Reference

Pancreatic toxic effects associated with co-administration of didanosine and tenofovir in HIV-infected adults

Pancreatic toxic effects associated with co-administration of didanosine and tenofovir in HIV-infected adults. Martinez, Esteban; Milinkovic, Ana; de Lazzari, Elisa; Ravasi, Giovanni; Blanco, Jose L.; Larrousse, Maria; Mallolas, Josep; Garcia, Felipe; Miro, Jose M.; Gatell, Jose M. (Infectious Diseases Unit, Hospital Clinic, University of Barcelona, Barcelona 08036, Spain). Lancet, 364(9428), 65-67 (English) 2004 Elsevier. CODEN: LANCAO. ISSN: 0140-6736. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) The rise in didanosine concns. in plasma when given with tenofovir raises concern for a high risk of toxic effects. Recommendations to reduce didanosine dose have been issued, but only for adults weighing more than 60 kg. We reviewed cases of pancreatitis in patients receiving didanosine plus tenofovir, didanosine alone, and tenofovir alone to assess the incidence of and risk factors for pancreatitis. Between Aug 1, 2001, and Nov 30, 2003, five of 185 (2.7%) patients receiving didanosine plus tenofovir, one of 182 (0.5%) on didanosine without tenofovir, and none of 208 on tenofovir without didanosine developed pancreatitis (p=0.016). Co-administration of both drugs vs. each of them individually was an independent risk factor for pancreatitis (crude hazard ratio 10.666, 95% CI 1.246-91.294, p=0.In this experiment, several chemicals are used like 69655-05-6 and 147127-20-6 031). These results suggest that the risk of pancreatitis is heightened when didanosine and tenofovir are given together. .

Transient early post-inoculation anti-retroviral treatment facilitates controlled infection with sparing of CD4+ T cells in gut-associated lymphoid tissues in SIVmac239-infected rhesus macaques, but not resistance to rechallenge

Transient early post-inoculation anti-retroviral treatment facilitates controlled infection with sparing of CD4+ T cells in gut-associated lymphoid tissues in SIVmac239-infected rhesus macaques, but not resistance to rechallenge.Some chemicals with cas registry numbers like 147127-20-6 are also used. Lifson, J. D.; Piatak, M., Jr.; Cline, A. N.; Rossio, J. L.; Purcell, J.; Pandrea, I.; Bischofberger, N.; Blanchard, J.; Veazey, R. S. (Retroviral Pathogenesis Laboratory, AIDS Vaccine Program, SAIC Frederick, Inc./NCI-Frederick, Frederick, MD 21702, USA). Journal of Medical Primatology, 32(4-5), 201-210 (English) 2003 Blackwell Publishing Ltd. CODEN: JMPMAO. ISSN: 0047-2565. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Like human immunodeficiency virus infection of humans, infection of rhesus macaques with pathogenic simian immunodeficiency virus (SIV) strains typically results in persistent progressive infection, leading to clin. significant immunosuppression. In previous studies, we administered short term anti-retroviral treatment, shortly after i.v. inoculation with SIVsmE660, in an effort to allow immunol. sensitization under conditions not characterized by overwhelming cytopathic infection compromising the developing immune response. We showed that such treatment allowed control of off treatment viremia and was assocd. with resistance to rechallenge. Control of off treatment viremia was assocd., at least in part, with CD8+ lymphocytes, based on in vivo CD8 depletion studies. In the present study, six rhesus macaques were infected i.v. with 100 MID(50) of SIVmac239; four then received 30 days of treatment with tenofovir 9-[2-(R)-(phosphonomethoxy)propyl]adenine (PMPA); 20-30 mg/kg, s.c. starting 24 h post-inoculation. Tenofovir-treated animals showed low (<500 copy Eq/mL) or undetectable (<100 copy Eq/mL) plasma SIV RNA levels during treatment, with undetectable plasma viremia following discontinuation of treatment. Plasma SIV RNA remained <100 copy Eq/mL, even after depletion of CD8+ lymphocytes, 6 wk after discontinuation of tenofovir treatment. In contrast to untreated infected control animals that showed substantial depletion of CD4+ T cells from gut-assocd. lymphoid tissues (GALT), tenofovir-treated animals showed sparing of GALT CD4+ T cells both during the treatment period and in the off treatment follow-up period. However, in contrast to earlier results with animals infected with SIVsmE660, in the present study, the animals did not develop readily measurable cellular anti-SIV immune responses, and did not resist homologous rechallenge with SIVmac239, administered 44 wk after the initial infection. Differences in the animals and virus strains employed may in part account for the differences in results obsd. Comparative anal. of virol. and immunol. parameters in this model system may provide important insights for understanding the basis of effective immunol. control of SIV infection. .