Antiretroviral drugs Archives - Revista Brasileira de Ginecologia e Obstetrícia
Summary
Rev Bras Ginecol Obstet. 2006;28(3):184-189
DOI 10.1590/S0100-72032006000300008
PURPOSE: to evaluate the chronic effects of nelfinavir on body weight gain of pregnant albino rats and their concepts, as well as on the number of implantations, reabsorptions, fetuses, placentae, and maternal and fetal mortality. METHODS: fifty pregnant EPM-1 Wistar albino rats were randomly divided into five groups: two controls, Contr1 (control of stress) and Contr2 (drug vehicle control), and 3 experimental groups, Exp40, Exp120, Exp360, which received 40, 120 or 360 mg/kg per day of oral solution of nelfinavir, respectively. The drug and the vehicle (distilled water) were administered twice a day (12/12 h) by gavage from the first up to the 20th day of pregnancy. After sacrifice under deep anesthesia, the following parameters were evaluated: number of implantations and reabsorptions, the weight of fetuses and placentae, and the number of intrauterine deaths as well as inspection for major malformations. Data were evaluated by ANOVA followed by the Kruskal-Wallis multiple comparison test. RESULTS: body weight gain during pregnancy was normal for all the groups, and no significant differences were detected between them. ANOVA did not reveal any significant effect of nelfinavir on the studied parameters. The means of number of fetuses were: control = 9.7±0.50; nelfinavir-treated groups = 9.7±0.81. Regarding the means of number of placentae and implantations, controls = 9.7±0.50; nelfinavir-treated groups = 9.6±0.78. The mean fetal weights were as follows: controls = 4.04±0.50; nelfinavir-treated groups = 3.91±0.33 g. Finally, control placental weights averaged 0.64±0.02; nelfinavir-treated groups = 0.67±0.02 g. CONCLUSION: nelfinavir was well tolerated at all the administered doses; no damage was produced on the fetuses.
Summary
Rev Bras Ginecol Obstet. 2006;28(3):184-189
DOI 10.1590/S0100-72032006000300008
PURPOSE: to evaluate the chronic effects of nelfinavir on body weight gain of pregnant albino rats and their concepts, as well as on the number of implantations, reabsorptions, fetuses, placentae, and maternal and fetal mortality. METHODS: fifty pregnant EPM-1 Wistar albino rats were randomly divided into five groups: two controls, Contr1 (control of stress) and Contr2 (drug vehicle control), and 3 experimental groups, Exp40, Exp120, Exp360, which received 40, 120 or 360 mg/kg per day of oral solution of nelfinavir, respectively. The drug and the vehicle (distilled water) were administered twice a day (12/12 h) by gavage from the first up to the 20th day of pregnancy. After sacrifice under deep anesthesia, the following parameters were evaluated: number of implantations and reabsorptions, the weight of fetuses and placentae, and the number of intrauterine deaths as well as inspection for major malformations. Data were evaluated by ANOVA followed by the Kruskal-Wallis multiple comparison test. RESULTS: body weight gain during pregnancy was normal for all the groups, and no significant differences were detected between them. ANOVA did not reveal any significant effect of nelfinavir on the studied parameters. The means of number of fetuses were: control = 9.7±0.50; nelfinavir-treated groups = 9.7±0.81. Regarding the means of number of placentae and implantations, controls = 9.7±0.50; nelfinavir-treated groups = 9.6±0.78. The mean fetal weights were as follows: controls = 4.04±0.50; nelfinavir-treated groups = 3.91±0.33 g. Finally, control placental weights averaged 0.64±0.02; nelfinavir-treated groups = 0.67±0.02 g. CONCLUSION: nelfinavir was well tolerated at all the administered doses; no damage was produced on the fetuses.
