- Email: [email protected]
Duration of isoniazid preventive therapy in HIV-infected patients – Authors' reply
Correspondence
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International Union Against Tuberculosis Committee on Prophylaxis. Efficacy of various durations of isoniazid preventive therapy for tuberculosis: five years of follow-up in the IUAT trial. Bull World Health Organ 1982; 60: 555–64. Comstock GW. How much isoniazid is needed for prevention of tuberculosis among immunocompetent adults? Int J Tuberc Lung Dis 1999; 3: 847–50. Johnson J L, Okwera A, Hom D L, et al. Duration of efficacy of treatment of latent tuberculosis infection in HIV-infected adults. AIDS 2001; 15: 2137–47. Kaplan G J, Fraser R I, Comstock G W. Tuberculosis in Alaska, 1970: the continued decline of the tuberculosis epidemic. Am Rev Respir Dis 1972; 105: 920–26.
Taraz Samandari and colleagues1 recommend 36 months of isoniazid prophylaxis for prevention of tuberculosis in individuals with HIV. In their study, isoniazid prophylaxis was given to all HIV patients residing in areas with a prevalence of latent tuberculosis of more than 30%. Most of the countries with a high prevalence of HIV and tuberculosis are developing countries with economic constraints. Isoniazid prophylaxis has been found to have little benefit in individuals with a negative tuberculin skin test (TST),2 so unnecessary exposure of such individuals to the side-effects of isoniazid and the associated waste of resources cannot be advocated. Additionally, high levels of primary resistance to isoniazid of up to 40·8% have been seen in different parts of the world.3 Therefore blindly giving isoniazid prophylaxis in these regions will be useless as well as costly and harmful. There are further chances of increasing drug resistance too. Isoniazid prophylaxis has repeatedly been shown to prevent development of tuberculosis and improve survival in TST-positive, isoniazid-susceptible patients and it needs to be used judiciously. I declare that I have no conflicts of interest.
Naveen Dutt [email protected] Government Medical College and Hospital, 160030 Chandigarh, India
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Samandari T, Agizew TB, Nyirenda S, et al. 6-month versus 36-month isoniazid preventive treatment for tuberculosis in adults with HIV infection in Botswana: a randomised, double-blind, placebo-controlled trial. Lancet 2011; 377: 1588–98. Bucher HC, Griffith LE, Guyatt GH, et al. Isoniazid prophylaxis for tuberculosis in HIV infection: a meta-analysis of randomized controlled trials. AIDS 1999; 13: 501–07. WHO. Anti-tuberculosis drug resistance in the world: report no. 4. Geneva: World Health Organization, 2008. http://www.who.int/tb/ publications/2008/drs_report4_26feb08.pdf (accessed Sept 12, 2011).
Authors’ reply Our study’s genesis and design were based on the hypothesis that 6 months of isoniazid preventive therapy was inadequate to prevent tuberculosis in HIV-infected people living in endemic settings. 6 months’ treatment was selected as the control group because it was at the time both the WHO recommendation and Botswana’s policy.1 We regard with caution Hans Rieder’s position that 9 or 12 months of isoniazid should have been the control treatment. Rieder cites two papers to support this position. The first paper was from a European trial done in the preHIV era in individuals with a positive tuberculin skin test (TST) and fibrotic lesions on chest radiographs. Of our TST-positive cohort, 93% had normal radiographs. Although none of the participants in the European trial was free of fibrotic lesions, this paper showed that among participants with lesions of less than 2 cm², there was no difference in tuberculosis incidence between 6-month and 12-month isoniazid recipients. This finding suggests that people with smaller (and presumably absent) radiographic lesions do not derive any benefit beyond 6 months. The second paper Rieder cites examined tuberculosis rates in Alaskans grouped by their estimated intakes of isoniazid. Although this analysis has been influential, its strength cannot be compared with results of randomised controlled trials. To date, no trial has compared 6 months versus 9 or 12 months of
isoniazid preventive therapy in HIVinfected people living in tuberculosisendemic countries. Rieder doubts that the benefit of 36 months’ isoniazid preventive therapy was through the prevention of reinfection—a consideration that we had not dismissed in our paper. He comments, though, that 12 months’ isoniazid preventive therapy in Alaska Natives had a two-decadelong benefit despite a high rate of reinfection. It should be recalled that the small Alaska Native population benefited from multiple tuberculosis control interventions including “casefinding, isolation and treatment” and were free of HIV.2,3 Furthermore, whereas the aforementioned European study showed that the benefit of 6 months’ isoniazid preventive therapy lasted at least 5 years, studies in Africa showed that in HIV-infected recipients of isoniazid preventive therapy, tuberculosis rates returned to levels as high as placebo recipients’ as early as 6 months after treatment completion.4,5 Although we earnestly wish for multipronged, Alaska-style tuberculosis control measures for the large populations of tuberculosis-endemic countries, 36 months’ isoniazid preventive therapy is now a proven, WHO-recommended option for the most tuberculosis-vulnerable population of HIV-infected people accessing care. We agree with Naveen Dutt that isoniazid preventive therapy is best targeted for TST-positive individuals and that each country should determine the appropriateness of isoniazid preventive therapy on the basis of isoniazid-resistance rates in new tuberculosis patients. We declare that we have no conflicts of interest.
