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1.  Opioid agonist therapy is associated with lower incidence of hepatitis C virus infection in young adult persons who inject drugs 
JAMA internal medicine  2014;174(12):1974-1981.
Injection drug use is the primary mode of transmission for hepatitis C virus (HCV) infection. Prior studies suggest opioid agonist therapy may reduce incidence of HCV among people who inject drugs, however, little is known about its effects in younger injectors.
To evaluate whether opioid agonist therapy was associated with a lower incidence of HCV in a cohort of young adult injectors.
Observational cohort study conducted January 2000 through August 2013 with quarterly interviews and blood samples.
San Francisco community outreach.
Young adult injectors (<30 years old) who were anti-HCV negative.
Recent (within past 3 months) substance use treatment: no treatment, non-opioid agonist forms of treatment, or opioid agonist therapy (methadone or buprenorphine) detoxification or maintenance.
Main Outcome(s) and Measure(s)
Incident HCV infection documented with a new positive HCV RNA result and/or a positive anti-HCV result. Cumulative HCV incidence rates and 95% confidence intervals were calculated assuming a Poisson distribution. Cox Proportional Hazards models were fit adjusting for age, gender, race, years of injection drug use, homelessness and incarceration.
Baseline characteristics of the sample (n=552) were: median age 23 (IQR: 20–26), 32% female, 73% Caucasian, 40% did not graduate high school, and 69% were homeless. Over the observation period of 680 person-years (py), there were 171 incident cases of HCV (incidence rate=25.1/100 py; 95% CI: 21.6–29.2). The rate ratio was significantly lower for participants who reported recent maintenance opioid agonist therapy (0.31; 95% CI: 0.14–0.65), but not for those who reported recent non-opioid agonist forms of treatment (0.63; 95% CI: 0.37–1.08), or opioid agonist detoxification (1.45; 95% CI: 0.80–2.69). After adjustment for other covariates, maintenance opioid agonist therapy was associated with lower relative hazards for becoming infected with HCV over time (AHR=0.39; 95% CI: 0.18–0.87).
Conclusions and Relevance
In this cohort of young adults who inject drugs, recent maintenance opioid agonist therapy was associated with lower incidence of HCV. Maintenance treatment with methadone or buprenorphine for opioid use disorders may be an important strategy to prevent spread of HCV among young injectors.
PMCID: PMC4506774  PMID: 25347412
HCV; PWID; injection drug use; methadone; buprenorphine
2.  Concordance of risk behavior reporting within HCV serodiscordant injecting partnerships of young injection drug users in San Francisco, CA 
Drug and alcohol dependence  2014;142:239-244.
Young injection drug users (IDU, under age 30) often inject with other IDU, creating an environment for risk of blood-borne disease transmission through sharing of needles and drug preparation equipment. Epidemiologic studies rely on self reported injection behavior data for measures of transmission risk, therefore we sought to quantify the degree of concordance of reported injecting risk behaviors between injecting dyads.
From May, 2006 through 2013 we enrolled 72 injecting dyads in San Francisco, California, who were hepatitis C virus (HCV) RNA discordant. Each partnership was followed prospectively for up to six months. Monthly interviews from each partner were date-matched and responses to relationship characteristics and risk behavior questions were compared. Concordance of reporting was estimated with the concordance correlation coefficient for longitudinal data (CCC) and the prevalence adjusted bias adjusted kappa (PABAK).
Participants had a median age of 26 (IQR: 23, 28) years and median years injecting of 7.0 (IQR: 3.0,10.6). Thirty-eight percent of the injecting dyads were also sexual partners. Concordance levels were highest for partnership characteristics, such as length of acquaintance, number of days cohabitating, and sexual intercourse in the past month (CCC = 0.95; 0.82, and 0.90, respectively). Shared injection risk behaviors such as injecting with the HCV+ partner’s previously used syringe and using contaminated injection preparation equipment had slight to fair agreement (CCC = 0.22; 0.23; PABAK = 0.43,0.36, respectively).
Concordance levels ranged from low to high. Potential sources of measurement error for low agreement items include recall and social-desirability biases and question interpretation.
