Effects of high-dose oral acyclovir on herpesvirus disease and survival in patients with advanced HIV disease

Youle, Michael; Gazzard, Brian; Johnson, Margaret; Cooper, David A.; Hoy, Jennifer; Busch, Heiner; Ruf, B.; Griffiths, Paul; Stephenson, Sally L.; Dancox, Mark; Bell, A.R.

doi:10.1097/00002030-199405000-00010

Cited by 77 publications

(27 citation statements)

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“…Examination of the causes of death did not reveal a significant reduction in clinically recognized herpesvirus disease. A similar trial, published by Youle et al (1994), was primarily designed to determine if high-dose aciclovir (800 mg qds) could reduce CMV disease in these patients. When the results of the Cooper analysis became available, survival was added as a second primary endpoint to the Youle trial.…”

Section: Results Of Trials Of Antiviral Chemotherapymentioning

confidence: 99%

A Proposal that Herpesviruses are Co-Factors of HIV Disease

Griffiths

1995

Antivir Chem Chemother

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SummaryThere is now extensive evidence that herpesviruses can interact with human immunodeficiency virus (HIV) in vitro. To determine if such interactions could be operative in vivo, evidence from AIDS autopsy series are reviewed. Using basic histopathological techniques, cytomegalovirus (CMV) and HIV coinfection of various individual cet'G has been demonstrated. Using cell culture, CMV has been detected ln 66% and herpes simplex virus in 11% of patients. Using immunocytochemistry, human herpesvirus type 6 (HHV-6) has been found in virtually all tissue sections. The hypothesis that these viruses contribute to the death of individuals with AIDS is supported by the results of two double-blind, placebocontrolled randomized trials of high-dose aciclovir and an observational study of the same drug. All three studies have shown improved survival. Thus, the case is made that herpesviruses act as co-factors of HIV disease, and that inhibition of such infections represents a potential way of reducing mortality in those with AIDS. This paper was presented as the case for in a debate on 'Herpesviruses as co-factors of HIV disease'. The case against was made by Don Jeffries (see page 22).

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Section: Results Of Trials Of Antiviral Chemotherapymentioning

confidence: 99%

A Proposal that Herpesviruses are Co-Factors of HIV Disease

Griffiths

1995

Antivir Chem Chemother

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“…With this regimen most HIV infected patients get cured with a lower risk of failure, relapse and acquired drug resistance 216 . Patients who have been treated previously must be assessed for risk of drug resistance, investigated for drug resistance using the Xpert MTB/Rif test, rapid molecular based line probe assays and culture, and treated with either primary, first line drugs if no drug resistance exists or with second line drugs if drug resistance, especially multi drug resistant TB, is present 238 .…”

Section: Treatment Of Tb In Hiv Infected Personsmentioning

confidence: 99%

Pulmonary Manifestations of HIV Disease

Chakaya¹

2011

HIV Infection in the Era of Highly Active Antiretroviral Treatment and Some of Its Associated Complications

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“…Patients with somewhat higher counts could therefore be recruited into controlled trials of prophylaxis against disease. Two such placebo-controlled trials of high-dose oral acyclovir have been reported, in both of which acyclovir failed to reduce the incidence of CMV disease (Cooper et al, 1993;Youle et et., 1994). This outcome contrasts with the successful prophylactic use of the same dose in BMT and renal transplant patients.…”

Section: Progress In Herpesvirus Management 203mentioning

confidence: 99%

“…Very recently a placebo-controlled trial of high-dose oral ganciclovir has reported reduced CMV retinitis (S. Spector, 1994, Abstract A9, Interscience Conference Antimicrobial Agents and Chemotherapy, Orlando, FL). Interestingly, each prophylactic study showed a statistically significant improvement in survival amongst patients treated with acyclovir (Cooper et et., 1993;Youle et sl., 1994). This result was initially greeted with scepticism, but data from an observational study of the MACS Cohort suggest that it is a true phenomenon (Stein et al, 1994).…”

Section: Progress In Herpesvirus Management 203mentioning

confidence: 99%

“…The frequent finding of CMV, HHV-6 and/or HSV in autopsy tissues from AIDS patients supports this possibility (Corbellino et al, 1993;Pillay et al, 1993b;Knox and Carrigan, 1994) and further studies are required to determine if any, or all, of these viruses could act as cofactors. Meanwhile, a three-arm study comparing low-dose acyclovir, high-dose acyclovir (as used by Cooper et al, 1993 andYoule et al, 1994) and valaciclovir is being conducted by the AIDS Clinical Trials Group (protocol 204) to define the dose required to achieve the survival benefit and these results are awaited with interest.…”

Section: Progress In Herpesvirus Management 203mentioning

confidence: 99%

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Progress in the Clinical Management of Herpesvirus Infections

Griffiths

1995

Antivir Chem Chemother

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SummaryAntiviral drug discovery has produced a series of drugs active against herpesviruses in vitro. Several of these are now licensed and/or have been used in clinical practice. This article reviews the mechanisms· of action of acyclovir, ganciclovir, penciclovir, sorivudine and foscarnet, the development of resistance to these drugs and their pharmacokinetic and cellular toxicities. Based upon the natural histories of HSV, VZV and CMV, treatment objectives for each virus are discussed and the performance of each drug matched against these objectives. Overall, it is concluded that the perfect drug for treating herpesviruses does not exist, but that significant progress has been made towards controlling several herpesvirus diseases. It.is suggested that further progress will require not just improved drug discovery programmes, but also an understanding of different pathogeneses and an appreciation by practising physicians that antiviral drugs must be given early in the infectious process to achieve the best results.

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Effects of high-dose oral acyclovir on herpesvirus disease and survival in patients with advanced HIV disease

Cited by 77 publications

References 0 publications

A Proposal that Herpesviruses are Co-Factors of HIV Disease

A Proposal that Herpesviruses are Co-Factors of HIV Disease

Pulmonary Manifestations of HIV Disease

Progress in the Clinical Management of Herpesvirus Infections

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