*Taraz Samandari, Themba Moeti, Elizabeth Talbot, Tefera Agizew, Samba Nyirenda [email protected]
www.thelancet.com Vol 378 October 1, 2011
Correspondence
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Anon. Preventive therapy against tuberculosis in people living with HIV: policy statement. Wkly Epidemiol Rec 1999; 74: 385–98. Comstock GW, Philip RN. Decline of the tuberculosis epidemic in Alaska. Public Health Rep 1961; 76: 19–24. Johnson MW. Results of 20 years of tuberculosis control in Alaska. Health Services Rep 1973; 88: 247–54. Quigley MA, Mwinga A, Hosp M, et al. Long-term effect of preventive therapy for tuberculosis in a cohort of HIV-infected Zambian adults. AIDS 2001; 15: 215–22. Johnson JL, Okwera A, Hom DL, et al. Duration of efficacy of treatment of latent tuberculosis infection in HIV-infected adults. AIDS 2001; 15: 2137–47.
Addressing Mississippi’s HIV/AIDS crisis We appreciate Talha Burki’s World Report (June 11, p 1994)1 regarding the Human Rights Watch report2 on Mississippi’s HIV/AIDS policies. Although Mississippi’s AIDS rates plateaued in recent years, racial disparities in HIV infection widened: African Americans represent 37% of the population, but account for 78% of new infections.3 Mississippi’s HIV/ AIDS and reproductive health policies warrant scrutiny and improvement. However, we note that individuals who qualify for treatment generally receive it; unlike many other American states, Mississippi currently has no waiting list for its AIDS Drug Assistance Program. Complex social and structural factors that contribute to Mississippi’s racial disparities in HIV infection also deserve more nuanced discussion. Many individuals, particularly African Americans, underestimate their risk of sexually transmitted diseases, including HIV. This phenomenon is compounded by the overwhelming stigma associated with HIV/AIDS among African Americans in southern USA; many individuals forego testing not only because of limited access to health services, but because of www.thelancet.com Vol 378 October 1, 2011
paralysing stigma.4 Additionally, complex sexual networks and a high prevalence of HIV within networks perpetuate high rates of HIV infection;5 50% of those who tested positive in 2010 had no identified risk behaviours.3 A comprehensive, culturally appropriate response to HIV/AIDS in Mississippi should focus not only on fully funding Medicaid and providing comprehensive testing and treatment services, but on social marketing and media campaigns designed to address HIV/AIDS stigma and raise awareness about the risks of HIV and sexually transmitted diseases. These steps would help normalise and stimulate more demand for HIV testing and treatment services and are crucial components of any policy to address racial disparities in HIV infection. AN has received support from the National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health (NIAAA/NIH) grant number K01 AA020228, and the National Institutes of Health, Center for AIDS Research (NIH/CFAR) grant number P30-AI-42853. None of these agencies had any role in the content analysis, writing of the letter, or in the decision to submit the letter for publication. AN receives consulting fees from Mylan. The other authors declare that they have no conflicts of interest.
*Amy Nunn, Arti Barnes, Alexandra Cornwall, Aadia Rana, Leandro Mena [email protected] Department of Medicine, Warren Alpert Medical School of Brown University, Providence, RI, USA (AN, AR); Division of Infectious Diseases, University of Mississippi Medical Center, Jackson, MS, USA (AB, LM); and *Division of Infectious Diseases, Miriam Hospital, Providence, RI 02906, USA (AN, AC) 1 2
3
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Burki TK. State policies worsen HIV/AIDS crisis in Mississippi. Lancet 2011; 377: 1994. Human Rights Watch. Rights at risk: state response to HIV in Mississippi. http://www. hrw.org/reports/2011/03/09/rights-risk-0 (accessed Sept 9, 2011). Mississippi State Department of Health. Reported cases of HIV disease in Mississippi, 2010. Jackson: Mississippi State Department of Health, STD/HIV Office, 2010. Lichtenstein B, Hook EW, Sharma AK. Public tolerance, private pain: stigma and sexually transmitted infections in the American Deep South. Cult Health Sex 2005; 7: 43–57. Oster AM, Dorell CG, Mena LA, Thomas PE, Toledo CA, Heffelfinger JD. HIV risk among young African American men who have sex with men: a case-control study in Mississippi. Am J Public Health 2011; 101: 137–14.