PMCID: PMC4471952  PMID: 25034898
Epidemiology; Drug users; Agreement; Young adult; Hepatitis C; Dyad
3.  Self-reported alcohol abstinence associated with ART initiation among HIV-infected persons in rural Uganda 
Drug and alcohol dependence  2013;134:10.1016/j.drugalcdep.2013.09.025.
There is limited data on the impact of anti-retroviral treatment (ART) initiation on alcohol consumption. We characterized predictors of abstaining from alcohol among HIV-infected individuals following ART initiation.
We analyzed data from a prospective cohort of HIV-infected adults in Mbarara, Uganda with quarterly measures of self-reported alcohol consumption, socio-demographics, health status, and blood draws. We used pooled logistic regression to evaluate predictors of becoming abstinent from alcohol for at least 90 days after baseline.
Among the 502 participants, 108 (21.5%) were current drinkers who consumed alcohol within 90 days of baseline, 206 (41.0%) were former drinkers, and 188 (37.5%) were lifetime abstainers at baseline. Among current drinkers, 67 (62.0%) drank at hazardous levels. 90 of current drinkers (83.3%) abstained from alcohol at least for 90 days over 3.6 median years of follow-up [IQR 2-4.8]; of those 69 (76.7%) remained abstinent for a median duration of follow-up of 3.25 years [1.6-4.5]. Becoming abstinent was independently associated with lower baseline AUDIT score (adjusted odds ratio [AOR] 0.95[95%CI 0.91-0.99]), baseline physical health score (AOR 0.92[0.87-0.97]), and decreases in physical health score at follow-up visits (AOR 0.92[0.88-0.97)). Alcohol abstinence was most likely to start immediately after ART initiation (AORs for 6 month versus 3 month visit: 0.25[0.10-0.61]; 9 month visit or later versus 3 month visit: 0.04[0.02-0.09]).
We found that a large majority of drinkers starting ART reported that they became and remained abstinent from alcohol. ART initiation may be an opportune time to implement interventions for alcohol consumption and other health behaviors.
PMCID: PMC3885244  PMID: 24169501
Alcohol; HIV; alcohol abstinence; hazardous drinking; ART-initiation; antiretroviral treatment; Uganda; Africa
4.  Comparison of Self-Reported Alcohol Consumption to Phosphatidylethanol Measurement among HIV-Infected Patients Initiating Antiretroviral Treatment in Southwestern Uganda 
PLoS ONE  2014;9(12):e113152.
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.
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.
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).
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.
PMCID: PMC4249861  PMID: 25436894
5.  Qualitative Study of Changes in Alcohol Use Among HIV-Infected Adults Entering Care and Treatment for HIV/AIDS in Rural Southwest Uganda 
AIDS and Behavior  2014;19(4):732-741.
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 (>18 years 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.
PMCID: PMC4392168  PMID: 25323678
HIV/AIDS; Uganda; Alcohol use; Behavior change
6.  Intimate Injection Partnerships Are at Elevated Risk of High-Risk Injecting: A Multi-Level Longitudinal Study of HCV-Serodiscordant Injection Partnerships in San Francisco, CA 
PLoS ONE  2014;9(10):e109282.
It is increasingly recognized that the risk for HIV and hepatitis C (HCV) transmission among people who inject drugs (PWID), such as syringe sharing, occurs in the context of relationships between (at least) two people. Evidence suggests that the risk associated with injection behavior varies with injection partner types.
We utilized longitudinal dyad-level data from a study of young PWID from San Francisco (2006 to 2013) to investigate the relationship-level factors influencing high-risk injecting within HCV-serodiscordant injection partners (i.e., individuals who injected together ≥5 times in the prior month). Utilizing data from 70 HCV-serodiscordant injection partnerships, we used generalized linear models to examine relationship-level predictors (i.e., partnership composition, partnership closeness, and partnership dynamics) of: (1) receptive syringe sharing (RSS); and (2) receptive cooker use (RCU), as reported by the HCV-negative injection partner.
As reported by the “at-risk” HCV-negative injection partner, receptive syringe sharing (RSS) and receptive cooker use (RCU) were 19% and 33% at enrollment, and 11% and 12% over all visits (total follow-up time 55 person-years) resulting in 13 new HCV-infections (incidence rate: 23.8/100 person-years). Person-level factors, injection partnership composition, and partnership dynamics were not significantly associated with either RSS or RCU. Instead, intimate injection partnerships (those who lived together and were also in a sexual relationship) were independently associated with a 5-times greater risk of both RSS and a 7-times greater risk of RCU when compared to injecting only partnerships.
