Safety and tolerability of maraviroc-containing regimens to prevent HIV infection in women

Roy M. Gulick; Timothy J. Wilkin; Ying Q. Chen; Raphael J. Landovitz; K. Rivet Amico; Alicia M. Young; Paul Richardson; Mark A. Marzinke; Craig W. Hendrix; Susan H. Eshleman; Ian McGowan; Leslie M. Cottle; Adriana Andrade; Cheryl Marcus; Karin L. Klingman; Wairimu Chege; Alex R. Rinehart; James F. Rooney; Philip Andrew; Robert A. Salata; Marc Siegel; Yukari C. Manabe; Ian Frank; Ken Ho; Jorge Santana; Joanne D. Stekler; Shobha Swaminathan; Marybeth McCauley; Sally Hodder; Kenneth H. Mayer

doi:10.7326/M17-0520

Safety and tolerability of maraviroc-containing regimens to prevent HIV infection in women

Roy M. Gulick, Timothy J. Wilkin, Ying Q. Chen, Raphael J. Landovitz, K. Rivet Amico, Alicia M. Young, Paul Richardson, Mark A. Marzinke, Craig W. Hendrix, Susan H. Eshleman, Ian McGowan, Leslie M. Cottle, Adriana Andrade, Cheryl Marcus, Karin L. Klingman, Wairimu Chege, Alex R. Rinehart, James F. Rooney, Philip Andrew, Robert A. SalataMarc Siegel, Yukari C. Manabe, Ian Frank, Ken Ho, Jorge Santana, Joanne D. Stekler, Shobha Swaminathan, Marybeth McCauley, Sally Hodder, Kenneth H. Mayer

School of Medicine

Research output: Contribution to journal › Article › peer-review

17 Scopus citations

Abstract

Background: Maraviroc (MVC) is a candidate drug for HIV preexposure prophylaxis (PrEP). Objective: To assess the safety and tolerability of MVC-containing PrEP over 48 weeks in U.S. women at risk for HIV infection. Design: Phase 2 randomized, controlled, double-blinded study of 4 antiretroviral regimens used as PrEP. (ClinicalTrials.gov: NCT01505114) Setting: 12 clinical research sites of the HIV Prevention Trials Network and AIDS Clinical Trials Group. Participants: HIV-uninfected women reporting condomless vaginal or anal intercourse with at least 1 man with HIV infection or unknown serostatus within 90 days. Intervention: MVC only, MVC-emtricitabine (FTC), MVC-tenofovir disoproxil fumarate (TDF), and TDF-FTC (control). Measurements: At each visit, clinical and laboratory (including HIV) assessments were done. Primary outcomes were grade 3 and 4 adverse events and time to permanent discontinuation of the study regimen. All randomly assigned participants were analyzed according to their original assignment. Results: Among 188 participants, 85% completed follow-up, 11% withdrew early, and 4% were lost to follow-up; 19% discontinued their regimen prematurely. The number discontinuing and the time to discontinuation did not differ among regimens. Grade 3 or 4 adverse events occurred in 5 (MVC), 13 (MVC-FTC), 9 (MVC-TDF), and 8 (TDF-FTC) participants; rates did not differ among regimens. One death (by suicide) occurred in the MVC-TDF group but was judged not to be related to study drugs. Of available plasma samples at week 48 (n = 126), 60% showed detectable drug concentrations. No new HIV infections occurred. Limitations: Participants were not necessarily at high risk for HIV infection. The regimen comprised 3 pills taken daily. The study was not powered for efficacy. Conclusion: Maraviroc-containing PrEP regimens were safe and well-tolerated compared with TDF-FTC in U.S. women. No new HIV infections occurred, although whether this was due to study drugs or low risk in the population is uncertain. Maraviroccontaining PrEP for women may warrant further study. Primary Funding Source: National Institutes of Health.

Original language	English (US)
Pages (from-to)	384-393
Number of pages	10
Journal	Annals of internal medicine
Volume	167
Issue number	6
DOIs	https://doi.org/10.7326/M17-0520
State	Published - Sep 19 2017

ASJC Scopus subject areas

Internal Medicine

Access to Document

10.7326/M17-0520

Cite this

Gulick, R. M., Wilkin, T. J., Chen, Y. Q., Landovitz, R. J., Amico, K. R., Young, A. M., Richardson, P., Marzinke, M. A., Hendrix, C. W., Eshleman, S. H., McGowan, I., Cottle, L. M., Andrade, A., Marcus, C., Klingman, K. L., Chege, W., Rinehart, A. R., Rooney, J. F., Andrew, P., ... Mayer, K. H. (2017). Safety and tolerability of maraviroc-containing regimens to prevent HIV infection in women. Annals of internal medicine, 167(6), 384-393. https://doi.org/10.7326/M17-0520

Gulick, RM, Wilkin, TJ, Chen, YQ, Landovitz, RJ, Amico, KR, Young, AM, Richardson, P, Marzinke, MA , Hendrix, CW , Eshleman, SH, McGowan, I, Cottle, LM, Andrade, A, Marcus, C, Klingman, KL, Chege, W, Rinehart, AR, Rooney, JF, Andrew, P, Salata, RA, Siegel, M, Manabe, YC, Frank, I, Ho, K, Santana, J, Stekler, JD, Swaminathan, S, McCauley, M, Hodder, S & Mayer, KH 2017, 'Safety and tolerability of maraviroc-containing regimens to prevent HIV infection in women', Annals of internal medicine, vol. 167, no. 6, pp. 384-393. https://doi.org/10.7326/M17-0520

@article{071d86b0f7834515b5ffd905ae931ca9,

title = "Safety and tolerability of maraviroc-containing regimens to prevent HIV infection in women",

abstract = "Background: Maraviroc (MVC) is a candidate drug for HIV preexposure prophylaxis (PrEP). Objective: To assess the safety and tolerability of MVC-containing PrEP over 48 weeks in U.S. women at risk for HIV infection. Design: Phase 2 randomized, controlled, double-blinded study of 4 antiretroviral regimens used as PrEP. (ClinicalTrials.gov: NCT01505114) Setting: 12 clinical research sites of the HIV Prevention Trials Network and AIDS Clinical Trials Group. Participants: HIV-uninfected women reporting condomless vaginal or anal intercourse with at least 1 man with HIV infection or unknown serostatus within 90 days. Intervention: MVC only, MVC-emtricitabine (FTC), MVC-tenofovir disoproxil fumarate (TDF), and TDF-FTC (control). Measurements: At each visit, clinical and laboratory (including HIV) assessments were done. Primary outcomes were grade 3 and 4 adverse events and time to permanent discontinuation of the study regimen. All randomly assigned participants were analyzed according to their original assignment. Results: Among 188 participants, 85% completed follow-up, 11% withdrew early, and 4% were lost to follow-up; 19% discontinued their regimen prematurely. The number discontinuing and the time to discontinuation did not differ among regimens. Grade 3 or 4 adverse events occurred in 5 (MVC), 13 (MVC-FTC), 9 (MVC-TDF), and 8 (TDF-FTC) participants; rates did not differ among regimens. One death (by suicide) occurred in the MVC-TDF group but was judged not to be related to study drugs. Of available plasma samples at week 48 (n = 126), 60% showed detectable drug concentrations. No new HIV infections occurred. Limitations: Participants were not necessarily at high risk for HIV infection. The regimen comprised 3 pills taken daily. The study was not powered for efficacy. Conclusion: Maraviroc-containing PrEP regimens were safe and well-tolerated compared with TDF-FTC in U.S. women. No new HIV infections occurred, although whether this was due to study drugs or low risk in the population is uncertain. Maraviroccontaining PrEP for women may warrant further study. Primary Funding Source: National Institutes of Health.",

author = "Gulick, {Roy M.} and Wilkin, {Timothy J.} and Chen, {Ying Q.} and Landovitz, {Raphael J.} and Amico, {K. Rivet} and Young, {Alicia M.} and Paul Richardson and Marzinke, {Mark A.} and Hendrix, {Craig W.} and Eshleman, {Susan H.} and Ian McGowan and Cottle, {Leslie M.} and Adriana Andrade and Cheryl Marcus and Klingman, {Karin L.} and Wairimu Chege and Rinehart, {Alex R.} and Rooney, {James F.} and Philip Andrew and Salata, {Robert A.} and Marc Siegel and Manabe, {Yukari C.} and Ian Frank and Ken Ho and Jorge Santana and Stekler, {Joanne D.} and Shobha Swaminathan and Marybeth McCauley and Sally Hodder and Mayer, {Kenneth H.}",

note = "Publisher Copyright: {\textcopyright} 2017 American College of Physicians.",

year = "2017",

month = sep,

day = "19",

doi = "10.7326/M17-0520",

language = "English (US)",

volume = "167",

pages = "384--393",

journal = "Annals of internal medicine",

issn = "0003-4819",

publisher = "American College of Physicians",

number = "6",

}

TY - JOUR

T1 - Safety and tolerability of maraviroc-containing regimens to prevent HIV infection in women

AU - Gulick, Roy M.

AU - Wilkin, Timothy J.

AU - Chen, Ying Q.

AU - Landovitz, Raphael J.

AU - Amico, K. Rivet

AU - Young, Alicia M.

AU - Richardson, Paul

AU - Marzinke, Mark A.

AU - Hendrix, Craig W.

AU - Eshleman, Susan H.

AU - McGowan, Ian

AU - Cottle, Leslie M.

AU - Andrade, Adriana

AU - Marcus, Cheryl

AU - Klingman, Karin L.

AU - Chege, Wairimu

AU - Rinehart, Alex R.

AU - Rooney, James F.

AU - Andrew, Philip

AU - Salata, Robert A.

AU - Siegel, Marc

AU - Manabe, Yukari C.

AU - Frank, Ian

AU - Ho, Ken

AU - Santana, Jorge

AU - Stekler, Joanne D.

AU - Swaminathan, Shobha

AU - McCauley, Marybeth

AU - Hodder, Sally

AU - Mayer, Kenneth H.

PY - 2017/9/19

Y1 - 2017/9/19

N2 - Background: Maraviroc (MVC) is a candidate drug for HIV preexposure prophylaxis (PrEP). Objective: To assess the safety and tolerability of MVC-containing PrEP over 48 weeks in U.S. women at risk for HIV infection. Design: Phase 2 randomized, controlled, double-blinded study of 4 antiretroviral regimens used as PrEP. (ClinicalTrials.gov: NCT01505114) Setting: 12 clinical research sites of the HIV Prevention Trials Network and AIDS Clinical Trials Group. Participants: HIV-uninfected women reporting condomless vaginal or anal intercourse with at least 1 man with HIV infection or unknown serostatus within 90 days. Intervention: MVC only, MVC-emtricitabine (FTC), MVC-tenofovir disoproxil fumarate (TDF), and TDF-FTC (control). Measurements: At each visit, clinical and laboratory (including HIV) assessments were done. Primary outcomes were grade 3 and 4 adverse events and time to permanent discontinuation of the study regimen. All randomly assigned participants were analyzed according to their original assignment. Results: Among 188 participants, 85% completed follow-up, 11% withdrew early, and 4% were lost to follow-up; 19% discontinued their regimen prematurely. The number discontinuing and the time to discontinuation did not differ among regimens. Grade 3 or 4 adverse events occurred in 5 (MVC), 13 (MVC-FTC), 9 (MVC-TDF), and 8 (TDF-FTC) participants; rates did not differ among regimens. One death (by suicide) occurred in the MVC-TDF group but was judged not to be related to study drugs. Of available plasma samples at week 48 (n = 126), 60% showed detectable drug concentrations. No new HIV infections occurred. Limitations: Participants were not necessarily at high risk for HIV infection. The regimen comprised 3 pills taken daily. The study was not powered for efficacy. Conclusion: Maraviroc-containing PrEP regimens were safe and well-tolerated compared with TDF-FTC in U.S. women. No new HIV infections occurred, although whether this was due to study drugs or low risk in the population is uncertain. Maraviroccontaining PrEP for women may warrant further study. Primary Funding Source: National Institutes of Health.

AB - Background: Maraviroc (MVC) is a candidate drug for HIV preexposure prophylaxis (PrEP). Objective: To assess the safety and tolerability of MVC-containing PrEP over 48 weeks in U.S. women at risk for HIV infection. Design: Phase 2 randomized, controlled, double-blinded study of 4 antiretroviral regimens used as PrEP. (ClinicalTrials.gov: NCT01505114) Setting: 12 clinical research sites of the HIV Prevention Trials Network and AIDS Clinical Trials Group. Participants: HIV-uninfected women reporting condomless vaginal or anal intercourse with at least 1 man with HIV infection or unknown serostatus within 90 days. Intervention: MVC only, MVC-emtricitabine (FTC), MVC-tenofovir disoproxil fumarate (TDF), and TDF-FTC (control). Measurements: At each visit, clinical and laboratory (including HIV) assessments were done. Primary outcomes were grade 3 and 4 adverse events and time to permanent discontinuation of the study regimen. All randomly assigned participants were analyzed according to their original assignment. Results: Among 188 participants, 85% completed follow-up, 11% withdrew early, and 4% were lost to follow-up; 19% discontinued their regimen prematurely. The number discontinuing and the time to discontinuation did not differ among regimens. Grade 3 or 4 adverse events occurred in 5 (MVC), 13 (MVC-FTC), 9 (MVC-TDF), and 8 (TDF-FTC) participants; rates did not differ among regimens. One death (by suicide) occurred in the MVC-TDF group but was judged not to be related to study drugs. Of available plasma samples at week 48 (n = 126), 60% showed detectable drug concentrations. No new HIV infections occurred. Limitations: Participants were not necessarily at high risk for HIV infection. The regimen comprised 3 pills taken daily. The study was not powered for efficacy. Conclusion: Maraviroc-containing PrEP regimens were safe and well-tolerated compared with TDF-FTC in U.S. women. No new HIV infections occurred, although whether this was due to study drugs or low risk in the population is uncertain. Maraviroccontaining PrEP for women may warrant further study. Primary Funding Source: National Institutes of Health.

UR - http://www.scopus.com/inward/record.url?scp=85029682296&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85029682296&partnerID=8YFLogxK

U2 - 10.7326/M17-0520

DO - 10.7326/M17-0520

M3 - Article

C2 - 28828489

AN - SCOPUS:85029682296

SN - 0003-4819

VL - 167

SP - 384

EP - 393

JO - Annals of internal medicine

JF - Annals of internal medicine

IS - 6

ER -

Safety and tolerability of maraviroc-containing regimens to prevent HIV infection in women

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this