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Association between phosphatidylethanol-measured alcohol use with HIV virologic non-suppression and all-cause mortality risk among people with HIV (PWH) on antiretroviral therapy (ART)

Aims Alcohol is hypothesized to have effects on the kynurenine pathway of tryptophan catabolism, a potential mechanism for alcohol-induced depression and aggression. A biomarker of this pathway, the plasma kynurenine to tryptophan ratio (K/T ratio), has been associated with HIV progression, mortality and depression. Our aim was to assess whether hazardous alcohol consumption is associated higher K/T ratio among people with HIV. Methods Participants were a subset of the Uganda Alcohol Research Collaboration on HIV/AIDS Cohort. Alcohol consumption was categorized (abstinent, moderate and hazardous alcohol use) using the Alcohol Use Disorders Identification Test—Consumption and phosphatidylethanol (PEth). K/T ratio was the primary outcome. We used linear regression adjusted for age, sex, FIB-4, hepatitis B surface antigen, log (HIV viral load) to estimate the association between alcohol consumption and K/T ratio. Results Compared to abstinent participants, hazardous drinkers and moderate drinkers had higher K/T ratio but these differences did not reach statistical significance. Conclusions Our results suggest that hazardous alcohol consumption, in the context of untreated HIV infection, may not significantly alter kynurenine to tryptophan ratio as a measure of activity of the kynurenine pathway of tryptophan metabolism.

Author(s): Hahn, Judith A; Murnane, Pamela M; Vittinghoff, Eric; Muyindike, Winnie R; Emenyonu, Nneka I; Fatch, Robin; Chamie, Gabriel; Haberer, Jessica E; Francis, Joel M; Kapiga, Saidi; Jacobson, Karen; Myers, Bronwyn; Couture, Marie Claude; DiClemente, Ralph J; Brown, Jennifer L; So-Armah, Kaku; Sulkowski, Mark; Marcus, Gregory M; Woolf-King, Sarah; Cook, Robert L; Richards, Veronica L; Molina, Patricia; Ferguson, Tekeda; Welsh, David; Piano, Mariann R; Phillips, Shane A; Stewart, Scott; Afshar, Majid; Page, Kimberly; McGinnis, Kathleen; Fiellin, David A; Justice, Amy C; Bryant, Kendall; Saitz, Richard | Abstract: BackgroundObjective measurement of alcohol consumption is important for clinical care and research. Adjusting for self-reported alcohol use, we conducted an individual participant data (IPD) meta-analysis to examine factors associated with the sensitivity of phosphatidylethanol (PEth), an alcohol metabolite, among persons self-reporting unhealthy alcohol consumption.MethodsWe identified 21 eligible studies and obtained 4073 observations from 3085 participants with Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) positive scores (≥3 for women and ≥4 for men) and PEth measurements. We conducted 1-step IPD meta-analysis using mixed effects models with random intercepts for study site. We examined the associations between demographic (sex, race/ethnicity, and age) and biologic (body mass index-BMI, hemoglobin, HIV status, liver fibrosis, and venous versus finger-prick blood collection) variables with PEth sensitivity (PEth≥8nng/ml), adjusting for the level of self-reported alcohol use using the AUDIT-C score.ResultsOne third (31%) of participants were women, 32% were African, 28% African American, 28% White, and 12% other race/ethnicity. PEth sensitivity (i.e., ≥8nng/ml) was 81.8%. After adjusting for AUDIT-C, we found no associations of sex, age, race/ethnicity, or method of blood collection with PEth sensitivity. In models that additionally included biologic variables, those with higher hemoglobin and indeterminate and advanced liver fibrosis had significantly higher odds of PEth sensitivity; those with higher BMI and those living with HIV had significantly lower odds of PEth sensitivity. African Americans and Africans had higher odds of PEth sensitivity than whites in models that included biologic variables.ConclusionsAmong people reporting unhealthy alcohol use, several biological factors (hemoglobin, BMI, liver fibrosis, and HIV status) were associated with PEth sensitivity. Race/ethnicity was associated with PEth sensitivity in some models but age, sex, and method of blood collection were not. Clinicians should be aware of these factors, and researchers should consider adjusting analyses for these characteristics where possible.

We assessed associations between hazardous alcohol use and latent tuberculosis infection (LTBI) among adults living with human immunodeficiency virus (HIV) in Uganda. We compared tuberculin skin test positivity across medium, high, and very-high alcohol use levels, classified by AUDIT-C scores. In multivariable analysis, very high use was associated with LTBI (adjusted odds ratio 1.61, 95% confidence interval: 1.03–2.50).

BACKGROUND HIV/AIDS is now a chronic illness due to effective antiretroviral therapy (ART) and involves routine follow-up care, including regular physical visits to the clinic. In the recent past, and in wake of the COVID-19 pandemic, there has been increased need for virtual care and intervention delivery, a modality known as mHealth, which includes cell phone-delivered services OBJECTIVE Here we describe cell phone use and its relationship with alcohol use in a cohort of persons with HIV (PWH) and latent tuberculosis (TB). METHODS We performed a cross-sectional analysis of baseline data from a cohort of PWH and latent TB in HIV care in south-western Uganda. We estimated proportions of cell phone and text message use and evaluated their associations with alcohol use, a common modifiable behaviour among PWH. Cell phone use (primary outcome) was defined as owning a cell phone that is turned on at least half of the day. Any alcohol use was defined as any self-reported alcohol use in the prior 3 months, and/or phosphatidylethanol (an alcohol biomarker) ≥8 ng/ml. RESULTS A total of 300 participants were included in the analysis, with a median age of 40 years; 48.7% were male. Majority (89.0%) of participants had access to a phone and of these 9.7% shared the phone with someone else. Eighty-seven percent owned a cell phone that is turned on at least half of the time; the majority (89.7%) rarely or never sent text messages, and over two-thirds (66.9%) rarely or never received text messages. 71.3% had any alcohol use. In adjusted analyses, any alcohol use was not significantly associated with cell phone use (adjusted OR [aOR]: 0.48, 95% confidence interval [CI]: 0.18-1.25, p-value=.13), or sending (aOR: 0.82, 95% CI: 0.28-2.37, p-value=.71) or receiving (aOR: 1.31, 95% CI: 0.70-2.47, p-value= .40) of text messages. CONCLUSIONS There is hope that mHealth interventions in this population can be carried out using cell phones due to their popularity; however, the interventions may need to employ methods that do not rely on the sending and receiving of text messages only. CLINICALTRIAL NCT 03302299

