Baseline self-perceived risk of HIV infection independently predicts the rate of HIV seroconversion in a prospective cohort of injection drug users

BACKGROUND: The identification of individuals at the highest risk of human immunodeficiency virus (HIV) infection is critical for targeting prevention strategies. We evaluated self-perceived risk of HIV infection and rates of subsequent HIV seroconversion among a prospective cohort study of injection drug users (IDUs). METHODS: We performed an analysis of the time to HIV infection among 994 baseline HIV negative IDUs enrolled in the Vancouver injection drug users study (VIDUS). IDUs were stratified based on their baseline self-perceived risk of HIV seroconversion (higher than others vs same or lower). Kaplan-Meier methods were used to estimate cumulative HIV incidence rates and Cox regression was used to determine adjusted relative hazards for HIV seroconversion. RESULTS: At the end of 24 months after enrolment into the cohort, the cumulative HIV incidence rate was significantly elevated among the 5.9% of the sample who perceived their risk for HIV infection to be higher at baseline (26.6% vs 7.8% log-rank P < 0.001). In a Cox model that adjusted for all variables that were associated with the time to HIV infection in univariate analyses, a higher baseline self-perceived risk of acquiring HIV infection (relative hazard RH: 2.48 [95% Confidence interval (CI): 1.51, 4.10]; P = 0.004) remained independently associated with time to HIV seroconversion. CONCLUSIONS: IDUs' perception of their risk for HIV seroconversion upon enrolment into a prospective cohort study was strongly and independently associated with the subsequent rate of HIV seroconversion. Since this risk marker remained independently associated with HIV seroconversion, even after adjustment for time-updated risk behaviours, our findings have major implications that may aid outreach workers in their efforts to identify IDUs who should be targeted with prevention efforts.     

Major decline of hepatitis C virus incidence rate over two decades in a cohort of drug users

Injecting drug users (DU) are at high risk for hepatitis C virus (HCV) and HIV infections. To examine the prevalence and incidence of these infections over a 20-year period (1985–2005), the authors evaluated 1276 DU from the Amsterdam Cohort Studies who had been tested prospectively for HIV infection and retrospectively for HCV infection. To compare HCV and HIV incidences, a smooth trend was assumed for both curves over calendar time. Risk factors for HCV seroconversion were determined using Poisson regression. Among ever-injecting DU, the prevalence of HCV antibodies was 84.5% at study entry, and 30.9% were co-infected with HIV. Their yearly HCV incidence dropped from 27.5/100 person years (PY) in the 1980s to 2/100 PY in recent years. In multivariate analyses, ever-injecting DU who currently injected and borrowed needles were at increased risk of HCV seroconversion (incidence rate ratio 29.9, 95% CI 12.6, 70.9) compared to ever-injecting DU who did not currently inject. The risk of HCV seroconversion decreased over calendar time. The HCV incidence in ever-injecting DU was on average 4.4 times the HIV incidence, a pattern seen over the entire study period. The simultaneous decline of both HCV and HIV incidence probably results from reduced risk behavior at the population level. Charlotte H.S.B. van den Berg and ColetteSmit contributed equally to this paper     

A parametric survival model with an interval-censored covariate

We present a parametric survival model whose particularity consists in the inclusion of an interval-censored covariate. The methodology is motivated by a study on injecting drug users in Badalona (Spain), most of whom suffered HIV infection as a result of their drug addiction. The study aims to examine the possible association between the elapsed time from first injecting drug use until HIV infection and the subsequent AIDS incubation period. Whereas the moment of HIV infection cannot be observed exactly and is therefore interval-censored, time until AIDS onset is doubly-censored. For the maximization of the resulting likelihood function, we use a numerical solver. Maximization is carried out by means of the mathematical programming language AMPL.     

Effects of different parametric estimates of seroconversion time on analysis of progression to AIDS among Italian HIV-positive haemophiliacs.

