Completed Research

Description: The primary objective of this double-blind, placebo-controlled, adaptive, randomized clinical trial is to evaluate the efficacy of extended-release naltrexone plus bupropion as a combination pharmacotherapy for methamphetamine use disorder. Secondary outcomes will assess the safety of naltrexone plus bupropion and determine the efficacy of the combination pharmacotherapy on other substance use outcomes, on depression symptom scores, and on quality of life ratings. 370 individuals with moderate or severe methamphetamine use disorder will be randomly assigned to the active medication combination arm or the matching placebo arm. Participants will have visits twice weekly during the 12 week medication phase and complete follow-up visits in weeks 13 and 16.

Status: This study has completed. Results can be found here

1. Trivedi MH, Walker R, Ling W, Dela Cruz A, Sharma G, Carmody T, Ghitza UE, Wahle A, Kim M, Shores-Wilson K, Sparenborg S, Coffin P, Schmitz J, Wiest K, Bart G, Sonne SC, Wakhlu S, Rush AJ, Nunes EV, Shoptaw S. Bupropion and Naltrexone in Methamphetamine Use Disorder. N Engl J Med. 2021 Jan 14;384(2):140-153. PMID: 33497547; PMCID: PMC8111570.

Relevance: Medication assisted treatment (MAT) is an essential part of evidence-based rapid response treatment and is highly effective in acute care settings. The California Bridge Program develops hospitals and emergency rooms as primary access points for addiction treatment. This intensive program provides training and technical assistance to acute care providers to encourage patients to enter and remain in treatment.

Description: UCLA CBAM is working in collaboration Public Health International (PHI) on a research study related to the Bridge Program that will (1) expand the assessment battery currently being used by PHI to make it comparable to other datasets currently being compiled in the setting of providing medication assisted therapy (MAT) in emergency care settings and (2) build a cohort of participants willing to be contacted for future research opportunities to test prospective hypotheses about long-term health outcomes when providing MAT in emergency health settings.

Status: This study has completed. Results can be found here:

1. Snyder H, Kalmin MM,  Moulin A, Campbell A, Goodman-Meza D, Padwa H, Clayton S, Speener M, Shoptaw S, Herring AA. Rapid Adoption of Low-Threshold Buprenorphine Treatment at California Emergency Departments Participating in the CA Bridge Program. Annals of Emergency Medicine. 2021 Dec;78(6):759-772. Epub 2021 Aug 2. PMID: 34353655.

Description: CBT4CBT (computer-based training for cognitive-behavioral therapy) is a seven-module computerized training in cognitive behavioral therapy. The proposed pilot study will examine the feasibility and acceptability of CBT4CBT in office-based medication treatment of opioid and alcohol use disorders.

Outcomes: Though this study has completed enrollment, data analysis is still underway. Results will be posted here once available.

Relevance: Methamphetamine (MA) addiction is a global health problem with high prevalence and great social and health costs in the United States and in the Republic of South Africa and there is a strong need for development and implementation of effective MA treatment approaches.

Description: This study will enroll treatment-seeking, MA-dependent individuals into an 8-week contingency management (CM) program. At the beginning and end of the program, participants will participate in MRI scans while performing a working memory task and will complete a battery of select neurocognitive and psychological assays to address two specific aims: (1) to determine whether changes in neural function within frontostriatal circuitry (neural pathways that connect frontal lobe regions with the basal ganglia (striatum)) that mediate motor, cognitive, and behavioral functions within the brain from baseline to end of the 8-week CM program are associated with parallel changes in measures of cognitive control and impulsivity and with MA abstinence outcomes; (2) to determine whether structural changes in frontostriatal circuitry over the 8-week CM intervention correspond with neurocognitive, psychological and MA abstinence measures. Findings from this study will describe associations between functional and structural indices of brain areas that support working memory, cognitive control/inhibition; performance on select neurocognitive and psychological assessments; and associations between these with MA abstinence outcomes. Study activities and the neuroscience data generated will provide preliminary data for a larger, adequately powered study that will test ways to optimize behavioral therapies for treating stimulant use disorder.

Outcomes: While some data continues to be analyzed, we have successfully published three papers to date.

1. Chukwuemeka N. Okafor, Dan J. Stein, Lisa Dannatt, Jonathan Ipser, Lara J. van Nunen, Marilyn T. Lake, Tamar Krishnamurti, Edythe D. London, Steve Shoptaw. Contingency management treatment for methamphetamine use disorder in South Africa. Drug and Alcohol Review. March 2020, 39, 216-222. https://pubmed.ncbi.nlm.nih.gov/31863530/
2. Marilyn T. Lake, Steven Shoptaw, Jonathan C. Ipser, Sae Takada, Lara J. van Nunen, Gosia Lipinska, Dan J. Stein and Edythe D. London. Decision-Making by Patients With Methamphetamine Use Disorder Receiving Contingency Management Treatment: Magnitude and Frequency Effects. Psychiatry, 18 February 2020. https://pubmed.ncbi.nlm.nih.gov/32180733/
3. Tamar Krishnamurtia, Kimberly Ling Murtaugh, Lara Van Nunen, Alexander L. Davis, Jonathan Ipser, Steven Shoptaw. Spending money to make change: Association of methamphetamine abstinence and voucher spending among contingency management pilot participants in South Africa. Journal of Substance Abuse Treatment. Volume 112, May 2020, Pages 60-67 https://www.sciencedirect.com/science/article/abs/pii/S0740547219305288

Relevance: Use of crystal methamphetamine (MA) leads to changes in sexual risk behavior, adherence to biomedical prevention, viral immunology, and mucosal inflammation that increase risk for HIV-1 transmission among MA-using men who have sex with men (MSM), their sexual partners, and their networks. Contingency Management (CM) offers a behavioral modification tool efficacious for reducing frequency of MA use, but the effects of CM on the behavioral and biological factors that promote HIV transmission in MSM networks have only been partially evaluated. The intersection of substance use, sexual risk behavior, and HIV transmission in MSM networks presents a critical problem for contemporary HIV prevention as HIV-uninfected MSM who use MA have a 16%-33% attributable risk for HIV infection, while only approximately 50% of HIV-infected MA-using MSM achieve and maintain virologic suppression.

Description: This study will compare different CM models of HIV status-neutral approaches to integrate substance use treatment with HIV prevention among MA-using MSM: Traditional CM targeted to MA abstinence and alternative CM based on ARV adherence in order to assess the logistics, feasibility, and preliminary estimates of effect of CM for ARV adherence.

Status: Results of this study have been published and can be found here

Blair CS, Gandhi M, Shoptaw S, Blades C, Clark JL. Contingency Management for Integrated Harm Reduction Among Men Who Have Sex with Men Who Use Methamphetamine in Los Angeles: A Pilot Assessment. AIDS Behav. 2022 Nov 21.

Description: In order to develop a tailored, practical, and efficacious smoking cessation intervention that starts with a behavioral platform and offers the potential for pharmacotherapy (in this instance, nicotine transdermal therapy using Nicoderm CQ®), 84 subjects ages 14-21 were recruited for this 24-week study. Participants reported smoking at least 5 cigarettes daily in the month before entry into the study and initiation of smoking at least 6 months before entry. All youth received 6 weeks of cognitive-behavioral motivational enhancement (CBME) and were offered up to 4 weeks of nicotine replacement therapy (NRT).

Outcomes: Participants reported significant declines in withdrawal and nicotine dependence scores during the course of the study period. Compared with baseline, youths reported lower scores on the MNWS (withdrawal) and CDS-12 (dependence) at the last intervention visit (week 6) and at each of the follow up visits (weeks 12, 16, and 24). In addition, youths self-reported smoking fewer cigarettes per day in the preceding week (7-day smoking point prevalence) at each of these study points compared with baseline smoking.

Description: This is a collaborative project of the national HIV Prevention Trials Network (HPTN), protocol #073 (HPTN 073). The trial will test Truvada®, an HIV treatment medication, for pre-exposure prophylaxis (PrEP). PrEP is a new HIV prevention method in which people who are HIV-negative can be prescribed a daily HIV treatment drug to reduce their risk of becoming infected. The FDA approved Truvada® for use as PrEP in 2012. The Los Angeles site will enroll 75 BMSM over a one-year period.

Outcomes: Key findings may be found at this link. CBAM staff and faculty contributed to the following publications from this study.

1. Hightow-Weidman LB, Magnus M, Beauchamp G, Hurt CB, Shoptaw S, Emel L, Piwowar-Manning E, Mayer KH, Nelson LE, Wilton L, Watkins P, Whitfield D, Fields SD, Wheeler D. Incidence and Correlates of Sexually Transmitted Infections Among Black Men Who Have Sex With Men Participating in the HIV Prevention Trials Network 073 Preexposure Prophylaxis Study. Clin Infect Dis. 2019 Oct 15;69(9):1597-1604. PMID: 30615169; PMCID: PMC6792108.
2. Wheeler DP, Fields SD, Beauchamp G, Chen YQ, Emel LM, Hightow-Weidman L, Hucks-Ortiz C, Kuo I, Lucas J, Magnus M, Mayer KH, Nelson LE, Hendrix CW, Piwowar-Manning E, Shoptaw S, Watkins P, Watson CC, Wilton L. Pre-exposure prophylaxis initiation and adherence among Black men who have sex with men (MSM) in three US cities: results from the HPTN 073 study. J Int AIDS Soc. 2019 Feb;22(2):e25223. PMID: 30768776; PMCID: PMC6376611.
3. Wheeler DP, Lucas J, Wilton L, Nelson LE, Hucks-Ortiz C, Watson CC, Hutchinson C, Mayer KH, Kuo I, Magnus M, Beauchamp G, Shoptaw S, Emel LM, Chen YQ, Hightow-Weidman L, Fields SD. Building effective multilevel HIV prevention partnerships with Black men who have sex with men: experience from HPTN 073, a pre-exposure prophylaxis study in three US cities. J Int AIDS Soc. 2018 Oct;21 Suppl 7(Suppl Suppl 7):e25180. PMID: 30334600; PMCID: PMC6193312.
4. Zhang Y, Clarke W, Marzinke MA, Piwowar-Manning E, Beauchamp G, Breaud A, Hendrix CW, Cloherty GA, Emel L, Rose S, Hightow-Weidman L, Siegel M, Shoptaw S, Fields SD, Wheeler D, Eshleman SH. Evaluation of a Multidrug Assay for Monitoring Adherence to a Regimen for HIV Preexposure Prophylaxis in a Clinical Study, HIV Prevention Trials Network 073. Antimicrob Agents Chemother. 2017 Jun 27;61(7):e02743-16.PMID: 28438932; PMCID: PMC5487665.
5. Whitfield DL, Beauchamp G, Fields S, Nelson L, Magnus M, Dācus JD, Paul J, Anderson P, Wheeler D. Risk compensation in HIV PrEP adherence among Black men who have sex with men in HPTN 073 study. AIDS Care. 2021 May;33(5):633-638. Epub 2020 Aug 24. PMID: 32835494; PMCID: PMC7902733.
6. Whitfield DL, Nelson LE, Komárek A, Turner D, Ni Z, Boyd DT, Taggart T, Ramos SR, Wilton L, Beauchamp GG, Hightow-Weidman L, Shoptaw SJ, Magnus M, Mayer KH, Fields SD, Wheeler DP; H. I. V. Prevention Trials Network (HPTN) 073 Study Team. Implementation of Client-Centered Care Coordination for HIV Prevention with Black Men Who Have Sex with Men: Activities, Personnel Costs, and Outcomes-HPTN 073. J Racial Ethn Health Disparities. 2022 Jan 8. Epub ahead of print. PMID: 34997550.
7. Dangerfield DT 2nd, Kuo I, Magnus M, Beauchamp G, Fields SD, Nelson L, Shoptaw S, Wilton L, Wheeler DP. Sexual Risk Profiles Among Black Sexual Minority Men: Implications for Targeted PrEP Messaging. Arch Sex Behav. 2021 Oct;50(7):2947-2954. Epub 2021 Sep 29. PMID: 34590218.
8. Ramos SR, Beauchamp G, Wheeler DP, Wilton L, Whitfield DL, Boyd DT, Hightow-Weidman L, Fields SD, Nelson LE, On Behalf Of The Hptn Team. Optimizing PrEP Continuance: A Secondary Analysis Examining Perceived Autonomy Support and Care Coordination Quality among Black MSM in HPTN 073. Int J Environ Res Public Health. 2022 Apr 8;19(8):4489. PMID: 35457367; PMCID: PMC9026517.

Relevance: Preliminary data have shown antibodies to be a potential efficacious intervention in preventing HIV-1 infection.

Description: This study will evaluate the safety, tolerability, and efficacy of the VRC01 antibody in preventing HIV-1 infection in healthy adults at high risk of HIV infection. Participants will be men who have sex with men (MSM) and transgender people in the U.S., Peru and Brazil. An equal number of study participants will be randomized to receive VRC01 mAb by IV infusion at a dose of 10 mg/kg or 30 mg/kg every 8 weeks, or to receive control infusions every 8 weeks. All participants will receive the VRC01 antibody or placebo by intravenous infusion at Weeks 0 (study entry), 8, 16, 24, 32, 40, 48, 56, 64, and 72. For 3 days following each infusion, participants will be asked to record and report any symptoms to study researchers. In addition to the infusion visits, participants will attend study visits at Weeks 4, 8 + 5 days, 12, 20, 28, 36, 44, 52, 60, 68, 76, 80, 84, 88, and 92. All study visits will include blood collection and HIV testing and counseling. Select study visits will include a medical history review, physical exam, urine collection, pregnancy testing for participants capable of becoming pregnant, risk reduction counseling, and an interview/questionnaire.

Outcomes: Results of this study can be found in the following publications:

1. Gilbert PB, Juraska M, deCamp AC, Karuna S, Edupuganti S, Mgodi N, Donnell DJ, Bentley C, Sista N, Andrew P, Isaacs A, Huang Y, Zhang L, Capparelli E, Kochar N, Wang J, Eshleman SH, Mayer KH, Magaret CA, Hural J, Kublin JG, Gray G, Montefiori DC, Gomez MM, Burns DN, McElrath J, Ledgerwood J, Graham BS, Mascola JR, Cohen M, Corey L. Basis and Statistical Design of the Passive HIV-1 Antibody Mediated Prevention (AMP) Test-of-Concept Efficacy Trials. Stat Commun Infect Dis. 2017 Jan;9(1):20160001. Epub 2017 Jun 6. PMID: 29218117; PMCID: PMC5714515.
2. Corey L, Gilbert PB, Juraska M, Montefiori DC, Morris L, Karuna ST, Edupuganti S, Mgodi NM, deCamp AC, Rudnicki E, Huang Y, Gonzales P, Cabello R, Orrell C, Lama JR, Laher F, Lazarus EM, Sanchez J, Frank I, Hinojosa J, Sobieszczyk ME, Marshall KE, Mukwekwerere PG, Makhema J, Baden LR, Mullins JI, Williamson C, Hural J, McElrath MJ, Bentley C, Takuva S, Gomez Lorenzo MM, Burns DN, Espy N, Randhawa AK, Kochar N, Piwowar-Manning E, Donnell DJ, Sista N, Andrew P, Kublin JG, Gray G, Ledgerwood JE, Mascola JR, Cohen MS; HVTN 704/HPTN 085 and HVTN 703/HPTN 081 Study Teams. Two Randomized Trials of Neutralizing Antibodies to Prevent HIV-1 Acquisition. N Engl J Med. 2021 Mar 18;384(11):1003-1014. PMID: 33730454; PMCID: PMC8189692.

DescriptionThe BROTHERS study, a project of the HIV Prevention Trials Network (HPTN) aimed to see if certain strategies can show promise for slowing down the spread of HIV among Black men who have sex with men (Black MSM). Another aim is to better understand the men’s lives and how that relates to HIV risk.

Outcomes: The overall rate of new HIV infection among Black MSM in this study was 2.8% per year, a rate that is nearly 50% higher than in White MSM in the U.S. Even more alarming, HPTN061 found that young Black MSM—those 30 years of age and younger—acquired HIV infection at a rate of 5.9% per year, three times the rate among US White MSM. The overall infection rate among Black MSM in this US study is comparable to the rate seen in the general populations of countries in sub-Saharan Africa hardest hit by the HIV epidemic. Further results can be found here.

The following publications have since been released using data gathered from the HPTN061 Study:

