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    1. A mulher e os ensaios clnicos no VIH This presentation has been produced as part of the Women for Positive Action initiative, supported by Abbott. Women for Positive Action aims to empower, educate and support women with HIV and the healthcare providers who treat them The slides overview the differential responses to therapy and uptake of clinical trials between men and women. The factors behind the under-representation of women in clinical trials and the importance of enrolling and retaining women in clinical trials are discussedThis presentation has been produced as part of the Women for Positive Action initiative, supported by Abbott. Women for Positive Action aims to empower, educate and support women with HIV and the healthcare providers who treat them The slides overview the differential responses to therapy and uptake of clinical trials between men and women. The factors behind the under-representation of women in clinical trials and the importance of enrolling and retaining women in clinical trials are discussed

    2. 2 ndice

    3. 3 Introduo In 2007 an estimated 33 million people were living with HIV1 The proportion of global HIV cases that are women is about 50%1 Women make up a higher proportion of new diagnoses, meaning the share of infections among women is increasing in several countries2 It is important to note that the number of cases of HIV infection in women are increasing in all parts of the world, albeit at different rates, and not just in the developing world. Most women with HIV are of childbearing potential2 Half of all new infections over 7000 daily are occurring among young people, and two-thirds of all new infections are among young women The proportion of women among people newly diagnosed with HIV in Western Europe increased from 25% in 1997 to 38% in 2002: 27.8% of newly registered Canadian HIV cases in 2006 were women3 3233% of all newly diagnosed HIV/AIDS cases in North America acquired the infection through heterosexual intercourse2 References UNAIDS/ WHO. AIDS epidemic update. 2007;UNAIDS/07.27E / JC1322E UNAIDS. Report on the Global AIDS Epidemic. 2008; UNAIDS/08.25E / JC1510E Public Health Agency of Canada. HIV/AIDS. Epi Updates November 2007 In 2007 an estimated 33 million people were living with HIV1 The proportion of global HIV cases that are women is about 50%1 Women make up a higher proportion of new diagnoses, meaning the share of infections among women is increasing in several countries2 It is important to note that the number of cases of HIV infection in women are increasing in all parts of the world, albeit at different rates, and not just in the developing world. Most women with HIV are of childbearing potential2 Half of all new infections over 7000 daily are occurring among young people, and two-thirds of all new infections are among young women The proportion of women among people newly diagnosed with HIV in Western Europe increased from 25% in 1997 to 38% in 2002: 27.8% of newly registered Canadian HIV cases in 2006 were women3 3233% of all newly diagnosed HIV/AIDS cases in North America acquired the infection through heterosexual intercourse2 References UNAIDS/ WHO. AIDS epidemic update. 2007;UNAIDS/07.27E / JC1322E UNAIDS. Report on the Global AIDS Epidemic. 2008; UNAIDS/08.25E / JC1510E Public Health Agency of Canada. HIV/AIDS. Epi Updates November 2007

    4. A mulher e o VIH - Sinopse

    5. 5 Diferenas de tipo biolgico entre homens e mulheres: efeitos sobre o VIH Os factores biolgicos so responsveis por uma susceptibilidade infeco por HIV, por parte das mulheres, 2 a 4 vezes superior dos homens1,2, 3 Tendencialmente, as mulheres so diagnosticadas com o VIH mais tarde do que os homens1,2 As cargas vricas tendem a ser inferiores nas mulheres, sobretudo se a contagem de CD4 for mais elevada4 O ndice de declnio da contagem de CD4 nas mulheres poder ser mais rpido, apesar de apresentarem normalmente uma carga vrica inferior5,6 Infeces recorrentes da flora vaginal, DIP aguda e risco acrescido de alteraes cervicais pr-cancergenas podero ocorrer concomitantemente com a maioria das manifestaes tambm verificadas nos homens Women are physiologically 2-4 times more susceptible to HIV:1,2,3 Women have a more delicate larger mucosal surface area and the female sexual organs are more vulnerable to tears and micro-lesions; a direct transmission route Untreated STIs increase womens risk of HIV infection Ejaculate is released in greater quantities and contains a higher viral content than vaginal secretions Women tend to present later than men, often diagnosed while pregnant, or as older women seeking treatment for an opportunistic infection Viral loads tend to be lower in women, especially when CD4 count is high4 A meta-analysis several studies of gender effects on viral load showed that HIV-infected women consistently have a 2-6-fold lower viral load than men. Possible biological explanations are variations in viral load and CD4 count throughout the menstrual cycle. These findings are significant as viral loads are used to guide initiation and modification of ART The rate of decline in CD4 count in women may be faster in spite of their generally lower viral load5,6 References WHO. Gender inequalities in HIV. Available at: http://www.who.int/gender/hiv_aids/en/. Accessed January 2008 Stratton SE and Watstein SB. The encyclopedia of HIV and AIDS. 2nd ed. New York: Facts on File. 2003. Pan American Health Organization. Gender and HIV. Women, Health and Development Program Fact Sheets 2008. Available at: http://www.paho.org/English/AD/GE/HIV.htm. Accessed January 2008 Ghandi M et al. Does patient sex affect Human Immunodeficiency Virus levels? Clinical Infectious Diseases 2002;35:313-322 Hubert JB et al. Gender, disease progression and response to HAART. Abstract presented at XIV International AIDS Conference, Barcelona, Spain 2002;ThOrC1448. Patterson K et al. Effects of Age and Sex on Immunological and Virological Responses to Initial HAART. HIV Medicine 2007;8:406-410.Women are physiologically 2-4 times more susceptible to HIV:1,2,3 Women have a more delicate larger mucosal surface area and the female sexual organs are more vulnerable to tears and micro-lesions; a direct transmission route Untreated STIs increase womens risk of HIV infection Ejaculate is released in greater quantities and contains a higher viral content than vaginal secretions Women tend to present later than men, often diagnosed while pregnant, or as older women seeking treatment for an opportunistic infection Viral loads tend to be lower in women, especially when CD4 count is high4 A meta-analysis several studies of gender effects on viral load showed that HIV-infected women consistently have a 2-6-fold lower viral load than men. Possible biological explanations are variations in viral load and CD4 count throughout the menstrual cycle. These findings are significant as viral loads are used to guide initiation and modification of ART The rate of decline in CD4 count in women may be faster in spite of their generally lower viral load5,6 References WHO. Gender inequalities in HIV. Available at: http://www.who.int/gender/hiv_aids/en/. Accessed January 2008 Stratton SE and Watstein SB. The encyclopedia of HIV and AIDS. 2nd ed. New York: Facts on File. 2003. Pan American Health Organization. Gender and HIV. Women, Health and Development Program Fact Sheets 2008. Available at: http://www.paho.org/English/AD/GE/HIV.htm. Accessed January 2008 Ghandi M et al. Does patient sex affect Human Immunodeficiency Virus levels? Clinical Infectious Diseases 2002;35:313-322 Hubert JB et al. Gender, disease progression and response to HAART. Abstract presented at XIV International AIDS Conference, Barcelona, Spain 2002;ThOrC1448. Patterson K et al. Effects of Age and Sex on Immunological and Virological Responses to Initial HAART. HIV Medicine 2007;8:406-410.

    6. 6 Diferenas de tipo social e cultural afectam o modo como as mulheres gerem o VIH A number of psychosocial factors increase the risk of HIV infection in women: Limited control over the means to practice low-risk sexual behaviour, such as condom use Social standing and inability to negotiate frequency of and nature of sexual interactions Violence may increase a womans vulnerability to HIV because: Forced sex may result in tears and lacerations that contribute to virus transmission Violence can prevent women from safe-sex negotiations and access to treatment Fear of violence may prevent women from getting tested for HIV and/or disclosing their HIV status to others References WHO. Gender inequalities in HIV. Available at: http://www.who.int/gender/hiv_aids/en/. Accessed January 2008 Stratton SE and Watstein SB. The encyclopedia of HIV and AIDS. 2nd ed. New York: Facts on File. 2003 Pan American Health Organization. Gender and HIV. Women, Health and Development Program Fact Sheets 2008. Available at: http://www.paho.org/English/AD/GE/HIV.htm. Accessed January 2008 A number of psychosocial factors increase the risk of HIV infection in women: Limited control over the means to practice low-risk sexual behaviour, such as condom use Social standing and inability to negotiate frequency of and nature of sexual interactions Violence may increase a womans vulnerability to HIV because: Forced sex may result in tears and lacerations that contribute to virus transmission Violence can prevent women from safe-sex negotiations and access to treatment Fear of violence may prevent women from getting tested for HIV and/or disclosing their HIV status to others References WHO. Gender inequalities in HIV. Available at: http://www.who.int/gender/hiv_aids/en/. Accessed January 2008 Stratton SE and Watstein SB. The encyclopedia of HIV and AIDS. 2nd ed. New York: Facts on File. 2003 Pan American Health Organization. Gender and HIV. Women, Health and Development Program Fact Sheets 2008. Available at: http://www.paho.org/English/AD/GE/HIV.htm. Accessed January 2008

    7. Resposta teraputica: diferenas entre homens e mulheres

    8. 8 Diferenas de gnero das intervenes teraputicas A prtica clnica constata diferenas de gnero, devido a uma srie de factores

    9. 9 Factores farmacocinticos na mulher There have been variable data reporting gender differences in disease outcome in women versus men with HIV Due to weight and fat distribution differences, standard doses for men may not be equivalent in women Administration of concomitant medications can affect the pharmacokinetic profile the extent of the differences and the type of concomitant medication may differ between men and women. For example, hormonal contraceptives or hormone replacement therapies may alter the metabolic action of some drugs A 20% increase in the AUC has been reported for women taking nevirapine (an NRTI) vs men, although the clinical significance of this finding is not clear. Body size and metabolic differences are possible determining factors of differences in pharmacokinetics between men and women. However, psychosocial, behavioural and attitudinal differences such as accessing treatment or delays in initiating therapy until pregnant explain most differences between men and women with HIV References Bacon MC et al. The Womens Interagency HIV Study: an Observational Cohort Brings Clinical Studies to the Bench. Clinical and Diagnostic Laboratory Immunology 2005;12:1013-1019. UK Collaborative HIV Cohort Steering Committee. The creation of a large UK-based multicentre cohort of HIV-infected individuals: The UK Collaborative HIV Cohort (UK CHIC) Study. HIV Medicine 2004;5:115-124 Rezza G et al. Plasma Viral Load Concentrations in Women and Men From Different Exposure Categories and With Known Duration of HIV Infection. JAIDS 2000;25:56-62. Moore AI et al. Gender differences in response to HAART. JAIDS 2003;1(3):188 Fletcher CV et al. Sex-Based Differences in Saquinavir Pharmacology and Virologic Response in AIDS Clinical Trials Group Study. Journal of Infectious Diseases 2004;189:1176-1184 Patterson K et al. Effects of age and sex on immunological and virological responses to initial highly active antiretroviral therapy. HIV Medicine 2007;8:406-410There have been variable data reporting gender differences in disease outcome in women versus men with HIV Due to weight and fat distribution differences, standard doses for men may not be equivalent in women Administration of concomitant medications can affect the pharmacokinetic profile the extent of the differences and the type of concomitant medication may differ between men and women. For example, hormonal contraceptives or hormone replacement therapies may alter the metabolic action of some drugs A 20% increase in the AUC has been reported for women taking nevirapine (an NRTI) vs men, although the clinical significance of this finding is not clear. Body size and metabolic differences are possible determining factors of differences in pharmacokinetics between men and women. However, psychosocial, behavioural and attitudinal differences such as accessing treatment or delays in initiating therapy until pregnant explain most differences between men and women with HIV References Bacon MC et al. The Womens Interagency HIV Study: an Observational Cohort Brings Clinical Studies to the Bench. Clinical and Diagnostic Laboratory Immunology 2005;12:1013-1019. UK Collaborative HIV Cohort Steering Committee. The creation of a large UK-based multicentre cohort of HIV-infected individuals: The UK Collaborative HIV Cohort (UK CHIC) Study. HIV Medicine 2004;5:115-124 Rezza G et al. Plasma Viral Load Concentrations in Women and Men From Different Exposure Categories and With Known Duration of HIV Infection. JAIDS 2000;25:56-62. Moore AI et al. Gender differences in response to HAART. JAIDS 2003;1(3):188 Fletcher CV et al. Sex-Based Differences in Saquinavir Pharmacology and Virologic Response in AIDS Clinical Trials Group Study. Journal of Infectious Diseases 2004;189:1176-1184 Patterson K et al. Effects of age and sex on immunological and virological responses to initial highly active antiretroviral therapy. HIV Medicine 2007;8:406-410