The purpose of this study was to estimate seroconversion time using different parametric methods and to assess their influence on the estimation of the incubation time between HIV infection and onset of AIDS. Study subjects were 712 HIV-positive haemophiliacs enrolled in the Italian National Registry of patients with congenital coagulation disorders. Seroconversion time was estimated using the mid-point of each seroconversion interval (MID), the median of each interval under an estimated uniform distribution with cutpoints at December 1981 and December 1985 (MUU), the median of each interval under an estimated Weibull distribution (MUW), and the median of three random values drawn from each interval under the Weibull distribution (RUW). Kaplan-Meier survival analysis showed that the cumulative incidence of AIDS over a 7-year period was 11.6 per cent (SE 1.3 per cent) when using the MID estimate of seroconversion time, 10.8 per cent (1.2 per cent) with the MUU estimate, and 13.4 per cent (1.3 per cent) and 12.3 per cent (1.3 per cent) when using MUW and RUW estimates, respectively. This study demonstrates that the estimate of seroconversion time does not seem to be a major factor affecting estimates of AIDS incidence since the different techniques for estimating HIV seroconversion time yielded very similar results.     

The relationship between HIV seroconversion illness, HIV test interval and time to AIDS in a seroconverter cohort

Seroconversion illness is known to be associated with more rapid HIV disease progression. However, symptoms are often subjective and prone to recall bias. We describe symptoms reported as seroconversion illness and examine the relationship between illness, HIV test interval (time between antibody-negative and anibody-positive test dates) and the effect of both on time to AIDS from seroconversion. We used a Cox model, adjusting for age, sex, exposure group and year of estimated seroconversion. Of 1820 individuals, information on seroconversion illness was available for 1244 of whom 423 (34%) reported symptomatic seroconversion. Persons with a short test interval (< or = 2 months) were significantly more likely to report an illness than people with a longer interval (OR 6.76, 95% CI 4.75-9.62). Time to AIDS was significantly faster (P = 0.01) in those with a short test interval. The HIV test interval is a useful replacement for information on seroconversion illness in studies of HIV disease progression.     

Hepatitis C virus infection among injection drug users: survival analysis of time to seroconversion

BACKGROUND: Time to hepatitis C virus (HCV) seroconversion in initially seronegative injection drug users has not been directly measured, and public health planning would benefit from specifying the window of opportunity for prevention of infection, and factors that affect timing of infection. METHODS: Four hundred eighty-four HCV antibody-negative injection drug users in Seattle, Washington were followed a median of 2.1 years to observe seroconversion. We examined time to HCV seroconversion in relation to subject characteristics using the Kaplan-Meier method and Cox proportional hazards regression. A weighted-average time to HCV seroconversion was calculated among new injectors (injecting < or = 2 years) using seroprevalence and seroincidence data. RESULTS: There were 134 HCV seroconversions (11.6 per 100 person-years at risk; the 25th percentile of time to seroconversion was 26.2 months). Injection with a syringe used by another injector (adjusted hazards ratio = 1.8; 95% confidence interval = 1.3-3.0) and sharing a cooker or cotton (1.8; 1.0-3.1) were associated with time to HCV seroconversion. Using the estimate of the mean time to seroconversion from first injection in new injectors who were HCV antibody-negative at enrollment (5.4 years), and the midpoint between first injection and study enrollment in new injectors who were HCV antibody-positive at enrollment (0.6 years), the weighted-average time to seroconversion after beginning to inject was estimated to be 3.4 years. CONCLUSION: The period of susceptibility to HCV infection in the majority of drug injectors appears to be long enough to justify the allocation of substantial resources toward interventions to reduce injection-related risk behavior in these individuals.     

Analysis of interval-censored data from circular migrant and non-migrant sexual partnerships using the EM algorithm

In epidemiological studies where subjects are seen periodically on follow-up visits, interval-censored data occur naturally. The exact time the change of state (such as HIV seroconversion) occurs is not known exactly, only that it occurred sometime within a specific time interval. Methods of estimation for interval-censored data are readily available when data are independent. However, methods for correlated interval-censored data are not well developed. This paper considers an approach for estimating the parameters when data are interval-censored and correlated within sexual partnerships. We consider the exact event times for interval-censored observations as unobserved data, only known to be between two time points. Dependency induced by sexual partnerships is modelled as frailties assuming a gamma distribution for frailties and an exponential distribution on the time to infection. This formulation facilitates application of the expectation-maximization (EM) algorithm. Maximization process maximizes the standard survival frailty model. Results show high degree of heterogeneity between sexual partnerships. Intervention strategies aimed at combating the spread of HIV and other sexually transmitted infections (STI)s should treat sexual partnerships as social units and fully incorporate the effects of migration in their strategies.     

Methods for estimating the AIDS incubation time distribution when date of seroconversion is censored

In most cohort studies on HIV infection and AIDS, data on time from seroconversion to AIDS or death are doubly censored, both at the time origin and at the endpoint of interest. In epidemiological research, the most frequently adopted approach is to restrict the analysis to persons with narrow seroconversion intervals and to impute the midpoint of this interval as date of seroconversion. For many cohort studies, the consequence is that a substantial proportion of the data is not used. We consider four methods that are expected to be less biased when all cohort data are used: two imputation methods, conditional mean and multiple imputation, and two likelihood maximization methods. We derive the likelihood structure of the cohort data and clarify its dependence on study design. All methods are applied to data from the Amsterdam cohort study among injection drug users. In a simulation study the data generation process of this cohort study is imitated. The performance of midpoint, conditional mean and multiple imputation are compared. With midpoint imputation, both an analysis using the full data set, as well as one restricted to the cases with small seroconversion intervals, is performed. Conditional mean imputation comes out as the preferred method. It gives best results with respect to mean squared error. Moreover, when confidence intervals are computed through standard methods that ignore the uncertainty in the imputed date of seroconversion, coverage probabilities are almost correct.     

Immunologic markers of progression to acquired immunodeficiency syndrome are time-dependent and illness-specific.

Since prevalent cohorts may be biased by the duration of human immunodeficiency virus (HIV) infection (onset bias), it is useful to assess the potential predictive value of markers in incident cohorts of HIV-positive subjects for whom the date of seroconversion is known or can reliably be estimated. Of 131 homosexual men with HIV-1 seroconversion from New York City and Washington, DC, who were evaluated annually beginning in 1982, 60 developed acquired immunodeficiency syndrome (AIDS) by the end of 1989. The prognostic significance of immunologic markers (proportion of CD4+ T-lymphocytes, neopterin, beta 2-microglobulin, serum interferon, and anti-p24 antibody) and of a virologic marker (HIV p24 antigen) was determined using measurements made at defined time intervals after the known or estimated date of HIV seroconversion. When measurements made 3 years after seroconversion were used, all markers except anti-p24 antibody were found to be significant estimators of AIDS risk in univariate analyses. In multivariate Cox regression modeling, the maximum information was obtained by including neopterin, interferon, and the CD4+ T-lymphocyte proportion. The predictive value of markers after HIV seroconversion could change considerably from one interval to another. Elevated levels of beta 2-microglobulin and neopterin significantly predicted the development of Kaposi's sarcoma. These two markers were highly correlated (r = 0.74). The authors conclude that immunologic markers can be important for an HIV staging system for estimating prognosis and facilitating early therapeutic intervention in HIV-positive patients.     

Estimating effectiveness in HIV prevention trials with a Bayesian hierarchical compound Poisson frailty model

Inconsistent results in recent HIV prevention trials of pre‐exposure prophylactic interventions may be due to heterogeneity in risk among study participants. Intervention effectiveness is most commonly estimated with the Cox model, which compares event times between populations. When heterogeneity is present, this population‐level measure underestimates intervention effectiveness for individuals who are at risk. We propose a likelihood‐based Bayesian hierarchical model that estimates the individual‐level effectiveness of candidate interventions by accounting for heterogeneity in risk with a compound Poisson‐distributed frailty term. This model reflects the mechanisms of HIV risk and allows that some participants are not exposed to HIV and, therefore, have no risk of seroconversion during the study. We assess model performance via simulation and apply the model to data from an HIV prevention trial. Copyright © 2016 John Wiley & Sons, Ltd.     