Our findings suggest a positive, and amplified effect of relationship factors on injecting drug risk behaviors among young PWID injection partnerships. The majority of interventions to reduce injection drug use related harms focus on individual-based education to increase drug use knowledge. Our findings support the need to expand harm reduction strategies to relationship-based messaging and interventions.
PMCID: PMC4186818  PMID: 25286346
7.  Efficacy of an alcohol-focused intervention for improving adherence to antiretroviral therapy (ART) and HIV treatment outcomes – a randomised controlled trial protocol 
BMC Infectious Diseases  2014;14:500.
Little research has examined whether alcohol reduction interventions improve antiretroviral therapy (ART) adherence and HIV treatment outcomes. This study assesses the efficacy of an intervention for reducing alcohol use among HIV patients on ART who are hazardous/harmful drinkers. Specific aims include adapting a blended Motivational Interviewing (MI) and Problem Solving Therapy (PST) intervention for use with HIV patients; evaluating the efficacy of the intervention for reducing alcohol consumption; and assessing counsellors’ and participants’ perceptions of the intervention.
A randomised controlled trial will evaluate the intervention among ART patients in public hospital-based HIV clinics in Tshwane, South Africa. We will recruit patients who are HIV-positive, on ART for at least 3 months, and classified as harmful/hazardous drinkers using the AUDIT-3. Eligible patients will be randomly assigned to one of three conditions. Patients in the experimental group will receive the MI-PST intervention to reduce harmful/hazardous alcohol use. Patients in the equal-attention wellness intervention group will receive an intervention focused on addressing health risk behaviours. Patients in the control condition will receive treatment as usual. Participants will complete an interviewer-administered questionnaire at baseline and 3, 6 and 12 months post-randomisation to assess alcohol consumption, ART adherence, physical and mental health. We will also collect biological specimens to test for recent alcohol consumption, CD4 counts and HIV RNA viral loads. The primary outcome will be reduction in the volume of alcohol consumed. Secondary outcomes include reduction in harmful/hazardous use of alcohol, reduction in biological markers of drinking, increase in adherence rates, reductions in viral loads, and increases in CD4 T-cell counts. A process evaluation will ascertain counsellors’ and participants’ perceptions of the acceptability and effectiveness of the interventions.
We have obtained ethical approval and approval from the study sites and regional and provincial health departments. The study has implications for clinicians, researchers and policy makers as it will provide efficacy data on how to reduce harmful/hazardous alcohol consumption among HIV patients and will shed light on whether reducing alcohol consumption impacts on HIV treatment adherence and other outcomes.
Trial registration
Pan African Clinical Trials Register Number: PACTR201405000815100.
PMCID: PMC4174635  PMID: 25212696
HIV/AIDS; Alcohol; South Africa; Randomised controlled trial; Brief intervention
8.  Injection Drug Use and Hepatitis C Virus Infection in Young Adult Injectors: Using Evidence to Inform Comprehensive Prevention 
The hepatitis C virus (HCV) virus epidemic is ongoing in the United States and globally. Incidence rates remain high, especially in young adult injection drug users. New outbreaks of HCV in the United States among young adults, in predominantly suburban and rural areas, have emerged and may be fueling an increase in HCV. This paper discusses some key HCV prevention strategies that to date have not been widely researched or implemented, and wherein future HCV prevention efforts may be focused: (1) reducing sharing of drug preparation equipment; (2) HCV screening, and testing and counseling; (3) risk reduction within injecting relationships; (4) injection cessation and “breaks”; (5) scaled-up needle/syringe distribution, HCV treatment, and vaccines, according to suggestions from mathematical models; and (6) “combination prevention.” With ongoing and expanding transmission of HCV, there is little doubt that there is a need for implementing what is in the prevention “toolbox” as well as adding to it. Strong advocacy and resources are needed to overcome challenges to providing the multiple and comprehensive programs that could reduce HCV transmission and associated burden of disease worldwide in people who inject drugs.
