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High-intensity cannabis use associated with lower plasma HIV-1 RNA viral load among recently-infected… Milloy, M-J; Marshall, Brandon David Lewis; Kerr, Thomas; Richardson, Lindsey; Hogg, Robert S.; Guillemi, Silvia; Montaner, Julio; Wood, Evan Mar 31, 2015

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High-intensity cannabis use associated with lower plasma HIV-1 RNA viral load among recently-infected people who use injection drugsM-J Milloy, PhD1,2 [Assistant professor], Brandon Marshall, PhD3 [Assistant professor], Thomas Kerr, PhD1,2 [Associate professor], Lindsey Richardson, DPhil1,4 [Assistant professor], Robert Hogg, PhD1,5 [Professor], Silvia Guillemi, MD1 [Physician], Julio SG Montaner, MD1,2 [Professor and Chair of AIDS Research], and Evan Wood, MD PhD1,2 [Professor]1British Columbia Centre for Excellence in HIV/AIDS, St. Paul’s Hospital, Vancouver, Canada2Division of AIDS, Department of Medicine, Faculty of Medicine, University of British Columbia, Vancouver, Canada3Department of Epidemiology, Public Health Program, Brown University, Rhode Island, USA4Department of Sociology, University of British Columbia, Vancouver, Canada5Faculty of Health Sciences, Simon Fraser University, Burnaby, CanadaAbstractIntroduction and Aims—Cannabis use is common among people who are living with HIV/AIDS. While there is growing pre-clinical evidence of the immunomodulatory and anti-viral effects of cannabinoids, their possible effects on HIV disease parameters in humans is largely unknown. Thus, we sought to investigate the possible effects of cannabis use on plasma HIV-1 RNA viral loads among recently-seroconverted illicit drug users.Design and Methods—We used data from two linked longitudinal observational cohorts of people who use injection drugs. Using multivariable linear mixed-effects modeling, we analysed the relationship between pVL and high-intensity cannabis use among participants who seroconverted following recruitment.Results—Between May, 1996 and March, 2012, 88 individuals seroconverted after recruitment and were included in these analyses. Median pVL in the first 365 days among all seroconverters was 4.66 log10 c/mL. In a multivariable model, at least daily cannabis use was associated with 0.51 log10 c/mL lower pVL (β = −0.51, Standard Error = 0.170, p-value = 0.003).Discussion—Consistent with the findings from recent in vitro and in vivo studies, including one conducted among lentiviral-infected primates, we observed a strong association between cannabis use and lower pVL following seroconversion among illicit drug-using participants.Send correspondence to: M-J Milloy, PhD, Research Scientist, Urban Health Research Initiative, British Columbia Centre for Excellence in HIV/AIDS, St. Paul’s Hospital 608–1081 Burrard Street, Vancouver, B.C., V6Z 1Y6 CANADA, Tel: (604) 682-2344 X 68473, Fax: (604) 806-8464, uhri-mjsm@cfenet.ubc.ca. HHS Public AccessAuthor manuscriptDrug Alcohol Rev. Author manuscript; available in PMC 2016 March 01.Published in final edited form as:Drug Alcohol Rev. 2015 March ; 34(2): 135–140. doi:10.1111/dar.12223.Author ManuscriptAuthor ManuscriptAuthor ManuscriptAuthor ManuscriptConclusion—Our findings support the further investigation of the immunomodulatory or anti-viral effects of cannabinoids among individuals living with HIV/AIDS.KeywordsPlasma HIV-1 RNA viral load; cannabis; cannabinoids; HIV infection; disease progressionINTRODUCTIONDespite the development of highly-active antiretroviral therapy (HAART), people who use illicit drugs continue to experience high levels of preventable HIV/AIDS-related morbidity and mortality (1). To date, studies from a wide variety of settings indicate that people who use illicit drugs (DU) have lower rates of HAART initiation (2), are less likely to achieve virological suppression (3), and experience higher rates of mortality (4).Beyond the barriers to optimal HAART access and adherence faced by people who use drugs, there are also concerns about the possibility of