Twenty five years of HIV infection in haemophilic men in Britain: an observational study
1 Department of Primary Care and Population Sciences, Royal Free and UC Medical School, London NW3 2PF,2 Haemophilia Centre and Haemostasis Unit, Royal Free NHS Trust, London
Introduction
The first HIV seroconversion in the United Kingdom in a man with haemophilia was in 1979.1 After HIV was identified, measures were taken to remove the risk of HIV transmission via blood products, and since 1986 no HIV infections have occurred through this route in the developed world. The epidemic is now 25 years old in haemophilic men. Although the introduction of highly active antiretroviral therapy (HAART) has altered the course of HIV infection, many haemophilic men died before this became available. It is important to monitor those remaining alive to determine their long term outcomes and to assess the impact of coinfection with hepatitis C virus.
, 百拇医药
Participants, methods, and results
The Royal Free Hospital haemophilia cohort, consisting of 111 men with haemophilia infected with HIV after treatment with contaminated clotting factor concentrates (median age 22 (range 2-77) years at infection), has been described previously.2 All are coinfected with hepatitis C virus. Follow-up time—calculated from seroconversion date to the date of death, last clinic visit (for those lost to follow-up), or 31 December 2004—ranged from 0.8 to 25.1 years (median 14.3). By 31 December 2004, 59 (53%) men had developed AIDS and 74 (67%) had died (54 after developing AIDS, 20 before AIDS). From 1996, when HAART was introduced, there have been only six new cases of AIDS but 20 deaths, compared with 53 AIDS cases and 54 deaths before 1996. Deaths since 1996 have been due to liver related causes (liver failure, cirrhosis, or hepatocellular carcinoma (7 deaths)), non-HIV related causes (5 deaths), HIV related causes (5 deaths), and unknown causes (3 deaths). Before 1996, 42 (78%) deaths were due to HIV related causes and only five (9%) due to liver related causes.
, 百拇医药
In 1989, using a method based on rates of CD4 cell count decline, we estimated that 60 men would have AIDS by 2000 (table).3 The observed numbers are remarkably consistent with these estimates, which is somewhat surprising as we had not anticipated the benefits of HAART. Possible explanations are that those who survived long enough to benefit from HAART had not been predicted to develop AIDS before 2000 in any case, and that any positive effects of HAART have been partly negated by the effects on survival of liver disease.
, 百拇医药
Predicted and observed numbers of AIDS cases occurring by the end of each year in the Royal Free Hospital haemophilia cohort, 1985-2000
The 23 patients remaining under care at the centre (14 patients have transferred elsewhere) have been followed for a median of 22.7 (19.7-25.1) years. Most (20) have received HAART, 14 of whom had already had antiretroviral treatment when starting HAART. The 20 patients have received a median of seven (3-11) antiretroviral drugs and have been exposed to antiretroviral therapy for a median of 9.9 (1.0-16.8) years. Although these patients' treatment histories would now be considered suboptimal, all currently have an HIV RNA level < 50 copies/ml and their median CD4 cell count is 326 (139-593) x 106 cells/l. The three patients who have not received HAART have had stable CD4 counts > 200x106 cells/l; viral loads have remained low in two patients, and moderate but stable (last viral load 18 234 copies/ml) in the third.
, 百拇医药
Comment
A small proportion of haemophilic men infected with HIV 20-25 years ago remain alive and well. Advances in haemophilia care had increased life expectancy from 40 years in the 1960s to 69 years by 1980.4 The HIV epidemic caused a reversal in these improvements that has been reversed only partially by HAART because coinfection with hepatitis C virus continues to cause deaths.5 Although treatment of hepatitis C is improving, responses remain poor among those coinfected with HIV. Continued development of new antiviral agents for both HIV and hepatitis C virus is essential to maintain the health of these patients.