    10. A mulher e os ensaios clnicos

    11. 11 O conhecimento de que dispomos limitado

    12. 12 Estudos relativamente escassos e poucas mulheres inscritas em ensaios de VIH This literature study, conducted in 2007, included data which met the following criteria: written in English, involved human subjects, involved adults and reported data on sex differences in the viroimmunological and clinical parameters during HAART. Reference Nicastri EN et al. Sex issues in HIV-1-infected persons during highly active antiretroviral therapy: a systematic review. Journal of Antimicrobial Chemotherapy 2007;60:724-732This literature study, conducted in 2007, included data which met the following criteria: written in English, involved human subjects, involved adults and reported data on sex differences in the viroimmunological and clinical parameters during HAART. Reference Nicastri EN et al. Sex issues in HIV-1-infected persons during highly active antiretroviral therapy: a systematic review. Journal of Antimicrobial Chemotherapy 2007;60:724-732

    13. 13 Estudos relativamente escassos com percentagem de mulheres superior a 50%: exemplos recentes Reference Nicastri EN et al. Sex issues in HIV-1-infected persons during highly active antiretroviral therapy: a systematic review. Journal of Antimicrobial Chemotherapy 2007;60:724-732 Reference Nicastri EN et al. Sex issues in HIV-1-infected persons during highly active antiretroviral therapy: a systematic review. Journal of Antimicrobial Chemotherapy 2007;60:724-732

    14. 14 Diferenas entre homens e mulheres: incio da HAART O tempo mdio de incio da HAART nas mulheres foi superior ao dos homens; 28 vs 17 semanas (a partir da data de inscrio no estudo)1 As mulheres tinham uma probabilidade duas vezes superior de apresentar dificuldades na toma aberta de medicao em casa do que os homens homossexuais/bisexuais2 As mulheres com dificuldades de toma de medicao em casa apresentavam uma probabilidade consideravelmente inferior de estar a seguir uma HAART2 O sexo feminino um indicador autnomo de no seguimento de uma HAART3,4 A study investigating ART-nave patients (2323 men and 1335 women) found that the median time to commencing ART from enrollment to the study was 28 weeks for women and 17 weeks for men (P = 0.0003 by logrank test). However, when adjusted for CD4 count and viral load at the point of enrollment this difference was no longer statistically significant1 A survey of 2864 people receiving treatment for HIV found that women had twice the odds of having difficulties in openly taking medication at home than homo/bisexual men2 women having difficulties taking medication openly at home had a substantially lower probability of being on HAART (0.59 compared to 0.78) even after adjusting for confounding factors2 Female sex is an independent predictor of not receiving HAART3,4 References Murri R et al. Access to antiretroviral treatment, incidence of sustained therapy interruptions, and risk of clinical events according to sex: evidence from the I.Co.N.A. Study. JAIDS 2003;34:18490 Sayles JN, Wong MD, Cunningham WE. The inability to take medications openly at home: does it help explain gender disparities in HAART use? Journal of Womens Health 2006;15:17381 McNaghten AD et al. Adult/Adolescent Spectrum of HIV Disease Group. Differences in prescription of antiretroviral therapy in a large cohort of HIV-infected patients. JAIDS 2003;32:499505 Giordano TP, White AC Jr, Sajja P et al. Factors associated with the use of highly active antiretroviral therapy in patients newly entering care in an urban clinic. JAIDS 2003;32:399405A study investigating ART-nave patients (2323 men and 1335 women) found that the median time to commencing ART from enrollment to the study was 28 weeks for women and 17 weeks for men (P = 0.0003 by logrank test). However, when adjusted for CD4 count and viral load at the point of enrollment this difference was no longer statistically significant1 A survey of 2864 people receiving treatment for HIV found that women had twice the odds of having difficulties in openly taking medication at home than homo/bisexual men2 women having difficulties taking medication openly at home had a substantially lower probability of being on HAART (0.59 compared to 0.78) even after adjusting for confounding factors2 Female sex is an independent predictor of not receiving HAART3,4 References Murri R et al. Access to antiretroviral treatment, incidence of sustained therapy interruptions, and risk of clinical events according to sex: evidence from the I.Co.N.A. Study. JAIDS 2003;34:18490 Sayles JN, Wong MD, Cunningham WE. The inability to take medications openly at home: does it help explain gender disparities in HAART use? Journal of Womens Health 2006;15:17381 McNaghten AD et al. Adult/Adolescent Spectrum of HIV Disease Group. Differences in prescription of antiretroviral therapy in a large cohort of HIV-infected patients. JAIDS 2003;32:499505 Giordano TP, White AC Jr, Sajja P et al. Factors associated with the use of highly active antiretroviral therapy in patients newly entering care in an urban clinic. JAIDS 2003;32:399405