Summary
Rev Bras Ginecol Obstet. 2004;26(5):369-375
DOI 10.1590/S0100-72032004000500005
OBJECTIVE: to assess the action of antiretroviral drugs on glycid metabolism and on the pancreas of pregnant Wistar rats. METHODS: adult pregnant Wistar rats weighing 200-230g were used. Azidothymidine, lamivudine and nelfinavir were administered to the animals at doses 10 times higher than those administered to pregnant women. The animals were divided into seven groups of 10 animals, including a control group. The animals were sacrificed on the 21st day of pregnancy and glycemia, insulinemia, glucagonemia, free fatty acids (FFA) and hepatic glycogen were measured. Direct counts of the number of immunohistochemically labeled insulin- and glucagon-producing cells were used to determine pancreatic damage. Data were analyzed statistically by the Student's t-test comparing each treated group with the control group. RESULTS: increased serum glucagon (control group: 88.2 pg/ml; treated groups: 99.7-120.7 pg/ml) and reduced insulin (control group: 6.2 muIU/ml; treated groups: 2.1-2.7 muIU/ml) were observed in all groups treated with antiretroviral drugs after 21 days of pregnancy. There was no significant difference between the experimental groups and the control in glycemia, plasma FFA or hepatic glycogen. Also, there was no significant difference in number of insulin- and glucagon-producing cells between the treated groups and the control. CONCLUSION: treatment of noninfected rats with antiretroviral drugs during pregnancy altered maternal glycid metabolism causing insulin decrease and glucagon elevation, with normal glycemia and unchanged number of pancreatic cells.
Summary
Rev Bras Ginecol Obstet. 2004;26(5):369-375
DOI 10.1590/S0100-72032004000500005
OBJECTIVE: to assess the action of antiretroviral drugs on glycid metabolism and on the pancreas of pregnant Wistar rats. METHODS: adult pregnant Wistar rats weighing 200-230g were used. Azidothymidine, lamivudine and nelfinavir were administered to the animals at doses 10 times higher than those administered to pregnant women. The animals were divided into seven groups of 10 animals, including a control group. The animals were sacrificed on the 21st day of pregnancy and glycemia, insulinemia, glucagonemia, free fatty acids (FFA) and hepatic glycogen were measured. Direct counts of the number of immunohistochemically labeled insulin- and glucagon-producing cells were used to determine pancreatic damage. Data were analyzed statistically by the Student's t-test comparing each treated group with the control group. RESULTS: increased serum glucagon (control group: 88.2 pg/ml; treated groups: 99.7-120.7 pg/ml) and reduced insulin (control group: 6.2 muIU/ml; treated groups: 2.1-2.7 muIU/ml) were observed in all groups treated with antiretroviral drugs after 21 days of pregnancy. There was no significant difference between the experimental groups and the control in glycemia, plasma FFA or hepatic glycogen. Also, there was no significant difference in number of insulin- and glucagon-producing cells between the treated groups and the control. CONCLUSION: treatment of noninfected rats with antiretroviral drugs during pregnancy altered maternal glycid metabolism causing insulin decrease and glucagon elevation, with normal glycemia and unchanged number of pancreatic cells.
Summary
Rev Bras Ginecol Obstet. 2004;26(1):31-36
DOI 10.1590/S0100-72032004000100005
PURPOSE: to experimentally evaluate the diabetogenic effects of antiretroviral drugs on pregnant Wistar rats and the perinatal effects on the offspring. METHODS: adult female pregnant Wistar rats weighing 200-230 g were used. The antiretroviral drugs zidovudine (ZDV), lamivudine (3TC) and nelfinavir (NFV) were used alone and in association at daily doses of ten times the dose normally used in pregnant women, proportionally to the animal's body weight. Seven groups were studied, including the control. The experiment started on day 0 of pregnancy and the pregnant animals were sacrificed on day 21. The fetuses were counted and weighed. Blood determinations of glucose, insulin, glucagon and lactate were performed on day 21. The retroperitoneal adipose tissue was weighed. Data were analyzed statistically by Student's t-test. RESULTS: the groups treated with 3TC, ZDV + 3TC and ZDV + 3TC + NFV showed decreasing values of maternal daily body weight gain, retroperitoneal adipose tissue weight and weight of fetuses (control group: 6.2 g; 3TC group variation: 4.1-5.6 g). The serum lactate levels were also decreased when compared to the control in these groups (control group: 5.8 mmol/mL; 3TC group variations: 3.2-3.7 mmol/mL). All antiretroviral-treated groups showed a decreasing number of fetuses when compared to the control (control group: 14.7; drug group variation: 11.1-12.7). All treated groups also showed decreasing serum values of insulin (control group: 6.2 µIU/mL; drug group variation: 2.1 to 2.7 µIU/mL) and increasing serum levels of glucagon when compared to the control (control group: 88.2 pg/mL; drug group variation: 99.7 to 120.7 pg/mL). There was no statistical significance of glucose levels when comparing treated groups to the control. CONCLUSIONS: the antiretroviral drugs interfered in carbohydrate metabolism of pregnant rats and reduced the number of fetuses. 3TC caused less maternal body weight gain, decreased fetus weight and lactate and insulin levels and increased serum glucagon.