1. Koblin, B., Mayer K., Eshleman, S., Wang, L., Mannheimer, S., del Rio, C., Shoptaw, S., Magnus, M., Buchbinder, S., Wilton, L., Ting-Yuan, L., Cummings, V., Piwowar-Manning, E., Fields, S., Griffith, S., Elharrar, V., Wheeler, D., for the HPTN 061 Protocol Team. Correlates of HIV acquisition in a cohort of black men who have sex with men in the United States: HIV Prevention Trials Network (HPTN) 061. PLoS ONE 8(7): e70413. doi:10.1371/journal.pone.0070413
2. Dyer, T.P., Regan, R., Wilton, L., Harawa, N.T., Ou, S.S., Wang, L., Shoptaw, S. Differences in substance use, psychosocial characteristics and HIV-related sexual risk behavior between black men who have sex with men only (BMSMO) and black men who have sex with men and women (BMSMW) in six US cities. Journal of Urban Health. 2013 Jul 30 (Epub ahead of print) PMCID: PMC in progress.
3. Marzinke MA, Clarke W, Wang L, Cummings V, Liu TY, Piwowar-Manning E, Breaud A, Griffith S, Buchbinder S, Shoptaw S, del Rio C, Magnus M, Mannheimer S, Fields SD, Mayer KH, Wheeler DP, Koblin BA, Eshleman SH, Fogel JM . Nondisclosure of HIV status in a clinical trial setting: antiretroviral drug screening can help distinguish between newly diagnosed and previously diagnosed HIV infection. Clin Infect Dis. 2014, 58: 117-20
4. Harawa N, Wilton L, Wang L, Mao C, Kuo I, Penniman T, Shoptaw S, Griffith S, Williams JK, Cummings V, Mayer K, Koblin B; HPTN 061 Study Team, Koblin B, HPTN 061 Study Team . Types of Female Partners Reported by Black Men Who Have Sex with Men and Women (MSMW) and Associations with Intercourse Frequency, Unprotected Sex and HIV and STI Prevalence. AIDS Behav. 2014, 18: 1548-59
5. Chen I, Cummings V, Fogel JM, Marzinke MA, Clarke W, Connor MB, Griffith S, Buchbinder S, Shoptaw S, Rio CD, Magnus M, Mannheimer S, Wheeler DP, Mayer KH, Koblin BA, Eshleman SH. Low-level Viremia Early in HIV Infection. J Acquir Immune Defic Syndr. 2014, 67: 405-8
6. Chen I, Connor MB, Clarke W, Marzinke MA, Cummings V, Breaud A, Fogel JM, Laeyendecker O, Fields SD, Donnell D, Griffith S, Scott HM, Shoptaw S, Rio CD, Magnus M, Mannheimer S, Wheeler DP, Mayer KH, Koblin BA, Eshleman SH . Antiretroviral drug use and HIV drug resistance among HIV-infected Black men who have sex with men: HIV Prevention Trials Network 061. J Acquir Immune Defic Syndr. 2015
7. Williams JK, Wilton L, Magnus M, Wang L, Wang J, Dyer TP, Koblin BA, Hucks-Ortiz C, Fields SD, Shoptaw S, Stephenson R, O’Cleirigh C, Cummings V; HIV Prevention Trials Network 061 Study Team . Relation of Childhood Sexual Abuse, Intimate Partner Violence, and Depression to Risk Factors for HIV Among Black Men Who Have Sex With Men in 6 US Cities. Am J Public Health. 2015, 105: 2473-81
8. Chen I, Huang W, Connor MB, Frantzell A, Cummings V, Beauchamp GG, Griffith S, Fields SD, Scott HM, Shoptaw S, Del Rio C, Magnus M, Mannheimer S, Tieu HV, Wheeler DP, Mayer KH, Koblin BA, Eshleman SH . CXCR4-using HIV variants in a cohort of Black men who have sex with men: HIV Prevention Trials Network 061. HIV Clin Trials. 2016, 17: 158-64
9. Levy ME, Phillips G 2nd, Magnus M, Kuo I, Beauchamp G, Emel L, Hucks-Ortiz C, Hamilton EL, Wilton L, Chen I, Mannheimer S, Tieu HV, Scott H, Fields SD, Del Rio C, Shoptaw S, Mayer K . A Longitudinal Analysis of Treatment Optimism and HIV Acquisition and Transmission Risk Behaviors Among Black Men Who Have Sex with Men in HPTN 061. AIDS and Behavior. 2017, 21: 2958-2972
10. Dyer, T. V., Khan, M. R., Regan, R., Harawa, N. T., Nelson, L. E., Wilton, L., Wang, L., Peng, L., Ou, S. S., Shoptaw, S. . Differential Patterns of Risk and Vulnerability Suggest the Need for Novel Prevention Strategies for Black Bisexual Men in the HPTN 061 Study. J Acquir Immune Defic Syndr. 2018, 78: 491-498
11. Chen I, Zhang Y, Cummings V, Cloherty GA, Connor M, Beauchamp G, Griffith S, Rose S, Gallant J, Scott HM, Shoptaw S, Del Rio C, Kuo I, Mannheimer S, Tieu HV, Hurt CB, Fields SD, Wheeler DP, Mayer KH, Koblin BA, Eshleman SH . Analysis of HIV Integrase Resistance in Black Men Who Have Sex with Men in the United States. AIDS Res Hum Retroviruses. 2017, 33: 745-748
12. Chen I, Chau G, Wang J, Clarke W, Marzinke MA, Cummings V, Breaud A, Laeyendecker O, Fields SD, Griffith S, Scott HM, Shoptaw S, Del Rio C, Magnus M, Mannheimer S, Tieu HV, Wheeler DP, Mayer KH, Koblin BA, Eshleman SH . Analysis of HIV Diversity in HIV-Infected Black Men Who Have Sex with Men (HPTN 061). PLoS One. 2016, 11: e0167629
13. Hermanstyne KA, Green HD Jr, Tieu HV, Hucks-Ortiz C, Wilton L, Shoptaw S . The Association Between Condomless Anal Sex and Social Support Among Black Men Who Have Sex With Men (MSM) in Six U.S. Cities: A Study Using Data from the HIV Prevention Trials Network BROTHERS Study (HPTN 061). AIDS Behav. 2019, 23: 1387-1395
14. Koblin BA, Mayer KH, Eshleman SH, Wang L, Mannheimer S, del Rio C, Shoptaw S, Magnus M, Buchbinder S, Wilton L, Liu TY, Cummings V, Piwowar-Manning E, Fields SD, Griffith S, Elharrar V, Wheeler D, for the HPTN 061 Protocol Team . Correlates of HIV Acquisition in a Cohort of Black Men Who Have Sex with Men in the United States: HIV Prevention Trials Network (HPTN) 061. PLoS One. 2013, 8: e70413
15. Hermanstyne KA, Green HD Jr., Cook R, Tieu HV, Dyer TV, Hucks-Ortiz C, Wilton L, Latkin C, Shoptaw S . Social Network Support and Decreased Risk of Seroconversion in Black MSM: Results of the BROTHERS (HPTN 061) Study. J Acquir Immune Defic Syndr. 2018, 78: 163-168

