Comparison of Self-Reported Alcohol Consumption to Phosphatidylethanol Measurement among HIV-Infected Patients Initiating Antiretroviral Treatment in Southwestern Uganda

Background: Alcohol consumption among HIV-infected patients may accelerate HIV disease progression or reduce antiretroviral therapy adherence. Self-reported alcohol use is frequently under-reported due to social desirability and recall bias. The aim of this study was to compare self-reported alcohol consumption to phosphatidylethanol (PEth), a biomarker of alcohol consumption, and to estimate the correlation between multiple measures of self-reported alcohol consumption with PEth. Methods: The Uganda AIDS Rural Treatment Outcomes (UARTO) cohort is located in southwestern Uganda and follows patients on ART to measure treatment outcomes. Patients complete standardized questionnaires quarterly including questions on demographics, health status and alcohol consumption. Baseline dried blood spots (DBS) were collected and retrieved to measure PEth. Results: One hundred fifty samples were tested, and 56 (37.3%) were PEth positive (≥8 ng/mL). Of those, 51.7% did not report alcohol use in the past month. Men were more likely to under-report compared to women, OR 2.9, 95% CI = 1.26, 6.65) and those in the higher economic asset categories were less likely to under-report compared to those in the lowest category (OR = 0.41 95% CI: 0.17, 0.94). Among self-reported drinkers (n = 31), PEth was highly correlated with the total number of drinking days in the last 30 (Spearman R = 0.73, p<0.001). Conclusions: Approximately half of HIV infected patients initiating ART and consuming alcohol under-report their use of alcohol. Given the high prevalence, clinicians should assess all patients for alcohol use with more attention to males and those in lower economic asset categories who deny alcohol use. Among those reporting current drinking, self-reported drinking days is a useful quantitative measure

Pregnancies among women living with HIV using contraceptives and antiretroviral therapy in western Kenya: a retrospective, cohort study

Background: Preventing unintended pregnancies is paramount for women living with HIV (WLHIV). Previous studies have suggested that efavirenz-containing antiretroviral therapy (ART) reduces contraceptive effectiveness of implants, but there are uncertainties regarding the quality of the electronic medical record (EMR) data used in these prior studies. Methods: We conducted a retrospective, cohort study of EMR data from 2011 to 2015 among WLHIV of reproductive age accessing HIV care in public facilities in western Kenya. We validated a large subsample of records with manual chart review and telephone interviews. We estimated adjusted incidence rate ratios (aIRRs) with Poisson regression accounting for the validation sampling using inverse probability weighting and generalized raking. Results: A total of 85,324 women contributed a total of 170,845 women-years (w-y) of observation time; a subset of 5080 women had their charts reviewed, and 1285 underwent interviews. Among implant users, the aIRR of pregnancy for efavirenz- vs. nevirapine-containing ART was 1.9 (95% CI 1.6, 2.4) using EMR data only and 3.2 (95% CI 1.8, 5.7) when additionally using both chart review and interview validated data. Among efavirenz users, the aIRR of pregnancy for depomedroxyprogesterone acetate (DMPA) vs. implant use was 1.8 (95% CI 1.5, 2.1) in EMR only and 2.4 (95% CI 1.0, 6.1) using validated data. Conclusion: Pregnancy rates are higher when contraceptive implants are concomitantly used with efavirenz-containing ART, though rates were similar to leading alternative contraceptive methods such as DMPA. Our data provides policymakers, program staff, and WLHIV greater confidence in guiding their decision-making around contraceptive and ART options. Our novel, 3-phase validation sampling provides an innovative tool for using routine EMR data to improve the robustness of data quality

Water Insecurity Is Associated With Lack of Viral Suppression and Greater Odds of Aids-Defining Illnesses Among Adults With HIV in Western Kenya

Reliable access to safe and acceptable water in sufficient quantities (i.e., water security) is important for medication adherence and limiting pathogen exposure, yet prior studies have only considered the role of food security as a social determinant of HIV-related health. Therefore, the objective of this analysis was to assess the relationships between household water insecurity and HIV-related outcomes among adults living with HIV in western Kenya (N = 716). We conducted a cross-sectional analysis of baseline data from Shamba Maisha (NCT02815579), a cluster randomized controlled trial of a multisectoral agricultural and asset loan intervention. Baseline data were collected from June 2016 to December 2017. We assessed associations between water insecurity and HIV-related outcomes, adjusting for clinical and behavioral confounders, including food insecurity. Each five-unit higher household water insecurity score (range: 0-51) was associated with 1.21 higher odds of having a viral load ≥ 1000 copies/mL (95% CI 1.07, 1.36) and 1.26 higher odds of AIDS-defining illness (95% CI 1.11, 1.42). Household water insecurity was not associated with CD4 cell count (B: 0.27; 95% CI -3.59, 13.05). HIV treatment and support programs should consider assessing and addressing water insecurity in addition to food insecurity to optimize HIV outcomes

The Kynurenine Pathway of Tryptophan Catabolism and AIDS-associated Kaposi\u27s Sarcoma in Africa