Sex-selected abortion in India Prabhat Jha and colleagues (June 4, p 1921)1 document increasing use of sex-selected abortion in India, with such abortions being more common in affluent families with educated mothers, and subsequent to having a first-born girl child. This is a very important study corresponding with other research documenting the effect that pervasive son preference in India has on the health and survival of female infants and girls. These effects include an increased risk of mortality for girls relative to boys aged 1–59 months,2,3 and lower health-care use for female compared with male infants and young children.3,4 To reduce these gender inequities, Jha and colleagues recommend “better monitoring and reporting of sex ratios by birth order”, and S V Subramanian and Daniel Corsi,5 in their accompanying Comment, recommend better enforcement of the policy against sex-selective abortion: the Pre-Natal Diagnostic Techniques Act. Such approaches presume that increased awareness and policy efforts will adequately affect gender inequities and improve the health and safety of women and girls. However, such approaches do not address the underlying cause of these inequities— ie, the lower value placed on the lives of girls relative to boys. Certainly, surveillance systems to track gender disparities in health and development and enforcement of policies to protect girls against these inequities are important. More important, however, is the need for solutions to increase the status of women and girls in society. Jha and colleagues’ findings show that improved education and wealth is insufficient to make this change, given the greater use of sex-selected abortion in these groups. New approaches to social change that improve women’s and girls’ status must be identified; and although Jha
2011 Human Rights Watch
Centers for Disease Control and Prevention, Atlanta, GA 30333, USA (TS, ET); Ministry of Health, Gaborone, Botswana (TM); and Botswana—USA Partnership (BOTUSA), Gaborone and Francistown, Botswana (TS, ET, TA, SN)
This online publication has been corrected. The corrected version first appeared at thelancet.com on November 25, 2011
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International Union Against Tuberculosis Committee on Prophylaxis. Efficacy of various durations of isoniazid preventive therapy for tuberculosis: five years of follow-up in the IUAT trial. Bull World Health Organ 1982; 60: 555–64. Comstock GW. How much isoniazid is needed for prevention of tuberculosis among immunocompetent adults? Int J Tuberc Lung Dis 1999; 3: 847–50. Johnson J L, Okwera A, Hom D L, et al. Duration of efficacy of treatment of latent tuberculosis infection in HIV-infected adults. AIDS 2001; 15: 2137–47. Kaplan G J, Fraser R I, Comstock G W. Tuberculosis in Alaska, 1970: the continued decline of the tuberculosis epidemic. Am Rev Respir Dis 1972; 105: 920–26.
Taraz Samandari and colleagues1 recommend 36 months of isoniazid prophylaxis for prevention of tuberculosis in individuals with HIV. In their study, isoniazid prophylaxis was given to all HIV patients residing in areas with a prevalence of latent tuberculosis of more than 30%. Most of the countries with a high prevalence of HIV and tuberculosis are developing countries with economic constraints. Isoniazid prophylaxis has been found to have little benefit in individuals with a negative tuberculin skin test (TST),2 so unnecessary exposure of such individuals to the side-effects of isoniazid and the associated waste of resources cannot be advocated. Additionally, high levels of primary resistance to isoniazid of up to 40·8% have been seen in different parts of the world.3 Therefore blindly giving isoniazid prophylaxis in these regions will be useless as well as costly and harmful. There are further chances of increasing drug resistance too. Isoniazid prophylaxis has repeatedly been shown to prevent development of tuberculosis and improve survival in TST-positive, isoniazid-susceptible patients and it needs to be used judiciously. I declare that I have no conflicts of interest.
Naveen Dutt [email protected] Government Medical College and Hospital, 160030 Chandigarh, India
1216
1
2
3
Samandari T, Agizew TB, Nyirenda S, et al. 6-month versus 36-month isoniazid preventive treatment for tuberculosis in adults with HIV infection in Botswana: a randomised, double-blind, placebo-controlled trial. Lancet 2011; 377: 1588–98. Bucher HC, Griffith LE, Guyatt GH, et al. Isoniazid prophylaxis for tuberculosis in HIV infection: a meta-analysis of randomized controlled trials. AIDS 1999; 13: 501–07. WHO. Anti-tuberculosis drug resistance in the world: report no. 4. Geneva: World Health Organization, 2008. http://www.who.int/tb/ publications/2008/drs_report4_26feb08.pdf (accessed Sept 12, 2011).
