Robin Fatch

Missed Opportunities for HIV Testing and Late-Stage Diagnosis among HIV-Infected Patients in Uganda

Background Late diagnosis of HIV infection is a major challenge to the scale-up of HIV prevention and treatment. In 2005 Uganda adopted provider-initiated HIV testing in the health care setting to ensure earlier HIV diagnosis and linkage to care. We provided HIV testing to patients at Mulago hospital in Uganda, and performed CD4 tests to assess disease stage at diagnosis. Methods Patients who had never tested for HIV or tested negative over one year prior to recruitment were enrolled between May 2008 and March 2010. Participants who tested HIV positive had a blood draw for CD4. Late HIV diagnosis was defined as CD4≤250 cells/mm. Predictors of late HIV diagnosis were analyzed using multi-variable logistic regression. Results Of 1966 participants, 616 (31.3%) were HIV infected; 47.6% of these (291) had CD4 counts ≤250. Overall, 66.7% (408) of the HIV infected participants had never received care in a medical clinic. Receiving care in a non-medical setting (home, traditional healer and drug stores) had a threefold increase in the odds of late diagnosis (OR = 3.2; 95%CI: 2.1–4.9) compared to receiving no health care. Conclusions Late HIV diagnosis remains prevalent five years after introducing provider-initiated HIV testing in Uganda. Many individuals diagnosed with advanced HIV did not have prior exposure to medical clinics and could not have benefitted from the expansion of provider initiated HIV testing within health facilities. In addition to provider-initiated testing, approaches that reach individuals using non-hospital based encounters should be expanded to ensure early HIV diagnosis.

Contraceptive Use and Associated Factors among Women Enrolling into HIV Care in Southwestern Uganda

Background. Preventing unintended pregnancies among women living with HIV is an important component of prevention of mother-to-child HIV transmission (PMTCT), yet few data exist on contraceptive use among women entering HIV care. Methods. This was a retrospective study of electronic medical records from the initial HIV clinic visits of 826 sexually active, nonpregnant, 18–49-year old women in southwestern Uganda in 2009. We examined whether contraceptive use was associated with HIV status disclosure to ones spouse. Results. The proportion reporting use of contraception was 27.8%. The most common method used was injectable hormones (51.7%), followed by condoms (29.6%), and oral contraceptives (8.7%). In multivariable analysis, the odds of contraceptive use were significantly higher among women reporting secondary education, higher income, three or more children, and younger age. There were no significant independent associations between contraceptive use and HIV status disclosure to spouse. Discussion. Contraceptive use among HIV-positive females enrolling into HIV care in southwestern Uganda was low. Our results suggest that increased emphasis should be given to increase the contraception uptake for all women especially those with lower education and income. HIV clinics may be prime sites for contraception education and service delivery integration.

Self-report of alcohol use increases when specimens for alcohol biomarkers are collected in persons with HIV in Uganda

