Antiretroviral therapy is a key determinant in the treatment and prevention of human immunodeficiency virus (HIV) infection. Initial treatment for patients with HIV infection generally includes two nucleoside reverse ...Antiretroviral therapy is a key determinant in the treatment and prevention of human immunodeficiency virus (HIV) infection. Initial treatment for patients with HIV infection generally includes two nucleoside reverse transcriptase inhibitors (NRTI) and a protease inhibitor (PI) or a nonnucleoside reverse transcriptase inhibitor (NNRTI). The combination antiretroviral therapy (refers to highly active antiretroviral therapy or HAART) showed a significant effect upon reducing morbidity and mortality of HIV disease. Cao and colleagues^1 began the clinical application of HAART in 1999 and completed the first clinical trial in China using a combination of two NRTIs and one PI. The result in using combivir (AZT+3TC) and indinavir (2 NRTIs+1 PI) are consistent with those reported in the literature.~2 In this study, we report the first virological and immunological outcomes in HIV infected Chinese patients treated with a combination of didanosine, stavudine and nevirapine (2 NRTIs+1 NNRTI) for 52 weeks.展开更多
Background An zidovudine （AZT）-substitution regimen containing 24-week stavudine （d4T） followed by long-term AZT for HIV therapy is potential to trade off short-term AZT-related anemia and long-term risks associat...Background An zidovudine （AZT）-substitution regimen containing 24-week stavudine （d4T） followed by long-term AZT for HIV therapy is potential to trade off short-term AZT-related anemia and long-term risks associated with d4T in resourcelimited settings.However,evidence is scarce.This study aims to assess the efficacy and safety of AZT-substitution regimen,aiming to find a regimen with better efficacy,less adverse events,and more affordability in resource-limited settings.Methods This prospective,multicenter study enrolled 499 （190 on d4T regimen,172 on AZT regimen,and 137 on AZT-substitution regimen） HIV-1-infected subjects who initiated combined antiretroviral therapy and attended follow-up visits over 96 weeks from 2009 to 2011.Lamivudine （3TC） and either nevirapine （NVP） or efavirenz （EFV） were the other two drugs in the antiretroviral regimens.Virologic and immunologic responses and adverse events were monitored at baseline and at weeks 4,12,24,36,48,60,72,84,and 96.Results In terms of hematological adverse effects,AZT-substitution group had similar safety profiles to d4T group and was superior to AZT group.In comparison with AZT-substitution group,AZT group was associated with higher risk of developing anemia （adjusted hazard ratio （aHR）for anemia ≥ grade Ⅱ,8.44,95％ CI 1.81-39.46） and neutropenia （aHR for neutropenia ≥ grade Ⅱ,1.86,95％ CI 1.19-2.93）.The prevalence of lipodystrophy in d4T group was 19.5％,while that in AZT-substitution group was zero.As to antiretroviral efficacy,these three groups showed no differences.Conclusion AZT-substitution regimen provides a relatively safe and effective first-line antiretroviral strategy in resource-limited settings.展开更多
Stavudine, a potent anti HIV and AIDS related complex, is one of the Nucleoside Analogue Reverse Transcriptase Inhibitors (NARTIs). It is phosphorylated intracellularly and then inhibits the viral reverse transcript...Stavudine, a potent anti HIV and AIDS related complex, is one of the Nucleoside Analogue Reverse Transcriptase Inhibitors (NARTIs). It is phosphorylated intracellularly and then inhibits the viral reverse transcriptase by acting as a false substrate. Modifications made on the hydrogen labile at the 5' position on the sugar is an interesting template for the elaboration of new potent anti HIV and AIDS drugs. The expected advantages of the modified stavudine prodrugs can be multiple: synergistic drug activities, enhancement of stavudine intracellular uptake, increase of stavudine brain delivery, and bypass of the first stavudine phosphorylation step into the cells. Nitric oxide synthase inhibitors of stavudine and nitric oxide donors of stavudine may hold significant promise for the treatment of HIV and AIDS.展开更多