HPTN 083: A Phase 2b/3 Double Blind Safety and Efficacy Study of Injectable Cabotegravir Compared to Daily Oral Tenofovir Disoproxil Fumarate/Emtricitabine (TDF/FTC), for Pre-Exposure Prophylaxis (PrEP) in HIV-Uninfected Cisgender Men and Transgender Women who have Sex with Men

Relevance: PrEP agents are needed that do not depend on daily or near-daily pill-taking. The development of alternative agents for PrEP, and/or more adherence-friendly schedules for currently available agents, could increase prevention choices and increase acceptability. Long-acting injectable agents have the potential to prevent HIV acquisition without relying on adherence to a daily oral regimen.

Description: Once randomized to one of two arms, participants will move through the steps below and followed for up to 4 and a half years:

Step 1:
Arm A – Daily oral CAB (30 mg tablets) and oral TDF/FTC placebo for five weeks
Arm B – Daily oral TDF/FTC (300 mg/200 mg fixed-dose combination tablets) and oral CAB placebo for five weeks
A participant that becomes HIV-infected during Step 1 of the study will permanently discontinue study product and will be terminated from the study, and referred for HIV-related care.
Step 2:
Arm A – CAB LA (600 mg as a single intramuscular [IM] injection at two time points 4 weeks apart and every 8 weeks thereafter) and daily oral TDF/FTC placebo.
Arm B – Daily oral TDF/FTC (300/200 mg fixed-dose combination tablets) and IM placebo at two time points 4 weeks apart and every 8 weeks thereafter (matching vehicle, identical volume as active injectable product in Arm A).
This step will continue until the required number of endpoints is reached.

A participant that becomes HIV-infected during Step 2 of the study will permanently discontinue study product, be placed on immediate suppressive ART, and be followed for 52 weeks after their last injection, after which their participation in the study will end and they will be transitioned to continued HIV-related care.

Step 3:
Both arms: Open-label daily oral TDF/FTC no later than 8 weeks after the last injection (in order to cover the pharmacokinetic (PK) tail for Arm A participants), for up to 48 weeks.
Participants will then transition to locally-available HIV prevention services, including services for PrEP, if available.
A participant with confirmed HIV infection during Step 3 will be followed at least for the duration of Step 3.

Status: This study has been completed. Results can be found here: https://www.hptn.org/research/studies/hptn-083

Description: This was a sub-study of the project “HIV/STD Risk Behaviors in Methamphetamine User Networks”. It sought measure the prevalence anal human papillomavirus (HPV) among HIV-negative MSM who use methamphetamine compared to those who do not use methamphetamine.

Outcomes: The supplemental project extends the breadth of research findings in the main study by documenting that the primary drivers of high-risk anal HPV are linked to HIV-infection, MSMW behaviors, and being African American. Use of methamphetamine was not a significant predictor of HPV infection.

1. Cranston RD, Murphy R, Weiss RE, Da Costa M, Palefsky J, Shoptaw S, Gorbach PM. Anal human papillomavirus infection in a street-based sample of drug using HIV-positive men. Int J STD AIDS. 2012 Mar;23(3):195-200. PMC in progress.

Relevance: Development of effective vaccines to protect individuals against HIV is a challenging and growing public health priority. The HVTN’s mission is to fully characterize the safety, immunogenicity, and efficacy of HIV vaccine candidates with the goal of developing a safe, effective vaccine as rapidly as possible for prevention of HIV globally.

Description: The HVTN 302 study is a phase 1 clinical trial looking to evaluate the safety and immunogenicity (how the immune system responds) to three different HIV trimer mRNA vaccines in healthy, HIV uninfected adults.

Status: This study has ended and data are being analyzed.

Description: This was a sub-study of the project “HIV/STD Risk Behaviors in Methamphetamine User Networks”. The purpose of the project was to assess the characteristics of the HIV virus in methamphetamine-using MSM that may be associated with efficient transmission of new infections. These characteristics include viral load, genotype, extent of treatment. We also sought to evaluate the behavioral similarities between individuals with treatment-resistant strains of HIV such as their patterns of methamphetamine use, sexual practices, and adherence to regimens with various HIV medication.

Outcomes: Findings from this project are particularly significant in that clinicians need evidence to guide decisions regarding whether or not to provide active substance using MSM with access to HAART medications. The reports from these efforts are the best controlled evidence showing that HAART medications swamp the significant effects of methamphetamine on HIV disease progression. Findings are highly significant in that they yield strong support for providing access to HAART medications for HIV-seropositve men who use stimulants.

Description: This study sought to establish methods of using real-time social networking data for HIV prevention by assessing 1) whether geolocated conversations about HIV risk behaviors can be extracted from social networking data, 2) the prevalence and content of these conversations, and 3) the feasibility of using HIV risk-related real-time social media conversations as a method to detect HIV outcomes.

Outcomes: Over 9800 geolocated tweets were extracted and used to create a map displaying the geographical location of HIV-related tweets. There was a significant positive relationship (p < .01) between HIV-related tweets and HIV cases. Results suggest the feasibility of using social networking data as a method for devaluating and detecting HIV risk behaviors and outcomes.

1. Young SD, Rivers C, Lewis B. Methods of using real-time social media technologies for detection and remote monitoring of HIV outcomes. Preventive Medicine. 2014 8 Feb (Epub Ahead of Print). PMC ID: PMC in progress.

Relevance: SARS-CoV-2 is the virus that causes the disease called COVID-19, short for “Coronavirus Disease of 2019”. Finding an effective vaccine for COVID-19 is one of several steps being taken to end this global pandemic.