Background Alcohol consumption is a critical driver of the HIV epidemic worldwide, particularly in sub-Saharan Africa, where unhealthy alcohol use and HIV are prevalent. Brief alcohol interventions are effective in reducing alcohol use; however, they depend on effective screening for unhealthy alcohol use, which is often underreported. Thus, there is a need to develop methods to improve reporting of unhealthy alcohol use as an essential step toward referral to brief alcohol interventions. Self-administered digital health screeners may improve reporting. Objective This study aimed to develop and test a digital, easy-to-use self-administered health screener. The health screener was designed to be implemented in a busy, underresourced HIV treatment setting and used by patients with varying levels of literacy. Methods We conducted a qualitative study at the Immune Suppression Syndrome (ISS) Clinic of Mbarara Regional Referral Hospital in Uganda to develop and test a digital self-administered health screener. The health screener included a training module and assessed behaviors regarding general health, HIV care, and mental health as well as sensitive topics such as alcohol use and sexual health. We conducted focus group discussions with clinicians and patients with HIV of the Mbarara ISS Clinic who consumed alcohol to obtain input on the need for and content, format, and feasibility of the proposed screener. We iteratively revised a tablet-based screener with a subset of these participants, piloted the revised screener, and conducted individual semistructured in-depth interviews with 20 participants who had taken part in our previous studies on alcohol and HIV, including those who had previously underreported alcohol use and with low literacy. Results A total of 45 people (n=5, 11% clinicians and n=40, 89% Mbarara ISS Clinic patients) participated in the study. Of the patient participants, 65% (26/40) were male, 43% (17/40) had low literacy, and all (40/40, 100%) had self-reported alcohol use in previous studies. Clinicians and patients cited benefits such as time savings, easing of staff burden, mitigation of patient-provider tension around sensitive issues, and information communication, but also identified areas of training required, issues of security of the device, and confidentiality concerns. Patients also stated fear of forgetting how to use the tablet, making mistakes, and losing information as barriers to uptake. In pilot tests of the prototype, patients liked the feature of a recorded voice in the local language and found the screener easy to use, although many required additional help and training from the study staff to complete the screener. Conclusions We found a self-administered digital health screener to be appealing to patients and clinicians and usable in a busy HIV clinic setting, albeit with concerns about confidentiality and training. Such a screener may be useful in improving reporting of unhealthy alcohol use for referral to interventions.

BACKGROUND Alcohol brief interventions are effective for reducing alcohol use; however, they depend on effective screening for unhealthy alcohol use, which is often under-reported. Self-administered digital health screeners may improve reporting. OBJECTIVE Our first aim was to develop a brief touch-screen tablet based health screener to be administered in an HIV clinic waiting room, to increase reporting of unhealthy alcohol use for persons with HIV in Uganda. Our second aim was to pilot test the health screener developed in Aim 1 to examine acceptability, ease of use, comfort with reporting, and to discuss how the results of such screening might be used. METHODS We conducted a qualitative study at the Immune Suppression Syndrome (ISS) Clinic of Mbarara Regional Referral Hospital in Uganda to develop and test a digital self-administered health screener. The health screener assessed behaviors regarding general health, HIV care, mental health, as well as sensitive topics such as alcohol use and sexual health. We conducted focus group discussions (FGD) with clinicians and patients of the Mbarara ISS Clinic with HIV who consume alcohol to obtain input on the need for, content, format, and feasibility of the proposed screener. We iteratively revised a tablet-based screener with a subset of these participants, piloted the revised screener and conducted individual semi-structured in-depth interviews (IDIs) with 20 prior alcohol study participants, including those who previously under-reported use and those with low literacy. RESULTS Forty-five people (five clinicians and forty Mbarara ISS Clinic patients) participated in the study. Of the patient participants, 65% were male, 43% had low literacy, and all had self-reported alcohol use in previous studies. Clinicians and patients cited benefits such as time savings, easing staff burden, and mitigating patient-provider tension around sensitive issues, and information communication, but also identified areas of training required, issues of security of the device, and confidentiality concerns. Patients also stated fear of forgetting how to use the tablet, making mistakes, and losing information. In pilot tests of the prototype, patients liked the feature of a recorded voice in the local language, found the screener easy to use, although many required help. CONCLUSIONS We found a self-administered digital health screener to be appealing to patients and clinicians, and usable in a busy HIV clinic setting, albeit there were concerns about confidentiality and training. Such a screener may be useful to improve reporting of unhealthy alcohol use for referral to interventions. CLINICALTRIAL N/A

Unhealthy alcohol use fuels difficulties with HIV disease management and potentiates secondary transmission of HIV but less is known about how these alcohol use expectancies may shape alcohol use behaviors, particularly in the presence of depressive symptomatology. In this paper, we utilize data from a prospective study of 208 people living with HIV in Southwest Uganda, to examine the correlates of alcohol use expectancies and their association with unhealthy alcohol use. Affective depressive symptoms were positively associated with alcohol use expectancies. Gender moderation was observed such that depression was more strongly associated with alcohol use expectancies among women. In unadjusted analyses, alcohol use expectancies were marginally associated with unhealthy alcohol use and this association was not significant in adjusted analyses. Findings underscore the need to strengthen screening for depression and alcohol use within HIV care services, particularly among women.