Chitosan-stavudine （d4T） conjugate with a succinic spacer was synthesized via carbodiimide coupling reaction and structurally characterized. In order to nanosize it for improving its therapeutic properties, the chit...Chitosan-stavudine （d4T） conjugate with a succinic spacer was synthesized via carbodiimide coupling reaction and structurally characterized. In order to nanosize it for improving its therapeutic properties, the chitosan-5＇-O-succinyl-d4T conjugate was crosslinked with sodium tripolyphosphate （TPP） to obtain the chitosan-d4T conjugate nano-prodrug. The morphologies of chitosan-d4T conjugate nanoparticles were observed by transmission electron microscopy （TEM）, and their zeta potential, particle size, and polydispersity （size distribution） were measured by the dynamic light scattering （DLS） techniques. In vitro drug release studies at pH 1.1 and pH 7.4 indicate that the crosslinked chitosan-d4T conjugate nano-prodrug can prevent the coupled d4T from leaking out before entering the target viral reservoirs and provide a mild sustained release without the burst release. The results reveal that constructing conjugated chitosan nano-prodrugs may be a promising approach for improving the therapy efficacy of drugs in antiviral treatment.展开更多
This study examined whether melanonychia was more prevalent in 1) HIV positive individuals compared to HIV negative persons, 2) HIV positives exposed to zidovudine and/or stavudine and 3) those with darker skin pigmen...This study examined whether melanonychia was more prevalent in 1) HIV positive individuals compared to HIV negative persons, 2) HIV positives exposed to zidovudine and/or stavudine and 3) those with darker skin pigmentation. Procedures. 267 HIV positive and 273 HIV negative patients were examined for presence or absence of melanonychia and level of skin pigmentation using the Fitzgerald scale. Pharmacy records were examined for determining exposure to zidovudine or stavudine. Chi square, odds ratios and logistic regression were used to examine the study questions Main Findings. Melanonychia appeared in 49.1% of 267 HIV positive and 21.8% of 273 HIV negative subjects. Adjusting for skin pigmentation, HIV positives were 4.1 times more likely to have melanonychia than HIV negatives. Melanonychia was present in 54% of those receiving zidovudine and in 42% of those receiving stavudine (OR = 2.73, p = 0.05). In a multivariate model in HIV positives which included skin type, prescription of zidovudine and/or Stavudine, only dark skin (OR = 14.62, p < 0.001) and zidovudine (OR = 2.65, p < 0.03) were significant. Principal Conclusions. HIV infected persons are prone to melanonychia. This is more frequent in darker skinned persons and is enhanced in those exposed to zidovudine.展开更多
I.How it started I entered the Rega Institute for Medical Research in August 1964,as a medical student,to start working under the guidance of Prof.Piet De Somer,then professor of microbiology at the Leuven School of M...I.How it started I entered the Rega Institute for Medical Research in August 1964,as a medical student,to start working under the guidance of Prof.Piet De Somer,then professor of microbiology at the Leuven School of Medicine.When I graduated展开更多
文摘Antiretroviral therapy is a key determinant in the treatment and prevention of human immunodeficiency virus (HIV) infection. Initial treatment for patients with HIV infection generally includes two nucleoside reverse transcriptase inhibitors (NRTI) and a protease inhibitor (PI) or a nonnucleoside reverse transcriptase inhibitor (NNRTI). The combination antiretroviral therapy (refers to highly active antiretroviral therapy or HAART) showed a significant effect upon reducing morbidity and mortality of HIV disease. Cao and colleagues^1 began the clinical application of HAART in 1999 and completed the first clinical trial in China using a combination of two NRTIs and one PI. The result in using combivir (AZT+3TC) and indinavir (2 NRTIs+1 PI) are consistent with those reported in the literature.~2 In this study, we report the first virological and immunological outcomes in HIV infected Chinese patients treated with a combination of didanosine, stavudine and nevirapine (2 NRTIs+1 NNRTI) for 52 weeks.
文摘Background An zidovudine （AZT）-substitution regimen containing 24-week stavudine （d4T） followed by long-term AZT for HIV therapy is potential to trade off short-term AZT-related anemia and long-term risks associated with d4T in resourcelimited settings.However,evidence is scarce.This study aims to assess the efficacy and safety of AZT-substitution regimen,aiming to find a regimen with better efficacy,less adverse events,and more affordability in resource-limited settings.Methods This prospective,multicenter study enrolled 499 （190 on d4T regimen,172 on AZT regimen,and 137 on AZT-substitution regimen） HIV-1-infected subjects who initiated combined antiretroviral therapy and attended follow-up visits over 96 weeks from 2009 to 2011.Lamivudine （3TC） and either nevirapine （NVP） or efavirenz （EFV） were the other two drugs in the antiretroviral regimens.Virologic and immunologic responses and adverse events were monitored at baseline and at weeks 4,12,24,36,48,60,72,84,and 96.Results In terms of hematological adverse effects,AZT-substitution group had similar safety profiles to d4T group and was superior to AZT group.In comparison with AZT-substitution group,AZT group was associated with higher risk of developing anemia （adjusted hazard ratio （aHR）for anemia ≥ grade Ⅱ,8.44,95％ CI 1.81-39.46） and neutropenia （aHR for neutropenia ≥ grade Ⅱ,1.86,95％ CI 1.19-2.93）.The prevalence of lipodystrophy in d4T group was 19.5％,while that in AZT-substitution group was zero.As to antiretroviral efficacy,these three groups showed no differences.Conclusion AZT-substitution regimen provides a relatively safe and effective first-line antiretroviral strategy in resource-limited settings.
文摘Stavudine, a potent anti HIV and AIDS related complex, is one of the Nucleoside Analogue Reverse Transcriptase Inhibitors (NARTIs). It is phosphorylated intracellularly and then inhibits the viral reverse transcriptase by acting as a false substrate. Modifications made on the hydrogen labile at the 5' position on the sugar is an interesting template for the elaboration of new potent anti HIV and AIDS drugs. The expected advantages of the modified stavudine prodrugs can be multiple: synergistic drug activities, enhancement of stavudine intracellular uptake, increase of stavudine brain delivery, and bypass of the first stavudine phosphorylation step into the cells. Nitric oxide synthase inhibitors of stavudine and nitric oxide donors of stavudine may hold significant promise for the treatment of HIV and AIDS.
基金Funded by the National Natural Science Foundation of China(Nos.20504018,20972014,20604010,20872010 and 20732004)the National Basic Research Program of China(No.2009CB930203)
文摘Chitosan-stavudine （d4T） conjugate with a succinic spacer was synthesized via carbodiimide coupling reaction and structurally characterized. In order to nanosize it for improving its therapeutic properties, the chitosan-5＇-O-succinyl-d4T conjugate was crosslinked with sodium tripolyphosphate （TPP） to obtain the chitosan-d4T conjugate nano-prodrug. The morphologies of chitosan-d4T conjugate nanoparticles were observed by transmission electron microscopy （TEM）, and their zeta potential, particle size, and polydispersity （size distribution） were measured by the dynamic light scattering （DLS） techniques. In vitro drug release studies at pH 1.1 and pH 7.4 indicate that the crosslinked chitosan-d4T conjugate nano-prodrug can prevent the coupled d4T from leaking out before entering the target viral reservoirs and provide a mild sustained release without the burst release. The results reveal that constructing conjugated chitosan nano-prodrugs may be a promising approach for improving the therapy efficacy of drugs in antiviral treatment.
文摘This study examined whether melanonychia was more prevalent in 1) HIV positive individuals compared to HIV negative persons, 2) HIV positives exposed to zidovudine and/or stavudine and 3) those with darker skin pigmentation. Procedures. 267 HIV positive and 273 HIV negative patients were examined for presence or absence of melanonychia and level of skin pigmentation using the Fitzgerald scale. Pharmacy records were examined for determining exposure to zidovudine or stavudine. Chi square, odds ratios and logistic regression were used to examine the study questions Main Findings. Melanonychia appeared in 49.1% of 267 HIV positive and 21.8% of 273 HIV negative subjects. Adjusting for skin pigmentation, HIV positives were 4.1 times more likely to have melanonychia than HIV negatives. Melanonychia was present in 54% of those receiving zidovudine and in 42% of those receiving stavudine (OR = 2.73, p = 0.05). In a multivariate model in HIV positives which included skin type, prescription of zidovudine and/or Stavudine, only dark skin (OR = 14.62, p < 0.001) and zidovudine (OR = 2.65, p < 0.03) were significant. Principal Conclusions. HIV infected persons are prone to melanonychia. This is more frequent in darker skinned persons and is enhanced in those exposed to zidovudine.
文摘I.How it started I entered the Rega Institute for Medical Research in August 1964,as a medical student,to start working under the guidance of Prof.Piet De Somer,then professor of microbiology at the Leuven School of Medicine.When I graduated
