- Email: [email protected]
HIVNET 012 and Petra
CORRESPONDENCE
and the importance of antiretroviral therapy to treat maternal HIV-1 infection. We agree that our goal should be appropriate antiretroviral therapy for all pregnant women and family members who require it. The hope is that existing programmes will expand to include the provision of care and treatment. However, as we work towards that goal, we must be pragmatic. Do we let 2000 infants become infected every day because we do not have access to optimum treatment but do have a proven effective intervention for mother-tochild transmission? And, does an HIV-1-infected pregnant woman in a developing country not have the right to make a decision to try to prevent infection of her child? Until we can provide these women with the antiretroviral drugs they deserve, the least we can do is to provide them with the means and the choice to protect their children. Catherine M Wilfert Elizabeth Glaser Pediatric AIDS Foundation, 1917 Wildcat Creek Road, Chapel Hill, NC 27516, USA (e-mail: [email protected]) 1
2
3
4
5
Jackson JB, Musoka P, Fleming T, et al. Intrapartum and neonatal single-dose nevirapine compared with zidovudine for prevention of mother-to-child transmission of HIV-1 in Kampala, Uganda: 18-month follow-up of the HIVNET 012 randomised trial. Lancet 2003; 362: 859–68. Beckerman KP. Long-term findings of HIVNET 012: the next steps. Lancet 2003; 362: 842–43. Havlir D, Eastman S, Gamst A, Richman DD. Nevirapine-resistant human immunodeficiency virus: kinetics of replication and estimated prevalence in untreated patients. J Virol 1996; 70: 7894–99. Eshleman SH, Mracna M, Guay LA, et al. Selection and fading of resistance mutations in women and infants receiving nevirapine to prevent HIV-1 vertical transmission (HIVNET012). AIDS 2001; 15: 2951–57. Cunningham CK, Chaix M-L, Rekacewicz C, et al. Development of resistance mutations in women receiving standard antiretroviral therapy who received intrapartum nevirapine to prevent human immunodeficiency virus type 1 transmission: a substudy of Pediatric AIDS Clinical Trials Group protocol 316. J Infect Dis 2002; 186: 181–88.
Sir—Karen Palmore Beckerman states in her Commentary1 that the HIVNET 012 protocol did not affect child survival. We strongly disagree with this assertion. First, the study was powered to assess significant differences in HIV-1 transmission, not survival. Second, as shown in figure 3, children in the nevirapine group fully achieved the expected level of survival benefit that would be mediated through the documented level of reduction in HIV-1 incidence. Third, the 18-month
mortality was higher in the zidovudine group than the nevirapine group (13·6% vs 10·6%),2 and these differences would be expected to widen owing to the higher number of HIV-1infected children in the zidvoudine group, and the increasing likelihood of HIV-1 disease progression as the children get older; HIVNET 012 will be able to assess this prospect, because infants are being followed-up until they reach 5 years of age. We agree with Beckerman that the effect of single-dose nevirapine on future treatment options is a concern that urgently needs research. We disagree that it is a foregone conclusion that there will be an adverse effect. Data from the Pediatric AIDS Clinical Trial Group3 protocol 316 indicate that nevirapine resistance was not reduced by coadministration of additional antiretrovirals if there was persistent viral replication when nevirapine was given; therefore coadministration of 2–3 days of postnatal zidovudine or lamivudine is unlikely to decrease resistance. We also agree with Beckerman that combination antiretroviral therapy during pregnancy and post partum will be better than single-dose nevirapine at reducing transmission and beneficial to maternal health, and is a goal to be worked towards. However, in Uganda today, despite the best intentions, fewer than 2% of HIV-1-infected individuals are receiving any form of antiretroviral treatment. Even with the expected implementation of the Global AIDS Fund and Bush AIDS Relief Program over the next few years, most HIV-1-infected individuals who need treatment will probably not receive it. In the meantime, 2000 babies are becoming HIV-1-infected each day. In our opinion, saving thousands of lives today with a simple, safe, affordable intervention should take precedence over the alternative of not using it because of concerns that future and uncertain treatment options might be limited with nevirapine’s use. *Brooks Jackson, Francis Mmiro, for the HIVNET 012 study team Department of Pathology, Johns Hopkins University, Carnegie 415, 600 North Wolfe Street, Baltimore, MD 21287, USA (e-mail: [email protected]) 1
2
3
Beckerman KP. Long-term findings of HIVNET 012: the next steps. Lancet 2003; 362: 842–43. Jackson JB, Musoke P, Fleming T, et al. Intrapartum and neonatal single-dose nevirapine compared with zidovudine for prevention of mother-to-child transmission of HIV-1 in Kampala, Uganda: 18 month follow-up of the HIVNET 012 randomised trial. Lancet 2003; 362: 859–68. Cunningham CK, Chaix M-L, Rekacewicz C, et al. Development of
resistance mutations in women receiving standard antiretroviral therapy who received intrapartum nevirapine to prevent perinatal human immunodeficiency virus type 1 transmission: a substudy of Pediatric AIDS Clinical Trials Group protocol 316. J Infect Dis 2002; 186: 181–88.