Description: The purpose of this study is to test Moderna’s vaccine candidate (mRNA-1273) to see if it can prevent illness if people are exposed to the SARS-CoV-2 virus in their everyday lives. This vaccine is not made from the SARS-CoV-2 virus. It is made from messenger ribonucleic acid (mRNA), a genetic code that tells cells how to make protein, which helps the body’s immune system make antibodies that can fight the virus. The vaccine cannot cause COVID-19 infection. This Phase 3 trial is being conducted at multiple clinic sites across the U.S. with a goal of enrolling 30,000 patients. Trial participants will receive 2 injections, approximately 28 days apart and will complete regular follow ups over the course of two years via phone calls, on-line surveys and additional in-person visits.

Status: This study is complete. See the results of an interim analysis.

Description: This was a sub-study of the project “HIV/STD Risk Behaviors in Methamphetamine User Networks”. The purpose this project was to investigate epidemiological clustering of HIV as revealed by viral phylogenetic analysis to support or refute epidemiological linkage of pairs of HIV infected individuals, to describe broad patterns of clustering of infections by ethnic group and by structural features, and to describe the epidemiology of drug resistant HIV within this population

Outcomes: In our initial findings, the frequency of high level drug resistance was over 40% in individuals with viral loads > 500 copies/ml. This suggests that in this sample, treatment response is highly polarized. Analyses suggest relatively little clustering of HIV sequences, despite HIV+ individuals having an extremely high odds (>25%) of recruiting other HIV+ individuals, suggesting that there is little overlap between HIV transmission networks and recruitment by respondent-driven sampling. This also is consistent with HIV+ individuals reporting not having sex with their recruiter.This supplement helped to develop a statistical package, written in the R programming language, which imports RDS data, and generates figures depicting the recruitment networks, and generates sample, equilibrium and population estimates of quantities of interest, such as HIV prevalence.

Description: This study assessed perceptions of pre-exposure prophylaxis (PrEP) and their association with PrEP adoption intention among a convenience sample of 224 low socioeconomic status Black men who have sex with men (BMSM) residing in Los Angeles. Participants received educational information about PrEP and completed an in-person interview.

Outcomes: More than half of the participants indicated a high intention to adopt PrEP. BMSM (18-29 years) were twice as likely to report a high intention to adopt PrEP compared to older BMSM (30+ years). Only a third of participants were aware of PrEP, and no participant had ever used PrEP. Negative perceptions were associated with a lower PrEP adoption intention and included being uncomfortable taking an HIV medicine when HIV-negative and not knowing if there are long-term side effects of taking an HIV medication.

1. Brooks, R. A., Landovitz, R. J., Regan, R., Lee, S. J., & Allen, V. C. (2015). Perceptions of and intentions to adopt HIV pre-exposure prophylaxis among black men who have sex with men in Los Angeles. International Journal of STD & AIDS. EPub 2015 Jul 26. PMID: 25638214.

Description: Genetic differences are thought to be an important biological predictor of response to treatment for addiction. The purpose of this project was to identify genetic factors influencing addiction severity and response to anti-addiction medications, with an emphasis on medications to treat methamphetamine dependence. We collected DNA specimens from a sample of well-phenotyped methamphetamine users who were participating in our clinical studies, including a pharmacogenetic clinical trial of bupropion for methamphetamine dependence. This outpatient study for treatment seeking, methamphetamine-dependent persons has been completed and we are analyzing the samples and data collected.

Outcomes: Results of this study can be found in the following publication:

1. Heinzerling KG, McCracken JT, Swanson AN, Ray LA, Shoptaw SJ. COMT Val158Met, BDNF Val66Met, and OPRM1 Asn40Asp and methamphetamine dependence treatment response: preliminary investigation. J Clin Psychopharmacol. 2012 Feb;32(1):135-7. doi: 10.1097/JCP.0b013e318240a48e. PMID: 22217949; PMCID: PMC3597465.

Relevance: Despite multiple clinical trials testing medications targeting dopaminergic, serotonergic, cholinergic, and gaba-ergic systems, no effective medication for methamphetamine (MA) use disorder is currently available.

Description: This is an inpatient, phase I safety-interaction trial of POMA (Pomaglumetad Methionil) in participants with MA (methamphetamine) use disorder. The goal of the study is to provide the initial safety, tolerability, and pharmacokinetic (PK) data required by the FDA to advance POMA to phase 2 safety and efficacy testing. In addition, the study will investigate potential effects of POMA on a laboratory self-administration model of MA relapse. The design is a randomized, double-blind, placebo-controlled multiple ascending-dose study in 24 non-treatment seeking participants with MA use disorder.

Status: This study has ended and data are currently being analyzed.

Relevance: Methamphetamine (MA) is more prevalent than many other drugs, including opioids, with 37 million users of MA and amphetamine worldwide and 1.4 million past-year users in the U.S. alone in 2016. The number of MA poisoning deaths has steadily risen in recent years, from >3,700 in 2014 to 10,333 in 2017. Importantly, MA has been recognized as contributing substantially to the U.S. opioid crisis, with about half of MA poisoning deaths also caused by opioids. In the U.S., the annual economic cost of MA use is estimated to be $23.4 billion and use is strongly associated with HIV transmission. There are no FDA-approved pharmacologic treatments for MA use disorder, a major gap in addiction medicine, especially because behavioral interventions alone have limited efficacy and would likely benefit from adjunctive pharmacologic therapy.

Description: Previous randomized, placebo-controlled, double-blind trials have demonstrated a net reduction in MA positive urines in participants given mirtazapine. Before moving on to a larger trial, the FDA has requested additional data on the effects mirtazapine on those individuals using both MA and opioids. This drug-drug interaction (DDI) study will provide that data.

Status: Enrollment in this trial has ended and data is currently being analyzed.

