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.
hepatitis C virus; viral sequencing; reinfection; intercalation; young IDU
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.
Young Intravenous Drug Users; Alcohol; Alcohol Dependence; Injecting Risk Behaviors
Alcohol; self-report; phosphatidylethanol; biomarker; bias; 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.
HIV risk; HIV testing; injection drug use; stigma; sub-Saharan Africa
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.
injection drug use; methamphetamine; MSM-IDU; prevalence; trends; young injectors
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.
epidemiology; liver disorders; public health
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.
Alcohol; biomarker; phosphatidylethanol; HIV; Africa
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.
Antiretroviral therapy; Alcohol use; Depression; Africa; Access to care
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.
drug users; epidemiology; hepatitis C; mortality; overdose; young adult
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.
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.
False positive; HIV testing algorithm; Rapid diagnostic tests; Qualitative PCR testing
Trials to evaluate the efficacy of preventive HCV vaccines will need participation from high risk HCV seronegative injection drug users (IDUs). To guide trial planning, we assessed willingness of young IDU in San Francisco to participate in HCV vaccine efficacy trials and evaluate knowledge of vaccine trial concepts: placebo, randomization and blinding. During 2006 and 2007, a total of 67 participants completed the survey. A substantial proportion (88%) would definitely (44%) or probably (44%) be willing to participate in a randomized trial, but knowledge of vaccine trial concepts was low. Reported willingness to participate in an HCV vaccine trial decreased with increasing trial duration, with 67% of participants surveyed willing to participate in a trial of one year duration compared to 43% of participants willing to participate in a trial of 4 years duration. Willingness to enroll in HCV vaccine trials was higher in young IDU than reported by most at-risk populations in HIV vaccine trials. Educational strategies will be needed to ensure understanding of key concepts prior to implementing HCV vaccine trials.
Hepatitis C; injection drug use; vaccine trial
Hepatitis C virus (HCV) genotype (GT) has become an important measure in the diagnosis and monitoring of HCV infection treatment. In the United States (U.S.) HCV GT 1 is reported as the most common infecting GT among chronically infected patients. In Europe, however, recent studies have suggested that the epidemiology of HCV GTs is changing.
We assessed HCV GT distribution in 460 patients from three HCV-infected high risk populations in San Francisco, and examined patterns by birth cohort to assess temporal trends. Multiple logistic regression was used to assess factors independently associated with GT 1 infection compared to other GTs (2, 3, and 4).
Overall, GT 1 was predominant (72.4%), however younger injection drug users (IDU) had a lower proportion of GT 1 infections (54.7%) compared to older IDU and HIV-infected patients (80.5% and 76.6%, respectively). Analysis by birth cohort showed increasing proportions of non-GT 1 infections associated with year of birth: birth before 1970 was independently associated with higher adjusted odds of GT 1: AOR 2.03 (95% CI: 1.23, 3.34). African-Americans as compared to whites also had higher adjusted odds of GT 1 infection (AOR: 3.37; 95% CI: 1.89, 5.99).
Although, HCV GT 1 remains the most prevalent GT, especially among older groups, changes in GT distribution could have significant implications for how HCV might be controlled on a population level and treated on an individual level.
hepatitis C virus; HCV; GT; injection drug use; HIV; birth cohort; African-American
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.
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.
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.
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.
Young injection drug users (IDU) are at high risk for hepatitis C virus (HCV). We sought to determine whether perceiving one's injecting partner to be HCV positive was associated with decreased odds of engaging in receptive needle/syringe sharing (RNS) or ancillary equipment sharing (AES) with that partner.
We conducted a cross-sectional study from 2003 to 2007 in San Francisco (n=212 participants) to examine whether perceived partner HCV status was associated with RNS and AES within injecting partnerships (n=492 partnerships) of young (under age 30) IDU who are HCV antibody negative.
RNS and AES (in the absence of RNS) occurred in 23% and 66% of injecting partnerships in the prior month. The odds of engaging in RNS were significantly lower for relationships in which the participant reported that his/her partner was HCV positive (odds ratio [OR] 0.49; 95% confidence interval [CI] 0.25-0.95). This association was attenuated when adjusted for reusing one's own needle/syringe (adjusted OR 0.57; 95% CI 0.28-1.15). The odds of engaging in AES were lower for participants who did not know the HCV status of their partner, only among non-sexual partnerships (OR 0.47; 95% CI 0.29-0.76).