Background We aimed to describe the prevalence of PTSD symptoms and its associated factors in persons living with HIV (PLWH) in Uganda who engage in heavy alcohol use. Methods We analyzed baseline data from the Drinkers Intervention to Prevent Tuberculosis study which enrolls PLWH with latent tuberculosis who engage in heavy alcohol consumption. Using the primary care Post Traumatic Stress Disorder (PTSD) screening scale from the DSM-5 (PC-PTSD-5), probable PTSD was defined as reporting ≥3 of 5 assessed symptoms. We conducted the Alcohol Use Disorders Identification Test-Consumption and assessed demographics, smoking, symptoms of depression, and spirituality/religiosity. Results Of 421 participants enrolled from 2018 through 2020, the majority (68.2%) were male, median age was 40 years (interquartile range [IQR]: 32–47), and median AUDIT-C score was 6 [IQR: 4–8]. Half (50.1%) of the participants reported ever experiencing a traumatic event, and 20.7% reported ≥3 symptoms of PTSD. The most commonly reported PTSD symptoms in the past 1 month in the entire sample were avoidance (28.3%), nightmares (27.3%), and being constantly on guard (21.6%). In multivariable logistic regression analyses, level of alcohol use was not associated with probable PTSD (adjusted odds ratio [AOR] for each AUDIT-C point: (1.02; 95% CI: 0.92–1.14; p = 0.69); however, lifetime smoking (AOR 1.89; 95% CI: 1.10–3.24) and reporting symptoms of depression (AOR 1.89; 95% CI: 1.04–3.44) were independently associated with probable PTSD. Conclusions and recommendations A history of traumatic events and probable PTSD were frequently reported among persons who engage in heavy drinking, living with HIV in Uganda. Level of alcohol use was not associated with probable PTSD in this sample of PLWH with heavy alcohol use, however other behavioral and mental health factors were associated with probable PTSD. These data highlight the high prevalence of PTSD in this group, and the need for screening and interventions for PTSD and mental health problems.

Background Self-report is widely used to assess alcohol use in research and clinical practice, but may be subject to social desirability bias. We aimed to determine if social desirability impacts self-reported alcohol use. Methods Among 751 human immunodeficiency virus (HIV)-infected patients from a clinic in southwestern Uganda, we measured social desirability using the Marlowe-Crowne Social Desirability Scale (SDS) Short Form C, self-reported alcohol use (prior 3 months) Alcohol Use Disorders Identification Test-Consumption (AUDIT-C), and phosphatidylethanol (PEth), a biomarker of prior 3 weeks' drinking. We conducted multiple regression analyses to assess the relationship between SDS score (low, medium, and high levels) and (i) any self-reported recent alcohol use, among those who were PEth-positive (≥8 ng/ml), and (ii) continuous AUDIT-C score, among those reporting any recent alcohol use. We controlled for PEth level, age, gender, education, economic assets, marital status, religion, spirituality/religiosity, social support, and study cohort. Results Of 751 participants, 59% were women; the median age was 31 years (interquartile range [IQR]: 26 to 39). Median SDS score was 9 (IQR: 4 to 10). Two-thirds (62%) self-reported any recent alcohol use; median AUDIT-C was 1 (IQR: 0 to 4). Among those who were PEth-positive (57%), 13% reported no recent alcohol use. Those with the highest SDS tertile had decreased odds of reporting any recent alcohol use compared to the lowest tertile, but the association did not reach statistical significance in multivariable analyses (adjusted odds ratio 0.55 [95% confidence interval (CI): 0.25, 1.23]). Among participants self-reporting recent alcohol use, SDS level was negatively associated with AUDIT-C scores (adjusted β: -0.70 [95% CI: -1.19, -0.21] for medium vs. low SDS and -1.42 [95% CI: -2.05, -0.78] for high vs. low SDS). Conclusions While use of objective measures (e.g., alcohol biomarkers) is desirable for measuring alcohol use, SDS scores may be used to adjust self-reported drinking levels by participants' level of social desirability in HIV research studies.

OBJECTIVE: We examined whether gender is associated with heavy drinking in three cohorts of people living with HIV (PLWH) in Mbarara, Uganda; St. Petersburg, Russia; and Boston, Massachusetts. METHOD: We conducted secondary analyses of baseline data collected from three cohorts in the Uganda Russia Boston Alcohol Network for Alcohol Research Collaboration on HIV/AIDS (URBAN ARCH) consortium. We used multiple logistic regression models to evaluate the association between gender and heavy drinking (defined in combination with self-report and phosphatidylethanol [PEth]) within each cohort. RESULTS: In unadjusted logistic regression models, we found no significant association between gender and heavy drinking in Russia or Boston. In Uganda, women were less likely than men to engage in heavy drinking (odds ratio = 0.38, 95% CI [0.26, 0.58], p < .01). These findings were invariant to adjustment for covariates. CONCLUSIONS: We did not detect associations between gender and heavy drinking in cohorts of PLWH in Russia or Boston, suggesting that heavy drinking may be as common in women living with HIV as in men living with HIV in these locations. Although these cohorts were enriched with heavy drinking participants, which limits broad extrapolation to PLWH in those settings, nonetheless the findings are concerning given the significant morbidity associated with alcohol use among PLWH and women in particular.

Background The risk of tuberculosis (TB) is high among people with HIV (PWH). Heavy alcohol drinking independently increases TB risk and approximately 25% of PWH globally engage in heavy drinking. While isoniazid (INH) preventive therapy decreases TB incidence and mortality among PWH, heavy drinking during INH is associated with liver toxicity and poor adherence. Interventions are, therefore, urgently needed to decrease alcohol use and improve adherence to INH in this population in settings with high prevalence of HIV and TB like Uganda. Methods The Drinkers’ Intervention to Prevent TB (DIPT) study is a 2×2 factorial randomized controlled trial among HIV/TB co-infected adults (≥18 years) who engage in heavy alcohol drinking and live in Uganda. The trial will allocate 680 participants with a 1:1:1:1 individual randomization to receive 6 months of INH and one of the following interventions: (1) no incentives (control), (2) financial incentives contingent on low alcohol use, (3) financial incentives contingent on high adherence to INH, and (4) escalating financial incentives for both decreasing alcohol use and increasing adherence to INH. Incentives will be in the form of escalating lottery-based monetary rewards. Participants will attend monthly visits to refill isoniazid medications, undergo liver toxicity monitoring, and, except for controls, determine eligibility for prizes. We will estimate (a) the effect of incentives contingent on low alcohol use on reduction in heavy drinking, measured via a long-term objective and self-reported metric of alcohol use, at 3- and 6-month study visits, and (b) the effect of incentives contingent on high adherence to INH, measured as >90% pill-taking days by medication event monitoring system cap opening. We will use qualitative methods to explore the mechanisms of any influence of financial incentives on HIV virologic suppression. Discussion This study will provide new information on low-cost strategies to both reduce alcohol use and increase INH adherence among people with HIV and TB infection who engage in heavy drinking in low-income countries with high HIV and TB prevalence. Trial registration ClinicalTrials.gov NCT03492216. Registered on April 10, 2018