Author’s reply Sir—Ed Cooper is correct to point out that “induction” of nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance is a misuse of the word (albeit a common one), which should be replaced by “selection” or “induction of detectable resistance”. Charles Darwin, we assume, would be among those most eager to examine the hypothesis that NNRTI resistance, which does not seem to render virus unfit,1 will “fade” to clinical insignificance. Catherine Wilfert argues that none of the single-dose nevirapine studies has shown 100% resistance, and indeed none has. However, Kantor and colleagues—the only group to examine 2-week, maternal HIV-1 clade C post-nevirapine samples— reported that 76% of exposed women had detectable resistance.2 Given that the assay used cannot detect minority or archived populations, the actual prevalence of clinically significant NNRTI resistance remains higher than 76% and, in fact, could approach 100%. The suggestion by Brooks Jackson and Francis Mmiro that the statistically insignificant difference in 18-month child survival between nevirapine and zidovudine prophylaxis groups “would be expected to widen” is a hope that many of us share. However, neither their own calculations of significance (p=0·253), nor the original study design and power calculations (as they point out) support such a conclusion. Jackson and Mmiro join Wilfert in pointing out that treatment with other antiretroviral agents did not prevent the appearance of NNRTI resistance in the Pediatric AIDS Clinical Trial Group Protocol (PACTG) 316.3 However 66% of the PACTG participants studied received suboptimal single or dual combination antiretroviral therapy and all patients had evidence of ongoing viral replication, with the lowest viral load reported being 152 copies per mL. Similarly, the Thai-US Centers for Disease Control collaboration4 found evidence of NNRTI resistance in 15% of women who received single-dose nevirapine during labour after zidovudine prophylaxis from 34 to 36 weeks of pregnancy. The median
THE LANCET • Vol 363 • January 17, 2004 • www.thelancet.com
For personal use. Only reproduce with permission from The Lancet.
245
CORRESPONDENCE
viral load at delivery was 3857 copies HIV-1 RNA per mL. With evidence of continued viral replication at delivery, women in both studies were essentially exposed to nevirapine monotherapy, just as in HIVNET 012. Many of our questions will be answered by studies already enrolling pregnant women. Among these, Boehringer-Ingelheim BIZA 1100.1413 is examining resistance detection after single-dose nevirapine in labour accompanied by 4 or 7 days of zidovudine plus lamivudine. Participating women in whom resistance is detected will be followed up for an unprecedented 18 months. On World AIDS Day (Dec 1, 2003), WHO released its bold and aggressive “3 By 5 Initiative” to treat 3 million HIV-infected individuals by 2005. The pharmaceutical cornerstone of that programme will be NNRTI-based triple antiretroviral combinations. The week previously, the South African Government announced its plans to provide free drugs to people living with HIV/AIDS; the week before that, the Indian Government announced plans for provision of free AIDS treatments. As these events overtake us in 2004, we might well find that communities, even in the developing world, will declare that vertical transmission rates of 16%, unabated AIDS-related maternal mortality, and NNRTI resistance resulting from single-dose nevirapine protocols, are all absolutely unacceptable. Karen Palmore Beckerman Bellevue Hospital Center, New York University School of Medicine, New York, NY 10016, USA (e-mail: [email protected]) 1
2
3
4
Deeks SG. Nonnucleoside reverse transcriptase inhibitor resistance. J Acquir Immun Defic Syndr Hum Retrovirol 2001; 26 (suppl 1): S25–33. Cantor R, Lee E, Johnston E, et al. Rapid flux in non-nucleoside reverse transcriptase inhibitior resistance mutations among subtype C HIV-1-infected women after single dose nevirapine. XII International HIV Drug Resistance Workshop: basic principles and clinical implications. Los Cabos, Mexico, 2003: abstr 78. Cunningham CD, Chaix M-L, Rekacewicz C, et al. Development of resistance mutations in women receiving standard antiretroviral therapy who received intrapartum nevirapine to prevent perinatal human immunodeficiency virus type 1 transmission: a substudy of Pediatric AIDS Clinical Trials Group Protocol 316. J Infect Dis 2002; 186: 181–88. Chaowana T, Chotpitayasunondh T, Vanpraper N, et al. Resistance mutations following a single-dose intrapartum administration of nevirapine to HIVinfected Thai women and their infants receiving short-course zidovudine. 10th Conference on Retroviruses and Opportunistic Infections. Boston, MA, 2003: abstr 855.