PMCID: PMC3722077  PMID: 23884063
hepatitis C virus; prevention; injection drug users; syringe access; counseling and testing; harm reduction; HCV treatment; HCV vaccine; combination prevention
9.  Abbreviated HIV counselling and testing and enhanced referral to care in Uganda: a factorial randomised controlled trial 
The lancet global health  2013;1(3):e137-e145.
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.
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 (NCT00648232).
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).
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.
US National Institute of Mental Health.
PMCID: PMC4129546  PMID: 25104262
10.  Decreases in self-reported alcohol consumption following HIV counseling and testing at Mulago Hospital, Kampala, Uganda 
BMC Infectious Diseases  2014;14:403.
Alcohol use has a detrimental impact on the HIV epidemic, especially in sub-Saharan Africa. HIV counseling and testing (HCT) may provide a contact opportunity to intervene with hazardous alcohol use; however, little is known about how alcohol consumption changes following HCT.
We utilized data from 2056 participants of a randomized controlled trial comparing two methods of HCT and subsequent linkage to HIV care conducted at Mulago Hospital in Kampala, Uganda. Those who had not previously tested positive for HIV and whose last HIV test was at least one year in the past were eligible. Participants were asked at baseline when they last consumed alcohol, and prior three month alcohol consumption was measured using the Alcohol Use Disorders Identification Test – Consumption (AUDIT-C) at baseline and quarterly for one year. Hazardous alcohol consumption was defined as scoring ≥3 or ≥4 for women and men, respectively. We examined correlates of alcohol use at baseline, and of hazardous and non-hazardous drinking during the year of follow-up using multinomial logistic regression, clustered at the participant level to account for repeated measurements.
Prior to HCT, 30% were current drinkers (prior three months), 27% were past drinkers (>3 months ago), and 44% were lifetime abstainers. One-third (35%) of the current drinkers met criteria for hazardous drinking. Hazardous and non-hazardous self-reported alcohol consumption declined after HCT, with 16% of baseline current drinkers reporting hazardous alcohol use 3 months after HCT. Independent predictors (p < 0.05) of continuing non-hazardous and hazardous alcohol consumption after HCT were sex (male), alcohol consumption prior to HCT (hazardous), and HIV status (negative). Among those with HIV, non-hazardous drinking was less likely among those taking antiretroviral therapy (ART).
HCT may be an opportune time to intervene with alcohol consumption. Those with HIV experienced greater declines in alcohol consumption after HCT, and non-hazardous drinking decreased for those with HIV initiating ART. HCT and ART initiation may be ideal times to intervene with alcohol consumption. Screening and brief intervention (SBI) to reduce alcohol consumption should be considered for HCT and HIV treatment venues.
PMCID: PMC4223423  PMID: 25038830
Alcohol; Africa; HIV; HIV counseling and testing; Antiretroviral therapy; Screening and brief intervention
11.  Preference, acceptability and implications of the rapid hepatitis C screening test among high-risk young people who inject drugs 
BMC Public Health  2014;14:645.
People who inject drugs (PWID) are at highest risk for hepatitis C virus (HCV) infection, yet many remain unaware of their infection status. New anti-HCV rapid testing has high potential to impact this.
Young adult (<30 years) active PWID were offered either the rapid OraQuick® or standard anti-HCV test involving phlebotomy, then asked to complete a short questionnaire about testing perceptions and preferences. Sample characteristics, service utilization, and injection risk exposures are assessed with the HCV testing choice as the outcome, testing preferences, and reasons for preference.
Of 129 participants: 82.9% (n = 107) chose the rapid test. There were no significant differences between those who chose rapid vs. standard testing. A majority (60.2%) chose the rapid test for quick results; most (60.9%) felt the rapid test was accurate, and less painful (53.3%) than the tests involving venipuncture.
OraQuick® anti-HCV rapid test was widely accepted among young PWID. Our results substantiate the valuable potential of anti-HCV rapid testing for HCV screening in this high risk population.