Summary
Rev Bras Ginecol Obstet. 2004;26(1):31-36
DOI 10.1590/S0100-72032004000100005
PURPOSE: to experimentally evaluate the diabetogenic effects of antiretroviral drugs on pregnant Wistar rats and the perinatal effects on the offspring. METHODS: adult female pregnant Wistar rats weighing 200-230 g were used. The antiretroviral drugs zidovudine (ZDV), lamivudine (3TC) and nelfinavir (NFV) were used alone and in association at daily doses of ten times the dose normally used in pregnant women, proportionally to the animal's body weight. Seven groups were studied, including the control. The experiment started on day 0 of pregnancy and the pregnant animals were sacrificed on day 21. The fetuses were counted and weighed. Blood determinations of glucose, insulin, glucagon and lactate were performed on day 21. The retroperitoneal adipose tissue was weighed. Data were analyzed statistically by Student's t-test. RESULTS: the groups treated with 3TC, ZDV + 3TC and ZDV + 3TC + NFV showed decreasing values of maternal daily body weight gain, retroperitoneal adipose tissue weight and weight of fetuses (control group: 6.2 g; 3TC group variation: 4.1-5.6 g). The serum lactate levels were also decreased when compared to the control in these groups (control group: 5.8 mmol/mL; 3TC group variations: 3.2-3.7 mmol/mL). All antiretroviral-treated groups showed a decreasing number of fetuses when compared to the control (control group: 14.7; drug group variation: 11.1-12.7). All treated groups also showed decreasing serum values of insulin (control group: 6.2 µIU/mL; drug group variation: 2.1 to 2.7 µIU/mL) and increasing serum levels of glucagon when compared to the control (control group: 88.2 pg/mL; drug group variation: 99.7 to 120.7 pg/mL). There was no statistical significance of glucose levels when comparing treated groups to the control. CONCLUSIONS: the antiretroviral drugs interfered in carbohydrate metabolism of pregnant rats and reduced the number of fetuses. 3TC caused less maternal body weight gain, decreased fetus weight and lactate and insulin levels and increased serum glucagon.
Summary
Rev Bras Ginecol Obstet. 2003;25(8):593-598
DOI 10.1590/S0100-72032003000800008
PURPOSE: to investigate the effect of antiretroviral drugs on the lipid metabolism in HIV-infected pregnant women. METHODS: a prospective study was conducted on 57 pregnant women. The women were divided into three groups: ZDV group, consisting of 20 HIV-infected women taking ZDV; TT group, consisting of 25 HIV-1-infected women on triple antiretroviral treatment (ZDV + 3TC + NFV), and control group, consisting of 12 pregnant women considered to be normal from a clinical and laboratory viewpoint. Demographic and anthropometric data were homogeneous. Patients with a personal and family history of hyperlipidemia were excluded. Blood samples were obtained for the determination of fasting lipids (total cholesterol, LDL and HDL, and triglycerides) at four periods during pregnancy (1st = 14-20 weeks; 2nd = 21-26 weeks; 3rd = 27-32 weeks and 4th = 33-38 weeks). Data were analyzed statistically using the nonparametric chi², Friedman and Kruskal-Wallis tests . RESULTS: the use of antiretroviral drugs during pregnancy induced no difference in total or HDL cholesterol but caused an increase from 76.5 and 84 mg/dL to 96 and 105 mg/dL in the concentration of the LDL fraction along gestation in ZDV and TT groups, respectively (p<0.01). A positive significant association was observed between triglycerides and viral burden in the ZDV group (r: 0.534; p=0.015). CONCLUSION: Antiretroviral agents during pregnancy increase serum LDL-colesterol levels. The risk of pregnancy regarding potentiation of long-term antiretroviral effects on lipid metabolism, remains to be established.
