{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T08:55:55Z","timestamp":1777452955274,"version":"3.51.4"},"reference-count":50,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2018,4,1]],"date-time":"2018-04-01T00:00:00Z","timestamp":1522540800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Antiviral Therapy"],"published-print":{"date-parts":[[2019,4]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Cancer is a leading cause of death in HIV-infected patients in the era of combination antiretroviral therapy (cART). Yet, there are no specific guidelines for the combined use of cART and chemotherapy in HIV-infected cancer patients. The cellular enzyme thymidylate synthase (TS) catalyses the conversion of dUMP to TMP, which is converted to TDP and ultimately to TTP, a building block in DNA synthesis. TS inhibitors are recommended in some cancers, particularly non-small cell lung cancer (NSCLC). Because TS inhibitors modulate intracellular concentrations of endogenous 2\u2032-deoxynucleotides, we hypothesized that TS inhibitors could impact the anti-HIV activity of nucleoside analogue reverse transcriptase inhibitors (NRTIs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We evaluated gemcitabine and pemetrexed, two approved TS inhibitors, on the anti-HIV activities of NRTIs in infectivity assays using peripheral blood mononuclear cells (PBMCs) and in humanized mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Gemcitabine enhanced the anti-HIV activities of tenofovir, abacavir and emtricitabine (FTC) in PBMCs. In contrast, pemetrexed had no effect on tenofovir, enhanced abacavir and, unexpectedly, decreased FTC and lamivudine (3TC) activities. Pemetrexed inhibitory effects on FTC and 3TC may be due to lower concentrations of active metabolites (FTCtp and 3TCtp) relative to their competing endogenous nucleotide (dCTP), as shown by decreases in FTCtp\/dCTP ratios. Gemcitabine enhanced tenofovir while pemetrexed abrogated FTC antiviral activity in humanized mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Chemotherapy with TS inhibitors can have opposing effects on cART, potentially impacting control of HIV and thereby development of viral resistance and size of the reservoir in HIV-infected cancer patients. Combinations of cART and chemotherapy should be carefully selected.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3851\/imp3285","type":"journal-article","created":{"date-parts":[[2018,12,21]],"date-time":"2018-12-21T07:28:48Z","timestamp":1545377328000},"page":"177-186","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":4,"title":["Disparate effects of Cytotoxic Chemotherapy on the Antiviral Activity of Antiretroviral Therapy: Implications for Treatments of HIV-Infected Cancer Patients"],"prefix":"10.1177","volume":"24","author":[{"given":"Sandra","family":"Medina-Moreno","sequence":"first","affiliation":[{"name":"Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan C","family":"Zapata","sequence":"additional","affiliation":[{"name":"Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mackenzie L","family":"Cottrell","sequence":"additional","affiliation":[{"name":"Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina \u2013 Chapel Hill, Chapel Hill, NC, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nhut M","family":"Le","sequence":"additional","affiliation":[{"name":"Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sijia","family":"Tao","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Center for AIDS Research, Emory University School of Medicine, Atlanta, GA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph","family":"Bryant","sequence":"additional","affiliation":[{"name":"Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edward","family":"Sausville","sequence":"additional","affiliation":[{"name":"Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raymond F","family":"Schinazi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Center for AIDS Research, Emory University School of Medicine, Atlanta, GA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela DM","family":"Kashuba","sequence":"additional","affiliation":[{"name":"Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina \u2013 Chapel Hill, Chapel Hill, NC, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert R","family":"Redfield","sequence":"additional","affiliation":[{"name":"Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alonso","family":"Heredia","sequence":"additional","affiliation":[{"name":"Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2018,4,1]]},"reference":[{"key":"bibr1-IMP3285","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cix392"},{"key":"bibr2-IMP3285","unstructured":"Panel on Antiretroviral Guidelines for Adults and Adolescents. 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