Authors’ reply Our study’s genesis and design were based on the hypothesis that 6 months of isoniazid preventive therapy was inadequate to prevent tuberculosis in HIV-infected people living in endemic settings. 6 months’ treatment was selected as the control group because it was at the time both the WHO recommendation and Botswana’s policy.1 We regard with caution Hans Rieder’s position that 9 or 12 months of isoniazid should have been the control treatment. Rieder cites two papers to support this position. The first paper was from a European trial done in the preHIV era in individuals with a positive tuberculin skin test (TST) and fibrotic lesions on chest radiographs. Of our TST-positive cohort, 93% had normal radiographs. Although none of the participants in the European trial was free of fibrotic lesions, this paper showed that among participants with lesions of less than 2 cm², there was no difference in tuberculosis incidence between 6-month and 12-month isoniazid recipients. This finding suggests that people with smaller (and presumably absent) radiographic lesions do not derive any benefit beyond 6 months. The second paper Rieder cites examined tuberculosis rates in Alaskans grouped by their estimated intakes of isoniazid. Although this analysis has been influential, its strength cannot be compared with results of randomised controlled trials. To date, no trial has compared 6 months versus 9 or 12 months of
isoniazid preventive therapy in HIVinfected people living in tuberculosisendemic countries. Rieder doubts that the benefit of 36 months’ isoniazid preventive therapy was through the prevention of reinfection—a consideration that we had not dismissed in our paper. He comments, though, that 12 months’ isoniazid preventive therapy in Alaska Natives had a two-decadelong benefit despite a high rate of reinfection. It should be recalled that the small Alaska Native population benefited from multiple tuberculosis control interventions including “casefinding, isolation and treatment” and were free of HIV.2,3 Furthermore, whereas the aforementioned European study showed that the benefit of 6 months’ isoniazid preventive therapy lasted at least 5 years, studies in Africa showed that in HIV-infected recipients of isoniazid preventive therapy, tuberculosis rates returned to levels as high as placebo recipients’ as early as 6 months after treatment completion.4,5 Although we earnestly wish for multipronged, Alaska-style tuberculosis control measures for the large populations of tuberculosis-endemic countries, 36 months’ isoniazid preventive therapy is now a proven, WHO-recommended option for the most tuberculosis-vulnerable population of HIV-infected people accessing care. We agree with Naveen Dutt that isoniazid preventive therapy is best targeted for TST-positive individuals and that each country should determine the appropriateness of isoniazid preventive therapy on the basis of isoniazid-resistance rates in new tuberculosis patients. We declare that we have no conflicts of interest.
*Taraz Samandari, Themba Moeti, Elizabeth Talbot, Tefera Agizew, Samba Nyirenda [email protected]
www.thelancet.com Vol 378 October 1, 2011
Correspondence
1
2
3
4
5
Anon. Preventive therapy against tuberculosis in people living with HIV: policy statement. Wkly Epidemiol Rec 1999; 74: 385–98. Comstock GW, Philip RN. Decline of the tuberculosis epidemic in Alaska. Public Health Rep 1961; 76: 19–24. Johnson MW. Results of 20 years of tuberculosis control in Alaska. Health Services Rep 1973; 88: 247–54. Quigley MA, Mwinga A, Hosp M, et al. Long-term effect of preventive therapy for tuberculosis in a cohort of HIV-infected Zambian adults. AIDS 2001; 15: 215–22. Johnson JL, Okwera A, Hom DL, et al. Duration of efficacy of treatment of latent tuberculosis infection in HIV-infected adults. AIDS 2001; 15: 2137–47.