246
Thought for food in the Philippines Sir—Your Nov 15 Editorial (p 1593)1 rightly states that legislation should be brought against the junk-food industry. The Australian government is reportedly moving to restrict the advertisement of junk food to prevent child obesity,2 and criticism of this industry has been made in developing countries, too.3 However, it is hard to enforce such legislation in developing countries, because many people believe that such foods are good, and governments sometimes welcome them. We have been observing the negative effect of junk food on human health in the Philippines for more than 10 years. We have found that poor people in urban areas commonly believe that instant noodles fortified with vitamin A and iron-supplemented canned sardines are healthier than vegetables.4 Perhaps this view is unsurprising considering that one of the government’s nutritional guidelines for Filipino children includes instant noodles.5 Moreover, whereas multivitamin tablets are seen as prestigious, the consumption of tropical, indigenous, and cheap vegetables, or having a vegetable garden in the backyard, are regarded as symbols of poverty. A strong WHO initiative will be necessary to restrict the advertisement of junk food and to change people’s beliefs about such food in developing countries where obesity is increasing. We hope that WHO introduces a universal guideline on not feeding children with junk food so that the governments of developing countries can protect their children from these damaging goods. *Shoko Miura, Masamine Jimba, Susumu Wakai Department of International Community Health, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan (e-mail: [email protected]) 1 2
3
4
5
The Lancet. Thought for food. Lancet 2003; 362: 1593. Zinn C. Australian Ministers threaten restrictions on junk food advertising. BMJ 2003; 327: 380. Fleck F. WHO challenges food industry in report on diet and health. BMJ 2003; 326: 515. Miura S, Kunii O, Wakai S. Home gardening in urban poor communities of the Philippines. Int J Food Sci Nutr 2003; 54: 77–88. Food and Nutrition Research Institute. Nutritional guidelines for Filipinos: revised edn. Manila: Food and Nutrition Research Institute, Department of Science and Technology, 2000: 34.
Treatment of multidrugresistant tuberculosis in Russian prisons Sir—Ben Aris (Nov 8, p 1557)1 highlights important shortfalls in the Russian public-health system and its devastating effect on health. Predetention facilities and penal colonies are breeding grounds for diseases such as tuberculosis, and contribute a third of all new tuberculosis cases in Russia each year.2 Médecins Sans Frontières (MSF) started work in Siberian prisons in 1996, and has treated 10 500 patients in collaboration with regional penal authorities using the WHO-led DOTS strategy up until our withdrawal from the region in September last year. During that period, our doctors were faced with a substantial number of patients with multidrug-resistant tuberculosis who cannot be cured with the first-line tuberculosis drugs we provide. In these prisons, around 22% of new cases and 40% of retreatment cases are multidrug-resistant, which are some of the highest rates recorded worldwide. Expensive treatment options, involving the use of quality second-line drugs for anything up to 2 years, were not available to us then. In an attempt to bring the hope of a cure to these prisoners, we, together with the regional authorities in Kemerovo, submitted an application to treat multidrug-resistant tuberculosis patients to the international body the Green Light Committee. We received approval to start using second-line drugs to treat initially 150 patients in the Siberian prison colonies. On application to the Russian Ministry of Health, however, we were surprised to find that the application to start treating these patients was rejected. Despite the fact that the treatment schemes proposed were based on internationally agreed guidelines, the Russian Ministry of Health rejected it on the grounds that the treatment schemes proposed contradicted the regulations of the Russian Pharmaceutical Committee. It therefore classified the DOTS-Plus pilot project as “experimental”, which is forbidden within the penal system under national law. The primary reasons given referred to Russian drug legislation that prohibits extended use of certain second-line drugs. Such legislation bears no relation to internationally recognised treatment principles on duration with potent drugs such as capreomycin, cycloserine, and fluoroquinolones. Further, the DOTS-Plus
THE LANCET • Vol 363 • January 17, 2004 • www.thelancet.com
For personal use. Only reproduce with permission from The Lancet.