Trends in human immunodeficiency virus incidence and risk behavior among injection drug users in montreal, Canada: a 16-year longitudinal study

The authors sought to investigate trends in the incidence of human immunodeficiency virus (HIV) infection, evaluate changes in risk behavior, and assess associations between syringe access programs and HIV seroconversion among injection drug users (IDUs) in Montreal, Canada, who were recruited and followed for a prospective cohort study between 1992 and 2008. Methods included Kaplan-Meier survival analysis and time-varying Cox regression models. Of 2,137 HIV-seronegative IDUs at enrollment, 148 became HIV-positive within 4 years (incidence: 3.3 cases/100 person-years; 95% confidence interval: 2.8, 3.9). An annual HIV incidence decline of 0.06 cases/100 person-years prior to 2000 was followed by a more rapid annual decline of 0.24 cases/100 person-years during and after 2000. Behavioral trends included increasing cocaine and heroin use and decreasing proportions of IDUs reporting any syringe-sharing or sharing a syringe with an HIV-positive person. In multivariate analyses, HIV seroconversion was associated with male gender, unstable housing, intravenous cocaine use, and sharing syringes or having sex with an HIV-positive partner. Always acquiring syringes from safe sources conferred a reduced risk of HIV acquisition among participants recruited after 2004, but this association was not statistically significant for participants recruited earlier. In conclusion, HIV incidence has declined in this cohort, with an acceleration of the reduction in HIV transmission after 2000.     

Use of Sentinel Surveillance and Geographic Information Systems to Monitor Trends in HIV Prevalence,Incidence, and Related Risk Behavior among Women Undergoing Syphilis Screening in a Jail Setting

Innovative methods are needed to systematically track the HIV epidemic and appropriately target prevention and care programs in vulnerable populations of women. We conducted sentinel surveillance among women entering the jail system of San Francisco from 1999 to 2001 to track trends in HIV incidence, HIV prevalence, and related risk behavior. Using geographic information software (GIS), we triangulated findings to examine the spatial distribution of risk and disease. A total of 1,577 female arrestees voluntarily screened for sexually transmitted diseases at intake were included. HIV incidence, estimated using the serologic testing algorithm for recent HIV seroconversion (STARHS), was 0.4% per year (95% confidence interval [95%CI] = 0.1–2.1). HIV prevalence was 1.8% (95%CI = 1.1–2.4). HIV infection was independently associated with age 30 to 39 years compared to all other ages, African-American race/ethnicity vs. non-African-American, and recent injection drug use. Maps showed that the communities in which arrested women reside are also those with the highest concentrations of newly detected female HIV cases, AIDS cases, and clients of substance use programs. The combined strategy of using sentinel surveillance in the jail setting and GIS to map the spatial distribution of disease provides a useful tool to identify patterns of risk in hard-to-reach, vulnerable populations of women.     

Risk of AIDS in HIV seroconverters: A comparison between intravenous drug users and homosexual males

A multicentre cohort study was conducted in Italy to estimate the risk of developing AIDS in 261 intravenous drug users and 89 homosexual males for whom the seroconversion period was known.Four years after HIV seroconversion, AIDS incidence, estimated by Kaplan-Meier survival technique, was 13.8% for intravenous drug users and 16.2% for homosexual males; the difference was not statistically significant.These findings suggest that four years after seroconversion the risk of developing AIDS in HIV seropositive intravenous drug users is no higher than that of subjects who acquired HIV infection through sexual contact.Corresponding author.     

AIDS risk reduction and reduced HIV seroconversion among injection drug users in Bangkok.

Human immunodeficiency virus (HIV) seroconversion was studied in a group of 173 injection drug users in Bangkok, Thailand, who had been previously tested for HIV and were interviewed and retested in the fall of 1989. Ten percent of the group had seroconverted. Two factors protected against HIV seroconversion: having stopped sharing injection equipment in response to the acquired immunodeficiency syndrome (AIDS) and having a regular sexual partner. The association between self-reported deliberate risk reduction and reduced HIV seroconversion among persons continuing to inject illicit drugs indicates that injection drug users can change their behavior in response to AIDS and will accurately report on the behavior change, and that the changes can protect against HIV infection.     

Risk behaviours and seroprevalence to HIV, HBV and HCV in patients of the AIDS information and prevention center in Valencia, Spain

OBJECTIVE: The purpose of this study was to describe the sociodemographic and serologic profiles in a first time consultant population at the Information and AIDS Prevention Center of Valencia (Spain). In addition, the HIV infection risk factors were analyzed. METHOD: A cross-sectional study was performed on 1,573 persons who consulted during the year 1995. Sociodemographic and infection risk practices data were recorded and serologic information about HIV, HBV and HCV infection were obtained. Exact binomial method with a 95% interval confidence was used to calculate infection prevalence and the chi square test to make comparisons between qualitative variables. RESULTS: Sex distribution was 66,1% males and 31,9% females; mean age was 29,01 (SD: 9.2) years. Sexual intercourse without condom (25.2%) and parenteral drug abusers (22.6%) were the more frequent risk groups seeking consultation about HIV infection. Global HIV infection prevalence was 12.7% (95% CI= 11,2-14,5%). Among HIV seropositive patients, sexual transmission accounted for 30.8% of cases, of which 69.4% were heterosexual relations. The HIV infection prevalence for different risk groups were the following: parenteral drug abusers 36.8% (95% CI= 31,7-42%), heterosexual intercourse with an HIV-infected partner 24.1% (95% CI= 17,1-32,2%) and homosexual intercourse between men 9,5% (95% CI= 5,8-14,5%). HCV antibody prevalence for parenteral drug abusers was 81.2% (95% CI= 76,7-85,1%). Risk practices with a statistically significant association with HIV infection were: being an injecting drug abuser, as well as having an HIV infected and/or a injecting drug abuser partner. CONCLUSIONS: Drug parenteral abusers are still the target population for prevention programs. Data suggest that prevention and sexual education programs must continue. The main effort should be focused on the young population and on sexual partners of injecting drug abusers and/or HIV seropositive partners.     

Risk of hepatitis C virus infection among young adult injection drug users who share injection equipment

Designing studies to examine hepatitis C virus (HCV) transmission via the shared use of drug injection paraphernalia other than syringes is difficult because of saturation levels of HCV infection in most samples of injection drug users (IDUs). The authors measured the incidence of HCV infection in a large cohort of young IDUs from Chicago, Illinois, and determined the risk of HCV seroconversion associated with specific forms of sharing injection paraphernalia. From 1997 to 1999, serum samples obtained from 702 IDUs aged 18-30 years were screened for HCV antibodies; prevalence was 27%. Seronegative participants were tested for HCV antibodies at baseline, at 6 months, and at 12 months. During 290 person-years of follow-up, 29 participants seroconverted (incidence: 10.0/100 person-years). The adjusted relative hazard of seroconversion, controlling for demographic and drug-use covariates, was highest for sharing "cookers" (relative hazard = 4.1, 95% confidence interval: 1.4, 11.8), followed by sharing cotton filters (relative hazard = 2.4, 95% confidence interval: 1.1, 5.0). Risks associated with syringe-sharing and sharing of rinse water were elevated but not significant. After adjustment for syringe-sharing, sharing cookers remained the strongest predictor of seroconversion (relative hazard = 3.5, 95% confidence interval: 1.3, 9.9). The authors conclude that sharing of injection equipment other than syringes may be an important cause of HCV transmission between IDUs.     

New evidence on intravenous cocaine use and the risk of infection with human immunodeficiency virus type 1.

To examine whether recent intravenous use of cocaine might be associated with increased risk of human immunodeficiency virus type 1 (HIV) infection, the authors studied 2,597 active intravenous drug users: 2,399 with recent cocaine injection and 198 with recent injection of heroin or other drugs but not cocaine. These subjects were adult residents of Baltimore City and the surrounding Maryland counties, recruited via outreach into the community between February 1988 and March 1989. In contrast to the first report on the cocaine-HIV association, the present study sample was not recruited solely from drug treatment programs. In the present study, estimated HIV seroprevalence was 26.4% for recent cocaine injectors as compared with 10.6% among all other recent intravenous drug users; the relative odds estimate was 3.03. In the untreated segment of the sample, HIV seroprevalence was 26.0% for recent cocaine injectors as compared with 8.9% among others (relative odds (RO) = 3.61). The estimated degree of association did not change appreciably when multiple logistic regression was used to hold constant potentially confounding and/or mediating variables such as receptive anal intercourse, number of sex partners, and use of injection equipment obtained at shooting galleries (RO = 2.64). Augmenting these cross-sectional data, preliminary prospective data showed excess risk of HIV seroconversion among recent cocaine injectors (estimated relative risk = 2.11). While other research has examined the cocaine-HIV association, the present study differs in that it has allowed a test for whether the association was a spurious artifact of studying drug users recruited solely from drug treatment programs, a broad array of alternative determinants of HIV infection have been held constant, and the association has been examined with seroconversion data. The results lend support to the abiding concern about the risk of HIV infection among cocaine users.     