, 百拇医药
What is already known on this topic
About a fifth of patients with haemophilia in the UK were infected with HIV between 1979 and 1985 after treatment with contaminated clotting factor concentrates
Coinfection with hepatitis C virus has contributed to mortality among these men
What this study adds
A small proportion of haemophilic men infected with HIV 20-25 years ago remain alive and well, but there has been an increasing number of deaths from liver related causes in this patient group as a consequence of coinfection with hepatitis C virus
, http://www.100md.com
This article was posted on bmj.com on 16 September 2005: http://bmj.com/cgi/doi/10.1136/bmj.38604.468785.DE
Contributors: CAS, CAL, and ANP produced the initial concept and design of the study. CAS analysed and interpreted the data and wrote the manuscript, and is guarantor for the study. ANP helped prepare the manuscript. AG and TTY were involved with coordinating the study and helped to create and clean the datasets. All authors commented on the interpretation of data and approved the final version of the manuscript.
, 百拇医药
Funding: The Royal Free haemophilia cohort study has in the past received funding from the Medical Research Council, UK (Grant No G9722348).
Competing interests: None declared.
Ethical approval: Not needed since all personal identifiers were removed before patient data were entered into the computer and only aggregate data are presented.
References
Lee CA, Webster A, Griffiths PD, Kernoff PBA. Symptomless HIV infection after more than ten years [letter]. Lancet 1990;335: 426.
, 百拇医药
Lee CA, Phillips A, Elford J, Miller EJ, Bofill M, Griffiths PD, et al. The natural history of human immunodeficiency virus infection in a haemophilic cohort. Br J Haematol 1989;73: 228-34.
Phillips A, Lee CA, Elford J, Janossy G, Bofill M, Timms A, et al. Prediction of progression to AIDS by analysis of CD4 lymphocyte counts in a haemophilic cohort. AIDS 1989;3: 737-41.
Chorba TL, Holman RC, Strine TW, Clarke MJ, Evatt BL. Changes in longevity and causes of death among persons with hemophilia A. Am J Hematol 1994;45: 112-21.
Quintana M, del Amo J, Barrasa A, Perez-Hoyos S, Ferreros I, Hernandez F, et al. Progression of HIV infection and mortality by hepatitis C infection in patients with haemophilia over 20 years. Haemophilia 2003;9: 605-12., http://www.100md.com(Caroline A Sabin, Andrew )
Introduction
The first HIV seroconversion in the United Kingdom in a man with haemophilia was in 1979.1 After HIV was identified, measures were taken to remove the risk of HIV transmission via blood products, and since 1986 no HIV infections have occurred through this route in the developed world. The epidemic is now 25 years old in haemophilic men. Although the introduction of highly active antiretroviral therapy (HAART) has altered the course of HIV infection, many haemophilic men died before this became available. It is important to monitor those remaining alive to determine their long term outcomes and to assess the impact of coinfection with hepatitis C virus.
, 百拇医药
Participants, methods, and results
The Royal Free Hospital haemophilia cohort, consisting of 111 men with haemophilia infected with HIV after treatment with contaminated clotting factor concentrates (median age 22 (range 2-77) years at infection), has been described previously.2 All are coinfected with hepatitis C virus. Follow-up time—calculated from seroconversion date to the date of death, last clinic visit (for those lost to follow-up), or 31 December 2004—ranged from 0.8 to 25.1 years (median 14.3). By 31 December 2004, 59 (53%) men had developed AIDS and 74 (67%) had died (54 after developing AIDS, 20 before AIDS). From 1996, when HAART was introduced, there have been only six new cases of AIDS but 20 deaths, compared with 53 AIDS cases and 54 deaths before 1996. Deaths since 1996 have been due to liver related causes (liver failure, cirrhosis, or hepatocellular carcinoma (7 deaths)), non-HIV related causes (5 deaths), HIV related causes (5 deaths), and unknown causes (3 deaths). Before 1996, 42 (78%) deaths were due to HIV related causes and only five (9%) due to liver related causes.
, 百拇医药
In 1989, using a method based on rates of CD4 cell count decline, we estimated that 60 men would have AIDS by 2000 (table).3 The observed numbers are remarkably consistent with these estimates, which is somewhat surprising as we had not anticipated the benefits of HAART. Possible explanations are that those who survived long enough to benefit from HAART had not been predicted to develop AIDS before 2000 in any case, and that any positive effects of HAART have been partly negated by the effects on survival of liver disease.
, 百拇医药
Predicted and observed numbers of AIDS cases occurring by the end of each year in the Royal Free Hospital haemophilia cohort, 1985-2000
The 23 patients remaining under care at the centre (14 patients have transferred elsewhere) have been followed for a median of 22.7 (19.7-25.1) years. Most (20) have received HAART, 14 of whom had already had antiretroviral treatment when starting HAART. The 20 patients have received a median of seven (3-11) antiretroviral drugs and have been exposed to antiretroviral therapy for a median of 9.9 (1.0-16.8) years. Although these patients' treatment histories would now be considered suboptimal, all currently have an HIV RNA level < 50 copies/ml and their median CD4 cell count is 326 (139-593) x 106 cells/l. The three patients who have not received HAART have had stable CD4 counts > 200x106 cells/l; viral loads have remained low in two patients, and moderate but stable (last viral load 18 234 copies/ml) in the third.
, 百拇医药
Comment
A small proportion of haemophilic men infected with HIV 20-25 years ago remain alive and well. Advances in haemophilia care had increased life expectancy from 40 years in the 1960s to 69 years by 1980.4 The HIV epidemic caused a reversal in these improvements that has been reversed only partially by HAART because coinfection with hepatitis C virus continues to cause deaths.5 Although treatment of hepatitis C is improving, responses remain poor among those coinfected with HIV. Continued development of new antiviral agents for both HIV and hepatitis C virus is essential to maintain the health of these patients.
, 百拇医药
What is already known on this topic
About a fifth of patients with haemophilia in the UK were infected with HIV between 1979 and 1985 after treatment with contaminated clotting factor concentrates
Coinfection with hepatitis C virus has contributed to mortality among these men
What this study adds
A small proportion of haemophilic men infected with HIV 20-25 years ago remain alive and well, but there has been an increasing number of deaths from liver related causes in this patient group as a consequence of coinfection with hepatitis C virus
, http://www.100md.com
This article was posted on bmj.com on 16 September 2005: http://bmj.com/cgi/doi/10.1136/bmj.38604.468785.DE
Contributors: CAS, CAL, and ANP produced the initial concept and design of the study. CAS analysed and interpreted the data and wrote the manuscript, and is guarantor for the study. ANP helped prepare the manuscript. AG and TTY were involved with coordinating the study and helped to create and clean the datasets. All authors commented on the interpretation of data and approved the final version of the manuscript.
, 百拇医药
Funding: The Royal Free haemophilia cohort study has in the past received funding from the Medical Research Council, UK (Grant No G9722348).
Competing interests: None declared.
Ethical approval: Not needed since all personal identifiers were removed before patient data were entered into the computer and only aggregate data are presented.
References
Lee CA, Webster A, Griffiths PD, Kernoff PBA. Symptomless HIV infection after more than ten years [letter]. Lancet 1990;335: 426.
, 百拇医药
Lee CA, Phillips A, Elford J, Miller EJ, Bofill M, Griffiths PD, et al. The natural history of human immunodeficiency virus infection in a haemophilic cohort. Br J Haematol 1989;73: 228-34.
Phillips A, Lee CA, Elford J, Janossy G, Bofill M, Timms A, et al. Prediction of progression to AIDS by analysis of CD4 lymphocyte counts in a haemophilic cohort. AIDS 1989;3: 737-41.
Chorba TL, Holman RC, Strine TW, Clarke MJ, Evatt BL. Changes in longevity and causes of death among persons with hemophilia A. Am J Hematol 1994;45: 112-21.
Quintana M, del Amo J, Barrasa A, Perez-Hoyos S, Ferreros I, Hernandez F, et al. Progression of HIV infection and mortality by hepatitis C infection in patients with haemophilia over 20 years. Haemophilia 2003;9: 605-12., http://www.100md.com(Caroline A Sabin, Andrew )