Because perceiving one's partner to be HCV positive was associated with decreased RNS, increased HCV testing and partner disclosure may be warranted. AES was common and was decreased only among non-sexual partnerships in which the HCV status of the partner was not known. This suggests that interventions to reduce AES in young IDU must be widespread.
The WHO clinical guidelines for HIV/AIDS are widely used in resource limited settings to represent the gold standard of CD4 counts for antiviral therapy initiation. The utility of the WHO-defined stage 1 and 2 clinical factors used in WHO HIV/AIDS clinical staging in predicting low CD4 cell count has not been established in Uganda. Although the WHO staging has shown low sensitivity for predicting CD4<200cells/mm3, it has not been evaluated at for CD4 cut-offs of <250cells/mm3 or <350 cells/mm3.
To validate the World Health Organisation HIV/AIDS clinical staging in predicting initiation of antiretroviral therapy in a low-resource setting and to determine the clinical predictors of low CD4 cell count in Uganda.
Data was collected on 395 participants from the Joint Clinical Research Centre, of whom 242 (61.3%) were classified as in stages 1 and 2 and 262 (68%) were females. Participants had a mean age of 36.8 years (SD 8.5). We found a significant inverse correlation between the CD4 lymphocyte count and WHO clinical stages. The sensitivity the WHO clinical staging at CD4 cell count of 250 cells/mm3 and 350cells/mm3 was 53.5% and 49.1% respectively. Angular cheilitis, papular pruritic eruptions and recurrent upper respiratory tract infections were found to be significant predictors of low CD4 cell count among participants in WHO stage 1 and 2.
The WHO HIV/AIDS clinical staging guidelines have a low sensitivity and about half of the participants in stages 1 and 2 would be eligible for ART initiation if they had been tested for CD4 count. Angular cheilitis and papular pruritic eruptions and recurrent upper respiratory tract infections may be used, in addition to the WHO staging, to improve sensitivity in the interim, as access to CD4 machines increases in Uganda.
Linkage to HIV care and survival in sub-Saharan Africa is not well documented. In 2004 we conducted a randomized trial among medical inpatients in Mulago Hospital to assess the impact of HIV counseling and testing (HCT) on linkage to care and survival. Participants were randomized to inpatient HCT (intervention) or outpatient HCT 1 week post-discharge (control); inpatient HCT was not available at Mulago during the study. Among 590 eligible patients, 85% (500) agreed to participate; 98.8% (248) in the intervention arm received HCT compared to 68.7% (171) in the control arm. Within 6 months, 62.2% (92) of surviving HIV-infected participants received HIV care; 15.0% (20) received antiretroviral medications (ARVs). Overall mortality among HIV-infected participants was 34.6% (72). HCT had significant impact on linkage to care among surviving participants. Referral for HCT was a missed opportunity for diagnosis. There is need for earlier diagnosis and linkage to HIV care among inpatients.
Provider Initiated HIV Testing and Counseling (PITC); Inpatient; Access to care; Survival; Africa
Homeless adults have an increased risk of infectious diseases due to sexual and drug-related behaviors and substandard living conditions. We investigated the prevalence and risk factors for presence of hepatitis A virus (HAV) antibodies among homeless and marginally housed adults.
We analyzed serologic and questionnaire data from a study of marginally housed and homeless adults in San Francisco during April 1999-March 2000. Sera were tested for total antibodies to HAV (anti-HAV). Data were analyzed using chi-square tests and logistic regression.
Of the 1138 adults in the study, 52% were anti-HAV-positive. The anti-HAV prevalence in this study population was 58% higher than the expected prevalence based on age-specific prevalence rates from the general population. Number of years of homelessness (≤1, 2-4, ≥5 years) was associated with anti-HAV prevalence (46%, 50%, and 61%, p<0.001). Other differences in anti-HAV prevalence (p<0.05) were ‘ever’ injected drugs (63% versus 42% for non-injectors), being foreign-born (75% versus 51% among US born), race (73%, 53% and 45% for Hispanic, White, and Black), and increasing age (38%, 49% and 62% among those aged <30, 30-49 and ≥50 years). These variables all remained significant in a multivariate model.