Inference for a linear regression model with an interval-censored covariate

Interval-censored observations of a response variable are a common occurrence in medical studies, and usually result when the response is the elapsed time until some event whose occurrence is periodically monitored. In this paper we consider a multivariate regression setting in which the explanatory variable is interval censored. Use of an ad hoc method of analysis for such data, such as taking the midpoint of the interval-censored covariate and applying ordinary least-squares, is not in general valid. We develop a likelihood approach, together with a two-step conditional algorithm, to jointly estimate the regression coefficients as well as the marginal distribution of the covariate. The resulting estimators are asymptotically normal. The performance of the method is assessed via simulations, and illustrated using data from a recent HIV/AIDS clinical trial to assess the association between waiting time between indinavir failure and subsequent viral load at enrolment. Extensions of the procedure to other parametric distributions are discussed.     

Seroconversion to HBV associated with seroconversion to HIV in a cohort of intravenous drug misusers in Turin,Italy

Between March 1986 and March 1994, the seroconversion to HBV associated to the seroconversion to HIV was investigated in 120 HIV seroconverters drawn from 2368 i.v. drug misusers screened for HIV, HBV and STDs. Among the 185 individuals susceptible to HIV and HBV at intake (41/120 HIV seroconverters and 144/364 HIV-negative controls), HBV seroconversion was associated with the seroconversion to HIV (p=0.006) and history of more than 3 sexual pratners per year (p=0.000). Only the history of more than 3 partners per year remained associated with the HBV seroconversion in the conditional regression. The associated seroconversion to HIV and HBV was linked to the short period of i.v. drug injections (p=0.032), history of more than 3 partners per year (p=0.000) and more than 3 i.v. drug injections per day (p=0.016). Compared to the seroconverters to HBV alone, the seroconverters to HBV and HIV were likely to have higher frequency of i.v. drug injection per day on univariate (p=0.031) and multivariate analysis (p=0.024). The seroconverters to both the viruses differed from the seroconverters to HIV alone in the year of drug debut (p=0.045), short period of i.v. drug use (p=0.048) and high frequence of injection per day (p=0.008). The multivariate analysis confirmed only the association with high frequency of injection per day (p=0.033). Higher risk of HIV seroconversion from the debut of i.v. drug use was observed in the subjects with concurrent HBV seroconversion (Log-Rank test:p=0.0008).Abbreviations ALT alanine aminotransferase - CI 95% confidence interval - HBcAb antibody to hepatitis B core antigen - HBsAg hepatitis B surface antigen - HBV Hepatitis B virus - HIV Human immunodeficiency virus - HR hazard ratio - OR Odds ratio - SD standard deviation - STDs sexually transmitted diseases     

Inference for cumulative incidence functions with informatively coarsened discrete event-time data

We consider the problem of comparing cumulative incidence functions of non-mortality events in the presence of informative coarsening and the competing risk of death. We extend frequentist-based hypothesis tests previously developed for non-informative coarsening and propose a novel Bayesian method based on comparing a posterior parameter transformation with its expected distribution under the null hypothesis of equal cumulative incidence functions. Both methods use estimates derived by extending previously published estimation procedures to accommodate censoring by death. The data structure and analysis goal are exemplified by the AIDS Link to the Intravenous Experience (ALIVE) study, where researchers are interested in comparing incidence of human immunodeficiency virus seroconversion by risk behavior categories. Coarsening in the forms of interval and right censoring and censoring by death in ALIVE is thought to be informative; thus, we perform a sensitivity analysis by incorporating elicited expert information about the relationship between seroconversion and censoring into the model.