PMCID: PMC4091768  PMID: 24965699
Hepatitis C virus; Rapid testing; Injection drug users
12.  Injecting Risk Behavior among Traveling Young Injection Drug Users: Travel Partner and City Characteristics 
Young injection drug users (IDUs), a highly mobile population, engage in high levels of injecting risk behavior, yet little is understood about how such risk behavior may vary by the characteristics of the cities to which they travel, including the existence of a syringe exchange program (SEP), as well as travel partner characteristics. In 2004–2005, we conducted a 6-month prospective study to investigate the risk behavior of 89 young IDUs as they traveled, with detailed information gathered about 350 city visits. In multivariable analyses, travel to larger urban cities with a population of 500,000–1,000,000 was significantly associated with injecting drugs (adjusted odds ratio (AOR) = 3.71; 95 % confidence interval (CI), 1.56–8.82), ancillary equipment sharing (AES; AOR = 7.05; 95 % CI, 2.25–22.06) and receptive needle sharing (RNS; AOR = 5.73; 95 % CI, 1.11–27.95), as compared with visits to smaller cities with populations below 50,000. Region of the country, and the existence of a SEP within the city visited, were not independently associated with injecting drugs, AES, or RNS during city visits. Traveling with more than one injecting partner was associated with injecting drugs during city visits (AOR = 2.77; 95 % CI, 1.46–5.27), when compared with traveling alone. Additionally, both non-daily and daily/almost daily alcohol use during city visits were associated with AES (AOR = 3.37; 95 % CI, 1.42–7.68; AOR = 3.03; 95 % CI, 1.32–6.97, respectively) as compared with no alcohol consumption. Traveling young IDUs are more likely to inject when traveling with other IDUs and to engage in higher risk injection behavior when they are in large cities. Risk behavior occurring in city visits, including equipment sharing and alcohol consumption, suggests further need for focused interventions to reduce risk for viral infection among this population.
PMCID: PMC3665972  PMID: 22744293
Young IDUs; Travelers; Injecting risk; Ancillary equipment sharing; Receptive needle sharing; City characteristics; Travel partners
13.  Alcohol consumption as a barrier to prior HIV testing in a population-based study in rural Uganda 
AIDS and behavior  2013;17(5):1713-1723.
Early receipt of HIV care and ART is essential for improving treatment outcomes, but is dependent first upon HIV testing. Heavy alcohol consumption is common in sub-Saharan Africa, a barrier to ART adherence, and a potential barrier to HIV care. We conducted a population-based study of 2,516 adults in southwestern Uganda from November-December 2007, and estimated the relative risk of having never been tested for HIV using sex-stratified Poisson models. More men (63.9%) than women (56.9%) had never been tested. In multivariable analysis, compared to women who had not consumed alcohol for at least 5 years, women who were current heavy drinkers and women who last drank alcohol 1-5 years prior, were more likely to have never been tested. Alcohol use was not associated with prior HIV testing among men. HIV testing strategies may thus need to specifically target women who drink alcohol.
PMCID: PMC3769173  PMID: 22878790
alcohol; HIV testing; Uganda; barriers; sub-Saharan Africa
14.  Higher risk of incident hepatitis C virus among young women who inject drugs compared with young men in association with sexual relationships: a prospective analysis from the UFO Study cohort 
BMJ Open  2014;4(5):e004988.
Female injection drug users (IDUs) may report differences in injection behaviours that put them at greater risk for hepatitis C virus (HCV). Few studies have examined these in association with HCV incidence.
Longitudinal data from a cohort of 417 HCV-uninfected IDU aged 30 or younger were analysed. Cox proportional hazards was used to model female sex as a predictor of new HCV infection. General estimating equation (GEE) analysis was used to model female sex as a predictor of HCV-associated risk behaviour prospectively.
Women were significantly more likely than men to become infected with HCV during study follow-up (HR 1.4, p<0.05), and were also more likely than men to report high-risk injecting behaviours, especially in the context of sexual and injecting relationships. Sex differences in injecting behaviours appeared to explain the relationship between sex and HCV infection.
Young women’s riskier injection practices lead to their higher rates of HCV infection. Further study on the impact of intimate partnership on women’s risk behaviour is warranted.
PMCID: PMC4039809  PMID: 24875490
Public Health
15.  Frequent Longitudinal Sampling of Hepatitis C Virus Infection in Injection Drug Users Reveals Intermittently Detectable Viremia and Reinfection 
Defining clear hepatitis C virus (HCV) infection outcomes, including reinfection and viral intercalation after clearance of infection, requires ongoing, frequent follow-up, most importantly with longitudinal viral sequencing. Patients who have cleared HCV infection may demonstrate sustained viral clearance despite ongoing HCV exposure.