Phosphatidylethanol (PEth) is a sensitive and specific biomarker of alcohol consumption in the prior 2-3 weeks. Standard, manual PEth testing using dried blood spots (DBS) is a multi-step time-consuming process. A novel, automated processing and testing method has been developed to decrease DBS processing and testing time. We conducted automated testing, using regioisomerically pure PEth reference material, on randomly selected DBS, which had previously been tested via manual methods and then stored for 3-6 years at-80°C, to compare the results (PEth 16:0/18:1 homologue). We chose samples for re-testing using categories found in the literature as follows: 1) PEth 200-1000ng/mL; 4) PEth >1000ng/mL. We calculated agreement between the categories using the weighted kappa statistic (n=49 DBS). We quantified agreement between continuous measures using the intraclass correlation coefficient (ICC), and further described the relationship between variables using Spearman correlation. The median PEth result was 155ng/mL (interquartile range [IQR]: 1-1312ng/mL) via automated methods and 98.8ng/mL (IQR: 10.2-625.0ng/mL) via manual methods. The weighted kappa comparing the automated to manual PEth results was 0.76 [95% Confidence Interval (CI): 0.66-0.86]. The ICC was 0.69 (95% CI: 0.54-0.79), and the Spearman correlation was 0.98 (95% CI: 0.95-0.99). While the new methods yielded somewhat higher PEth values, we found good to excellent agreement between clinically relevant PEth categories. Automated DBS processing and testing using new reference standards are promising methods for PEth testing.

Hazardous drinking by persons living with HIV (PLHIV) is a well-established determinant of sub-optimal HIV care and treatment outcomes. Despite this, to date, few interventions have sought to reduce hazardous drinking among PLHIV in sub-Saharan Africa (SSA). We describe an iterative cultural adaptation of an evidence-based multi-session alcohol reduction intervention for PLHIV in southwestern Uganda. The adaptation process included identifying core, theoretically informed, intervention elements, and conducting focus group discussions and cognitive interviews with community members, HIV clinic staff and patients to modify key intervention characteristics for cultural relevance and saliency. Adaptation of evidence-based alcohol reduction interventions can be strengthened by the inclusion of the target population and key stakeholders in shaping the content, while retaining fidelity to core intervention elements.

Background Isoniazid preventive therapy (IPT) reduces tuberculosis reactivation and mortality among persons living with HIV (PLWH), yet hepatotoxicity concerns exclude “regular and heavy alcohol drinkers” from IPT. We aimed to determine the prevalence of elevated liver transaminases among PLWH on antiretroviral therapy (ART) who engage in alcohol use. Setting The Immune Suppression Syndrome Clinic of Mbarara, Uganda. Methods We defined elevated liver transaminases as ≥1.25 times (X) the upper limit of normal (ULN) for alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST). We evaluated the associations of current alcohol use and other variables of interest (sex, body mass index, and ART regimen) with elevated transaminases at study screening, using multivariable logistic regression to obtain adjusted odds ratios (aOR) and 95% confidence intervals (CI). Results Among 1301 participants (53% female, median age 39 years, 67.4% current alcohol use), 18.8% (95% CI: 16.8–21.1) had elevated transaminases pre-IPT, with few (1.1%) severe (≥5X the ULN). The proportion with any elevation among those currently using alcohol and those abstaining was 22.3% and 11.6%, respectively (p Conclusions Pre-IPT elevated transaminases among PLWH receiving ART were common, similar to prior estimates, but severe elevations were rare. Current drinking and male sex were independently associated with elevated transaminases. Further research is needed to determine the implications of such transaminase elevations and alcohol use on providing IPT.

Although there is evidence of individual associations between depressive symptoms and hazardous alcohol use with suboptimal antiretroviral therapy (ART) adherence among people living with HIV (PLWH), few studies have established how the two risk factors may interact to predict viral suppression. We conducted secondary data analyses with two cohorts of Ugandan PLWH (N = 657) to investigate the hypothesized interaction between depressive symptoms (Center for Epidemiological Studies Depression Scale) and hazardous alcohol use (Alcohol Use Disorder Identification Test -Consumption and/or Phosphatidylethanol biomarker) prior to ART initiation with viral suppression (

Background Tuberculosis (TB) is the leading cause of death among people living with HIV (PLWH), and current evidence suggests that heavy alcohol users have an increased risk of developing TB disease compared to non-drinkers. Not known is whether the increased risk for TB disease among alcohol users may reflect higher rates of latent TB infection (LTBI) among this population. We assessed the latent TB infection prevalence based on tuberculin skin testing (TST) and examined association with current alcohol use among HIV-infected persons on antiretroviral therapy (ART) in south-western Uganda. Methods We included PLWH at the Mbarara Regional Hospital HIV clinic, who were either current alcohol consumers (prior 3 months) or past year abstainers (2:1 enrolment ratio). Participants were recruited for a study of isoniazid preventive therapy for LTBI. TST was performed using 5 tuberculin units of purified protein derivative. The primary outcome was a positive TST reading (≥5mm induration), reflecting LTBI. We used logistic regression analyses to assess the cross-sectional association between self-reported current alcohol use and a positive TST. Results Of the 295 of 312 (95%) who returned for TST reading, 63% were females and 63% were current alcohol drinkers. The TST positive prevalence was 27.5% (95% confidence interval [CI]: 22.6% - 32.9%). The odds of a positive TST for current alcohol users compared to abstainers was 0.76 (95% CI: 0.41, 1.41), controlling for gender, age, body mass index, history of smoking, and prior unhealthy alcohol use. Conclusions The prevalence of LTBI among PLWH on ART in south-western Uganda was moderate and LTBI poses a risk for future infectious TB. Although alcohol use is common, we did not detect an association between current drinking or prior unhealthy alcohol use and LTBI. Further studies to evaluate the association between LTBI and different levels of current drinking (heavy versus not) are needed.