There is a significant overlap between the problem of heavy alcohol consumption and the HIV epidemic in sub-Saharan Africa (SSA). Heavy alcohol consumption has direct health consequences and increases the risk of HIV transmission, incomplete adherence and disease progression in SSA [1]. However, the criterion validity of patient-reported alcohol consumption by HIV-infected persons in SSA is unknown. Valid report is necessary for implementing interventions to reduce alcohol consumption that could in turn reduce the burden of HIV disease [2]. We investigated the effect of introducing biologic measures on self-report of alcohol consumption among persons on HIV antiretroviral therapy (ART) in Mbarara, Uganda. In Uganda, the adult HIV prevalence is 6.5% and 47% with CD4 counts or ≤ 400 copies/ml) were selected (29 incompletely suppressed, 32 suppressed), matched on sex (52.5% female) and duration on ART (within six months); all had been enrolled in the parent study for at least six months. Parent study activities included baseline and quarterly structured interviews and blood draws. Participants were asked at baseline when, if ever, they last consumed any alcohol, and at follow-up, how often they consumed alcohol in the prior three months. We re-categorized these as never, ever but not within the prior three months, and within the prior three months, using the most current survey and all previous surveys. The nested study activities, which were conducted within a median of 1 day (IQR: 0–30) after a parent study visit, included a structured interview, breath analysis, and blood and urine specimen collection. The nested study survey asked when the participants last consumed alcohol, if ever. The biomarkers examined were phosphatidylethanol (PEth) in whole blood and ethyl glucuronide/ethyl sulfate in urine (UEtG/UEtS). We previously found that PEth is 88.0% sensitive and 88.5% specific for detecting any alcohol consumption in the prior 21 days, and 76.4% sensitive and 100% specific for detecting any alcohol consumption in the prior three months in persons infected with HIV in Uganda [4]. We conducted breath analysis to determine that breath alcohol was zero, to avoid in-vitro formation of PEth [5]. UEtG has been 89.3% sensitive and 98.9% specific for detecting very recent (prior 1–3 days) alcohol consumption [6], and sensitivity may be increased when combined with UEtS [7]. All protocols were approved by the Institutional Review Boards of the Mbarara University of Sciences and Technology, the Uganda National Council for Science and Technology, and the University of California, San Francisco. All participants gave informed consent for the parent study and, subsequently, for the nested study. In the parent study, 20% of participants reported drinking any alcohol in the prior three months, 39% reported drinking alcohol more than three months prior, and 41% reported never drinking alcohol (Table 1). In the nested study that included concurrent biomarkers, there was a two-fold increase in reporting any alcohol consumption in the prior three months, from 20% to 41% (McNemar’s p<0.01). The results were similar when the sample was limited to those who completed both the parent and nested study interviews on the same day (n=30) and when stratified by viral suppression status (data not shown). We were unable to determine whether self-report validity varied by religion; ten participants were of religions that prohibit alcohol (Moslems and “Saved” Christians). Self report differed by sex (Table 1), with self-reported three-month alcohol consumption increasing from 6.3% to 34.4% (p<0.01) among the women and from 34.5% to 48.3% among the men (p=0.13). Table 1 When last consumed alcohol, by self-report in parent study versus nested study with concurrent specimen collection for biomarkers of alcohol consumption, overall and by sex. We examined the associations between the biomarkers and self-reported recent alcohol consumption. Few, six in the parent study and ten in the nested study, reported alcohol consumption in the prior three days, therefore we do not report UEtG/UEtS results. PEth was detectable (>8 ng/ml) for 83% (10/12) and 80% (20/25) of those reporting any alcohol consumption in the three months in the parent and nested studies, respectively. In addition, PEth was detectable for 27% (13/49) and 8% (3/36) of those denying prior three month alcohol consumption in the parent and nested studies, respectively. Furthermore, PEth was detectable in 10 of the 13 (77%) persons who denied prior three month alcohol consumption in the parent study but who later reported drinking in the nested study, corroborating evidence of under-report in the parent study. Under-report of alcohol consumption may reflect fear that ART will be denied if alcohol consumption is admitted [8], or may reflect social desirability bias. The greater under-report by women is consistent with increased stigma for drinking incurred by women [9]. Alternatively, repeated alcohol consumption questions may increase recall. However, there is a trend in the parent cohort towards decreasing self-reported alcohol consumption over time rather than the opposite (data not shown). Biomarker procedures discussed during the informed consent process just prior to the nested study survey may have had an impact on self-report. Biological measures have been used to improve the accuracy of self-report previously [10–14] with mixed results. To our knowledge, this is the first study in SSA to show that self-reported alcohol consumption on a survey is increased when biomarker measurement of alcohol exposure is conducted concurrently. There are important implications of under-reported alcohol consumption for persons infected with HIV. On the individual level, non-disclosure of alcohol use prevents health care providers from providing interventions to protect patients from the direct negative effects of alcohol or indirect effects on HIV treatment adherence and treatment outcomes. On the population level, under-reported alcohol consumption hampers research of the public health consequences of alcohol. More work is needed to determine the context in which alcohol consumption is under-reported and to develop methods to improve assessment of alcohol consumption. Research is needed to determine the number and type of biological specimens needed to gain valid self report; it is possible that a minimally invasive and inexpensive measure such as a breath test may suffice.