Overall anti-HAV prevalence was elevated in this San Francisco homeless population compared to the general US population. These data show that anti-HAV was associated with homelessness independent of other known risk factors such as being foreign-born, race, and injection drug use. This increase indicates an excess risk of HAV infection and the potential need to offer hepatitis A vaccination as part of homeless services.
hepatitis A virus; homeless
The rationale for screening populations at risk for hepatitis C virus infection (HCV) includes the possibility of altering risk behaviors that impact disease progression and transmission. This study prospectively examined young injection drug users (IDU) to determine if behaviors changed after they were made aware of HCV seroconversion.
We estimated the effects of HCV seroconversion coupled with post-test counseling on risk behaviors (alcohol use, non-injection and injection drug use, lending and sharing injecting equipment, and having sex without a condom) and depression symptoms using conditional logistic regression, fitting odds-ratios for immediately after disclosure and 6 and 12 months later, and adjusting for secular effects.
112 participants met inclusion criteria, i.e. they were documented HCV seronegative at study onset and subsequently seroconverted during the follow-up period, with infection confirmed by HCV RNA testing. HCV seroconversion was independently associated with a decreased likelihood of consuming alcohol (OR=0.51; 95% CI: 0.27 to 0.97, p=0.04) and using non-injection drugs (OR=0.40; 95% CI: 0.20 to 0.81, p=0.01) immediately after disclosure, however, results were not sustained over time. There were significant (p<0.05) declines in the use of alcohol, injection and non-injection drugs, and sharing equipment associated with time that were independent from the effect of seroconversion.
Making young IDU aware of their HCV seroconversion may have a modest effect on alcohol and non-injection drug use that is not sustained over time.
Hepatitis C virus; injection drug use; screening
Homeless adults have an increased risk of infectious diseases due to sexual and drug-related behaviors and substandard living conditions. We investigated the prevalence and risk factors for presence of hepatitis A virus (HAV) antibodies among homeless and marginally housed adults.
We analyzed serologic and questionnaire data from a study of marginally housed and homeless adults in San Francisco from April 1999 to March 2000. We tested seroprevalance for total antibodies to HAV (anti-HAV) and analyzed data using Chi-square tests and logistic regression.
Of the 1,138 adults in the study, 52% were anti-HAV positive. The anti-HAV prevalence in this study population was 58% higher than the expected prevalence based on age-specific prevalence rates from the general population. Number of years of homelessness (≤1, 2–4, and ≥5 years) was associated with anti-HAV prevalence (46%, 50%, and 61%, respectively, p<0.001). We found other differences in anti-HAV prevalence (p<0.05) for ever having injected drugs (63% vs. 42% for non-injectors), being foreign-born (75% vs. 51% among U.S.-born), race/ethnicity (72%, 53%, and 45% for Hispanic, white, and black people, respectively), and increasing age (38%, 49%, and 62% among those aged <35, 35–45, and >45 years, respectively). These variables all remained significant in a multivariate model.
We found overall anti-HAV prevalence elevated in this San Francisco homeless population compared with the general U.S. population. These data show that anti-HAV was associated with homelessness independent of other known risk factors, such as being foreign-born, race/ethnicity, and injection drug use. This increase indicates an excess risk of HAV infection and the potential need to offer hepatitis A vaccination as part of homeless services.
Hepatitis C virus (HCV) infection, clearance and reinfection are best studied in injection drug users (IDU) who have the highest incidence and are representative of most infections.
A prospective cohort of HCV negative young IDU was followed from 2000 to 2007, to identify acute and incident HCV and prospectively study infection outcomes.
Among 1,191 young IDU screened, 731 (61.4%) were HCV negative, and 520 (71.1%) were enrolled into follow-up. Cumulative HCV incidence was 26.7 per 100 person years of observation (PYO) (95% CI, 21.5, 31.6). 95 (70.4%) of 135 acute/incident HCV infections were followed; 21% cleared HCV. Women had a significantly higher incidence of viral clearance compared to men (age-adjusted relative hazard 2.91, 95% CI, 1.68, 5.03) and also showed a significantly faster rate of early HCV viremia decline. Estimated reinfection rate was 24.6 per 100 PYO (95% CI, 11.7, 51.6). Among seven individuals, multiple episodes of HCV reinfection and re-clearance were observed.