In HIV-infected drinkers, alcohol types more likely to cause inflammation could plausibly increase the risk of HIV disease progression. We therefore assessed the association between alcohol type and plasma HIV RNA level (HIV viral load) among HIV-infected drinkers not on antiretroviral therapy (ART) in Russia and Uganda. We analyzed the data of participants from cohorts in Russia and Uganda and assessed their HIV viral load at enrollment by the alcohol type predominantly consumed. We defined predominant alcohol type as the alcohol type contributing >50% of total alcohol consumption in the 1 month (Russia) or 3 months (Uganda) prior to enrollment. Using multiple linear regression, we compared log10 HIV viral load by predominant alcohol type, controlling for age, gender, socioeconomic status, total number of standard drinks, frequency of drinking ≥6 drinks/occasion, and in Russia, history of injection drug use. Most participants (99.2% of 261 in Russia and 98.9% of 352 in Uganda) predominantly drank one alcohol type. In Russia, we did not find evidence for differences in viral load levels between drinkers of fortified wine (n = 5) or hard liquor (n = 49), compared to drinkers of beer/low-ethanol-content cocktails (n = 163); however, wine/high-ethanol-content cocktail drinkers (n = 42) had higher mean log10 viral load than beer/low-ethanol-content cocktail drinkers (β = 0.38, 95% CI 0.07-0.69; p = 0.02). In Uganda, we did not find evidence for differences in viral load levels between drinkers of locally-brewed beer (n = 41), commercially-distilled spirits (n = 38), or locally-distilled spirits (n = 43), compared to drinkers of commercially-made beer (n = 218); however, wine drinkers (n = 8) had lower mean log10 HIV viral load (β = -0.65, 95% CI -1.36 to 0.07, p = 0.08), although this did not reach statistical significance. Among HIV-infected drinkers not yet on ART in Russia and Uganda, we observed an association between the alcohol type predominantly consumed and the HIV viral load level in the Russia sample. These exploratory results suggest that, in addition to total number of drinks and drinking patterns, alcohol type might be a dimension of alcohol use that merits examination in studies of HIV and alcohol related outcomes.

HIV and alcohol use are two serious and co-existing problems in sub-Saharan Africa. We examined the relationship between spirituality and/or religiousness (SR) and unhealthy alcohol use among treatment-naïve HIV-infected adults attending the HIV clinic in Mbarara, Uganda. Unhealthy alcohol was defined as having either an Alcohol Use Disorders Identification Test – Consumption score of ≥4 for men or ≥3 for women, or having a phosphatidylethanol level of ≥50ng/ml based on analysis of dried blood-spot specimens. Of the 447 participants, 67.8% were female; the median age was 32 years (interquartile range [IQR]: 27–40). About half reported being Protestant (49.2%), 35.1 % Catholic, and 9.2% Muslim. The median SR score was high (103 [IQR: 89–107]); 43.3% drank at unhealthy levels. Higher SR scores were associated with lower odds of unhealthy drinking (adjusted odds ratio [aOR]: 0.83 per standard deviation [SD] increase; 95% confidence interval [CI] 0.66–1.03). The “religious behavior” SR sub-scale was significantly associated with unhealthy alcohol use (aOR: 0.72 per SD increase; 95% CI 0.58–0.88). Religious institutions, which facilitate expression of religious behavior, may be helpful in promoting and maintaining lower levels of alcohol use.

Food insecurity (FI) is a documented problem associated with adverse health outcomes among HIV-infected populations. Little is known about the relationship between alcohol use and FI. We assessed whether heavy alcohol use was associated with FI among HIV-infected, antiretroviral therapy (ART)-naïve cohorts in Uganda and Russia. Inverse probability of treatment weighted logistic regression models were used to evaluate the association using cross-sectional baseline data. FI was experienced by half of the Russia cohort (52%) and by a large majority of the Uganda cohort (84%). We did not detect an association between heavy alcohol use and FI in either cohort (Russia: AOR=0.80, 95% CI 0.46, 1.40; Uganda: AOR=1.00, 95% CI 0.57, 1.74) or based on the overall combined estimate (AOR=0.89, 95% CI 0.60, 1.33). Future studies should explore the determinants of FI in HIV-infected populations to inform strategies for its mitigation.

Background Alcohol use may accelerate HIV disease progression, but the plausible biological mechanisms have not been clearly elucidated. Methods HIV-positive persons who were not on antiretroviral therapy (ART) completed the baseline assessment for a longitudinal study examining the association of alcohol use with HIV disease markers. Oversampling drinkers, baseline samples were tested for markers of monocyte activation (soluble CD14 [sCD14]), inflammation (interleukin-6 [IL-6]-6), and coagulation (d-dimer). We defined “unhealthy alcohol use” as testing positive using the Alcohol Use Disorders Identification Test—Consumption (≥3 for women and ≥4 for men) in the past 3 months or testing positive using a biomarker of heavy drinking, phosphatidylethanol (≥50 ng/ml). Multiple linear regression was used to examine the associations of unhealthy alcohol use with sCD14, log10 IL-6, and d-dimer. Results Compared to those who were abstinent from alcohol, unhealthy drinkers had significantly higher sCD14 levels (mean = 1,676 vs. 1,387 ng/ml; mean difference [95% confidence interval (CI)] = 289 [83, 495], p

