated with bacterial vaginosis among HIV-1 infected adolescents

Bacterial vaginosis (BV) is a common vaginal disorder in women of reproductive age, especially among women with HIV-1 infection. Several bacterial products including lipopolysaccharides (LPS), lipoteichoic acids (LTA), and peptidoglycans (PGN) are stimulatory ligands for Toll-like receptors (TLRs), and recent evidence indicates the important role of variation in TLR genes for permitting overgrowth of gram negative and BV-type flora. We assessed whether genetic polymorphisms in five TLR genes (TLR1, TLR2, TLR4, TLR6, and TLR9) could be determinants of differential host immune responses to BV in 159 HIV-1-positive African American adolescents enrolled in the Reaching for Excellence in Adolescent Care and Health (REACH) study. BV was assessed biannually and diagnosed either by a Nugent score of at least 7 of 10, or using the Amsel criteria. Cox-proportional hazards regression models, adjusted for concurrent Chlamydia and Gonorrhea infections, douching, and absolute CD4 cell count, were used to identify host genetic factors associated with BV. Two SNPs were associated with BV as diagnosed by the Nugent score and the combined criteria: a minor allele G of rs4986790 (frequency=0.07), which encodes a His to Tyr substitution in TLR4 (HR=1.47, 95% CI 1.15-1.87) and rs187084 (frequency=0.24) on TLR9. The minor allele of rs1898830 (frequency=0.13) was associated with an increased hazard of BV defined by the Amsel criteria (HR=1.86, 95% CI 1.17-2.95). Further studies are warranted to confirm the associations of TLR gene variants and also to understand the underlying pathways and immunogenetic correlates in the context of HIV-1 infection.

HIV-Infected Women's Relationships With Their Health Care Providers in the Rural Deep South: An Exploratory Study

Through this qualitative study we explored the patient/provider relationships of rural HIV-infected women. Thirty-nine women from rural Alabama were recruited to participate in one of four focus groups. The focus groups were audiorecorded, and the participants were asked to complete surveys measuring patient/provider trust. The verbatim-transcribed audio recordings were analyzed using content analysis. The participants’ descriptions of their relationships with health care providers were represented by three major thematic categories: caring, informative, and competent. These findings provide a foundation for further research on the role of patient/provider relationships in the health outcomes of HIV disease in rural, resource-poor settings.

Structural community factors and sub-optimal engagement in HIV care among low-income women in the Deep South of the USA

Abstract This study describes the ways in which poverty and other structural factors create a risk environment for sub-optimal engagement in HIV care among low-income women living with HIV in the Southern USA, contributing to existing health disparities. We conducted a qualitative study in 2012, involving in-depth interviews with 14 stakeholders (service providers and representatives of community-based organisations) and 7 focus-group discussions with 46 women living with HIV (89% African American). A thematic approach in the context of the social ecological model guided data analysis. Data were coded and analysed using NVivo qualitative software. The findings suggested that structural community factors, such as poverty, poor employment opportunities, limited access to healthcare resources, stigma, transportation challenges and access to illicit substances, may work independently and in synergy to impact women’s health seeking behaviour and decision-making, thereby influencing their ability to engage in HIV care. Interventions designed to improve engagement in HIV care should address structural factors to bolster low-income women’s ability to engage in care.

Identifying Symptom Patterns in People Living With HIV Disease.

&NA; Symptoms guide disease management, and patients frequently report HIV‐related symptoms, but HIV symptom patterns reported by patients have not been described in the era of improved antiretroviral treatment. The objectives of our study were to investigate the prevalence and burden of symptoms in people living with HIV and attending an outpatient clinic. The prevalence, burden, and bothersomeness of symptoms reported by patients in routine clinic visits during 2011 were assessed using the 20‐item HIV Symptom Index. Principal component analysis was used to identify symptom clusters and relationships between groups using appropriate statistic techniques. Two main clusters were identified. The most prevalent and bothersome symptoms were muscle aches/joint pain, fatigue, and poor sleep. A third of patients had seven or more symptoms, including the most burdensome symptoms. Even with improved antiretroviral drug side‐effect profiles, symptom prevalence and burden, independent of HIV viral load and CD4+ T cell count, are high.