Potential for false positive HIV test results with the serial rapid HIV testing algorithm

BackgroundRapid HIV tests provide same-day results and are widely used in HIV testing programs in areas with limited personnel and laboratory infrastructure. The Uganda Ministry of Health currently recommends the serial rapid testing algorithm with Determine, STAT-PAK, and Uni-Gold for diagnosis of HIV infection. Using this algorithm, individuals who test positive on Determine, negative to STAT-PAK and positive to Uni-Gold are reported as HIV positive. We conducted further testing on this subgroup of samples using qualitative DNA PCR to assess the potential for false positive tests in this situation.ResultsOf the 3388 individuals who were tested, 984 were HIV positive on two consecutive tests, and 29 were considered positive by a tiebreaker (positive on Determine, negative on STAT-PAK, and positive on Uni-Gold). However, when the 29 samples were further tested using qualitative DNA PCR, 14 (48.2%) were HIV negative.ConclusionAlthough this study was not primarily designed to assess the validity of rapid HIV tests and thus only a subset of the samples were retested, the findings show a potential for false positive HIV results in the subset of individuals who test positive when a tiebreaker test is used in serial testing. These findings highlight a need for confirmatory testing for this category of individuals.

Abbreviated HIV counselling and testing and enhanced referral to care in Uganda: a factorial randomised controlled trial.

Summary Background HIV counselling and testing and linkage to care are crucial for successful HIV prevention and treatment. Abbreviated counselling could save time; however, its effect on HIV risk is uncertain and methods to improve linkage to care have not been studied. Methods We did this factorial randomised controlled study at Mulago Hospital, Uganda. Participants were randomly assigned to abbreviated or traditional HIV counselling and testing; HIV-infected patients were randomly assigned to enhanced linkage to care or standard linkage to care. All study personnel except counsellors and the data officer were masked to study group assignment. Participants had structured interviews, given once every 3 months. We compared sexual risk behaviour by counselling strategy with a 6·5% non-inferiority margin. We used Cox proportional hazards analyses to compare HIV outcomes by linkage to care over 1 year and tested for interaction by sex. This trial is registered with ClinicalTrials.gov (NCT00648232). Findings We enrolled 3415 participants; 1707 assigned to abbreviated counselling versus 1708 assigned to traditional. Unprotected sex with an HIV discordant or status unknown partner was similar in each group (232/823 [27·9%] vs 251/890 [28·2%], difference −0·3%, one-sided 95% CI 3·2). Loss to follow-up was lower for traditional counselling than for abbreviated counselling (adjusted hazard ratio [HR] 0·61, 95% CI 0·44–0·83). 1003 HIV-positive participants were assigned to enhanced linkage (n=504) or standard linkage to care (n=499). Linkage to care did not have a significant effect on mortality or receipt of co-trimoxazole. Time to treatment in men with CD4 cell counts of 250 cells per μL or fewer was lower for enhanced linkage versus standard linkage (adjusted HR 0·60, 95% CI 0·41–0·87) and time to HIV care was decreased among women (0·80, 0·66–0·96). Interpretation Abbreviated HIV counselling and testing did not adversely affect risk behaviour. Linkage to care interventions might decrease time to enrolment in HIV care and antiretroviral treatment and thus might affect secondary HIV transmission and improve treatment outcomes. Funding US National Institute of Mental Health.

Declining and rebounding unhealthy alcohol consumption during the first year of HIV care in rural Uganda, using phosphatidylethanol to augment self-report.