Under-reporting of alcohol use by HIV-infected patients could adversely impact clinical care. This study examined factors associated with under-reporting of alcohol consumption by patients who denied alcohol use in clinical and research settings using an alcohol biomarker. We enrolled ART-naïve, HIV-infected adults at Mbarara Hospital HIV clinic in Uganda. We conducted baseline interviews on alcohol use, demographics, Spirituality and Religiosity Index (SRI), health and functional status; and tested for breath alcohol content and collected blood for phosphatidylethanol (PEth), a sensitive and specific biomarker of alcohol use. We determined PEth status among participants who denied alcohol consumption to clinic counselors (Group 1, n = 104), and those who denied alcohol use on their research interview (Group 2, n = 198). A positive PEth was defined as ≥8 ng/ml. Multiple logistic regression models were used to examine whether testing PEth-positive varied by demographics, literacy, spirituality, socially desirable reporting and physical health status. Results showed that, among the 104 participants in Group 1, 28.8% were PEth-positive. The odds of being PEth-positive were higher for those reporting prior unhealthy drinking (adjusted odds ratio (AOR): 4.7, 95% confidence interval (CI): 1.8, 12.5). No other factors were statistically significant. Among the 198 participants in Group 2, 13.1% were PEth-positive. The odds of being PEth-positive were higher for those reporting past unhealthy drinking (AOR: 4.6, 95% CI: 1.8, 12.2), the Catholics (AOR: 3.8, 95% CI: 1.3, 11.0) compared to Protestants and lower for the literate participants (AOR: 0.3, 95% CI: 0.1, 0.8). We concluded that under-reporting of alcohol use to HIV clinic staff was substantial, but it was lower in a research setting that conducted testing for breath alcohol and PEth. A report of past unhealthy drinking may highlight current alcohol use among deniers. Strategies to improve alcohol self-report are needed within HIV care settings in Uganda.

The practical feasibility of using prostate specific antigen (PSA) as a biomarker of semen exposure was examined among HIV-infected Ugandan women. Vaginal fluids were obtained with self-collected swabs and a qualitative rapid test (ABAcard®p30) was used to detect PSA. Trained laboratory technicians processed samples on-site and positive PSA tests were compared to self-reported unprotected vaginal sex (UVS) in the last 48h. A total of 77 women submitted 126 samples for PSA testing at up to three study visits. Of these samples, 31% (n=39/126) were PSA positive, and 64% (n=25/39) of the positive PSA samples were accompanied by self-report of no UVS at the study visit the PSA was collected. There were no reported difficulties with specimen collection, storage, or processing. These findings provide preliminary data on high levels of misreported UVS among HIV-infected Ugandan women using practically feasible methods for PSA collection and processing.

Interactive toxicity beliefs regarding mixing alcohol and antiretroviral therapy (ART) may influence ART adherence. HIV-infected patients in Uganda completed quarterly visits for 1year, or one visit at 6months, depending on study randomization. Past month ART non-adherence was less than daily or

Unhealthy alcohol use is a crucial driver of HIV in sub-Saharan Africa, and interventions are needed. The goal of this study was to assess whether assessment itself (assessment reactivity) causes declines in alcohol use in a research study in persons with HIV in Uganda.Study participants were adult patients of the Immune Suppression Syndrome (ISS) Clinic in Mbarara, Uganda, who were new to HIV care and reported any alcohol consumption in the prior year. Participants were randomized to (a) a study cohort, with structured interviews, breath alcohol analysis tests, and blood draws conducted quarterly, or (b) a minimally assessed arm that engaged in these procedures only once, at 6 months after baseline. The main outcome was unhealthy drinking at 6 months, defined as Alcohol Use Disorders Identification Test-Consumption [AUDIT-C] positive (≥3 for women, ≥4 for men) or phosphatidylethanol (PEth; an alcohol biomarker) level ≥ 50 ng/ml. We also examined this outcome stratified by gender.We examined 175 and 139 persons in the quarterly assessed versus minimally assessed arms, respectively. Overall, 54.8% were male, the median age was 30 (interquartile range: 25-36), and 58.0% initiated anti-retroviral therapy at 6 months. Nearly equal proportions (53.7% and 51.1% in the study quarterly assessed vs. minimally assessed arm, respectively) engaged in unhealthy drinking in the 3 months before the 6-month study visit (p = .64), and we found no evidence of interaction by gender (p = .36).We found no evidence of assessment reactivity in a study that included quarterly study visits. Assessment is not sufficient to act as an intervention itself in this population with high levels of unhealthy drinking. Interventions are needed to decrease alcohol consumption in this population.

While alcohol is a known risk factor for HIV infection in sub-Saharan Africa (SSA), studies designed to investigate the temporal relationship between alcohol use and unprotected sex are lacking. The purpose of this study was to determine if alcohol used at the time of a sexual event is associated with unprotected sex at that same event. Data for this study were collected as part of two longitudinal studies of HIV-infected Ugandan adults. A structured questionnaire was administered at regularly scheduled cohort study visits in order to assess the circumstances (e.g., alcohol use, partner-type) of the Most Recent Sexual Event (MRSE). Generalized estimating equation (GEE) logistic regression models were used to examine the association between alcohol use (by the participant, the sexual partner, or both the participant and the partner) and the odds of unprotected sex at the sexual event while controlling for participant gender, age, months since HIV diagnosis, unhealthy alcohol use in the prior 3 months, partner-type, and HIV status of partner. A total of 627 sexually active participants (57% women) reported 1,817 sexual events. Of these events, 19% involved alcohol use and 53% were unprotected. Alcohol use by one’s sexual partner (aOR) = 1.70; 95%CI = 1.14, 2.54) or by both partners (aOR: 1.78; 95%CI: 1.07, 2.98), during the MRSE significantly increased the odds of unprotected sex at that same event. These results add to the growing event-level literature in SSA and support a temporal association between alcohol used prior to a sexual event, and subsequent unprotected sex.

The brewing of alcohol in Ugandan households is common, yet little is known about its relationship with alcohol consumption in HIV-infected individuals. We performed a cross-sectional analysis to assess the association between household brewing and unhealthy alcohol consumption among 387 HIV-infected adults in a prospective study examining the association between alcohol consumption and HIV-disease progression. Household brewing was defined as participants reporting that they or a household member home-brewed alcohol. Logistic regression was used to assess the association between household brewing and unhealthy alcohol consumption, defined as phosphatidylethanol (PEth) level ≥50 ng/ml or AUDIT-C (modified to measure the prior 3 months) positive. Sixty-six (17.0 %) participants reported household brewing. Household brewers had higher odds of unhealthy alcohol consumption (AOR 2.27, 95 % CI 1.26-4.12). Among HIV-infected individuals, household brewing was associated with unhealthy alcohol consumption. Interventions to reduce alcohol consumption in this population could target household brewers.