deleterious direct effects of specific illicit drugs on HIV disease progression (5). A number of studies have identified links between common psychoactive agents, including cannabis, heroin and cocaine, and relevant immunologic or virologic parameters (6–10). For example, morphine was found to promote, in a dose-dependent fashion, the replication of HIV-1 in a culture of human peripheral blood mononuclear cells (9). Similarly, long-term cocaine administration was associated with immune system impairment in a murine model of retroviral infection (7). However, among people living with HIV/AIDS (PLWHA) in the pre-HAART era, the evidence on the relationship between illicit drugs and HIV disease progression was contradictory and, in the HAART era, disease course is largely driven by patterns of exposure to combination antiretroviral therapy (5).High levels of cannabis use are reported by people living with HIV/AIDS, in attempts to ameliorate the side-effects of antiretroviral therapy as well as recreationally (11,12). Although many jurisdictions are reforming legal prohibitions to facilitate licit access to so-called medical marijuana, the scientific evidence base for cannabinoids is limited and their effect on HIV disease parameters such as plasma HIV-1 RNA viral load (pvL) is largely unknown. However, there is a growing body of literature from pre-clinical studies identifying immunomodulatory and anti-viral capacities of cannabinoids (13–15). Recently, Molina et al. used simian immunodeficiency virus (SIV)-infected rhesus macaques, a model system for lentiviral infection, to experimentally test the possible effects of delta-9-tetrahydrocannabinol (Δ9-THC), the primary psychoactive constituent of cannabis (16). Animals exposed to chronic administration of Δ9-THC prior to and following SIV infection exhibited lower plasma SIV-RNA viral loads and lengthened survival. In this study, we sought to replicate these findings in humans by retrospectively analyzing data from individuals newly-infected with HIV in order to investigate the possible effects of cannabis on pVL.Milloy et al. Page 2Drug Alcohol Rev. Author manuscript; available in PMC 2016 March 01.Author ManuscriptAuthor ManuscriptAuthor ManuscriptAuthor ManuscriptMETHODSData for these analyses was accessed from the Vancouver Injection Drug User Study (VIDUS) and the AIDS Care Cohort to evaluate Exposure to Survival Services (ACCESS), two linked prospective observational cohorts based in Vancouver, Canada. These studies have previously been described in greater detail elsewhere (17,18). Briefly, VIDUS is an ongoing prospective cohort of HIV-negative people who use injection drugs (IDU), while ACCESS is an ongoing prospective cohort of HIV-positive people who use illicit drugs (DU). Both studies, which operate out of the same facility, began recruitment in May, 1996 and focused on the city’s Downtown Eastside (DTES) neighbourhood, a post-industrial area with high rates of poverty, illicit drug use and HIV infection. Individuals are eligible for inclusion if they are aged ≥ 18 years and have used illicit drugs via injection (VIDUS) or any illicit drug other than cannabis (ACCESS) in the previous month and can provide written informed consent.In both studies, at the baseline and every biannual study visit thereafter, participants respond to an interviewer-administered questionnaire on illicit drug use patterns and related issues, are examined by a study nurse and provide blood for serologic analyses. All VIDUS participants are tested for HIV infection at each six-month follow-up. Baseline HIV-negative individuals who seroconvert during follow-up are transferred from the VIDUS to the ACCESS study. Both the VIDUS and ACCESS studies have been approved by the University of British Columbia/Providence Healthcare Research Ethics Board.In this study, we included all individuals who tested negative for HIV infection at the baseline VIDUS visit and then seroconverted to HIV infection as indicated by a positive and confirmed test either through the study or from a healthcare provider. We estimated the date of seroconversion as the mid-point between the date of the last negative antibody test and the first positive antibody test. We excluded individuals who did not have ≥ 1 interview in ACCESS within 365 days of the estimated date of seroconversion.Information on HIV serostatus and illicit drug use gathered through the interview and examination process is augmented by data on HIV/AIDS clinical monitoring and antiretroviral therapy (ART) held by the British Columbia Centre for Excellence in HIV/AIDS (BCCfE), as described in detail elsewhere (19). Briefly, the BCCfE has provided ART and related care free of charge to all individuals living with HIV/AIDS in British Columbia by government mandate since 1992. Through a confidential linkage to BCCfE data, a complete retrospective and prospective clinical profile, including data on all ART dispensations and the results of every plasma HIV-1 RNA viral load (pVL) tests conducted in the province of BC is available for each study participant. In this study, we excluded all individuals who did not undergo ≥ 1 pVL test within 365 of the estimated date of seroconversion. We also censored individuals from the date of the first dispensation of any antiretroviral therapy during the first 365 days following the estimated date of seroconversion.Using this analytic sample, we tested the hypothesis that high-intensity cannabis use was (i.e., ≥ daily use) associated with lower pVL independent of possible confounding factors. Milloy et al. Page 3Drug Alcohol Rev. Author manuscript; available in PMC 2016 March 01.Author ManuscriptAuthor ManuscriptAuthor ManuscriptAuthor ManuscriptOur outcome of interest was all pVL measurements taken during the first 365 days following the estimated date of seroconversion. These were obtained through the confidential linkage detailed above and included all measurements conducted through the study as well as any conducted outside of the study setting, for example, by a participant’s personal physician. The Roche Amplicor Monitor assay was used to determine pVL from participant blood samples (Roche Molecular Systems, Pleasanton, California, United States.)The primary explanatory variable was cannabis use in the six month period prior to the interview, dichotomized as ≥ daily vs. < daily. We also included secondary explanatory variables that we hypothesized might be associated with both cannabis use and pVL, such as: Age (per year increase); sex (female vs. male); Caucasian ancestry (yes vs. no); any injection drug use in the past six months (yes vs. no); any non-injection drug use in the past six months (defined as the use of any illicit drug other than cannabis via a non-parenteral route; yes vs. no), and any alcohol use. Because we have previously observed poorer housing status to be associated with higher pVL as well as well as malnutrition, we also included homelessness (yes vs. no). All of these variables save sex and ancestry were time-updated and refer to the six month period prior to the interview.As a first step, we built a boxplot to visually compare all pVL measurements stratified by high-intensity cannabis use. Next, we used contingency tables including Odds Ratios (OR) and p-values to investigate the distribution of all explanatory variables stratified by the median of the first pVL observation from each participant. To model the relationship between pVL and cannabis use while accounting for multiple observations per participant, we systematically fit a series of linear mixed effects models with random intercepts and random slopes, as in previous longitudinal analyses of pVL. All models included the primary explanatory variable; to some we added terms for one-knot b-splines or natural spline fit to the time since estimated seroconversion. Models also included Gaussian or autoregressive correlation matrices. We selected the final model form through an examination of each model’s Aikaike Information Criterion. Using this form, we fit models for the outcome and each explanatory