Description: To date, no medications have been approved expressly for the treatment of methamphetamine dependence, leaving few options for doctors and patients battling this particular addiction. This clinical trial sought to determine the safety and tolerability of the medication ibudilast in non-treatment seeking, methamphetamine-dependent volunteers.The study took place at the Harbor-UCLA Medical Center in Torrance.

Preliminary outcomes of the trial were presented at the 2013 College of Problems on Drug Dependence Conference in San Diego. Click here to read the press release and stay tuned for additional results.

Outcomes:

1. DeYoung, D. Z., Heinzerling, K. G., Swanson, A. N., Tsuang, J., Furst, B. A., Yi, Y., … & Shoptaw, S. J. (2016). Safety of Intravenous Methamphetamine Administration During Ibudilast Treatment. Journal of clinical psychopharmacology. 2016 Aug;36(4):347-54.
2. Li MJ, Briones MS, Heinzerling KG, Kalmin MM, Shoptaw SJ. Ibudilast attenuates peripheral inflammatory effects of methamphetamine in patients with methamphetamine use disorder. Drug Alcohol Depend. 2020 Jan 1;206:107776. Epub 2019 Nov 26. PMID: 31812878; PMCID: PMC7012103.
3. Worley MJ, Swanson A-N, Heinzerling KG, Roche DJ, Shoptaw S. Ibudilast attenuates subjective effects of methamphetamine in a placebo-controlled inpatient study. Drug Alcohol Depend. 2016 May 1;162:245-50. Epub 2016 Mar 3. Erratum in: Drug Alcohol Depend. 2018 Sep 1;190:120. PMID: 26993372; PMCID: PMC5349508.

Relevance: Despite numerous clinical trials, no medication has been approved to treat methamphetamine (MA) dependence. As a result, novel approaches to medication development for MA dependence, including linked medication development, where work in early safety trials can be used to inform the importance of continued (or not) assessment of novel or combination pharmacotherapies, is needed.

Description: Following up on the Phase I safety trial, the objective of this study is to test the safety and potential efficacy of ibudilast to treat methamphetamine dependence. The study hypotheses are that ibudilast will reduce methamphetamine use and increase treatment retention more than placebo among patients seeking treatment for methamphetamine dependence. As HIV infection is a common complication of methamphetamine dependence, half of the participants will be HIV positive and the study will assess whether ibudilast also improves HIV related outcomes (e.g. medication adherence, CD4 count, risk behaviors).

Outcomes: Results of this study can be found in the following publication:

1. Heinzerling KG, Briones M, Thames AD, Hinkin CH, Zhu T, Wu YN, Shoptaw SJ. Randomized, Placebo-Controlled Trial of Targeting Neuroinflammation with Ibudilast to Treat Methamphetamine Use Disorder. J Neuroimmune Pharmacol. 2020 Jun;15(2):238-248. Epub 2019 Dec 9. PMID: 31820289; PMCID: PMC8651052.

Relevance: Alcohol Use Disorder (AUD) affects 18 million Americans, and is linked to 80,000 deaths a year, presenting a staggering $224 billion dollar economic loss to society. Yet, there are only four medications approved by the FDA to treat AUD.

Description: The primary objective of this study is to compare the efficacy of HORIZANT® with a placebo on individuals with AUD. The secondary objectives are to assess other treatment benefits such as reduction in alcohol consumption, reduction in cravings of alcohol, mood, sleep quality, smoking quantity and frequency, and safety.

Outcomes: Results of this study can be found in the following publication:

1. Falk DE, Ryan ML, Fertig JB, Devine EG, Cruz R, Brown ES, Burns H, Salloum IM, Newport DJ, Mendelson J, Galloway G, Kampman K, Brooks C, Green AI, Brunette MF, Rosenthal RN, Dunn KE, Strain EC, Ray L, Shoptaw S, Ait-Daoud Tiouririne N, Gunderson EW, Ransom J, Scott C, Leggio L, Caras S, Mason BJ, Litten RZ; National Institute on Alcohol Abuse and Alcoholism Clinical Investigations Group (NCIG) Study Group. Gabapentin Enacarbil Extended-Release for Alcohol Use Disorder: A Randomized, Double-Blind, Placebo-Controlled, Multisite Trial Assessing Efficacy and Safety. Alcohol Clin Exp Res. 2019 Jan;43(1):158-169. Epub 2018 Dec 9. PMID: 30403402; PMCID: PMC6317996.

Description: The purpose of this pilot clinical trial was to determine the safety of bupropion for methamphetamine abuse/dependence among adolescents. Nineteen adolescents were randomly assigned to bupropion sustained release 150mg twice daily or placebo for 8 weeks in addition to outpatient substance abuse counseling.

Outcomes: Bupropion was well-tolerated except for one female in the bupropion group who was hospitalized for suicidal ideation during a methamphetamine relapse. Those participants who received bupropion and females in the study provided significantly fewer methamphetamine-free urine tests compared to participants receiving placebo and males respectively. Results do not support the feasibility of additional trials of bupropion for adolescent methamphetamine abuse/dependence. Future studies should investigate the influence of gender on adolescent methamphetamine abuse and treatment outcomes. This study was funded by the National Institute on Drug Abuse grant number R21 DA026513.

A publication has been released using data gathered from this study:

1. Heinzerling KG, Gadzhyan J, van Oudheusden H, Rodriguez F, McCracken J, Shoptaw S. Pilot randomized trial of bupropion for adolescent methamphetamine abuse/dependence. J Adolesc Health. 2013 Apr;52(4):502-5.

Randomized, placebo-controlled trial of bupropion for the treatment of methamphetamine dependence

Description: This study sought to compare bupropion to placebo for reducing methamphetamine (MA) use, increasing retention, and reducing the severity of depressive symptoms and MA-cravings. Additionally, a secondary objective compared bupropion to placebo for reducing cigarette smoking among MA dependent participants. Following a 2-week, non-medication baseline screening period, 73 treatment-seeking MA dependent participants were randomly assigned to bupropion sustained release (150 mg twice daily; N= 36) or placebo (twice daily; N= 37) for 12-weeks under double-blind conditions. Participants attended clinic thrice weekly to provide urine samples analyzed for MA-metabolite, to complete research measures and assessments, and to receive contingency management and weekly cognitive behavioral therapy sessions.

