Publications

The association between sexual violence and depression is well known, but the temporal aspects of the association have not been well established. We analyzed data from a cohort of 173 HIV-positive women in rural Uganda who were interviewed every 3 months for a median of 1.8 years of follow-up. The method of generalized estimating equations (GEE) was used to model the marginal expectation of depression symptom severity (Hopkins Symptom Checklist for Depression), mental health-related quality of life (MOS-HIV Mental Health Summary), and heavy drinking (Alcohol Use Disorders Identification Test) as a function of self-reported forced-sex victimization in the 3 months prior to interview. Estimates were adjusted for variables known to confound the association between victimization and mental health status. To assess any potential reciprocal relationships, we reversed the temporal ordering of the exposures and outcomes and refitted similar GEE models. In multivariable analyses, victimization was associated with greater depression symptom severity (b = 0.17; 95% CI = [0.02, 0.33]) and lower mental health-related quality of life (b = -5.65; 95% CI = [-9.34, -1.96]), as well as increased risks for probable depression (adjusted relative risk [ARR] = 1.58; 95% CI = [1.01, 2.49) and heavy drinking (ARR = 3.99; 95% CI = [1.84, 8.63]). We did not find strong evidence of a reciprocal relationship. Our findings suggest that forced sex is associated with adverse mental health outcomes among HIV-positive women in rural Uganda. Given the substantial mental health-related impacts of victimization, effective health sector responses are needed.

OBJECTIVE

Programme implementers have argued that the increasing availability of antiretroviral therapy (ART) will reduce the stigma of HIV. We analyzed data from Uganda to assess how HIV-related stigma has changed during a period of ART expansion.

DESIGN

Serial cross-sectional surveys.

METHODS

We analyzed data from the Uganda AIDS Rural Treatment Outcomes study during 2007-2012 to estimate trends in internalized stigma among people living with HIV (PLHIV) at the time of treatment initiation. We analyzed data from the Uganda Demographic and Health Surveys from 2006 to 2011 to estimate trends in stigmatizing attitudes and anticipated stigma in the general population. We fitted regression models adjusted for sociodemographic characteristics, with year of data collection as the primary explanatory variable.

RESULTS

We estimated an upward trend in internalized stigma among PLHIV presenting for treatment initiation [adjusted b = 0.18; 95% confidence interval (CI), 0.06-0.30]. In the general population, the odds of reporting anticipated stigma were greater in 2011 compared with 2006 [adjusted odds ratio (OR) = 1.80; 95% CI, 1.51-2.13], despite an apparent decline in stigmatizing attitudes (adjusted OR = 0.62; 95% CI, 0.52-0.74).

CONCLUSION

Internalized stigma has increased over time among PLHIV in the setting of worsening anticipated stigma in the general population. Further study is needed to better understand the reasons for increasing HIV-related stigma in Uganda and its impact on HIV prevention efforts.

OBJECTIVE

Microbial translocation and innate immune action characterize HIV infection. Continued gut mucosal dysfunction during treatment and its relationship to CD4 T-cell recovery has not been well described.

DESIGN

A cross-sectional study was performed of antiretroviral therapy (ART)-suppressed (immunologic responders with CD4 > 500 cells/μl and immunologic nonresponders with CD4 < 350 cells/μl), untreated HIV-infected, and seronegative participants consenting to gut biopsies and a blood draw.

METHODS

Neutrophil infiltration as a surrogate response to epithelial breach, colorectal epithelial proliferation as a measure of repair, and mucosal apoptosis by immunohistochemistry were determined in gut biopsies. Plasma markers of monocyte activation (sCD14), immune activation (interleukin-6), and indoleamine 2,3-dioxygenase-1 activity (plasma kynurenine/tryptophanratio) were concurrently measured.

RESULTS

Each HIV-infected group had greater neutrophil infiltration than controls. Similarly, untreated HIV-infected participants and ART-suppressed immunologic responders had increased epithelial proliferation compared with controls, but immunologic nonresponders had no appreciable increase in epithelial proliferation despite elevated neutrophil infiltration. The CD4 T-cell count was positively correlated with epithelial proliferation and was modestly negatively correlated with neutrophil infiltration in ART-suppressed patients. Epithelial proliferation was inversely correlated with mucosal apoptosis, and apoptosis was linked to plasma sCD14 and modestly to kynurenine/tryptophan ratio.

