Faculty Bibliography

Human immunodeficiency virus type 1 (HIV-1) was discovered in the early 1980s when the virus had already established a pandemic. For at least three decades the epidemic in the Western World has been dominated by subtype B infections, as part of a sub-epidemic that traveled from Africa through Haiti to United States. However, the pattern of the subsequent spread still remains poorly understood. Here we analyze a large dataset of globally representative HIV-1 subtype B strains to map their spread around the world over the last 50years and describe significant spread patterns. We show that subtype B travelled from North America to Western Europe in different occasions, while Central/Eastern Europe remained isolated for the most part of the early epidemic. Looking with more detail in European countries we see that the United Kingdom, France and Switzerland exchanged viral isolates with non-European countries than with European ones. The observed pattern is likely to mirror geopolitical landmarks in the post-World War II era, namely the rise and the fall of the Iron Curtain and the European colonialism. In conclusion, HIV-1 spread through specific migration routes which are consistent with geopolitical factors that affected human activities during the last 50years, such as migration, tourism and trade. Our findings support the argument that epidemic control policies should be global and incorporate political and socioeconomic factors.

AIMS/OBJECTIVE:To test, among US students: (1) whether perceived harmfulness of marijuana has changed over time, (2) whether perceived harmfulness of marijuana changed post-passage of state medical marijuana laws (MML) compared with pre-passage; and (3) whether perceived harmfulness of marijuana statistically mediates and/or modifies the relation between MML and marijuana use as a function of grade level. DESIGN/METHODS:Cross-sectional nationally representative surveys of US students, conducted annually, 1991-2014, in the Monitoring the Future study. SETTING/METHODS:Surveys conducted in schools in all coterminous states; 21 states passed MML between 1996 and 2014. PARTICIPANTS/METHODS:The sample included 1 134 734 adolescents in 8th, 10th and 12th grades. MEASUREMENTS/METHODS:State passage of MML; perceived harmfulness of marijuana use (perceiving great or moderate risk to health from smoking marijuana occasionally versus slight or no risk); and marijuana use (prior 30 days). Data were analyzed using time-varying multi-level regression modeling. FINDINGS/RESULTS:The perceived harmfulness of marijuana has decreased significantly since 1991 (from an estimated 84.0% in 1991 to 53.8% in 2014, P < 0.01) and, across time, perceived harmfulness was lower in states that passed MML [odds ratio (OR) = 0.86, 95% confidence interval (CI) = 0.75-0.97]. In states with MML, perceived harmfulness of marijuana increased among 8th graders after MML passage (OR = 1.21, 95% CI = 1.08-1.36), while marijuana use decreased (OR = 0.81, 95% CI = 0.72-0.92). Results were null for other grades, and for all grades combined. Increases in perceived harmfulness among 8th graders after MML passage was associated with ~33% of the decrease in use. When adolescents were stratified by perceived harmfulness, use in 8th graders decreased to a greater extent among those who perceived marijuana as harmful. CONCLUSIONS:While perceived harmfulness of marijuana use appears to be decreasing nationally among adolescents in the United States, the passage of medical marijuana laws (MML) is associated with increases in perceived harmfulness among young adolescents and marijuana use has decreased among those who perceive marijuana to be harmful after passage of MML.

OBJECTIVE:Although our understanding of viral transmission among people who inject drugs (PWID) has improved, we still know little about when and how many times each injector transmits HIV throughout the duration of infection. We describe HIV dynamics in PWID to evaluate which preventive strategies can be efficient. DESIGN:Due to the notably scarce interventions, HIV-1 spread explosively in Russia and Ukraine in 1990s. By studying this epidemic between 1995 and 2005, we characterized naturally occurring transmission dynamics of HIV among PWID. METHOD:We combined publicly available HIV pol and env sequences with prevalence estimates from Russia and Ukraine under an evolutionary epidemiology framework to characterize HIV transmissibility between PWID. We then constructed compartmental models to simulate HIV spread among PWID. RESULTS:In the absence of interventions, each injector transmits on average to 10 others. Half of the transmissions take place within 1 month after primary infection, suggesting that the epidemic will expand even after blocking all the post-first month transmissions. Primary prevention can realistically target the first month of infection, and we show that it is very efficient to control the spread of HIV-1 in PWID. Treating acutely infected on top of primary prevention is notably effective. CONCLUSION:As a large proportion of transmissions among PWID occur within 1 month after infection, reducing and delaying transmissions through scale-up of harm reduction programmes should always form the backbone of HIV control strategies in PWID. Growing PWID populations in the developing world, where primary prevention is scarce, constitutes a public health time bomb.

BACKGROUND:Young Black men who have sex with men (YBMSM) are at highest risk for HIV seroconversion in the United States. Successful movement through the HIV care continuum is an important intervention for limiting onwards HIV transmission. OBJECTIVE:Little data exists on how substances most commonly used by YBMSM, such as marijuana, are related to the HIV continuum, which represents the primary aim of this study. METHODS:A cohort of YBMSM (n = 618) was generated through respondent-driven sampling. Frequency of marijuana use and marijuana use as a sex-drug were assessed across the HIV care continuum using weighted logistic regression models. RESULTS:Study participants reported more intermittent marijuana use (n = 254, 56.2%) compared to heavy use (n = 198, 43.8%). Our sample contained 212 (34.3%) HIV seropositive participants of which 52 (24.5%) were unaware of their HIV positive status. Study participants who were heavy marijuana users were more likely to be unaware of their HIV seropositive status (AOR: 4.18; 95% CI 1.26, 13.89). All other stages in the care continuum demonstrated no significant differences between those who use marijuana intermittently or heavily or as a sex-drug and nonusers. CONCLUSIONS:YBMSM who used marijuana heavily were more likely to be HIV-positive unaware than those who never used marijuana. Findings were inconclusive regarding the relationships between marijuana use and other HIV care continuum metrics. However, knowledge of ones' HIV status is a critical requirement for engaging in care and may have implications for onwards HIV transmission.