Background. Detection of hepatitis C virus (HCV) reinfection and intercalation (ie, intermittent recurrent bouts of viremia with homologous virus interspersed with aviremic periods) requires extensive and frequent evaluation and viral sequencing.
Methods. HCV infection outcomes were studied prospectively in active injection drug users with recurrent HCV RNA–positive tests after serial negative results. HCV viremia and viral sequences (Core/E1) were assessed from monthly blood samples.
Results. Viral clearance, reinfection, and intercalating infection were all detected. Among 44 participants with apparently resolved HCV (26 incident HCV clearers and 18 enrolled with already resolved infection), 36 (82%) remained persistently HCV RNA negative, but 8 demonstrated intermittent recurrent viremia. Four of these (50%) had confirmed reinfection with a heterologous virus; 3 demonstrated viral intercalation, and 1 was not classifiable as either. Estimated incidence of first reinfection was 5.4 per 100 person-years (95% confidence interval, 2.0–14.5). Six (75%) participants, including 3 of 4 with reinfection, demonstrated sustained viral clearance for a median of 26 months since last HCV RNA test.
Conclusions. These results show that frequent monitoring and viral sequencing are required to correctly assess HCV outcomes and estimate incidence of reinfection (which was previously overestimated). Sustained clearance may take many months and occur after episodes of reinfection and viral intercalation. Three of 4 subjects who had confirmed reinfection showed evidence of long-term clearance. Viral intercalation occurs with significant frequency. Further studies of these events, especially immunological, are needed to inform HCV clinical care and vaccine development.
PMCID: PMC3540042  PMID: 23090930
hepatitis C virus; viral sequencing; reinfection; intercalation; young IDU
16.  Hazardous alcohol consumption among young adult IDU and its association with high risk behaviors* 
Drug and alcohol dependence  2012;127(0):143-149.
Heavy alcohol consumption has been associated with risk-taking behaviors in intravenous drug users (IDU). However, limited information exists on the relationship between alcohol use and injecting and sexual risk in young adult IDU (<30 years) who are at risk for hepatitis C virus (HCV) and HIV infection.
We conducted a cross-sectional study of young adult IDU in San Francisco (2006-2012) who had not previously tested positive for HCV. Participants completed a structured interview and HCV testing. We examined whether hazardous drinking (Alcohol Use Disorders Test – Consumption [AUDIT-C] 3-9 for women and 4-9 for men) and probable dependent drinking (AUDIT-C 10-12) levels were associated with injecting and sexual risk behaviors and HCV status, indicated by adjusted odds ratios (AOR) in separate models adjusted for potential confounders.
Of the 326 participants, 139 (42.6%) were hazardous drinkers and 82 (25.2%) were probable dependent drinkers; thus over two-thirds evidenced problem drinking. Being a hazardous drinker was significantly associated with injecting drug residue from another's drug preparation equipment (AOR 1.93). Probable dependent drinking was significantly associated sharing non-sterile drug preparation equipment (AOR 2.59), and inversely, with daily/near daily injecting (AOR 0.42). Both heavy drinking levels were associated with having ≥2 sexual partners (AOR 2.43 and 2.14). Drinking category was not associated with HCV test results.
The young adult IDU reported consuming alcohol at very high levels, which was associated with some unsafe sexual and injecting behaviors. Our study demonstrates the urgent need to intervene to reduce alcohol consumption in this population.