CONCLUSIONS

Neutrophil infiltration and mucosal apoptosis remain abnormally high despite ART. Epithelial proliferation increases in HIV, but may be impaired in immunologic nonresponders. Whether mucosal apoptosis is a cause or consequence of epithelial proliferative defects is unclear, but appears to be associated with systemic inflammation. The impact of ART and interventions targeting the gut epithelial barrier in treated HIV infection warrant further investigation.

Little is known about trends in depression at antiretroviral therapy (ART) initiation among people living with HIV (PLHIV) in low- and middle-income countries. We used data from an ongoing cohort of treatment-naïve PLHIV in rural Uganda to estimate secular trends in depression among PLHIV at ART initiation. We fitted linear regression models with depression symptom severity as the outcome variable and year of cohort entry (2005-2012) as the explanatory variable, adjusting for socio-demographic variables and assessing physical health score, body mass index (BMI), and CD4 count as potential mediators of a secular trend in depression symptom severity. There was a statistically significant negative association between year of entry and depression symptom severity, suggesting a 3.1 % relative decline in the mean depression symptom severity score at ART initiation in each year of study recruitment after the first year. This trend remained statistically significant after inclusion of baseline socio-demographic characteristics to the model and appeared to be driven by improved physical health scores, but not CD4 count or BMI.

Depression is one of the most prevalent psychiatric comorbidities of HIV and one of the greatest barriers to HIV self-care and adherence. Despite this, little consensus exists on how to best measure depression among people living with HIV/AIDS (PLWHA) in African settings. Measurement of depression among PLWHA may be confounded by somatic symptoms. Some research recommends excluding these items to enhance measurement validity; sensitivity may be lost with this approach. We sought to characterize depression among a cohort (N = 453) of PLWHA initiating antiretroviral therapy in Uganda via factor analysis of a widely used measure of depression, the Hopkins Symptom Checklist (HSCLD). Common factor analysis was performed, associations between HSCLD and the Mental Health subscale of the Medical Outcomes Study HIV (MOS-HIV) estimated, and a Cronbach's alpha calculated to examine validity. Factor analysis yielded two factors: (1) somatic-cognitive symptoms and (2) behavioral disengagement. Persons with more versus less advanced disease (CD4 cell count of ≤200 cells/mm(3)) showed no statistically significant differences in depression scores (1.7 vs. 1.7, P ≥ 0.5). Both factors were significantly associated with the MOS-HIV (P < .01). Factor one was highly reliable (α = .81); factor two had only modest reliability (α = .65). Somatic-cognitive symptoms of depression and disengagement from life's activities appear to be distinct components of depression in this sample. Consideration of somatic items may be valuable in identifying depression in this setting.

UNLABELLED

The anti-inflammatory agent, mesalamine (5-aminosalicylic acid) has been shown to decrease mucosal inflammation in ulcerative colitis. The effect of mesalamine in HIV-infected individuals, who exhibit abnormal mucosal immune activation and microbial translocation (MT), has not been established in a placebo-controlled trial. We randomized 33 HIV-infected subjects with CD4 counts <350 cells/mm3 and plasma HIV RNA levels <40 copies/ml on antiretroviral therapy (ART) to add mesalamine vs. placebo to their existing regimen for 12 weeks followed by a 12 week crossover to the other arm. Compared to placebo-treated subjects, mesalamine-treated subjects did not experience any significant change in the percent CD38+HLA-DR+ peripheral blood CD4+ and CD8+ T cells at week 12 (P = 0.38 and P = 0.63, respectively), or in the CD4+ T cell count at week 12 (P = 0.83). The percent CD38+HLA-DR+ CD4+ and CD8+ T cells also did not change significantly in rectal tissue (P = 0.86, P = 0.84, respectively). During the period of mesalamine administration, plasma sCD14, IL-6, D-dimer, and kynurenine to tryptophan ratio were not changed significantly at week 12 and were similarly unchanged at week 24. This study suggests that, at least under the conditions studied, the persistent immune activation associated with HIV infection is not impacted by the anti-inflammatory effects of mesalamine.

TRIAL REGISTRATION

ClinicalTrials.gov NCT01090102.