Summary
Rev Bras Ginecol Obstet. 2003;25(8):593-598
DOI 10.1590/S0100-72032003000800008
PURPOSE: to investigate the effect of antiretroviral drugs on the lipid metabolism in HIV-infected pregnant women. METHODS: a prospective study was conducted on 57 pregnant women. The women were divided into three groups: ZDV group, consisting of 20 HIV-infected women taking ZDV; TT group, consisting of 25 HIV-1-infected women on triple antiretroviral treatment (ZDV + 3TC + NFV), and control group, consisting of 12 pregnant women considered to be normal from a clinical and laboratory viewpoint. Demographic and anthropometric data were homogeneous. Patients with a personal and family history of hyperlipidemia were excluded. Blood samples were obtained for the determination of fasting lipids (total cholesterol, LDL and HDL, and triglycerides) at four periods during pregnancy (1st = 14-20 weeks; 2nd = 21-26 weeks; 3rd = 27-32 weeks and 4th = 33-38 weeks). Data were analyzed statistically using the nonparametric chi², Friedman and Kruskal-Wallis tests . RESULTS: the use of antiretroviral drugs during pregnancy induced no difference in total or HDL cholesterol but caused an increase from 76.5 and 84 mg/dL to 96 and 105 mg/dL in the concentration of the LDL fraction along gestation in ZDV and TT groups, respectively (p<0.01). A positive significant association was observed between triglycerides and viral burden in the ZDV group (r: 0.534; p=0.015). CONCLUSION: Antiretroviral agents during pregnancy increase serum LDL-colesterol levels. The risk of pregnancy regarding potentiation of long-term antiretroviral effects on lipid metabolism, remains to be established.
Summary
Rev Bras Ginecol Obstet. 2003;25(7):465-471
DOI 10.1590/S0100-72032003000700002
PURPOSE: to investigate the effect of antiretroviral drugs on carbohydrate metabolism in HIV-infected pregnant women and on fetal and neonatal prognosis. METHODS: a prospective study was conducted on 57 pregnant women. The women were divided into three groups: ZDV group, taking zidovudine (n=20), TT group, taking zidovudine + lamivudine + nelfinavir (n=25), and control group (n=12). Blood samples were obtained for the determination of the area under the curve (AUC) after a 75-g oral glucose test at four periods during pregnancy (1st=14-20 weeks, 2nd= 21-26 weeks, 3rd=27-32 weeks and 4th=33-38 weeks). Perinatal prognosis was based on prematurity rates, intrauterine growth restriction (IUGR), low birth weight, perinatal mortality, and vertical HIV-1 transmission. Data were analyzed statistically using the nonparametric c² test, Friedman test and Kruskal-Wallis test. RESULTS: the median values of the AUC were 11.685 mg/dL for the control group, 13.477 mg/dL for the ZDV Group, and 13.650 mg/dL for the TT group (p=0.049). The antiretroviral agents had no deleterious effects on prematurity, low birth weight, IUGR rates or on Apgar score. There was no case of vertical transmission of HIV-1. CONCLUSIONS: an association was detected between the use of triple therapy and the development of carbohydrate intolerance during pregnancy. This association was not shown with ZDV alone. The antiretroviral agents had no deleterious effects on perinatal prognosis.