PMCID: PMC3762448  PMID: 22819868
Young Intravenous Drug Users; Alcohol; Alcohol Dependence; Injecting Risk Behaviors
17.  Self-report of alcohol use increases when specimens for alcohol biomarkers are collected in persons with HIV in Uganda 
PMCID: PMC3495104  PMID: 23138732
Alcohol; self-report; phosphatidylethanol; biomarker; bias; sub-Saharan Africa
18.  People who Inject Drugs, HIV Risk, and HIV Testing Uptake in Sub-Saharan Africa 
Dramatic rises in injection drug use (IDU) in sub-Saharan Africa account for increasingly more infections in a region already overwhelmed by the HIV epidemic. There is no known estimate of the number of people who inject drugs (PWID) in the region, or the associated HIV prevalence in PWID. We reviewed literature with the goal of describing high-risk practices and exposures in PWID in sub-Saharan Africa, as well as current HIV prevention activities aimed at drug use. The literature search looked for articles related to HIV risk, injection drug users, stigma, and HIV testing in sub-Saharan Africa. This review found evidence demonstrating high rates of HIV in IDU populations in sub-Saharan Africa, high-risk behaviors of the populations, lack of knowledge regarding HIV, and low HIV testing uptake. There is an urgent need for action to address IDU in order to maintain recent decreases in the spread of HIV in sub-Saharan Africa.
PMCID: PMC3800507  PMID: 23164598
HIV risk; HIV testing; injection drug use; stigma; sub-Saharan Africa
19.  Trends in methamphetamine use in young injection drug users in San Francisco from 1998 to 2004: the UFO Study 
Drug and alcohol review  2008;27(3):286-291.
To describe temporal trends in methamphetamine use among young injection drug users (IDU) in San Francisco.
Design and Methods
Secondary analysis of cross-sectional baseline data collected for a longitudinal study of young IDU from 1998 to 2004. Participants were 1445 young IDU (< 30 years old) who reported injection in the previous month, English-speaking, and recruited by street outreach methods. We examined trends for: lifetime (ever) and recent (30-day) methamphetamine use, including injected and non-injected, and by age group and sexual risk behaviour [men who have sex with men injecting drug users (MSM-IDU), male IDU (non-MSM) and female IDU].
In 1998, 1999, 2000, 2001, 2003 and 2004 we interviewed 237, 276, 431, 310, 147 and 44 participants, respectively. Overall, median age was 22 years [interquartile range (IQR) 20 – 25], 30.3% were women and median duration of injecting was 4.4 years (IQR 2 – 7). Prevalence of methamphetamine use was high, with 50.1% reporting recent injection, but overall there were no temporal increases in reported ‘ever’ injected use. Recent methamphetamine injection (past 30 days) increased significantly, and peaked at 60% in 2003. MSM-IDU had higher methamphetamine injection ever (92.3%) and recently (59.5%) compared to heterosexual male (non-MSM) IDU (81.6% and 47.3%, respectively) and to female IDU (78.4% and 46.1%, respectively).
Despite reports of ubiquitous increases in methamphetamine use, there were no significant increases in 6 years in ever injecting methamphetamine overall among young IDU. MSM-IDU who reported the highest methamphetamine use overall reported some increases in recent injected use. The methamphetamine ‘epidemic’ was probably under way among young IDU earlier than other populations.
PMCID: PMC3747037  PMID: 18368610
injection drug use; methamphetamine; MSM-IDU; prevalence; trends; young injectors
20.  The association between use of non-injection drug implements and hepatitis C virus antibody status in homeless and marginally housed persons in San Francisco 
Up to 17 000 persons in the USA became infected with hepatitis C virus (HCV) in 2007, and many cases have unknown transmission routes. To date research on transmission of HCV via shared implements used to snort or smoke non-injection drugs has been inconclusive.
We tested stored sera for HCV antibodies (anti-HCV) in a large population-based study of homeless and marginally housed persons in San Francisco. We examined the association between sharing implements used for snorting and smoking drugs and anti-HCV while controlling for sociodemographic variables in those who denied everinjecting drugs (n = 430). We also examined the association of anti-HCV status with history of incarceration, tattoo and piercing history, sexual history and alcohol consumption.
Seventeen percent of our sample was anti-HCV positive. We found no statistically significant associations with sharing implements used to smoke or snort drugs with anti-HCV status in our various multivariate models. There was a statistically significant negative association between ever snorting cocaine and anti-HCV status (adjusted odds ratio: 0.39; 95% confidence interval: 0.21–0.73). There were no other statistically significant associations with any other measured covariates in multivariate analyses.
Our findings suggest that sharing implements to snort or smoke drugs is not a significant risk factor for anti-HCV-positive status.