Background: Alcohol is heavily consumed in sub-Saharan Africa and affects HIV transmission and treatment and is difficult to measure. Our goal was to examine the test characteristics of a direct metabolite of alcohol consumption, phosphatidylethanol (PEth). Methods: Persons infected with HIV were recruited from a large HIV clinic in southwestern Uganda. We conducted surveys and breath alcohol concentration (BRAC) testing at 21 daily home or drinking establishment visits, and blood was collected on day 21 (n = 77). PEth in whole blood was compared with prior 7-, 14-, and 21-day alcohol consumption. Results: (i) The receiver operator characteristic area under the curve (ROC-AUC) was highest for PEth versus any consumption over the prior 21 days (0.92; 95% confidence interval [CI]: 0.86 to 0.97). The sensitivity for any detectable PEth was 88.0% (95% CI: 76.0 to 95.6) and the specificity was 88.5% (95% CI: 69.8 to 97.6). (ii) The ROC-AUC of PEth versus any 21-day alcohol consumption did not vary with age, body mass index, CD4 cell count, hepatitis B virus infection, and antiretroviral therapy status, but was higher for men compared with women (p = 0.03). (iii) PEth measurements were correlated with several measures of alcohol consumption, including number of drinking days in the prior 21 days (Spearman r = 0.74, p

HIV/AIDS and food insecurity are two of the leading causes of morbidity and mortality in sub-Saharan Africa, with each heightening the vulnerability to, and worsening the severity of, the other. Less research has focused on the social determinants of food insecurity in resource-limited settings, including social support and HIV-related stigma. In this study, we analyzed data from a cohort of 456 persons from the Uganda AIDS Rural Treatment Outcomes study, an ongoing prospective cohort of persons living with HIV/AIDS (PLWHA) initiating HIV antiretroviral therapy in Mbarara, Uganda. Quarterly data were collected by structured interviews. The primary outcome, food insecurity, was measured with the Household Food Insecurity Access Scale. Key covariates of interest included social support, internalized HIV-related stigma, HIV-related enacted stigma, and disclosure of HIV serostatus. Severe food insecurity was highly prevalent overall (38%) and more prevalent among women than among men. Social support, HIV disclosure, and internalized HIV-related stigma were associated with food insecurity; these associations persisted after adjusting for household wealth, employment status, and other previously identified correlates of food insecurity. The adverse effects of internalized stigma persisted in a lagged specification, and the beneficial effect of social support further persisted after the inclusion of fixed effects. International organizations have increasingly advocated for addressing food insecurity as part of HIV/AIDS programming to improve morbidity and mortality. This study provides quantitative evidence on social determinants of food insecurity among PLWHA in resource-limited settings and suggests points of intervention. These findings also indicate that structural interventions to improve social support and/or decrease HIV-related stigma may also improve the food security of PLWHA.

To assess whether T-cell activation independently predicts the extent of CD4(+) T-cell recovery and mortality in HIV-infected Ugandans initiating antiretroviral therapy (ART).Prospective cohort study.HIV-infected adults starting ART and achieving a plasma HIV RNA level (VL) less than 400 copies/ml by month 6 were sampled from the Uganda AIDS Rural Treatment Outcomes (UARTO) cohort in Mbarara, Uganda. CD4 count, VL, and the percentage-activated (CD38(+)HLA-DR(+)) T cells were measured every 3 months.Of 451 HIV-infected Ugandans starting ART, most were women (70%) with median pre-ART values: age, 34 years; CD4 count, 135 cells/μl; and VL, 5.1 log(10) copies/ml. Of these, 93% achieved a VL less than 400 copies/ml by month 6 and were followed for a median of 24 months, with 8% lost to follow-up at 3 years. Higher pre-ART CD8(+) T-cell activation was associated with diminished CD4 recovery after year 1, after adjustment for pre-ART CD4 count, VL, and sex (P = 0.017). Thirty-four participants died, 15 after month 6. Each 10% point increase in activated CD8(+) T cells at month 6 of suppressive ART was associated with a 1.6-fold increased hazard of subsequent death after adjusting for pretherapy CD4 count (P = 0.048).Higher pre-ART CD8(+) T-cell activation independently predicts slower CD4(+) T-cell recovery and higher persistent CD8(+) T-cell activation during ART-mediated viral suppression independently predicts increased mortality among HIV-infected Ugandans. Novel therapeutic strategies aimed at preventing or reversing immune activation during ART are needed in this setting.

Lipodystrophy is commonly reported in Africa after antiretroviral therapy (ART) is initiated, but few studies have objectively measured changes in body composition. Body composition was determined in 76 HIV-infected participants from Mbarara, Uganda after starting a thymidine-analog regimen, and annual change was determined using repeated measures analysis. We measured skinfolds (tricep, thigh, subscapular, and abdomen), circumferences (arm, hip, thigh, waist), and total lean and fat mass (using bioelectric impedance analysis). A cross-sectional sample of 49 HIV-uninfected participants was studied for comparison. At baseline, most body composition measures were lower in HIV-infected than uninfected participants, but waist circumference was similar. After 12 months on ART, there was little difference in body composition measures between HIV-infected and uninfected participants; median waist circumference appeared higher in HIV-infected participants (79 vs. 75 cm; p = 0.090). Among HIV-infected participants, increases were observed in total lean and fat mass, circumference, and skinfold measures; only the increase in tricep skinfold did not reach statistical significance (+1.05 mm; 95% confidence interval: −0.24, 2.34; p = 0.11). Regional anthropometry in peripheral and central body sites increased over 12 months after ART initiation in HIV-infected persons from southwestern Uganda, suggesting a restoration to health. Gains in the tricep skinfold, a reliable marker of subcutaneous fat, appeared blunted, which could indicate an inhibitory effect of zidovudine on peripheral subcutaneous fat recovery.