Background—Other than Kaposi\u27s sarcoma (KS)-associated herpesvirus and CD4+ T cell lymphopenia, the mechanisms responsible for KS in the context of HIV are poorly understood. One recently explored pathway of HIV pathogenesis involves induction of the enzyme indoleamine 2,3 dioxygenase-1 (IDO), which catabolizes tryptophan into kynurenine and several other immunologically active metabolites that suppress T cell proliferation. We investigated the role of IDO in the development of KS in HIV disease. Methods—In a case-control study among untreated HIV-infected Ugandans, cases were adults with KS and controls were without KS. IDO activity was assessed by the ratio of plasma kynurenine to tryptophan levels (KT ratio), measured by liquid chromatography tandem mass spectrometry. Results—We studied 631 HIV-infected subjects: 222 KS cases and 409 controls. Non-KS controls had a higher median plasma KT ratio (130, IQR: 90 to190 nM/μM) than cases (110, IQR: 90 to 150 nM/μM) (p = 0.004). After adjustment for age, sex, CD4 count and plasma HIV RNA level, subjects with the highest (fourth quartile) plasma KT ratios had a 59% reduction (95% CI: 27% to 77%) in the odds of KS compared to those with the lowest (first quartile) levels. KS was also independently associated with lower CD4+ count, higher plasma HIV RNA, and men. Conclusions—Among HIV-infected individuals, greater activity of the kynurenine pathway of tryptophan catabolism, as evidenced by higher levels of plasma KT ratio, was associated with lower occurrence of KS. Some consequences of immune activation in HIV infection might actually suppress certain cancers

Duration of Viral Suppression and Risk of Rebound Viremia with First-Line Antiretroviral Therapy in Rural Uganda.

Little is known about associations between viral suppression, adherence, and duration of prior viral suppression in sub-Saharan Africa. Study participants were from the UARTO study in Mbarara, Uganda. We fit regression models to characterize relationships between average adherence, treatment interruptions, and rebound viremia (&gt;400 copies/mL) following a previously undetectable result. Our goal was to understand the impact of prior viral suppression on these relationships. 396 participants contributed 2864 quarterly visits. Restricted to periods with average adherence &lt;50&nbsp;%, each 10&nbsp;% increase in adherence reduced the odds of rebound viremia by 74&nbsp;% [adjusted odds ratio (AOR)&nbsp;=&nbsp;0.26, P&nbsp;=&nbsp;0.002] and 29&nbsp;% (AOR&nbsp;=&nbsp;0.71, P&nbsp;=&nbsp;0.057) during the first 12&nbsp;months of suppression and beyond 12&nbsp;months respectively, interaction term P&nbsp;=&nbsp;0.018. Among periods with adherence ≥50&nbsp;%, the risk of rebound viremia decreased with increasing adherence during the first 12&nbsp;months of viral suppression (AOR&nbsp;=&nbsp;0.73 for each 10&nbsp;% increase, P&nbsp;=&nbsp;0.001), but not thereafter (AOR&nbsp;=&nbsp;1.09, P&nbsp;=&nbsp;0.67), interaction term P&nbsp;=&nbsp;0.027. In contrast, 72-h interruptions, were associated with increased rebound viremia during the first 12&nbsp;months (AOR&nbsp;=&nbsp;1.30, P&nbsp;=&nbsp;0.009) and after (AOR&nbsp;=&nbsp;1.39, P&nbsp;=&nbsp;0.005), interaction term P&nbsp;=&nbsp;0.69. Completing 12&nbsp;months of viral suppression decreases the impact of average adherence, but not prolonged treatment interruptions, on risk of rebound viremia

Preferences for Multipurpose Technology and Non-oral Methods of Antiretroviral Therapy Among Women Living With HIV in Western Kenya: A Survey Study

IntroductionUnderstanding interests in and preferences for multipurpose technology (MPT) for the co-administration of contraception and antiretroviral therapy (ART) and alternative, non-oral ART methods among women living with HIV (WLHIV) is vital to successful implementation of future treatment options, such as long-acting injectable ART.MethodsBetween May 2016 and March 2017 we conducted a cross-sectional telephone survey of 1,132 WLHIV of reproductive potential with prior experience using intermediate- or long-acting contraceptive methods in western Kenya. We present descriptive statistics and multinomial logistic regression to evaluate predictors of interest in specific MPT and non-oral ART methods.ResultsTwo-thirds (67%) reported interest in MPT, with the most common reason for interest being ease of using a single medication for both purposes of HIV treatment and pregnancy prevention (26%). Main reasons for lack of interest in MPT were need to stop/not use contraception while continuing ART (21%) and risk of side effects (16%). Important characteristics of MPT were effectiveness for pregnancy prevention (26%) and HIV treatment (24%) and less than daily dosing (19%). Important characteristics of non-oral ART methods were less than daily dosing (47%), saving time accessing ART (16%), and effectiveness of HIV treatment (15%). The leading preferred methods for both MPT and non-oral ART were injectables (50 and 54%) and implants (32 and 31%). Prior use of a contraceptive implant or injectable predicted interest in similar methods for both MPT and non-oral ART methods, while this relationship did not appear to vary between younger vs. older WLHIV.DiscussionMost WLHIV in western Kenya are interested in MPT for HIV treatment and contraception. Prior exposure to contraceptive implants or injectables appears to predict interest in similar methods of MPT and non-oral ART. Developers of MPT and non-oral ART methods should strongly consider WLHIV's preferences, including their changing reproductive desires

Correction: Incidence and Predictors of Pregnancy among a Cohort of HIV-Positive Women Initiating Antiretroviral Therapy in Mbarara, Uganda.

