Consensus symposium on combined antiviral therapy

Jong, Menno D. de; Boucher, Charles A.; Galasso, George J.; Hirsch, Martin S.; Kern, Earl R.; Lange, Joep M. A.; Richman, Douglas D.

doi:10.1016/0166-3542(95)00910-8

Cited by 21 publications

(13 citation statements)

References 96 publications

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“…The preexistence of mutations capable of conferring resistance to antiretroviral drugs in treatment-naive patients had been predicted based on the large viral burden and high virus turnover and mutational rates (3). More recently, several groups have indeed observed this phenomenon (5,12,20,28). We noted the presence of three clones harboring resistance mutations to ddI, ddC, and 3TC and to the NNRTI in drugnaive subjects.…”

Section: Discussionmentioning

confidence: 53%

In vivo compartmentalization of human immunodeficiency virus: evidence from the examination of pol sequences from autopsy tissues

Wong

Ignacio

Torriani

et al. 1997

J Virol

266

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High rates of mutation and replication of human immunodeficiency virus (HIV) allow for the continuous generation of diverse genetic variants in vivo. Selective pressures within the microenvironments of different anatomic compartments result in the emergence of dominant quasispecies which can be distinguished by their envelope sequences. It is not known whether comparable tissue-specific selective pressures lead to the independent evolution of pol sequences within different tissue compartments, nor is it known how differing rates of virus turnover in tissues might affect the pace of such evolution. These issues are of importance for the formulation of a model for the emergence of drug resistance in vivo and for a general understanding of virus trafficking and virus turnover. Regions of the HIV type 1 reverse transcriptase (RT) which carry the majority of the known resistance codons to RT inhibitors (700 nucleotides from each clone) were cloned and sequenced directly from autopsied brain, spleen, and lymph node specimens from four subjects who had received zidovudine therapy. Clones from proviral DNA (143) and from viral cDNA (14) were analyzed. In three of four subjects, a discordance in distribution of resistance codons was noted. Moreover, brain-derived sequences appeared to be phylogenetically distinct from spleen-and lymph node-derived sequences even after exclusion of resistance codons from analysis. In each case, evidence for differential immune selective pressure, based on comparison of inferred amino acid sequences corresponding to known major histocompatibility complex class I cytotoxic T-lymphocyte epitopes, was found. These observations support the concept of anatomically distinct, independently evolving quasispecies (virodemes).

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Section: Discussionmentioning

confidence: 53%

In vivo compartmentalization of human immunodeficiency virus: evidence from the examination of pol sequences from autopsy tissues

Wong

Ignacio

Torriani

et al. 1997

J Virol

266

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“…If available, the following should be done: combinations associated with phenotypic reversion should be chosen; drugs for which development of resistance requires multiple viral mutations should be selected; and finally, drugs in which the viral mutations conferring resistance do not overlap should be combined. 38 The present strategy in the HIV field is ''the prevention of the emergence of resistance,'' which requires ''prolonged effective therapy in order to achieve complete suppression of viral replication'' (Richmann DD, personal communication, September 1997). This should also become the goal and approach in hepatitis B.…”

Section: In the Post-olt Setting Would A Combination Of Hbig Plusmentioning

confidence: 99%

Hepatitis B virus surface antigen and polymerase gene variants: Potential virological and clinical significance

Locarnini

1998

Hepatology

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“…Monotherapy with these new antiviral agents is unlikely to be sufficient for the eradication of HBV infection in the majority of patients. As with the lessons learned in the treatment of HIV infection, combination therapy with two or more reverse transcriptase inhibitors or a reverse transcriptase inhibitor and a protease inhibitor increased the extent and duration of response in CD4 cell counts and HIV RNA viral load [92,93]. Thus it is conceivable that in HBV infection, combination therapy with two or more nucleoside analogues may be more effective than either agent used alone.…”

Section: Combination Therapymentioning

confidence: 93%

Treatment of chronic hepatitis B: New antiviral therapies

Yao

Gish

1999

Curr Gastroenterol Rep

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Chronic hepatitis B infection is the most important cause of cirrhosis and hepatocellular carcinoma worldwide. Interferon-alpha has been shown to be effective in approximately one third of patients, and response seems to be sustained in long-term follow-up studies in Western countries. New treatments using lamivudine and other nucleoside analogues such as famciclovir, lobucavir, and adfovir showed promising results although sustained suppression of viral replication is unusual after discontinuation of therapy. The results of recent clinical studies using these nucleoside analogues are discussed in detail in this review. Other important issues such as drug resistance and the role of combination therapy are also addressed.

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Consensus symposium on combined antiviral therapy

Cited by 21 publications

References 96 publications

In vivo compartmentalization of human immunodeficiency virus: evidence from the examination of pol sequences from autopsy tissues

In vivo compartmentalization of human immunodeficiency virus: evidence from the examination of pol sequences from autopsy tissues

Hepatitis B virus surface antigen and polymerase gene variants: Potential virological and clinical significance

Treatment of chronic hepatitis B: New antiviral therapies

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