and the importance of antiretroviral therapy to treat maternal HIV-1 infection. We agree that our goal should be appropriate antiretroviral therapy for all pregnant women and family members who require it. The hope is that existing programmes will expand to include the provision of care and treatment. However, as we work towards that goal, we must be pragmatic. Do we let 2000 infants become infected every day because we do not have access to optimum treatment but do have a proven effective intervention for mother-tochild transmission? And, does an HIV-1-infected pregnant woman in a developing country not have the right to make a decision to try to prevent infection of her child? Until we can provide these women with the antiretroviral drugs they deserve, the least we can do is to provide them with the means and the choice to protect their children. Catherine M Wilfert Elizabeth Glaser Pediatric AIDS Foundation, 1917 Wildcat Creek Road, Chapel Hill, NC 27516, USA (e-mail: [email protected]) 1
2
3
4
5
Jackson JB, Musoka P, Fleming T, et al. Intrapartum and neonatal single-dose nevirapine compared with zidovudine for prevention of mother-to-child transmission of HIV-1 in Kampala, Uganda: 18-month follow-up of the HIVNET 012 randomised trial. Lancet 2003; 362: 859–68. Beckerman KP. Long-term findings of HIVNET 012: the next steps. Lancet 2003; 362: 842–43. Havlir D, Eastman S, Gamst A, Richman DD. Nevirapine-resistant human immunodeficiency virus: kinetics of replication and estimated prevalence in untreated patients. J Virol 1996; 70: 7894–99. Eshleman SH, Mracna M, Guay LA, et al. Selection and fading of resistance mutations in women and infants receiving nevirapine to prevent HIV-1 vertical transmission (HIVNET012). AIDS 2001; 15: 2951–57. Cunningham CK, Chaix M-L, Rekacewicz C, et al. Development of resistance mutations in women receiving standard antiretroviral therapy who received intrapartum nevirapine to prevent human immunodeficiency virus type 1 transmission: a substudy of Pediatric AIDS Clinical Trials Group protocol 316. J Infect Dis 2002; 186: 181–88.
Sir—Karen Palmore Beckerman states in her Commentary1 that the HIVNET 012 protocol did not affect child survival. We strongly disagree with this assertion. First, the study was powered to assess significant differences in HIV-1 transmission, not survival. Second, as shown in figure 3, children in the nevirapine group fully achieved the expected level of survival benefit that would be mediated through the documented level of reduction in HIV-1 incidence. Third, the 18-month
mortality was higher in the zidovudine group than the nevirapine group (13·6% vs 10·6%),2 and these differences would be expected to widen owing to the higher number of HIV-1infected children in the zidvoudine group, and the increasing likelihood of HIV-1 disease progression as the children get older; HIVNET 012 will be able to assess this prospect, because infants are being followed-up until they reach 5 years of age. We agree with Beckerman that the effect of single-dose nevirapine on future treatment options is a concern that urgently needs research. We disagree that it is a foregone conclusion that there will be an adverse effect. Data from the Pediatric AIDS Clinical Trial Group3 protocol 316 indicate that nevirapine resistance was not reduced by coadministration of additional antiretrovirals if there was persistent viral replication when nevirapine was given; therefore coadministration of 2–3 days of postnatal zidovudine or lamivudine is unlikely to decrease resistance. We also agree with Beckerman that combination antiretroviral therapy during pregnancy and post partum will be better than single-dose nevirapine at reducing transmission and beneficial to maternal health, and is a goal to be worked towards. However, in Uganda today, despite the best intentions, fewer than 2% of HIV-1-infected individuals are receiving any form of antiretroviral treatment. Even with the expected implementation of the Global AIDS Fund and Bush AIDS Relief Program over the next few years, most HIV-1-infected individuals who need treatment will probably not receive it. In the meantime, 2000 babies are becoming HIV-1-infected each day. In our opinion, saving thousands of lives today with a simple, safe, affordable intervention should take precedence over the alternative of not using it because of concerns that future and uncertain treatment options might be limited with nevirapine’s use. *Brooks Jackson, Francis Mmiro, for the HIVNET 012 study team Department of Pathology, Johns Hopkins University, Carnegie 415, 600 North Wolfe Street, Baltimore, MD 21287, USA (e-mail: [email protected]) 1
2
3
Beckerman KP. Long-term findings of HIVNET 012: the next steps. Lancet 2003; 362: 842–43. Jackson JB, Musoke P, Fleming T, et al. Intrapartum and neonatal single-dose nevirapine compared with zidovudine for prevention of mother-to-child transmission of HIV-1 in Kampala, Uganda: 18 month follow-up of the HIVNET 012 randomised trial. Lancet 2003; 362: 859–68. Cunningham CK, Chaix M-L, Rekacewicz C, et al. Development of
resistance mutations in women receiving standard antiretroviral therapy who received intrapartum nevirapine to prevent perinatal human immunodeficiency virus type 1 transmission: a substudy of Pediatric AIDS Clinical Trials Group protocol 316. J Infect Dis 2002; 186: 181–88.