variable and a final multivariable model including all explanatory variables. All statistical analyses were conducted using R version 2.15.1 (R Foundation for Statistical Computing, Vienna, Austria.)RESULTSBetween May, 1996 and March, 2012, 149 individuals who were HIV-negative at their VIDUS baseline interview later tested positive for HIV infection. Of these, 88 (62%) individuals completed at least one ACCESS interview and had ≥ 1 pVL observation within the 365 days following the estimated date of seroconversion and therefore were included in these analyses. Individuals included did not differ from those excluded by gender, age or ancestry (all p > 0.05.)These 88 individuals contributed 184 pVL observations during the study period. The median of all pVL observations was 4.66 log10 c/mL (inter-quartile range [IQR] = 4.11 – 5.08.) As shown in Figure 1, median pVL was 0.55 log10 c/mL lower during periods of at least daily cannabis use compared to others (4.73 vs. 4.18, p = 0.003.) In the cross-sectional analyses of Milloy et al. Page 4Drug Alcohol Rev. Author manuscript; available in PMC 2016 March 01.Author ManuscriptAuthor ManuscriptAuthor ManuscriptAuthor Manuscriptall explanatory variables stratified by the value of the first pVL observation (> 4.7 vs. ≤ 4.7 log10 c/mL) shown in Table 1, there was no significant difference observed between individuals reporting at least daily cannabis use (Odds Ratio = 0.34, 95% Confidence Interval = 0.08 – 1.45, p-value = 0.184.) At least daily cannabis use was associated with lower pVL (β = −0.44, SE = 0.170, p-value = 0.010) in a bivariate linear mixed effects model with no spline term and a Gaussian correlation matrix. In a multivariable linear mixed effects model, at least daily cannabis use was independently associated with lower pVL (β = −0.51, SE = 0.170, p-value = 0.003) after adjustment for age, gender, ancestry, homelessness, alcohol use, injection drug use and non-injection drug use.DISCUSSIONIn this study, we observed significantly lower pVL among people reporting at least daily cannabis use in the first year following HIV seroconversion. This difference persisted in a multivariable statistical model in which high-intensity cannabis use was associated with 0.51 lower log10 c/mL pVL after adjustment for possible confounders.We are aware of only two studies that have assessed the relationship between exposure to cannabis and pVL (20,21). In 2003, Abrams et al. observed no significant differences in pVL among 67 HIV-positive patients randomly assigned to smoke marijuana, ingest a 2.5-capsule of dronabinol (Δ9-THC) or ingest a placebo capsule three times daily before meals for 21 days (21). More recently, Ghosn et al. found that cannabis use during sexual intercourse was significantly associated with higher likelihoods of elevated seminal plasma viral load in an observational study of 157 men who have sex with men on successful combination antiretroviral therapy (20). Unlike our study among ART-naïve individuals, both studies were conducted among individuals engaged on ART. Also, Ghosn et al. did not adjust their multivariable results for ART adherence, allowing for the possibility that the observed association was the result of the neuropsychological effects of cannabis use on adherence to treatment.As our results were derived from an observational study where exposure to cannabis was not randomly assigned, we cannot exclude the possibility that the observed association was the result of unmeasured confounding or some other form of error. However, the results were robust to adjustment by possible confounders and, in addition, we do not believe individuals differentially reported cannabis use based on their pVL levels. Although an abundance of caution should be exercised whenever inferring similarities between data generated in primates and human participants, the observed association is consistent with the findings of Molina et al. from their experiment involving chronic exposure to Δ9-THC among rhesus macaques experimentally infected with