In this large sample of young IDU, females show demonstrative differences in their rates of viral clearance and kinetics of early viral decline. Recurring reinfection and re-clearance suggest possible protection against persistent infection. These results should inform HCV clinical care and vaccine development.
hepatitis C virus; HCV; injection drug use; acute HCV infection; clearance; viral load; reinfection; female
Access to free antiretroviral therapy (ART) in sub-Saharan Africa has been steadily increasing, and the success of large-scale ART programs depends on early initiation of HIV care. However, little is known about the stage at which those infected with HIV present for treatment in sub-Saharan Africa.
We conducted a cross-sectional analysis of initial visits to the Immune Suppression Syndrome Clinic of the Mbarara University Teaching Hospital, including patients who had their initial visit between February 2007 and February 2008 (N=2311).
Median age was 33 years (range 16–81). 64% were female. Over one-third (40%) were categorized as late presenters, that is World Health Organization disease stage 3 or 4. Male gender, age 46 to 60 (versus younger), lower education level, being unemployed, living in a household with others, being unmarried, and lack of spousal HIV status disclosure were independently associated with late presentation, while being pregnant, having young children, and consuming alcohol in the prior year were associated with early presentation.
Targeted public health interventions to facilitate earlier entry into HIV care are needed, as well as additional study to determine whether late presentation is due to delays in testing versus delays in accessing care.
Antiretroviral therapy; access; sub-Saharan Africa; late presentation
Heavy alcohol use is commonplace among HIV-infected individuals; however, the extent that alcohol use adversely impacts HIV disease progression has not been fully elucidated. Fairly strong evidence suggests that heavy alcohol consumption results in behavioral and biological processes that likely increase HIV disease progression, and experimental evidence of the biological effect of heavy alcohol on simian immunodeficiency virus in macaques is quite suggestive. However, several observational studies of the effect of heavy alcohol consumption on HIV progression conducted in the 1990s found no association of heavy alcohol consumption with time to AIDS diagnosis, while some more recent studies showed associations of heavy alcohol consumption with declines of CD4 cell counts and nonsuppression of HIV viral load. We discuss several plausible biological and behavioral mechanisms by which alcohol may cause HIV disease progression, evidence from prospective observational human studies, and suggest future research to further illuminate this important issue.
Alcohol; HIV disease progression; CD4; HIV viral load; Adherence; Prospective studies; Nutrition; Immune activation; Bacterial translocation
Alcohol affects the transmission and treatment of HIV, yet may be under-reported in resource-limited settings. We compared self-reported alcohol consumption with levels of plasma carbohydrate-deficient transferrin (%CDT), a biomarker of heavy alcohol consumption, in persons initiating antiretroviral therapy in Uganda. Almost seven percent (6.7%) of persons reporting abstaining and 10% reporting consuming 1–40 drinks in the prior month tested positive for %CDT, and actual under-report may be higher due to low sensitivity of %CDT. These results suggest likely under-report in those reporting abstaining and current drinking. Improved identification of heavy alcohol consumption is needed for research and clinical purposes.
Carbohydrate-deficient transferrin; Biological markers; Alcohol drinking; HIV; Antiretroviral therapy; Uganda
Hepatitis C virus (HCV) causes significant morbidity and mortality in injecting drug users (IDU) worldwide. HCV vaccine candidates have shown promise for reducing the infectivity of acute infection and averting chronic infection, yet the impact of varying levels of vaccine efficacy and vaccine delivery strategies on the HCV epidemic in IDU have not been explored.
We utilized extensive data on injecting behavior collected in the UFO Study of young IDU in San Francisco to construct a stochastic individual-based model that reflects heterogeneous injecting risk behavior, historical HCV trends, and existing information on viral dynamics and vaccine characteristics.
Our modeled HCV rate closely paralleled observed HCV incidence in San Francisco, with estimated incidence of 59% per person year (ppy) early in the epidemic, and 27% ppy after risk reduction was introduced. Chronic HCV infection, the clinically relevant state of HCV infection that leads to liver disease and hepatocellular cancer, was estimated at 22% ppy (±3%) early in the epidemic and 14% ppy (±2%) after risk reduction was introduced. We considered several scenarios, and highlight that a vaccine with 50% to 80% efficacy targeted to high-risk or sero-negative IDU at a high vaccination rate could further reduce chronic HCV incidence in IDU to 2–7% ppy 30 years after its introduction.
Our results underscore the importance of further efforts to develop both HCV vaccines and optimal systems of delivery to IDU populations.
Hepatitis C virus; injecting drug users; dynamic modeling; hepatitis C virus vaccine