Current models for implementing electronic health records (EHRs) in resource-limited settings may not be scalable because they fail to address human-resource and cost constraints. This paper describes an implementation model which relies on shared responsibility between local sites and an external three-pronged support infrastructure consisting of: (1) a national technical expertise center, (2) an implementer's community, and (3) a developer's community. This model was used to implement an open-source EHR in three Ugandan HIV-clinics. Pre–post time–motion study at one site revealed that Primary Care Providers spent a third less time in direct and indirect care of patients (p

As global access to antiretroviral therapy (ART) for HIV-infected patients expands rapidly, optimizing outcomes of patients starting complicated, potentially toxic and life-long regimens in resource limited settings is an emerging public health priority. Because of the scale and speed of the global roll-out, observational studies originating from routine clinical care in settings practicing the “public health approach” (Gilks et al., 2006) will necessarily provide the first and largest source of evidence to guide treatment strategies. The quality of this evidence is therefore crucial for optimizing outcomes among millions of HIV-infected patients starting ART. Among the various threats to the validity of the evidence originating from sites practicing routine delivery of ART in Africa, losses to follow-up are increasingly perceived as being among the most important (Rosen et al., 2007). Losses to follow-up occur in a high proportion of patients initiating ART (Rosen et al., 2007, Wools-Kaloustian et al., 2006, Braitstein et al., 2006), and it is now well appreciated that these losses lead to substantial underestimation of mortality (Geng et al., 2008, Braitstein et al., 2006, Yiannoutsos et al., 2008). It is likely, furthermore, that these losses are differential on both determinants of interest (e.g., pre-therapy CD4+ T cell count) and outcomes (e.g., mortality) and therefore represent a form of selection bias (Rothman, 2008). Therefore, equally important, but perhaps less well appreciated, is that losses to follow-up can lead to invalid findings in analyses to identify determinants of mortality. The direction of the bias is unpredictable: both spurious determinants can be identified and actual relationships can be missed – both with the potential to mislead public health efforts. Losses to follow-up, therefore, represent a serious threat to the integrity of scientific evidence guiding the global delivery of ART. Previously, we presented a sampling-based approach to address losses to follow-up among HIV-infected patients on ART in Uganda (Geng et al., 2008) and Kenya (Yiannoutsos et al., 2008). Although finding outcomes in all patients who are lost to follow-up is frequently prohibitive because lost patients are too numerous, we demonstrated that determining outcomes in a representative sample of lost patients is feasible. Outcomes in this sample of patients lost to follow-up were used as an unbiased estimate of outcomes in all lost patients. These outcomes were incorporated into analyses through simple probability weights that can be implemented in standard statistical software. In our initial application of this approach, we found that sampling-based correction increased the cumulative incidence of mortality following ART initiation nearly five-fold from 1.7 to 7.5% at 1 year and from 2.3 to 12.2% at 3 years (Geng et al., 2008). We now demonstrate the effect of this sampling-based approach on analyses to identify determinants of mortality among HIV-infected patients initiating ART in a prototypical ART delivery program in Uganda. .

Getting the right information to providers can improve quality of care. We set out to provide patient-specific Electronic Medical Record (EMR)-based clinical summaries for providers taking care of HIV-positive adult patients in the resource-limited setting of Mbarara, Uganda.We evaluated the impact of implementing these clinical summaries using time-motion techniques and provider surveys.After implementation of EMR-based clinical summaries, providers spent more time in direct care of patients (2.9 min vs. 2.3 min, p0.001), and the length of patient visits was reduced by 11.5 min. Survey respondents indicated that clinical summaries improved care, reduced mistakes, and were generally accurate. Current antiretroviral medication, patient identifying information, adherence information, current medication, and current medical problems were among the highest-rated elements of the summary.By taking advantage of data stored in EMRs, efficiency and quality of care can be improved through clinical summaries, even in settings with limited resources.

To assess the association between antiretroviral therapy (ART) and fertility history and desire among HIV-positive Ugandan women, we conducted a cross-sectional study among HIV-positive Ugandan women aged 18–50 years who attended an HIV clinic at Mbarara University in western Uganda between November 1, 2005 and June 6, 2006. Of 538 women approached, 501 were enrolled. ART use was associated with increased odds of fertility desire (AOR 2.99, 95% CI 1.38–6.28), and decreased odds of pregnancy (AOR 0.56, 95% CI 0.33–0.95) and live birth (AOR 0.30, 95% CI 0.13–0.66). ART was associated with an increase in fertility desire, but was not associated with an increase in fertility. Additional studies will be needed to determine if this greater fertility desire among ART-treated women leads to an increase in fertility as ART use expands.

To maximize scarce intervention dollars, pediatricians and other adolescent health professionals must position health promotion efforts in mediums that most effectively reach youth. This may be especially true in resource-limited settings where access to primary health care and medications is limited. To improve the efficiency and impact of disease prevention and health promotion efforts in resource-limited settings, we examine sources of health information cited by adolescents in Mbarara Uganda. Participants in the Uganda Media and You survey were students aged 12-18 (n = 500) randomly identified in five secondary schools in Mbarara municipality, Uganda. Ninety-three percent of eligible and invited youth completed the cross-sectional, pencil-and-paper survey. Four in five adolescents (81%) indicated they turned to parents, teachers, and other adults while around half read a book/went to the library (56%) or turned to siblings and friends (50%) for information about health and disease. More than one in three (38%) indicated that they used the computer and Internet to search for health information. Older versus younger respondents tended to rely upon siblings and friends for all types of health questions. On the other hand, younger versus older youth were significantly more likely to turn to parents, teachers, and other adults for their questions about sexual health. Adults may be an important component of effective disease prevention and health promotion campaigns. Multiple delivery methods may be especially effective for reaching older adolescents. Technology also may be an important health promotion tool in resource-limited settings.

Alcohol has a substantial negative impact on the HIV epidemic in sub-Saharan Africa, particularly in Uganda, where heavy alcohol consumption is common. Using a content analytic approach, this qualitative study characterizes changes in alcohol use among 59 HIV-infected Ugandan adults (>18years old), who reported any alcohol use in the previous year as they entered HIV care. Most participants reported attempting to cease or reduce alcohol intake over the study period. Reasons for decreased use included advice from clinicians, interference with social obligations, threats to financial security, and negative impact on social standing. Participants reported difficulty abstaining from alcohol, with incentives to continue drinking including desire for social inclusion, stress relief, and enjoyment of alcohol. These contrasting incentives created a moral quandary for some participants, who felt 'pulled' between 'good' and 'bad' influences. Results suggest brief interventions addressing self-identified obstacles to change may facilitate long-term reductions in drinking in this population.