SIV (16). In that study, monkeys exposed to Δ9-THC exhibited lower viral loads in plasma and cerebrospinal fluids, greater retention of body mass, attenuated inflammation and lengthened survival compared to placebo.The current findings should be evaluated in light of a growing body of evidence generated from pre-clinical settings on the structure and function of the endocannabinoid receptor system and its possible role in HIV disease. Cannabinoids, including Δ9-THC, bind to receptors expressed by cells in the nervous and immune systems (22) and, in addition to Milloy et al. Page 5Drug Alcohol Rev. Author manuscript; available in PMC 2016 March 01.Author ManuscriptAuthor ManuscriptAuthor ManuscriptAuthor Manuscripttheir well-known psychoactive effects, have been shown to have immunosuppressive and anti-inflammatory properties (22–25). These may be the result of cannabinoid-mediated changes in immunologic functioning through pathways including the production of pro-inflammatory cytokines and lymphocytes (25,26). In individuals infected with HIV, the creation and maintenance of chronic inflammatory states is correlated with increased viral replication driven by cytokines such as TNF-α. In addition to these immunomodulatory pathways, a direct antiviral effect of cannabinoids has been proposed (6,27). One experiment showed WIN55,212-2, a synthetic cannabinoid receptor agonist, suppressed replication of HIV-1 in microglia, the major cell type productively infected in the human nervous system (6).To conclude, we retrospectively analyzed longitudinal cohort data from individuals who use injection drugs and were recently infected with HIV. In a multivariate model controlling for possible confounders, at least daily cannabis use was associated with 0.51 log10 c/mL lower plasma HIV-1 RNA viral load. We believe this is the first study to describe a possibly beneficial effect for cannabinoids on HIV disease progression among humans. Our results support further investigation of the possible virological and immunological aspects of cannabinoid exposure among people living with HIV/AIDS.AcknowledgmentsThe authors thank the study participants for their contribution to the research as well as current and past researchers and staff. We would specifically like to thank Kristie Starr, Deborah Graham, Tricia Collingham, Caitlin Johnston, Steve Kain and Calvin Lai for their research and administrative assistance. The study was supported by the US National Institutes of Health (R01DA021525) and the Canadian Institutes of Health Research (MOP-79297, RAA-79918). M–J Milloy is supported by the Canadian Institutes of Health Research (CIHR) and the Michael Smith Foundation for Health Research.Dr. Julio Montaner is supported by the British Columbia Ministry of Health; through an Avant-Garde Award (No. 1DP1DA026182–01) from the National Institute of Drug Abuse (NIDA), at the US National Institutes of Health (NIH); and through a KT Award from the Canadian Institutes of Health Research (CIHR). He has also received financial support from the International AIDS Society, United Nations AIDS Program, World Health Organization, National Institutes of Health Research-Office of AIDS Research, National Institute of Allergy & Infectious Diseases, The United States President’s Emergency Plan for AIDS Relief (PEPfAR), Bill & Melinda Gates Foundation, French National Agency for Research on AIDS & Viral Hepatitis (ANRS), the Public Health Agency of Canada, the University of British Columbia, Simon Fraser University, Providence Health Care and Vancouver Coastal Health Authority. He has received grants from Abbott, Biolytical, Boehringer-Ingelheim, Bristol-Myers Squibb, Gilead Sciences, Janssen, Merck and ViiV Healthcare.This work was funded in part by a Tier 1 Canada Research Chair in Inner-City Medicine held by Evan Wood.References1. Collaboration of Observational HIV Epidemiological Research Europe (COHERE) in EuroCoord. Lewden C, Bouteloup V, De Wit S, Sabin C, Mocroft A, et al. All-cause mortality in treated HIV-infected adults with CD4 ≥500/mm3 compared with the general population: evidence from a large European observational cohort collaboration. International Journal of Epidemiology. 2012 Apr; 41(2):433–45. [PubMed: 22493325] 2. McGowan CC, Weinstein DD, Samenow CP, Stinnette SE, Barkanic G, Rebeiro PF, et al. Drug Use and Receipt of Highly Active Antiretroviral Therapy among HIV-Infected Persons in Two U.S. Clinic Cohorts. Kallas EG, editor. PLoS ONE. 2011 Apr 25.6(4):e18462. [PubMed: 21541016] 3. Cescon A, Cooper C, Chan K, Palmer A, Klein M, Machouf N, et al. Factors associated with virological suppression among HIV-positive individuals on highly active antiretroviral therapy in a multi-site Canadian cohort. HIV Medicine. 2010 Nov 8; 12(6):352–60. [PubMed: 21059167] Milloy et al. Page 6Drug Alcohol Rev. Author manuscript; available in PMC 2016 March 01.Author ManuscriptAuthor ManuscriptAuthor ManuscriptAuthor Manuscript4. 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Mientjes GH, Miedema F, van Ameijden EJ, van den Hoek AA, Schellekens PT, Roos MT, et al. Frequent injecting impairs lymphocyte reactivity in HIV-positive and HIV-negative drug users. AIDS. 1991 Jan; 5(1):35–41. [PubMed: 1829366] 9. Peterson PK, Sharp BM, Gekker G, Portoghese PS, Sannerud K, Balfour HH. Morphine promotes the growth of HIV-1 in human peripheral blood mononuclear cell cocultures. AIDS. 1990 Sep; 4(9):869–73. [PubMed: 2174676] 10. Brown SM, Stimmel B, Taub RN, Kochwa S, Rosenfield RE. Immunologic dysfunction in heroin addicts. Arch Intern Med. 1974 Dec; 134(6):1001–6. [PubMed: 4433182] 11. Bonn-Miller MO, Oser ML, Bucossi MM, Trafton JA. Cannabis use and HIV antiretroviral therapy adherence and HIV-related symptoms. J Behav Med. 2012 Oct 7.12. Hoffmann DE, Weber E. Medical marijuana and the law. N Engl J Med. 2010 Apr 22; 362(16):1453–7. [PubMed: 20410512] 13. Rom S, Persidsky Y. Cannabinoid Receptor 2: Potential Role in Immunomodulation and Neuroinflammation. Jrnl Neuroimmune Pharm. 2013 Mar 8.14. Costantino, CM.; Gupta, A.; Yewdall, AW.; Dale, BM.; Devi, LA.; Chen, BK. Wu, Y., editor. Cannabinoid receptor 2-mediated attenuation of CXCR4-tropic HIV infection in primary CD4+ T cells; PLoS ONE [Internet]. 2012 Mar 20. p. e33961Available from: http://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=22448282&retmode=ref&cmd=prlinks15. Molina PE, Amedee A, LeCapitaine NJ, Zabaleta J, Mohan M, Winsauer P, et al. Cannabinoid neuroimmune modulation of SIV disease. Jrnl Neuroimmune Pharm. 2011 Dec; 6(4):516–27.16. Molina PE, Winsauer P, Zhang P, Walker E, Birke L, Amedee A, et al. Cannabinoid administration attenuates the progression of simian immunodeficiency virus. AIDS Research and Human Retroviruses. 2011 Jun; 27(6):585–92. [PubMed: 20874519] 17. Strathdee S, Patrick DM, Currie SL, Cornelisse PG, Rekart ML, Montaner JS, et al. Needle exchange is not enough: lessons from the Vancouver injecting drug use study. AIDS. 1997 Jul; 11(8):F59–65. [PubMed: 9223727] 18. Strathdee S, Palepu A, Cornelisse PG, Yip B, O’shaughnessy MV, Montaner JS, et al. Barriers to use of free antiretroviral therapy in injection drug users. JAMA: The Journal of the American Medical Association. 1998 Aug 12; 280(6):547–9.19. Wood E, Hogg RS, Lima VD, Kerr T, Yip B, Marshall BDL, et al. Highly active antiretroviral therapy and survival in HIV-infected injection drug users. JAMA: The Journal of the American Medical Association. 2008 Aug 6; 300(5):550–4.20. Ghosn J, Leruez-Ville M, Blanche J, Delobelle A, Beaudoux C, Mascard L, et al. HIV-1 DNA Levels in Peripheral Blood Mononuclear Cells and Cannabis Use are Associated With Intermittent HIV Shedding in Semen of Men Who Have Sex With Men on Successful Antiretroviral Regimens. Clin Infect Dis. 2014 May 28; 58(12):1763–70. [PubMed: 24647014] 21. Abrams DI, Hilton JF, Leiser RJ, Shade SB, Elbeik TA, Aweeka FT, et al. Short-term effects of cannabinoids in patients with HIV-1 infection: a randomized, placebo-controlled clinical trial. Ann Intern Med. 2003 Aug 19; 139(4):258–66. [PubMed: 12965981] 22. Di Marzo V, Bifulco M, De Petrocellis L. The endocannabinoid system and its therapeutic exploitation. Nat Rev Drug Discov. 2004 Sep; 3(9):771–84. [PubMed: 15340387] Milloy et al. Page 7Drug Alcohol Rev. Author manuscript; available in PMC 2016 March 01.Author ManuscriptAuthor ManuscriptAuthor ManuscriptAuthor Manuscript23. Ehrhart J, Obregon D, Mori T, Hou H, Sun N, Bai Y, et al. Stimulation of cannabinoid receptor 2 (CB2) suppresses microglial activation. J Neuroinflammation. 2005; 2:29. [PubMed: 16343349] 24. Faubert Kaplan BL, Kaminski NE. Cannabinoids inhibit the activation of ERK MAPK in PMA/Io-stimulated mouse splenocytes. Int Immunopharmacol. 2003 Oct; 3(10–11):1503–10. [PubMed: 12946447] 25. Klein TW, Lane B, Newton CA, Friedman H. The cannabinoid system and cytokine network. Proc Soc Exp Biol Med. 2000 Oct; 225(1):1–8. [PubMed: 10998193] 26. Zhu LX, Sharma S, Stolina M, Gardner B, Roth MD, Tashkin DP, et al. Delta-9-tetrahydrocannabinol inhibits antitumor immunity by a CB2 receptor-mediated, cytokine-dependent pathway. J Immunol. 2000 Jul 1; 165(1):373–80. [PubMed: 10861074] 27. Rock RB, Gekker G, Hu S, Sheng WS, Cabral GA, Martin BR, et al. WIN55,212–2-mediated inhibition of HIV-1 expression in microglial cells: involvement of cannabinoid receptors. J Neuroimmune Pharmacol. 2007 Jun; 2(2):178–83. [PubMed: 18040842] Milloy et al. Page 8Drug Alcohol Rev. Author manuscript; available in PMC 2016 March 01.Author ManuscriptAuthor ManuscriptAuthor ManuscriptAuthor ManuscriptFigure 1. Boxplot of plasma HIV-1 RNA viral load observations stratified by cannabis use among 88 people who use illicit drugs with recent HIV infectionMilloy et al. Page 9Drug Alcohol Rev. Author manuscript; available in PMC 2016 March 01.Author ManuscriptAuthor ManuscriptAuthor ManuscriptAuthor ManuscriptAuthor ManuscriptAuthor ManuscriptAuthor ManuscriptAuthor ManuscriptMilloy et al. Page 10Table 1Characteristics of 88 people who use injection drugs with recent HIV infection stratified by first plasma HIV-1 RNA viral load (pVL) observation (≤ 4.7 log10 c/mL vs. > 4.7)CharacteristicpVL ≤ 4.742 (47.7)n (%)pVL > 4.746 (52.3)n (%)OR195% CI2p-valueCannabis use < Daily35 (83.3)43 (93.5)1.00 ≥ Daily7 (16.7)3 (6.5)0.340.08 – 1.450.184Age (per 10 years) Median (IQR)3.6 (2.9 – 4.0)3.6 (2.9 – 4.5)1.000.89 – 1.140.955Gender Male21 (50.0)28 (60.9)1.00 Female21 (50.0)18 (39.1)0.640.28 – 1.500.391Ancestry Non-Caucasian22 (52.4)18 (39.1)1.00 Caucasian20 (47.6)28 (60.9)1.710.73 – 3.990.284Homeless No37 (88.1)42 (91.3)1.00 Yes5 (11.9)4 (8.7)0.700.18 – 2.820.731Injection drug use No3 (7.1)3 (6.5)1.00 Yes39 (92.9)43 (93.5)1.100.21 – 5.790.908Non-injection drug use No11 (26.2)20 (43.5)1.00 Yes31 (73.8)26 (56.5)0.460.19 – 1.140.090Alcohol use No17 (40.5)25 (54.3)1.00 Yes25 (59.5)21 (45.7)0.570.25 – 1.330.1931 Odds Ratio;Drug Alcohol Rev. Author manuscript; available in PMC 2016 March 01.Author ManuscriptAuthor ManuscriptAuthor ManuscriptAuthor ManuscriptMilloy et al. Page 112 95% Confidence IntervalDrug Alcohol Rev. Author manuscript; available in PMC 2016 March 01.Author ManuscriptAuthor ManuscriptAuthor ManuscriptAuthor ManuscriptMilloy et al. Page 12Table 2Bivariable and multivariable analyses of factors associated with plasma HIV-1 RNA viral load (copies/mL, per log10) among 88 individuals who use injection drugs recently infected with HIV-1CharacteristicBivariableMultivariableβSE1p-valueβSE1p-valueCannabis use (≥ Daily vs. < daily)2−0.440.1700.010−0.510.1700.003Age (per year older)  0.010.0110.193  0.010.0110.419Gender (Female vs. male)−0.330.1770.064−0.200.1830.284Ancestry (Caucasian vs. non)  0.370.1760.034  0.350.1800.056Homelessness (Yes vs. no)2  0.300.1860.102  0.440.1910.023Injection drug use (Yes vs. no)2−0.350.2740.202−0.450.2730.103Non-injection drug use (Yes vs. no)2−0.010.1240.960  0.020.1350.863Alcohol use (Yes vs. no)2−0.130.1330.323−0.170.1450.2321 Standard Error;2 Refers to six-month period prior to interviewDrug Alcohol Rev. Author manuscript; available in PMC 2016 March 01.


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