    15. 15 Diferenas entre homens e mulheres: adeso a HAART e interrupo do tratamento Os resultados apurados relativamente adeso so pouco claros, e alguns estudos no detectaram diferenas entre os sexos1 Contudo, alguns estudos apuraram que as mulheres registam um ndice de adeso inferior ao dos homens (18% vs 25%)2 mais provvel o diagnstico de depresso nas mulheres do que nos homens (34% vs 29%)2 mais provvel que as mulheres venham a interromper o tratamento do que os homens do mesmo grupo de exposio 35.8% vs 24.4% entre toxicodependentes 22.1% vs 13.3% entre heterossexuais3 A literature review showed no difference in adherence between the sexes1 However, there are individual reports of differences: A retrospective cohort study reported that women are less adherent (18% vs 25%) and more likely to be diagnosed with depression (34% vs 29%)2 Women are more likely to have an interruption than men in the same exposure group (35.8% vs 24.4% among drug users; 22.1% vs 13.3% among heterosexuals)3 Women with HIV are known to be particularly vulnerable to experiencing depressive symptoms, and persistent depression has been associated with reduced adherence to HAART and significantly poorer survival rates. The relationship of gender, depression, medical care, and mental health care with adherence in 1,827 female and 3,246 male drug users on combination antiretroviral therapy was investigated. While women had lower adherence and an increased chance of being diagnosed with depression, there was a slightly stronger association between mental health care and adherence in women than in men. Women with a diagnosis of depression who received psychiatric care in combination with antidepressant therapy had nearly 2-fold greater adjusted odds of adherence than depressed women without either care However, it was also thought that men were more likely to take advantage of mental health services available through drug-treatment programs than women were. This correlates to other evidence which indicates that women are less likely to receive care from an HIV specialty provider, or receive antiretroviral therapy4 References Ammassari A et al. Relationship between HAART adherence and adipose tissue alterations. JAIDS 2002;31:S1404 Turner BJ et al. Relationship of gender, depression, and health care delivery with antiretroviral adherence in HIV infected drug users. Journal of General Internal Medicine 2003;18:248-257 Touloumi et al. CASCADE Collaboration. Highly active antiretroviral therapy interruption: predictors and virological and immunologic consequences. Journal of Antimicrobial Chemotherapy 2007;60:724-732 Shapiro MF et al. Variations in the care of HIV infected adults in the United States: results from the HIV Cost and Services Utilisation Study. Journal of the American Medical Association 1999;281:2305-15 A literature review showed no difference in adherence between the sexes1 However, there are individual reports of differences: A retrospective cohort study reported that women are less adherent (18% vs 25%) and more likely to be diagnosed with depression (34% vs 29%)2 Women are more likely to have an interruption than men in the same exposure group (35.8% vs 24.4% among drug users; 22.1% vs 13.3% among heterosexuals)3 Women with HIV are known to be particularly vulnerable to experiencing depressive symptoms, and persistent depression has been associated with reduced adherence to HAART and significantly poorer survival rates. The relationship of gender, depression, medical care, and mental health care with adherence in 1,827 female and 3,246 male drug users on combination antiretroviral therapy was investigated. While women had lower adherence and an increased chance of being diagnosed with depression, there was a slightly stronger association between mental health care and adherence in women than in men. Women with a diagnosis of depression who received psychiatric care in combination with antidepressant therapy had nearly 2-fold greater adjusted odds of adherence than depressed women without either care However, it was also thought that men were more likely to take advantage of mental health services available through drug-treatment programs than women were. This correlates to other evidence which indicates that women are less likely to receive care from an HIV specialty provider, or receive antiretroviral therapy4 References Ammassari A et al. Relationship between HAART adherence and adipose tissue alterations. JAIDS 2002;31:S1404 Turner BJ et al. Relationship of gender, depression, and health care delivery with antiretroviral adherence in HIV infected drug users. Journal of General Internal Medicine 2003;18:248-257 Touloumi et al. CASCADE Collaboration. Highly active antiretroviral therapy interruption: predictors and virological and immunologic consequences. Journal of Antimicrobial Chemotherapy 2007;60:724-732 Shapiro MF et al. Variations in the care of HIV infected adults in the United States: results from the HIV Cost and Services Utilisation Study. Journal of the American Medical Association 1999;281:2305-15