Addressing Mississippi’s HIV/AIDS crisis We appreciate Talha Burki’s World Report (June 11, p 1994)1 regarding the Human Rights Watch report2 on Mississippi’s HIV/AIDS policies. Although Mississippi’s AIDS rates plateaued in recent years, racial disparities in HIV infection widened: African Americans represent 37% of the population, but account for 78% of new infections.3 Mississippi’s HIV/ AIDS and reproductive health policies warrant scrutiny and improvement. However, we note that individuals who qualify for treatment generally receive it; unlike many other American states, Mississippi currently has no waiting list for its AIDS Drug Assistance Program. Complex social and structural factors that contribute to Mississippi’s racial disparities in HIV infection also deserve more nuanced discussion. Many individuals, particularly African Americans, underestimate their risk of sexually transmitted diseases, including HIV. This phenomenon is compounded by the overwhelming stigma associated with HIV/AIDS among African Americans in southern USA; many individuals forego testing not only because of limited access to health services, but because of www.thelancet.com Vol 378 October 1, 2011
paralysing stigma.4 Additionally, complex sexual networks and a high prevalence of HIV within networks perpetuate high rates of HIV infection;5 50% of those who tested positive in 2010 had no identified risk behaviours.3 A comprehensive, culturally appropriate response to HIV/AIDS in Mississippi should focus not only on fully funding Medicaid and providing comprehensive testing and treatment services, but on social marketing and media campaigns designed to address HIV/AIDS stigma and raise awareness about the risks of HIV and sexually transmitted diseases. These steps would help normalise and stimulate more demand for HIV testing and treatment services and are crucial components of any policy to address racial disparities in HIV infection. AN has received support from the National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health (NIAAA/NIH) grant number K01 AA020228, and the National Institutes of Health, Center for AIDS Research (NIH/CFAR) grant number P30-AI-42853. None of these agencies had any role in the content analysis, writing of the letter, or in the decision to submit the letter for publication. AN receives consulting fees from Mylan. The other authors declare that they have no conflicts of interest.
*Amy Nunn, Arti Barnes, Alexandra Cornwall, Aadia Rana, Leandro Mena [email protected] Department of Medicine, Warren Alpert Medical School of Brown University, Providence, RI, USA (AN, AR); Division of Infectious Diseases, University of Mississippi Medical Center, Jackson, MS, USA (AB, LM); and *Division of Infectious Diseases, Miriam Hospital, Providence, RI 02906, USA (AN, AC) 1 2
3
4
5
Burki TK. State policies worsen HIV/AIDS crisis in Mississippi. Lancet 2011; 377: 1994. Human Rights Watch. Rights at risk: state response to HIV in Mississippi. http://www. hrw.org/reports/2011/03/09/rights-risk-0 (accessed Sept 9, 2011). Mississippi State Department of Health. Reported cases of HIV disease in Mississippi, 2010. Jackson: Mississippi State Department of Health, STD/HIV Office, 2010. Lichtenstein B, Hook EW, Sharma AK. Public tolerance, private pain: stigma and sexually transmitted infections in the American Deep South. Cult Health Sex 2005; 7: 43–57. Oster AM, Dorell CG, Mena LA, Thomas PE, Toledo CA, Heffelfinger JD. HIV risk among young African American men who have sex with men: a case-control study in Mississippi. Am J Public Health 2011; 101: 137–14.
Sex-selected abortion in India Prabhat Jha and colleagues (June 4, p 1921)1 document increasing use of sex-selected abortion in India, with such abortions being more common in affluent families with educated mothers, and subsequent to having a first-born girl child. This is a very important study corresponding with other research documenting the effect that pervasive son preference in India has on the health and survival of female infants and girls. These effects include an increased risk of mortality for girls relative to boys aged 1–59 months,2,3 and lower health-care use for female compared with male infants and young children.3,4 To reduce these gender inequities, Jha and colleagues recommend “better monitoring and reporting of sex ratios by birth order”, and S V Subramanian and Daniel Corsi,5 in their accompanying Comment, recommend better enforcement of the policy against sex-selective abortion: the Pre-Natal Diagnostic Techniques Act. Such approaches presume that increased awareness and policy efforts will adequately affect gender inequities and improve the health and safety of women and girls. However, such approaches do not address the underlying cause of these inequities— ie, the lower value placed on the lives of girls relative to boys. Certainly, surveillance systems to track gender disparities in health and development and enforcement of policies to protect girls against these inequities are important. More important, however, is the need for solutions to increase the status of women and girls in society. Jha and colleagues’ findings show that improved education and wealth is insufficient to make this change, given the greater use of sex-selected abortion in these groups. New approaches to social change that improve women’s and girls’ status must be identified; and although Jha
2011 Human Rights Watch
Centers for Disease Control and Prevention, Atlanta, GA 30333, USA (TS, ET); Ministry of Health, Gaborone, Botswana (TM); and Botswana—USA Partnership (BOTUSA), Gaborone and Francistown, Botswana (TS, ET, TA, SN)
This online publication has been corrected. The corrected version first appeared at thelancet.com on November 25, 2011
1217