Author’s reply Sir—Ed Cooper is correct to point out that “induction” of nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance is a misuse of the word (albeit a common one), which should be replaced by “selection” or “induction of detectable resistance”. Charles Darwin, we assume, would be among those most eager to examine the hypothesis that NNRTI resistance, which does not seem to render virus unfit,1 will “fade” to clinical insignificance. Catherine Wilfert argues that none of the single-dose nevirapine studies has shown 100% resistance, and indeed none has. However, Kantor and colleagues—the only group to examine 2-week, maternal HIV-1 clade C post-nevirapine samples— reported that 76% of exposed women had detectable resistance.2 Given that the assay used cannot detect minority or archived populations, the actual prevalence of clinically significant NNRTI resistance remains higher than 76% and, in fact, could approach 100%. The suggestion by Brooks Jackson and Francis Mmiro that the statistically insignificant difference in 18-month child survival between nevirapine and zidovudine prophylaxis groups “would be expected to widen” is a hope that many of us share. However, neither their own calculations of significance (p=0·253), nor the original study design and power calculations (as they point out) support such a conclusion. Jackson and Mmiro join Wilfert in pointing out that treatment with other antiretroviral agents did not prevent the appearance of NNRTI resistance in the Pediatric AIDS Clinical Trial Group Protocol (PACTG) 316.3 However 66% of the PACTG participants studied received suboptimal single or dual combination antiretroviral therapy and all patients had evidence of ongoing viral replication, with the lowest viral load reported being 152 copies per mL. Similarly, the Thai-US Centers for Disease Control collaboration4 found evidence of NNRTI resistance in 15% of women who received single-dose nevirapine during labour after zidovudine prophylaxis from 34 to 36 weeks of pregnancy. The median
THE LANCET • Vol 363 • January 17, 2004 • www.thelancet.com
For personal use. Only reproduce with permission from The Lancet.
245
CORRESPONDENCE
viral load at delivery was 3857 copies HIV-1 RNA per mL. With evidence of continued viral replication at delivery, women in both studies were essentially exposed to nevirapine monotherapy, just as in HIVNET 012. Many of our questions will be answered by studies already enrolling pregnant women. Among these, Boehringer-Ingelheim BIZA 1100.1413 is examining resistance detection after single-dose nevirapine in labour accompanied by 4 or 7 days of zidovudine plus lamivudine. Participating women in whom resistance is detected will be followed up for an unprecedented 18 months. On World AIDS Day (Dec 1, 2003), WHO released its bold and aggressive “3 By 5 Initiative” to treat 3 million HIV-infected individuals by 2005. The pharmaceutical cornerstone of that programme will be NNRTI-based triple antiretroviral combinations. The week previously, the South African Government announced its plans to provide free drugs to people living with HIV/AIDS; the week before that, the Indian Government announced plans for provision of free AIDS treatments. As these events overtake us in 2004, we might well find that communities, even in the developing world, will declare that vertical transmission rates of 16%, unabated AIDS-related maternal mortality, and NNRTI resistance resulting from single-dose nevirapine protocols, are all absolutely unacceptable. Karen Palmore Beckerman Bellevue Hospital Center, New York University School of Medicine, New York, NY 10016, USA (e-mail: [email protected]) 1
2
3
4
Deeks SG. Nonnucleoside reverse transcriptase inhibitor resistance. J Acquir Immun Defic Syndr Hum Retrovirol 2001; 26 (suppl 1): S25–33. Cantor R, Lee E, Johnston E, et al. Rapid flux in non-nucleoside reverse transcriptase inhibitior resistance mutations among subtype C HIV-1-infected women after single dose nevirapine. XII International HIV Drug Resistance Workshop: basic principles and clinical implications. Los Cabos, Mexico, 2003: abstr 78. Cunningham CD, Chaix M-L, Rekacewicz C, et al. Development of resistance mutations in women receiving standard antiretroviral therapy who received intrapartum nevirapine to prevent perinatal human immunodeficiency virus type 1 transmission: a substudy of Pediatric AIDS Clinical Trials Group Protocol 316. J Infect Dis 2002; 186: 181–88. Chaowana T, Chotpitayasunondh T, Vanpraper N, et al. Resistance mutations following a single-dose intrapartum administration of nevirapine to HIVinfected Thai women and their infants receiving short-course zidovudine. 10th Conference on Retroviruses and Opportunistic Infections. Boston, MA, 2003: abstr 855.
