Skip to main content
×
Home
    • Aa
    • Aa

The effect of CMV infection on progression of human immunodeficiency virus disease in a cohort of haemophilic men followed for up to 13 years from seroconversion

  • C. A. Sabin (a1), A. N. Phillips (a1), C. A. Lee (a2), G. Janossy (a3), V. Emery (a4) and P. D. Griffiths (a4)...
Summary
Summary

The effect of prior infection with cytomegalovirus (CMV) on progression of HIV disease in a cohort of 111 men with haemophilia was studied after 13 years followup. The relative hazards associated with CMV positivity on progression to AIDS, death and a CD4 count of 0·05 × 109/1 were 2·28, 2·42 and 2·34, respectively. CMV seropositive patients were significantly older than the seronegative and this was controlled for by using a Cox proportional hazards model. The relative hazards for the three endpoints decreased to 1·89, 1·82 and 1·93 respectively and were marginally non-significant (P = 0·05, 0·08 and 0·08 for the three endpoints respectively). We conclude that this cohort continues to show evidence of a ‘co-factor’ effect associated with prior infection with CMV which is confounded by age but not completely explained by age differences. The potential biological significance of these results is discussed in the context of recent controlled clinical trials which show a survival benefit from long-term high-dose acyclovir, a drug with activity in vivo against CMV and other herpesviruses.

Copyright
References
Hide All
1.Biggar RJ. AIDS incubation in 1891 HIV seroconverters from different exposure groups. AIDS 1990; 4: 1059–66.
2.Chevret S, Costagliola D, Lefrère J et al. , A new approach to estimating AIDS incubation times: results in homosexual infected men. J Epidemiol Comm Health 1992; 46: 582–6.
2.Bacchetti P. Estimating the incubation period of AIDS by comparing population infection and diagnosis patterns. J Am Stat Assoc 1990; 412: 1002–8.
4.Phillips AN, Sabin CA, Elford J et al. , Use of CD4 lymphocyte count to predict long term survival free of AIDS after HIV infection. BMJ 1994; 309: 309–13.
5.Griffiths PD. Studies to define viral cofactors for human immunodeficiency virus. Infect Ag Dis 1992; 1: 237–44.
6.Gendelman HE, Phelps W, Feigenbaum L et al. , Transactivation of the human immunodeficiency virus long terminal repeat sequence by DNA viruses. Proc Nat Acad Sci USA 1986; 83: 9759–63.
7.Davis MG, Kenney SC, Kamine J et al. , Immediate-early gene region of human cytomegalovirus transactivates the promoter of human immunodeficiency virus. Proc Nat Acad Sci USA 1987; 84: 8642–6.
8.Kenney S, Kamine J, Markovitz D et al. , An Epstein–Barr virus immediate-early gene product transactivates gene expression from the human immunodeficiency virus long terminal repeat. Proc Nat Acad Sci USA 1988; 85: 1652–6.
9.Siddiqui A, Gaynor R, Srinivasan A et al. , Trans-activation of viral enhancers including long terminal repeat of the human immunodeficiency virus by the hepatitis B virus X protein. Virology 1989; 169: 479–84.
10.Moss AR, Bacchetti P, Osmond D et al. , Seropositivity for HIV and the development of AIDS or AIDS-related condition: three-year follow-up of the San Francisco General Hospital Cohort. BMJ 1988; 296: 745–50.
11.Blaxhult A, Granath F, Lidman K et al. , The influence of age on the latency period to AIDS in people infected by HIV through blood transfusion. AIDS 1990; 4: 125–9.
12.Phillips AN, Lee CA, Elford J et al. , More rapid progression to AIDS in older HIV-infected people: the role of CD4+ T-cell counts. J Acquir Immune Defic Syndr 1991; 4: 970–5.
13.Berry NJ, MacDonald Burns D, Wannamethee G et al. , Serological studies on the acquisition of antibodies to cytomegalovirus, herpes simplex virus and human immunodeficiency virus among general hospital patients and those attending a clinic for sexually transmitted diseases. J Med Virol 1988; 24: 385–93.
14.Griffiths PD, Baboonian C. A prospective study of primary cytomegalovirus infection during pregnancy: final report. Br J Obstet Gynaecol 1984; 91: 307–15.
15.Webster A, Lee CA, Cook DG et al. , Cytomegalovirus infection and progression towards AIDS in haemophiliacs with human immunodeficiency virus infection. Lancet 1989; ii: 63–6.
16.Jackson JB, Erice A, Englund JA et al. , Prevalence of cytomegalovirus antibody in hemophiliacs and homosexuals infected with human immunodeficiency virus type 1. Transfusion 1988; 28: 187–9.
17.Rugman FP, Mannion PT, Hay CR et al. , Cytomegalovirus, serum beta 2 microglobulin and progression to AIDS in HIV-seropositive haemophiliacs. Lancet 1989; ii: 631.
18.Becherer PR, Smiley ML, Matthews TJ et al. , Human immunodeficiency virus-1 disease progression in hemophiliacs. Am J Hem 1990; 34: 204–9.
19.Rabkin CS, Hatzakis A, Griffiths PD et al. , Cytomegalovirus infection and risk of AIDS in human immunodeficiency virus-infected hemophilia patients. J Infect Dis 1993; 168: 1260–3.
20.Lee CA, Phillips AN, Elford J et al. , The natural history of human immunodeficiency virus infection in a haemophilic cohort. Brit J Haematol 1989; 73: 228–34.
21.Phillips AN, Lee CA, Elford J et al. , Serial CD4 lymphocyte counts and development of AIDS. Lancet 1991; 337: 389–92.
22.Bofill M, Janossy G, Lee CA et al. , Laboratory control values for CD4 and CD8 T lymphocytes. Implications for HIV diganosis. Clin Exp Immunol 1992; 88: 243–52.
23.Berry NJ, Grundy JE, Griffiths PD. Radioimmunoassay for the detection of IgG antibodies to herpes simplex virus and its use as a prognostic indicator of HSV excretion in transplant recipients. J Med Virol 1987; 21: 147–54.
24.Altman DG. Practical statistics for medical research. London, UK: Chapman and Hall, 1991.
25.Kaplan EL, Meier P. Non-parametric estimation from incomplete observations. J Am Stat Assoc 1958; 53: 457–81.
26.Cox DR, Oakes D. Analysis of survival data. London: Chapman and Hall, 1984.
27.SAS Inst Inc. SAS Technical Report P-217. SAS/STAT Software: The PHREG Procedure. Version 6. Cary, NC: 1991.
28.Phillips AN, Elford J, Sabin CA et al. , Immunodeficiency and the risk of death in HIV infection. JAMA 1992; 268: 2662–6.
29.Centers for Disease Control. 1993 Revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults. MMWR 1992; 41 (No. RR-17): 117
30.Webster A, Grundy JE, Lee CA et al. , Cytomegalovirus infection and progression to AIDS. Lancet 1989; ii: 681.
31.Pillay D, Lipman MCI, Lee CA et al. , A clinico-pathological audit of opportunistic viral infections in HIV-infected patients. AIDS 1993; 7: 969–74.
32.Youle MS, Gazzard BG, Johnson MA et al. , Effects of high-dose oral acyclovir on herpesvirus disease and survival in patients with advanced HIV disease: a double-blind, placebo-controlled study. AIDS 1994; 8: 641–9.
33.Cooper DA, Pehrson PO, Pedersen C et al. , The efficacy and safety of zidovudine alone or as cotherapy with acyclovir for the treatment of patients with AIDS and AIDS-related complex: a double-blind, randomized trial. AIDS 1993; 7: 197207.
34.Meyers JD, Reed EC, Shepp DH et al. , Acyclovir for prevention of cytomegalovirus infection and disease after allogenic marrow transplantation. N Engl J Med 1988; 318: 70–5.
35.Balfour HR, Chace BA, Stapleton JT et al. , A randomized, placebo-controlled trial of oral acyclovir for the prevention of cytomegalovirus disease in recipients of renal allografts. N Engl J Med 1989; 320: 1381–7.
36.Prentice HG, Gluckman E, Powles RL et al. , Impact of long-term acyclovir on cytomegalovirus infection and survival after allogeneic bone marrow transplantation. European Acyclovir for CMV Prophylaxis Study Group. Lancet 1994; 343: 749–53.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Epidemiology & Infection
  • ISSN: 0950-2688
  • EISSN: 1469-4409
  • URL: /core/journals/epidemiology-and-infection
Please enter your name
Please enter a valid email address
Who would you like to send this to? *
×

Metrics

Full text views

Total number of HTML views: 0
Total number of PDF views: 3 *
Loading metrics...

Abstract views

Total abstract views: 30 *
Loading metrics...

* Views captured on Cambridge Core between September 2016 - 23rd October 2017. This data will be updated every 24 hours.