Frequent Cocaine Use is Associated with Larger HIV Latent Reservoir Size

Background With the success of combination antiretroviral therapy, HIV is now treated as a chronic disease, including among drug users. Cocaine—one of the most frequently abused illicit drugs among persons living with HIV (PLWH)— slows the decline of viral production after ART, and is associated with higher HIV viral load, more rapid HIV progression, and increased mortality. We examined the impact of cocaine use on the CD4+ T-cell HIV Latent Reservoir (HLR) in virally suppressed PLWH. Methods CD4+ T-cell genomic DNA was isolated from peripheral blood mononuclear cells collected from 434 women of diverse ancestry (i.e., 75% Black, 14% Hispanic, 12% White) who self-reported cocaine use (i.e., 160 cocaine users, 59 prior users, 215 non-users). Participants had to have an undetectable HIV RNA viral load measured by commercial assay for at least 6 months. The Intact Proviral HIV DNA Assay (IPDA) provided estimates of intact provirus per 106 CD4+ T-cells. Results The HLR size differed by cocaine use (i.e., median [interquartile range]: 72 [14, 193] for never users, for prior users 165 [63, 387], 184 [28, 502] for current users), which was statistically significantly larger in both prior (p=0.023) and current (p=0.001) cocaine users compared with never users. Conclusion Our study is the first to provide evidence that cocaine use may contribute to a larger replication competent HLR in CD4* T-cells among virologically suppressed women living with HIV. Our findings are important, because women are under-represented in HIV reservoir studies and in studies of the impact of cocaine use on outcomes among PLWH. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement Data collection and the contributions of Bradley E. Aouizerat, Josephine N. Garcia, Carlos V. Domingues, Ke Xu, Bryan C. Quach, Grier P. Page, Dana B. Hancock, and Eric Otto Johnson were supported by R66 DA047011, R66 DA047011-S1, and R33 DA047011. Clinical data and specimens used in this manuscript were collected by the Women's Interagency HIV Study (WIHS), now the MACS/WIHS Combined Cohort Study (MWCCS). MWCCS (Principal Investigators): Atlanta CRS (Ighovwerha Ofotokun, Anandi Sheth, and Gina Wingood), U01- HL146241; Bronx CRS (Kathryn Anastos and Anjali Sharma), U01-HL146204; Brooklyn CRS (Deborah Gustafson and Tracey Wilson), U01-HL146202; Data Analysis and Coordination Center (Gypsyamber D'Souza, Stephen Gange and Elizabeth Golub), U01-HL146193; Chicago-Cook County CRS (Mardge Cohen and Audrey French), U01-HL146245; Northern California CRS (Bradley Aouizerat, Jennifer Price, and Phyllis Tien), U01-HL146242; Metropolitan Washington CRS (Seble Kassaye and Daniel Merenstein), U01-HL146205; Miami CRS (Maria Alcaide, Margaret Fischl, and Deborah Jones), U01- HL146203; UAB-MS CRS (Mirjam-Colette Kempf, Jodie Dionne-Odom, and Deborah Konkle-Parker), U01-HL146192; UNC CRS (Adaora Adimora and Michelle Floris-Moore), U01-HL146194. The MWCCS is funded primarily by the National Heart, Lung, and Blood Institute (NHLBI), with additional co-funding from the Eunice Kennedy Shriver National Institute Of Child Health & Human Development (NICHD), National Institute On Aging (NIA), National Institute Of Dental & Craniofacial Research (NIDCR), National Institute Of Allergy And Infectious Diseases (NIAID), National Institute Of Neurological Disorders And Stroke (NINDS), National Institute Of Mental Health (NIMH), National Institute On Drug Abuse (NIDA), National Institute Of Nursing Research (NINR), National Cancer Institute (NCI), National Institute on Alcohol Abuse and Alcoholism (NIAAA), National Institute on Deafness and Other Communication Disorders (NIDCD), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institute on Minority Health and Health Disparities (NIMHD), and in coordination and alignment with the research priorities of the National Institutes of Health, Office of AIDS Research (OAR). MWCCS data collection is also supported by UL1-TR000004 (UCSF CTSA), UL1-TR003098 (JHU ICTR), UL1- TR001881 (UCLA CTSI), P30-AI-050409 (Atlanta CFAR), P30-AI-073961 (Miami CFAR), P30-AI-050410 (UNC CFAR), P30-AI-027767 (UAB CFAR), and P30-MH-116867 (Miami CHARM). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Informed consent was provided by all participants via protocols approved by institutional review committees at each affiliated institution: New York University, RTI International, and Yale University. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Data may be obtained through the MACS/WIHS Combined Cohort Study collaboration and Concept Sheet process.