AIMS We examined whether unhealthy alcohol consumption, which negatively impacts HIV outcomes, changes after HIV care entry overall and by several factors. We also compared using phosphatidylethanol (PEth, an alcohol biomarker) to augment self-report to using self-report alone. DESIGN A prospective 1-year observational cohort study with quarterly visits. SETTING Large rural HIV clinic in Mbarara, Uganda. PARTICIPANTS A total of 208 adults (89 women and 119 men) entering HIV care, reporting any prior year alcohol consumption. MEASUREMENTS Unhealthy drinking was PEth+ (≥ 50 ng/ml) or Alcohol Use Disorders Identification Test-Consumption+ (AUDIT-C+, over 3 months, women ≥ 3; men ≥ 4). We calculated adjusted odds ratios (AOR) for unhealthy drinking per month since baseline, and interactions of month since baseline with perceived health, number of HIV symptoms, antiretroviral therapy (ART), gender and self-reported prior unhealthy alcohol use. FINDINGS The majority of participants (64%) were unhealthy drinkers (PEth+ or AUDIT-C+) at baseline. There was no significant trend in unhealthy drinking overall [per-month AOR: 1.01; 95% confidence interval (CI) = 0.94-1.07], while the per-month AORs were 0.91 (95% CI = 0.83-1.00) and 1.11 (95% CI = 1.01-1.22) when participants were not yet on ART and on ART, respectively (interaction P-value < 0.01). In contrast, 44% were AUDIT-C+; the per-month AORs for being AUDIT-C+ were 0.89 (95% CI = 0.85-0.95) overall, and 0.84 (95% CI = 0.78-0.91) and 0.97 (95% CI = 0.89-1.05) when participants were not on and were on ART, respectively. CONCLUSIONS Unhealthy alcohol use among Ugandan adults entering HIV care declines prior to the start of anti-retroviral therapy but rebounds with time. Augmenting self-reported alcohol use with biomarkers increases the ability of current alcohol use measurements to detect unhealthy alcohol use.

Comparison of Traditional and Novel Self-Report Measures to an Alcohol Biomarker for Quantifying Alcohol Consumption Among HIV-Infected Adults in Sub-Saharan Africa

BACKGROUND In Sub-Saharan Africa (SSA), HIV-infected patients may underreport alcohol consumption. We compared self-reports of drinking to phosphatidylethanol (PEth), an alcohol biomarker. In particular, we assessed beverage-type-adjusted fractional graduated frequency (FGF) and quantity frequency (QF) measures of grams of alcohol, novel nonvolume measures, and the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C). METHODS We analyzed cohort entry data from the Biomarker Research of Ethanol Among Those with HIV cohort study (2011 to 2013). Participants were HIV-infected past-year drinkers, newly enrolled into care. Self-report measures included FGF and QF grams of alcohol, the AUDIT-C, number of drinking days, and novel adaptations of FGF and QF methods to expenditures on alcohol, time spent drinking, and symptoms of intoxication. PEth levels were measured from dried blood spots. We calculated Spearmans rank correlation coefficients of self-reports with PEth and bias-corrected bootstrap 95% confidence intervals (CIs) for pairwise differences between coefficients. RESULTS A total of 209 subjects (57% men) were included. Median age was 30; interquartile range (IQR) 25 to 38. FGF grams of alcohol over the past 90 days (median 592, IQR 43 to 2,137) were higher than QF grams (375, IQR 33 to 1,776), p < 0.001. However, both measures were moderately correlated with PEth: ρ = 0.58, 95% CI 0.47 to 0.66 for FGF grams and 0.54, 95% CI 0.43 to 0.63 for QF grams (95% CI for difference -0.017 to 0.099, not statistically significant). AUDIT-C, time drinking, and a scale of symptoms of intoxication were similarly correlated with PEth (ρ = 0.35 to 0.57). CONCLUSIONS HIV-infected drinkers in SSA likely underreport both any alcohol consumption and amounts consumed, suggesting the need to use more objective measures like biomarkers when measuring drinking in this population. Although the FGF method may more accurately estimate drinking than QF methods, the AUDIT-C and other nonvolume measures may provide simpler alternatives.

Phosphatidylethanol confirmed alcohol use among ART-naïve HIV-infected persons who denied consumption in rural Uganda

ABSTRACT 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.

Characterization of HIV Recent Infection Among High-Risk Men at Public STI Clinics in Mumbai

We examined associations with HIV recent infection and estimated transmitted drug resistance (TDR) prevalence among 3345 men at sexually transmitted infection clinics in Mumbai (2002–2005). HIV seroincidence was 7.92% by the BED-CEIA and was higher at a clinic located near brothels (12.39%) than at a hospital-based clinic (3.94%). HIV recent infection was associated with a lifetime history of female sex worker (FSW) partners, HSV-2, genital warts, and gonorrhea. TDR prevalence among recent infection cases was 5.7%. HIV testing services near sex venues may enhance case detection among high-risk men who represent a bridging population between FSWs and the men’s other sexual partners.