PMCID: PMC3699061  PMID: 22451327
epidemiology; liver disorders; public health
21.  Phosphatidylethanol (PEth) as a biomarker of alcohol consumption in HIV positives in sub-Saharan Africa 
Alcohol is heavily consumed in sub-Saharan Africa and affects HIV transmission and treatment but is difficult to measure. Our goal was to examine the test characteristics of a direct metabolite of alcohol consumption, phosphatidylethanol (PEth).
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 to prior 7-, 14-, and 21-day alcohol consumption.
1) 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% CI: 0.86-0.97). The sensitivity for any detectable PEth was 88.0% (95% CI: 76.0-95.6%) and the specificity was 88.5% (95% CI: 69.8-97.6%). 2) The ROC-AUC of PEth versus any 21-day alcohol consumption did not vary by age, body mass index, CD4 cell count, hepatitis B virus infection and antiretroviral therapy status, but was higher for men compared to women (p=0.03). 3) PEth measurements were correlated with several measures of alcohol consumption, including number of drinking days in the prior 21 (Spearman r=0.74, p<0.001) and BRAC (r=0.75, p<0.001).
The data add support to the body of evidence for PEth as a useful marker of alcohol consumption with high ROC-AUC, sensitivity, and specificity. Future studies should further address the period and level of alcohol consumption for which PEth is detectable.
PMCID: PMC3310261  PMID: 22150449
Alcohol; biomarker; phosphatidylethanol; HIV; Africa
22.  Alcohol Use, Depressive Symptoms and the Receipt of Antiretroviral Therapy in Southwest Uganda 
AIDS and behavior  2007;12(4):605-612.
Alcohol use and depressive symptoms are associated with reduced access to antiretroviral therapy (ART) in the developed world. Whether alcohol use and depressive symptoms limit access to ART in resource-limited settings is unknown. This cross-sectional study examined the association between alcohol use, depressive symptoms and the receipt of ART among randomly selected HIV-positive persons presenting for primary health care services at an outpatient HIV clinic in Uganda. Depressive symptoms were defined by the Hopkins Symptom Checklist and alcohol use was measured through frequency of consumption questions. Antiretroviral use was assessed using a standardized survey and confirmed by medical record review. Predictors of ART use were determined via logistic regression. Among 421 HIV-infected patients, factors associated with the receipt of ART were having at least primary education, having an opportunistic infection in the last 3 months, and not drinking within the last year.
PMCID: PMC3591721  PMID: 17968651
Antiretroviral therapy; Alcohol use; Depression; Africa; Access to care
23.  Mortality Among Young Injection Drug Users in San Francisco: A 10-Year Follow-up of the UFO Study 
American Journal of Epidemiology  2012;175(4):302-308.
This study examined associations between mortality and demographic and risk characteristics among young injection drug users in San Francisco, California, and compared the mortality rate with that of the population. A total of 644 young (<30 years) injection drug users completed a baseline interview and were enrolled in a prospective cohort study, known as the UFO (“U Find Out”) Study, from November 1997 to December 2007. Using the National Death Index, the authors identified 38 deaths over 4,167 person-years of follow-up, yielding a mortality rate of 9.1 (95% confidence interval: 6.6, 12.5) per 1,000 person-years. This mortality rate was 10 times that of the general population. The leading causes of death were overdose (57.9%), self-inflicted injury (13.2%), trauma/accidents (10.5%), and injection drug user-related medical conditions (13.1%). Mortality incidence was significantly higher among those who reported injecting heroin most days in the past month (adjusted hazard ratio = 5.8, 95% confidence interval: 1.4, 24.3). The leading cause of death in this group was overdose, and primary use of heroin was the only significant risk factor for death observed in the study. These findings highlight the continued need for public health interventions that address the risk of overdose in this population in order to reduce premature deaths.
PMCID: PMC3271816  PMID: 22227793
drug users; epidemiology; hepatitis C; mortality; overdose; young adult
24.  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 one's 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.
PMCID: PMC3469089  PMID: 23082069
25.  Potential for false positive HIV test results with the serial rapid HIV testing algorithm 
BMC Research Notes  2012;5:154.
Rapid 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.
Of 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.
Although 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.
PMCID: PMC3392728  PMID: 22429706
False positive; HIV testing algorithm; Rapid diagnostic tests; Qualitative PCR testing

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