Summary
Rev Bras Ginecol Obstet. 2003;25(7):465-471
DOI 10.1590/S0100-72032003000700002
PURPOSE: to investigate the effect of antiretroviral drugs on carbohydrate metabolism in HIV-infected pregnant women and on fetal and neonatal prognosis. METHODS: a prospective study was conducted on 57 pregnant women. The women were divided into three groups: ZDV group, taking zidovudine (n=20), TT group, taking zidovudine + lamivudine + nelfinavir (n=25), and control group (n=12). Blood samples were obtained for the determination of the area under the curve (AUC) after a 75-g oral glucose test at four periods during pregnancy (1st=14-20 weeks, 2nd= 21-26 weeks, 3rd=27-32 weeks and 4th=33-38 weeks). Perinatal prognosis was based on prematurity rates, intrauterine growth restriction (IUGR), low birth weight, perinatal mortality, and vertical HIV-1 transmission. Data were analyzed statistically using the nonparametric c² test, Friedman test and Kruskal-Wallis test. RESULTS: the median values of the AUC were 11.685 mg/dL for the control group, 13.477 mg/dL for the ZDV Group, and 13.650 mg/dL for the TT group (p=0.049). The antiretroviral agents had no deleterious effects on prematurity, low birth weight, IUGR rates or on Apgar score. There was no case of vertical transmission of HIV-1. CONCLUSIONS: an association was detected between the use of triple therapy and the development of carbohydrate intolerance during pregnancy. This association was not shown with ZDV alone. The antiretroviral agents had no deleterious effects on perinatal prognosis.
Summary
Rev Bras Ginecol Obstet. 2002;24(10):647-652
DOI 10.1590/S0100-72032002001000003
PURPOSE: to evaluate experimentally the effects of antiretroviral drugs used alone and in association upon the fertility of pregnant Wistar rats and the perinatal effects on the offspring. METHODS: adult female pregnant Wistar rats weighing 200-230 g were used. The antiretroviral drugs zidovudine (AZT), lamivudine (3TC) and nelfinavir (NFV) were used alone and in association at daily doses of ten times the dose normally used in pregnant women, proportionally to the animal's body weight. Seven groups were studied, including the control one. The experiment started on day 0 and the pregnant animals were sacrificed on day 21. The alive and dead fetuses, the total implantation sites and the total numbers of corporea lutea were used to calculate the fertility values. The statistical analysis was performed by Student's t test and by the Mann-Whitney test. RESULTS: there were no significant statistical differences regarding preimplantation loss and implantation efficiency values of the rats treated with isolated and associated antiretroviral drugs. There was a significant increase in the postimplantation loss values (control group: 7.6%; drug groups variation: 20.2-26.7%), a decrease in the fetal viability values (control group: 92.4%, drug groups variation: 73.3-79.8%), and a decreasing number of fetuses per animal (control group: 14.7; drug groups variation: 11.1-12.7). There was a significant weight reduction of the female rats and of the offspring of animals treated with 3TC, AZT + 3TC and AZT + 3TC + NFV. CONCLUSION: with the administration of high antiretroviral doses, important fertility effects could be observed, which showed that less histotoxic antiretroviral drugs must be studied in order to warrant the safety of using these medicines in pregnant HIV-1 - infected women.
Summary
Rev Bras Ginecol Obstet. 2002;24(10):647-652
DOI 10.1590/S0100-72032002001000003
PURPOSE: to evaluate experimentally the effects of antiretroviral drugs used alone and in association upon the fertility of pregnant Wistar rats and the perinatal effects on the offspring. METHODS: adult female pregnant Wistar rats weighing 200-230 g were used. The antiretroviral drugs zidovudine (AZT), lamivudine (3TC) and nelfinavir (NFV) were used alone and in association at daily doses of ten times the dose normally used in pregnant women, proportionally to the animal's body weight. Seven groups were studied, including the control one. The experiment started on day 0 and the pregnant animals were sacrificed on day 21. The alive and dead fetuses, the total implantation sites and the total numbers of corporea lutea were used to calculate the fertility values. The statistical analysis was performed by Student's t test and by the Mann-Whitney test. RESULTS: there were no significant statistical differences regarding preimplantation loss and implantation efficiency values of the rats treated with isolated and associated antiretroviral drugs. There was a significant increase in the postimplantation loss values (control group: 7.6%; drug groups variation: 20.2-26.7%), a decrease in the fetal viability values (control group: 92.4%, drug groups variation: 73.3-79.8%), and a decreasing number of fetuses per animal (control group: 14.7; drug groups variation: 11.1-12.7). There was a significant weight reduction of the female rats and of the offspring of animals treated with 3TC, AZT + 3TC and AZT + 3TC + NFV. CONCLUSION: with the administration of high antiretroviral doses, important fertility effects could be observed, which showed that less histotoxic antiretroviral drugs must be studied in order to warrant the safety of using these medicines in pregnant HIV-1 - infected women.