    16. 16 Diferenas entre homens e mulheres: episdios adversos durante a HAART In an observational study in HIV patients receiving stavudine (d4t) treatment in South Africa, all 14 cases of lactic acidosis were in females, with a mortality rate of 29%1 In Canada, a large population-based study confirmed the significantly greater risk of developing lactic acidosis in women compared with men2 There is conflicting data over whether Nevirapine poses a greater risk for liver toxicity in women3 The nucleoside drug classes (still widely used in the developing world) are associated with a number of adverse events that are greater in women vs men: AZT-associated anaemia and d4T-associated hyperlactataemia and lipodystrophy References Geddes R et al. A high incidence of nucleoside reverse transcriptase inhibitor (NRTI)-induced lactic acidosis in HIV-infected patients in a South African context. South African Medical Journal 2006;96:7224. Boulassel MR et al. Gender and long-term metabolic toxicities from antiretroviral therapy in HIV-1 infected persons. Journals of Medical Virology 2006;78:115863. De Lazzari E at al. Risk of hepatotoxicity in virologically suppressed HIV patients switching to nevirapine according to gender and CD4 count. 46th ICAAC, San Francisco 2006;Abstract H-1064 In an observational study in HIV patients receiving stavudine (d4t) treatment in South Africa, all 14 cases of lactic acidosis were in females, with a mortality rate of 29%1 In Canada, a large population-based study confirmed the significantly greater risk of developing lactic acidosis in women compared with men2 There is conflicting data over whether Nevirapine poses a greater risk for liver toxicity in women3 The nucleoside drug classes (still widely used in the developing world) are associated with a number of adverse events that are greater in women vs men: AZT-associated anaemia and d4T-associated hyperlactataemia and lipodystrophy References Geddes R et al. A high incidence of nucleoside reverse transcriptase inhibitor (NRTI)-induced lactic acidosis in HIV-infected patients in a South African context. South African Medical Journal 2006;96:7224. Boulassel MR et al. Gender and long-term metabolic toxicities from antiretroviral therapy in HIV-1 infected persons. Journals of Medical Virology 2006;78:115863. De Lazzari E at al. Risk of hepatotoxicity in virologically suppressed HIV patients switching to nevirapine according to gender and CD4 count. 46th ICAAC, San Francisco 2006;Abstract H-1064

    17. A importncia da mulher nos ensaios clnicos

    18. 18 As mulheres utilizam mais recursos farmacuticos, mas esto pouco representadas em ensaios clnicos

    19. 19 Representao reduzida de mulheres em ensaios clnicos de novas TAR Women are under-represented in the majority of clinical studies, such that effective gender comparisons are not possible References Derived from a slide of John Bartlett, CROI 2006Women are under-represented in the majority of clinical studies, such that effective gender comparisons are not possible References Derived from a slide of John Bartlett, CROI 2006

    20. Directrizes para a incluso de mulheres em estudos clnicos 20

    21. 21 A importncia da mulher nos ensaios clnicos

    22. 22 A gravidez passou a ser uma realidade de vida das mulheres seropositivas References Stratton SE and Watstein SB. The encyclopedia of HIV and AIDS. 2nd ed. New York: Facts on File. 2003 Finer LB et al. Disparities in Rates of Unintended Pregnancy In the United States, 1994 and 2001. Perspectives on Sexual and Reproductive Health, 2006,38(2):9096 Koenig LJ et al. Young, seropositive, and pregnant: epidemiologic and psychosocial perspectives on pregnant adolescents with human immunodeficiency virus infection. American Journal of Obstetrics and Gynecology 2007;S123-S131 References Stratton SE and Watstein SB. The encyclopedia of HIV and AIDS. 2nd ed. New York: Facts on File. 2003 Finer LB et al. Disparities in Rates of Unintended Pregnancy In the United States, 1994 and 2001. Perspectives on Sexual and Reproductive Health, 2006,38(2):9096 Koenig LJ et al. Young, seropositive, and pregnant: epidemiologic and psychosocial perspectives on pregnant adolescents with human immunodeficiency virus infection. American Journal of Obstetrics and Gynecology 2007;S123-S131

    23. 23 Uma parcela significativa de gravidezes entre mulheres seropositivas no planeada Entre 334 mulheres submetidas a TARV, menos de metade referiu ter planeado a sua actual gravidez O regime de TARV na concepo normalmente apenas adequado a mulheres no grvidas Foram prescritos muitos regimes diferentes a mulheres em idade de concepo, entre os quais: regimes com base em ddI+d4T (9.6%) regimes com base em EFV (13.5%) Uma vez grvidas, as doentes submetidas a EFV ou ddI tiveram muitas vezes de alterar a TARV (OU 13.2 P<0.001; 1.8 P=0.033, respectivamente) Os mdicos devero ter em conta o potencial de concepo deste grupo de doentes, ao iniciar a TARV Women with HIV infection, like other women, may wish to plan pregnancy to start a family, control the size of their family, or avoid pregnancy Anticipating for the possibility of pregnancy, whether planned or unplanned, is an important component of care Health professionals should enable women to make reproductive choices by counselling, education and provision of contraception at the time of HIV diagnosis and during follow up With access to optimal management, becoming pregnant and giving birth to a healthy, HIV negative baby is possible for the vast majority of women of childbearing age References Floridia M et al. Short communication: Antiretroviral therapy at conception in pregnant women with HIV in Italy: wide range of variability and frequent exposure to contraindicated drugs. Antiviral Therapy 2006;11:941-946Women with HIV infection, like other women, may wish to plan pregnancy to start a family, control the size of their family, or avoid pregnancy Anticipating for the possibility of pregnancy, whether planned or unplanned, is an important component of care Health professionals should enable women to make reproductive choices by counselling, education and provision of contraception at the time of HIV diagnosis and during follow up With access to optimal management, becoming pregnant and giving birth to a healthy, HIV negative baby is possible for the vast majority of women of childbearing age References Floridia M et al. Short communication: Antiretroviral therapy at conception in pregnant women with HIV in Italy: wide range of variability and frequent exposure to contraindicated drugs. Antiviral Therapy 2006;11:941-946

    24. Inscrever e manter as mulheres em ensaios clnicos

    25. 25 Factores de tipo social, logstico e cientfico afectam a participao das mulheres em ensaios Os obstculos no so bem compreendidos ou definidos Thalidomide and diethylstilbestrol (DES) were used in the 1950s and 60s Since then, all women between the time of first menstruation until menopause were defined as potentially pregnant A policy of exclusion prohibited all such women from pharmaceutical research for fear of causing foetal harm Thalidomide and diethylstilbestrol (DES) were used in the 1950s and 60s Since then, all women between the time of first menstruation until menopause were defined as potentially pregnant A policy of exclusion prohibited all such women from pharmaceutical research for fear of causing foetal harm

    26. 26 Equilbrio das implicaes ticas Exposio no primeiro trimestre da gravidez levanta uma srie de consideraes ticas

    27. 27 Compreenso das motivaes e dos obstculos participao em ensaios

    28. 28 Informar as mulheres e prever obstculos e motivaes para a participao em ensaios Any attempt to put pressure on an individual to take part in research is unethical Patients must make their own fully-informed decisions, knowing all the potential risks and benefits of enrolling in the study Information and support should anticipate issues that are likely to impact women e.g. additional clinic visits and impact on work and family life Any attempt to put pressure on an individual to take part in research is unethical Patients must make their own fully-informed decisions, knowing all the potential risks and benefits of enrolling in the study Information and support should anticipate issues that are likely to impact women e.g. additional clinic visits and impact on work and family life

    29. 29 Os protocolos de estudo podero ser mais benficos para as mulheres? Alterao de requisitos de concepo Incluso de fase aberta / seguimento para mulheres que engravidem Absteno de uso de linguagem crtica como, por exemplo, as mulheres no desistem devido gravidez, mas so convertidas para outra fase do protocolo Desenvolvimento de redes de centros que prestem assistncia a um grande volume de mulheres Disponibilizar encaminhamento, centros e investigadores que prestem orientao sobre como tornar as consultas e os estudos mais acessveis e benficas para as mulheres Cuidados infantis Despesas de transporte Confidencialidade

    30. 30 O que acontece se uma mulher engravida enquanto integra um ensaio clnico?