AIMS/OBJECTIVE:To estimate the influence of non-medical use of prescription opioids (NMUPO) on heroin initiation among US veterans receiving medical care. DESIGN/METHODS:Using a multivariable Cox regression model, we analyzed data from a prospective, multi-site, observational study of HIV-infected and an age/race/site-matched control group of HIV-uninfected veterans in care in the United States. Approximately annual behavioral assessments were conducted and contained self-reported measures of NMUPO and heroin use. SETTING/METHODS:Veterans Health Administration (VHA) infectious disease and primary care clinics in Atlanta, Baltimore, New York, Houston, Los Angeles, Pittsburgh and Washington, DC. PARTICIPANTS/METHODS:A total of 3396 HIV-infected and uninfected patients enrolled into the Veterans Aging Cohort Study who reported no life-time NMUPO or heroin use, had no opioid use disorder diagnoses at baseline and who were followed between 2002 and 2012. MEASUREMENTS/METHODS:The primary outcome measure was self-reported incident heroin use and the primary exposure of interest was new-onset NMUPO. Our final model was adjusted for socio-demographics, pain interference, prior diagnoses of post-traumatic stress disorder and/or depression and self-reported other substance use. FINDINGS/RESULTS:Using a multivariable Cox regression model, we found that non-medical use of prescription opioids NMUPO was associated positively and independently with heroin initiation [adjusted hazard ratio (AHR) = 5.43, 95% confidence interval (CI) = 4.01, 7.35]. CONCLUSIONS:New-onset non-medical use of prescription opioids (NMUPO) is a strong risk factor for heroin initiation among HIV-infected and uninfected veterans in the United States who reported no previous history of NMUPO or illicit opioid use.

With the increasing legalization of cannabis, understanding the consequences of cannabis use is particularly timely. We examined the association between cannabis use and dependence, prospectively assessed between ages 18-38, and economic and social problems at age 38. We studied participants in the Dunedin Longitudinal Study, a cohort (n=1,037) followed from birth to age 38. Study members with regular cannabis use and persistent dependence experienced downward socioeconomic mobility, more financial difficulties, workplace problems, and relationship conflict in early midlife. Cannabis dependence was not linked to traffic-related convictions. Associations were not explained by socioeconomic adversity, childhood psychopathology, achievement orientation, or family structure; cannabis-related criminal convictions; early onset of cannabis dependence; or comorbid substance dependence. Cannabis dependence was associated with more financial difficulties than alcohol dependence; no difference was found in risks for other economic or social problems. Cannabis dependence is not associated with fewer harmful economic and social problems than alcohol dependence.

OBJECTIVES:To assess the association between medical marijuana laws (MMLs) and the odds of a positive opioid test, an indicator for prior use. METHODS:We analyzed 1999-2013 Fatality Analysis Reporting System (FARS) data from 18 states that tested for alcohol and other drugs in at least 80% of drivers who died within 1 hour of crashing (n = 68 394). Within-state and between-state comparisons assessed opioid positivity among drivers crashing in states with an operational MML (i.e., allowances for home cultivation or active dispensaries) versus drivers crashing in states before a future MML was operational. RESULTS:State-specific estimates indicated a reduction in opioid positivity for most states after implementation of an operational MML, although none of these estimates were significant. When we combined states, we observed no significant overall association (odds ratio [OR] = 0.79; 95% confidence interval [CI] = 0.61, 1.03). However, age-stratified analyses indicated a significant reduction in opioid positivity for drivers aged 21 to 40 years (OR = 0.50; 95% CI = 0.37, 0.67; interaction P < .001). CONCLUSIONS:Operational MMLs are associated with reductions in opioid positivity among 21- to 40-year-old fatally injured drivers and may reduce opioid use and overdose.

OBJECTIVE:Estimates for the contribution of transmission arising from acute HIV infections (AHIs) to overall HIV incidence vary significantly. Furthermore, little is known about AHI-attributable transmission among people who inject drugs (PWID), including the extent to which interventions targeting chronic infections (e.g. HAART as prevention) are limited by AHI transmission. Thus, we estimated the proportion of transmission events attributable to AHI within the mature HIV epidemic among PWID in New York City (NYC). DESIGN:Modeling study. METHODS:We constructed an interactive sexual and injecting transmission network using an agent-based model simulating the HIV epidemic in NYC between 1996 and 2012. Using stochastic microsimulations, we cataloged transmission from PWID based on the disease stage of index agents to determine the proportion of infections transmitted during AHI (in primary analyses, assumed to last 3 months). RESULTS:Our calibrated model approximated the epidemiological features of the mature HIV epidemic in NYC between 1996 and 2012. Annual HIV incidence among PWID dropped from approximately 1.8% in 1996 to 0.7% in 2012. Over the 16-year period, AHI accounted for 4.9% (10th/90th percentile: 0.1-12.3%) of incident HIV cases among PWID. The annualized contribution of AHI increased over this period from 3.6% in 1996 to 5.9% in 2012. CONCLUSION:Our results suggest that, in mature epidemics such as NYC, between 3% and 6% of transmission events are attributable to AHI among PWID. Current HIV treatment as prevention strategies are unlikely to be substantially affected by AHI-attributable transmission among PWID populations in mature epidemic settings.