Outcomes: There were no statistically-significant effects for bupropion relative to placebo on MA use verified by urine drug screens, for reducing the severity of depressive symptoms or MA-cravings, or on study retention. In a post hoc analysis, there was a statistically-significant effect of bupropion treatment on MA use among participants with lighter (0–2 MA-positive urines), but not heavier (3–6 MA-positive urines) MA use during baseline. Bupropion treatment was also associated with significantly reduced cigarette smoking, by almost five cigarettes per day (p = 0.0002). Bupropion was no more effective than placebo in reducing MA use in planned analyses, though bupropion did reduce cigarette smoking. Post hoc findings of an effect for bupropion among baseline light, but not heavy, MA users suggests further evaluation of bupropion for light-MA users is warranted.

A publication has been released using data gathered from this study:

1. Heinzerling, K. G., Swanson, A. N., Hall, T. M., Yi, Y., Wu, Y., & Shoptaw, S. J. (2014). Randomized, placebo-controlled trial of bupropion in methamphetamine-dependent participants with less than daily methamphetamine use. Addiction (Abingdon, England), 109(11), 1878–1886. https://pubmed.ncbi.nlm.nih.gov/24894963/

Relevance: The opioid epidemic is U.S.’s most widespread behavioral public health problem, with a higher number of deaths due to overdose in 2016 compared to deaths due to HIV at the peak of the AIDS epidemic. Medication assisted treatment (MAT) for opioid use disorder (OUD) is highly efficacious. However, only a fraction of persons with OUD access MAT and treatment non-adherence and drop out is common. There is a dire need to improve systems to address these issues and to expand the use of MAT for many patients who are out of care.

Description: This NIH-funded project is conducted in collaboration with the technology company Q2i, developer of the Opioid Addiction Recover Support platform (OARS). In Phase 1 of the study, we will conduct interviews with physicians and patients using OARS to determine the feasibility and acceptability of using the platform in a primary care setting. The platform will then be modified according to our results and we will move into a second phase to assess the effectiveness of OARS in improving opioid agonist treatment outcomes and to evaluate sustainability and return on investment.

Status: This study has completed enrollment and is currently in the data analysis phase.

Relevance: Pre-Exposure Prophylaxis (PrEP) has the potential to reduce the number of new HIV infections among high-risk black and Latino men who have sex with men (BLMSM). However, issues related to the adoption of PrEP may negatively influence PrEP disclosure, diffusion, adherence and retention among BLMSM who adopt PrEP. The findings from this study will inform the development of intervention activities that seeks to prevent or moderate the negative social experiences associated with PrEP adoption and facilitate diffusion, adherence and retention to PrEP among minority MSM.

Description: The goal of this study is to learn about the experiences of BLMSM who have adopted PrEP and to assess its influence on PrEP disclosure, adherence and retention, and the diffusion of PrEP information to other potential BLMSM PrEP consumers. The specific aims of this study are: 1) to examine the experiences of BLMSM PrEP adopters; 2) to assess the extent and context of PrEP disclosure and dissemination of PrEP information by BLMSM PrEP users to other potential BLMSM PrEP consumers; and 3) to examine adherence and retention to PrEP, over time, among BLMSM PrEP adopters. BLMSM PrEP adopters will complete both a baseline and a 3-6-month follow-up interview. Follow-up interviews will assess changes in PrEP retention, adherence, disclosure and dissemination. Interviews with BLMSM non-PrEP adopters will determine the factors that may have influenced decisions to seek or not seek PrEP. Interviews will also be conducted with 20 medical providers to assess their perceptions of PrEP and PrEP stigma and concerns about the implementation of PrEP. The findings from this study will inform the development of intervention activities that seek to prevent or mitigate the negative social experiences associated with PrEP adoption and to optimize diffusion and retention to PrEP among minority MSM.

Outcomes: Two papers were published from this study.

1. Brooks, R. A., Cabral, A., Nieto, O., Fehrenbacher, A., & Landrian, A. (2019). Experiences of Pre-Exposure Prophylaxis Stigma, Social Support, and Information Dissemination Among Black and Latina Transgender Women Who Are Using Pre-Exposure Prophylaxis. Transgender health, 4(1), 188–196. https://pubmed.ncbi.nlm.nih.gov/31482134/
2. Brooks, R. A., Nieto, O., Landrian, A., & Donohoe, T. J. (2019). Persistent stigmatizing and negative perceptions of pre-exposure prophylaxis (PrEP) users: implications for PrEP adoption among Latino men who have sex with men. AIDS care, 31(4), 427–435. https://pubmed.ncbi.nlm.nih.gov/30021456/

Description: The goal of this Phase II study is to test the early efficacy of the medication varenicline in treating methamphetamine dependence. The safety and tolerability of varenicline for the treatment of methamphetamine was tested previously and pilot data on the medication’s effectiveness was found to be promising.

Outcomes: Varenicline was well tolerated, but was not found to be universally efficacious for achieving MA abstinence in this Phase 2 clinical trial.

1. Briones M, Worley M, DeYoung D, Swanson AN, Heinzerling KG, Shoptaw S. Varenicline for the treatment of methamphetamine dependence. Drug and Alcohol Dependence. 2015 Nov 1;156:e28.
2. Briones M, Shoptaw S, Cook R, Worley M, Swanson AN, Moody DE, Fang WB, Tsuang J, Furst B, Heinzerling K. Varenicline treatment for methamphetamine dependence: A randomized, double-blind phase II clinical trial. Drug Alcohol Depend. 2018 Aug 1;189:30-36. Epub 2018 May 25. PMID: 29860057; PMCID: PMC6391991.