    31. Alternativas aos ensaios clnicos

    32. 32 Ensaios controlados e randomizados Os ECR proporcionam o nvel mais elevado de prova quando se trata de dar resposta a questes especficas do foro clnico com relevncia estatstica Possuem as suas limitaes: integram normalmente um universo de indivduos menos diversificado do que existe normalmente na prtica clnica diria (por exemplo, menos mulheres, doentes com menos complicaes) nem sempre reflectem os cenrios clnicos habituais em que a maioria das pessoas recebe tratamento muitas vezes dispendiosos e morosos bons para dar resposta a questes especficas, mas no para gerar hipteses novas ou para explorar questes mais alargadas

    33. 33 Alternativas aos ensaios controlados e randomizados Post-hoc analyses, retrospective studies and chart reviews are ways to study data that has already been collected or looking at completed studies in a new way. Case-control studies look at patients who already have HIV or their condition and look back to see if there are characteristics of these patients that differ from a control group. If the evidence found from these alternatives to randomized controlled trials is convincing enough, then resources can be allocated to more comprehensive studies. Regulatory authorities, drug manufacturers and clinicians are increasingly recognising the benefits of data from registries and observational studies, while still accepting their limitations.Post-hoc analyses, retrospective studies and chart reviews are ways to study data that has already been collected or looking at completed studies in a new way. Case-control studies look at patients who already have HIV or their condition and look back to see if there are characteristics of these patients that differ from a control group. If the evidence found from these alternatives to randomized controlled trials is convincing enough, then resources can be allocated to more comprehensive studies. Regulatory authorities, drug manufacturers and clinicians are increasingly recognising the benefits of data from registries and observational studies, while still accepting their limitations.

    34. 34 Registos de doentes Randomized Controlled Trials (RCTs) are considered the gold standard when testing the efficacy and effectiveness of healthcare interventions. They involve splitting the trial participants into a randomly allocated intervention group and a control group. The outcomes of these two groups are then compared to measure the effectiveness of the intervention. If done correctly this form of clinical trial compares like for like and therefore eliminates the effects of confounding factors on the data. Randomized Controlled Trials (RCTs) are considered the gold standard when testing the efficacy and effectiveness of healthcare interventions. They involve splitting the trial participants into a randomly allocated intervention group and a control group. The outcomes of these two groups are then compared to measure the effectiveness of the intervention. If done correctly this form of clinical trial compares like for like and therefore eliminates the effects of confounding factors on the data.

    35. 35 Registos de mulheres seropositivas Exemplo: Antiretroviral Pregnancy Registry (APR) www.apregistry.com Estudo internacional prospectivo de registo de exposio, criado em 1989 Recolhe dados sobre resultados de nascimentos, em particular, anomalias nascena na sequncia da exposio a teraputica anti-retrovrica durante a gravidez Os registos so benficos sobretudo perante um grande volume de doentes Os registos apresentam vrias limitaes, nomeadamente: O relatrio passivo poder traduzir-se em representao excessiva das anomalias Poder ser difcil determinar que frmaco est na raiz do problema, em caso de prescrio de um combinado

    36. Estudos de caso

    37. 37 Estudo de caso 1: uma potencial candidata a inscrio em ensaio clnico Informao padro acerca do que implica um ensaio clnico, para que a mulher possa tomar uma deciso cabalmente informada Informao acerca de cuidados infantis, como proceder caso no possa comparecer a uma consulta, etc. Critrios de incluso de contraceptivos, o que isso significa e como proceder caso venha a engravidar Implicaes para a criana que vai nascer Implicaes para a prpria Implicaes para o ensaio clnico Pormenores acerca de onde poder obter mais informaes e aconselhamento, caso necessrio

    38. 38 Estudo de caso 2: potencial desistente de ensaio clnico Os problemas e necessidades especficos dela, evitando dar qualquer impresso de culpabilizao ou desiluso pela desistncia Explorar de que modo o centro ou o patrocinador poder prestar apoio para que esta consiga comparecer s consultas Prestao de informao e de apoio, utilizando linguagem que seja relevante para ela e para as suas necessidades Anlise das opes de continuidade da teraputica por parte dela, caso abandone o estudo Reassegur-la de que apesar de muitos doentes no completarem a durao total do estudo, a participao dos mesmos continua a ser vlida

    39. 39 Estudo de caso 3: gravidez durante um ensaio clnico Dar resposta a questes acerca dos efeitos que o frmaco experimental poder ter na gravidez dela Analisar as opes de continuidade do ensaio, por exemplo, por meio de converso para uma fase aberta do protocolo, caso admissvel Seguimento durante e aps a gravidez Opes de continuidade da teraputica Evitar dar qualquer impresso de culpabilizao ou desiluso pela desistncia Reassegur-la de que apesar de muitos doentes no completarem a durao total do estudo, a participao dos mesmos continua a ser vlida

    40. Obrigado pela ateno H perguntas?