246
Thought for food in the Philippines Sir—Your Nov 15 Editorial (p 1593)1 rightly states that legislation should be brought against the junk-food industry. The Australian government is reportedly moving to restrict the advertisement of junk food to prevent child obesity,2 and criticism of this industry has been made in developing countries, too.3 However, it is hard to enforce such legislation in developing countries, because many people believe that such foods are good, and governments sometimes welcome them. We have been observing the negative effect of junk food on human health in the Philippines for more than 10 years. We have found that poor people in urban areas commonly believe that instant noodles fortified with vitamin A and iron-supplemented canned sardines are healthier than vegetables.4 Perhaps this view is unsurprising considering that one of the government’s nutritional guidelines for Filipino children includes instant noodles.5 Moreover, whereas multivitamin tablets are seen as prestigious, the consumption of tropical, indigenous, and cheap vegetables, or having a vegetable garden in the backyard, are regarded as symbols of poverty. A strong WHO initiative will be necessary to restrict the advertisement of junk food and to change people’s beliefs about such food in developing countries where obesity is increasing. We hope that WHO introduces a universal guideline on not feeding children with junk food so that the governments of developing countries can protect their children from these damaging goods. *Shoko Miura, Masamine Jimba, Susumu Wakai Department of International Community Health, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan (e-mail: [email protected]) 1 2
3
4
5
The Lancet. Thought for food. Lancet 2003; 362: 1593. Zinn C. Australian Ministers threaten restrictions on junk food advertising. BMJ 2003; 327: 380. Fleck F. WHO challenges food industry in report on diet and health. BMJ 2003; 326: 515. Miura S, Kunii O, Wakai S. Home gardening in urban poor communities of the Philippines. Int J Food Sci Nutr 2003; 54: 77–88. Food and Nutrition Research Institute. Nutritional guidelines for Filipinos: revised edn. Manila: Food and Nutrition Research Institute, Department of Science and Technology, 2000: 34.
Treatment of multidrugresistant tuberculosis in Russian prisons Sir—Ben Aris (Nov 8, p 1557)1 highlights important shortfalls in the Russian public-health system and its devastating effect on health. Predetention facilities and penal colonies are breeding grounds for diseases such as tuberculosis, and contribute a third of all new tuberculosis cases in Russia each year.2 Médecins Sans Frontières (MSF) started work in Siberian prisons in 1996, and has treated 10 500 patients in collaboration with regional penal authorities using the WHO-led DOTS strategy up until our withdrawal from the region in September last year. During that period, our doctors were faced with a substantial number of patients with multidrug-resistant tuberculosis who cannot be cured with the first-line tuberculosis drugs we provide. In these prisons, around 22% of new cases and 40% of retreatment cases are multidrug-resistant, which are some of the highest rates recorded worldwide. Expensive treatment options, involving the use of quality second-line drugs for anything up to 2 years, were not available to us then. In an attempt to bring the hope of a cure to these prisoners, we, together with the regional authorities in Kemerovo, submitted an application to treat multidrug-resistant tuberculosis patients to the international body the Green Light Committee. We received approval to start using second-line drugs to treat initially 150 patients in the Siberian prison colonies. On application to the Russian Ministry of Health, however, we were surprised to find that the application to start treating these patients was rejected. Despite the fact that the treatment schemes proposed were based on internationally agreed guidelines, the Russian Ministry of Health rejected it on the grounds that the treatment schemes proposed contradicted the regulations of the Russian Pharmaceutical Committee. It therefore classified the DOTS-Plus pilot project as “experimental”, which is forbidden within the penal system under national law. The primary reasons given referred to Russian drug legislation that prohibits extended use of certain second-line drugs. Such legislation bears no relation to internationally recognised treatment principles on duration with potent drugs such as capreomycin, cycloserine, and fluoroquinolones. Further, the DOTS-Plus
THE LANCET • Vol 363 • January 17, 2004 • www.thelancet.com
For personal use. Only reproduce with permission from The Lancet.