Hostname: page-component-78c5997874-dh8gc Total loading time: 0 Render date: 2024-11-15T02:07:17.291Z Has data issue: false hasContentIssue false
  • English
  • Français

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

Published online by Cambridge University Press:  15 May 2009

C. A. Sabin ,
A. N. Phillips ,
C. A. Lee ,
G. Janossy ,
V. Emery  and
P. D. Griffiths
C. A. Sabin
Affiliation:
Department of Public Health, Royal Free Hospital School of Medicine, Rowland Hill Street, London NW3 2PF, UK
A. N. Phillips
Affiliation:
Department of Public Health, Royal Free Hospital School of Medicine, Rowland Hill Street, London NW3 2PF, UK
C. A. Lee
Affiliation:
Haemophilia Centre and Department of Haematology, Royal Free Hospital and School of Medicine
G. Janossy
Affiliation:
Department of Clinical Immunology, Royal Free Hospital School of Medicine
V. Emery
Affiliation:
Department of Virology, Royal Free Hospital School of Medicine
P. D. Griffiths
Affiliation:
Department of Virology, Royal Free Hospital School of Medicine
Rights & Permissions [Opens in a new window]

Summary

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

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.

Type
Research Article
Information
Epidemiology & Infection , Volume 114 , Issue 2 , April 1995 , pp. 361 - 372
Copyright
Copyright © Cambridge University Press 1995

References

REFERENCES

1.Biggar, RJ. AIDS incubation in 1891 HIV seroconverters from different exposure groups. AIDS 1990; 4: 1059–66.Google ScholarPubMed
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.CrossRefGoogle ScholarPubMed
2.Bacchetti, P. Estimating the incubation period of AIDS by comparing population infection and diagnosis patterns. J Am Stat Assoc 1990; 412: 1002–8.Google Scholar
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.CrossRefGoogle ScholarPubMed
5.Griffiths, PD. Studies to define viral cofactors for human immunodeficiency virus. Infect Ag Dis 1992; 1: 237–44.Google ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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.Google ScholarPubMed
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.CrossRefGoogle Scholar
14.Griffiths, PD, Baboonian, C. A prospective study of primary cytomegalovirus infection during pregnancy: final report. Br J Obstet Gynaecol 1984; 91: 307–15.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
18.Becherer, PR, Smiley, ML, Matthews, TJ et al. , Human immunodeficiency virus-1 disease progression in hemophiliacs. Am J Hem 1990; 34: 204–9.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle Scholar
21.Phillips, AN, Lee, CA, Elford, J et al. , Serial CD4 lymphocyte counts and development of AIDS. Lancet 1991; 337: 389–92.Google ScholarPubMed
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.CrossRefGoogle Scholar
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.CrossRefGoogle ScholarPubMed
24.Altman, DG. Practical statistics for medical research. London, UK: Chapman and Hall, 1991.Google Scholar
25.Kaplan, EL, Meier, P. Non-parametric estimation from incomplete observations. J Am Stat Assoc 1958; 53: 457–81.CrossRefGoogle Scholar
26.Cox, DR, Oakes, D. Analysis of survival data. London: Chapman and Hall, 1984.Google Scholar
27.SAS Inst Inc. SAS Technical Report P-217. SAS/STAT Software: The PHREG Procedure. Version 6. Cary, NC: 1991.Google Scholar
28.Phillips, AN, Elford, J, Sabin, CA et al. , Immunodeficiency and the risk of death in HIV infection. JAMA 1992; 268: 2662–6.CrossRefGoogle ScholarPubMed
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): 1–17Google Scholar
30.Webster, A, Grundy, JE, Lee, CA et al. , Cytomegalovirus infection and progression to AIDS. Lancet 1989; ii: 681.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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: 197–207.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle Scholar
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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed