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      Contracepção hormonal e anti-retrovirais em mulheres infectadas pelo HIV Translated title: Hormonal contraception and antiretroviral therapy among HIV-infected women

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          Abstract

          Há controvérsia sobre a relação entre o uso de contraceptivos hormonais e o risco de adquirir o vírus da imunodeficiência humana (HIV), e pouco se sabe sobre os efeitos da contracepção hormonal em mulheres infectadas (efeitos colaterais, distúrbios menstruais, progressão da doença, interações com terapias anti-retrovirais). O objetivo deste artigo foi revisar os dados disponíveis quanto à vulnerabilidade ao HIV e à sua transmissibilidade na vigência do uso de contraceptivos hormonais bem como as conseqüências potenciais do uso desses contraceptivos por mulheres HIV-positivas sob terapia anti-retroviral (TARV), com ênfase nas interações medicamentosas. Concluiu-se que ainda não é possível elaborar recomendações, baseadas em evidências, sobre a contracepção hormonal em mulheres portadoras do HIV sob TARV. Assim, os infectologistas e os ginecologistas devem estar atentos às interações potenciais que possam representar aumento de efeitos adversos, individualizando a orientação sobre os esteróides contraceptivos, suas doses e vias de administração, considerando a TARV em uso.

          Translated abstract

          There is much controversy regarding the realtionship between the use of hormonal contraceptives and the risk of acquiring human immunodeficiency virus (HIV), and little is known about the effects of hormonal contraception in HIV-infected women (adverse events, menstrual disorders, disease progression, antiretroviral therapy interactions). The aim of the present study was to review available data regarding HIV vulnerability and transmission associated with hormonal contraceptives and the use of these contraceptives by women on antiretroviral therapy, with emphasis on drug interactions. In conclusion, it was not possible to offer evidence-based recommendations for the use of hormonal contraceptives among HIV-infected women under antiretroviral therapy. Infectious disease specialists and gynecologists providing care should be cautious about potential drug interaction leading to increase in adverse events, individualizing contraceptive drugs, route, and dosage, according to the antiretroviral therapy under use.

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          Most cited references27

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          Clinical importance of the cytochromes P450.

          The human cytochrome P450 (CYP) superfamily comprises 57 genes. These genes code for enzymes that can have a role in: metabolism of drugs, foreign chemicals, arachidonic acid and eicosanoids; cholesterol metabolism and bile-acid biosynthesis; steroid synthesis and metabolism; vitamin D(3) synthesis and metabolism; retinoic acid hydroxylation; and those of still unknown function. Cytochrome P450 was once believed to be mainly a hepatic drug detoxication system, but is now understood to include a myriad of enzymic reactions implicated in important life processes. Mutations in many CYP genes cause inborn errors of metabolism and contribute to many clinically relevant diseases.
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            Comparison of sequential three-drug regimens as initial therapy for HIV-1 infection.

            The optimal sequencing of antiretroviral regimens for the treatment of infection with human immunodeficiency virus type 1 (HIV-1) is unknown. We compared several different antiretroviral treatment strategies. This multicenter, randomized, partially double-blind trial used a factorial design to compare pairs of sequential three-drug regimens, starting with a regimen including zidovudine and lamivudine or a regimen including didanosine and stavudine in combination with either nelfinavir or efavirenz. The primary end point was the length of time to the failure of the second three-drug regimen. A total of 620 subjects who had not previously received antiretroviral therapy were followed for a median of 2.3 years. Starting with a three-drug regimen containing efavirenz combined with zidovudine and lamivudine (but not efavirenz combined with didanosine and stavudine) appeared to delay the failure of the second regimen, as compared with starting with a regimen containing nelfinavir (hazard ratio for failure of the second regimen, 0.71; 95 percent confidence interval, 0.48 to 1.06), as well as to delay the second virologic failure (hazard ratio, 0.56; 95 percent confidence interval, 0.29 to 1.09), and significantly delayed the failure of the first regimen (hazard ratio, 0.39) and the first virologic failure (hazard ratio, 0.34). Starting with zidovudine and lamivudine combined with efavirenz (but not zidovudine and lamivudine combined with nelfinavir) appeared to delay the failure of the second regimen, as compared with starting with didanosine and stavudine (hazard ratio, 0.68), and significantly delayed both the first and the second virologic failures (hazard ratio for the first virologic failure, 0.39; hazard ratio for the second virologic failure, 0.47), as well as the failure of the first regimen (hazard ratio, 0.35). The initial use of zidovudine, lamivudine, and efavirenz resulted in a shorter time to viral suppression. The efficacy of antiretroviral drugs depends on how they are combined. The combination of zidovudine, lamivudine, and efavirenz is superior to the other antiretroviral regimens used as initial therapy in this study. Copyright 2003 Massachusetts Medical Society
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              Pharmacokinetic interaction between nevirapine and ethinyl estradiol/norethindrone when administered concurrently to HIV-infected women.

              To determine the effects of nevirapine (NVP), a nonnucleoside reverse-transcriptase inhibitor of HIV-1 and P450 inducer, on the pharmacokinetics (PK) of ethinyl estradiol (EE)/norethindrone (NET), a widely used oral contraceptive, and to assess the effects of EE/NET on the steady-state PK of NVP. Ten HIV-1-infected women underwent intensive PK sampling after single-dose administration of EE/NET (days 0-1). Oral NVP 200 mg once daily (days 2-15), followed by 200 mg twice daily (days 16-29), was added to background potent antiretroviral therapy. On day 30, intensive PK sampling was performed after concurrent administration of NVP 200 mg and a single dose of EE/NET. Concomitant administration of NVP at steady state with EE/NET resulted in a significant (29%) median reduction in the area under the plasma concentration time curve (AUC(infinity)) and a significant reduction in mean residence time (MRT) and half-life (t(1/2)) of EE. There was a significant (18%) median reduction in the AUC(infinity) for NET that was not associated with a detectable change in NET C(max), MRT, or t(1/2). Oral contraceptives should not be the primary method of birth control in women of child-bearing potential who are treated with NVP.
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                Author and article information

                Journal
                rbgo
                Revista Brasileira de Ginecologia e Obstetrícia
                Rev. Bras. Ginecol. Obstet.
                Federação Brasileira das Sociedades de Ginecologia e Obstetrícia (Rio de Janeiro, RJ, Brazil )
                0100-7203
                1806-9339
                November 2006
                : 28
                : 11
                : 680-684
                Affiliations
                [02] Campinas SP orgnameUNICAMP orgdiv1CAISM orgdiv2Divisão de Obstetrícia Brasil
                [01] Campinas SP orgnameUniversidade Estadual de Campinas orgdiv1Faculdade de Ciências Médicas orgdiv2Departamento de Tocoginecologia Brasil
                Article
                S0100-72032006001100008 S0100-7203(06)02801108
                7170a96a-4bdb-41c4-88c1-238e4ab762bf

                This work is licensed under a Creative Commons Attribution 4.0 International License.

                History
                : 30 November 2006
                : 07 August 2006
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 27, Pages: 5
                Product

                SciELO Brazil

                Categories
                Revisão

                Contraceptives, oral, hormonal,Antiretroviral therapy, highly active,HIV,HIV infections,Anticoncepcionais orais hormonais,Anticoncepção,Terapia anti-retroviral de alta atividade,Infecções por HIV,Contraception

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