[This corrects the article DOI: 10.1371/journal.pone.0063411.]

HIV-infected women on antiretroviral treatment have increased mortality during pregnant and postpartum periods

ObjectiveTo assess the impact of pregnancy on mortality among HIV-infected Ugandan women initiating ART.DesignProspective cohort study.MethodsHIV-infected women initiating ART in the Uganda AIDS Rural Treatment Outcomes study were assessed quarterly for self-reported pregnancy. The association between pregnancy and postpartum ('pregnancy-related') follow-up periods and mortality was assessed with Cox proportional hazards models adjusted for age, CD4 cell count, plasma HIV-1 RNA levels, and ART duration.ResultsThree hundred and fifty-four women with median age 33 years (IQR: 27-37) and CD4 142 cells/μl (IQR: 82-213) were followed for a median of 4.0 years (IQR: 2.5-4.8) after ART initiation, with 3 and 7% loss-to-follow-up at years 1 and 5. One hundred and nine women experienced pregnancy. Five deaths occurred during pregnancy-related follow-up and 16 during nonpregnancy-related follow-up, for crude mortality rates during the first year after ART initiation of 12.57/100 PYs and 3.53/100 PYs (rate ratio 3.56, 95% CI: 0.97-11.07). In adjusted models, the impact of pregnancy-related follow-up on mortality was highest at ART initiation (aHR: 21.48, 95% CI: 3.73-123.51), decreasing to 13.44 (95% CI 3.28-55.11) after 4 months, 8.28 (95% CI 2.38-28.88) after 8 months, 5.18 (95% CI: 1.36-19.71) after 1 year, and 1.25 (95% CI: 0.10-15.58) after 2 years on ART. Four of five maternal deaths occurred postpartum.ConclusionPregnancy and the postpartum period were associated with increased mortality in HIV-infected women initiating ART, particularly during early ART. Contraception proximate to ART initiation, earlier ART initiation, and careful monitoring during the postpartum period may reduce maternal mortality in this setting

Relationship Power, Antiretroviral Adherence, and Physical and Mental Health Among Women Living with HIV in Rural Kenya.

Little is known about the association of gender-based power imbalances and health and health behaviors among women with HIV (WWH). We examined cross-sectional baseline data among WWH in a cluster-randomized control trial (NCT02815579) in rural Kenya. We assessed associations between&nbsp;the Sexual Relationship Power Scale (SRPS) and ART adherence, physical and mental health, adjusting for sociodemographic and social factors. SRPS consists of two subscales: relationship control (RC) and decision-making dominance. Women in the highest and middle tertiles for RC had a 7.49 point and 8.88 point greater Medical Outcomes Study-HIV mental health score, and a 0.27 and 0.29 lower odds of depression, respectively, compared to women in the lowest tertile. We did not find associations between SPRS or its subscales and ART adherence.&nbsp;Low sexual relationship power, specifically low RC, may be associated with poor mental health among WWH. Intervention studies aimed to improve RC among WWH should be studied to determine their effect on improving mental health

Cooking fuel and respiratory symptoms among people living with HIV in rural Uganda

Household air pollution (HAP) and chronic HIV infection are each associated with significant respiratory morbidity. Little is known about relationships between HAP and respiratory symptoms among people living with HIV. The objective of this study was to investigate the relationship between cooking fuel type and chronic respiratory symptoms in study participants from the Uganda AIDS Rural Treatment Outcomes Study. Study participants were enrolled at the time of antiretroviral therapy initiation and seen quarterly from 2005 to 2014 for health-focused questionnaires, CD4 count and HIV viral load. We used multivariable logistic regression and generalised estimating equations, with each study visit as a unit of observation, to investigate relationships between cooking fuel type and chronic respiratory symptoms. We observed an association between cooking with firewood (versus charcoal) and chronic cough among HIV-infected females in rural Uganda (adjusted OR 1.41, 95% CI 1.00–1.99; p=0.047). We did not observe an association between cooking fuel type and respiratory symptoms among males (adjusted OR 0.88, 95% CI 0.47–1.63; p=0.658). Associations between cooking fuel and chronic cough in this HIV-infected cohort may be influenced by sex-based roles in meal preparation. This study raises important questions about relationships between household air pollution, HIV infection and respiratory morbidity