Benefit of treatment interruption in HIV-infected patients with multiple therapeutic failures

Katlama, Christine; Dominguez, Stéphanie; Gourlain, Karine; Duvivier, Claudine; Delaugerre, Constance; Legrand, Mayeule; Tubiana, Roland; Reynes, Jacques; Molina, Jean‐Michel; Peytavin, Gilles; Cálvez, Vincent; Costagliola, Dominique

doi:10.1097/00002030-200401230-00011

Cited by 79 publications

(61 citation statements)

References 29 publications

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“…Other options such as complete or partial structured treatment interruptions have failed to show consistent benefit or not undergone careful scrutiny in clinical trials. [22][23][24] Complicating these decisions is the relative paucity of data regarding the rate at which anti-retroviral resistance develops after the onset of virologic treatment failure in patients receiving highly active anti-retroviral therapy (HAART). [25][26][27] The purpose of this study was to define the time to accrual of genotypic resistance mutations, particularly thymidine analogue mutations (TAMs) and major protease inhibitor mutations, in persons with a persistently detectable plasma viral load (pVL) despite being on a stable antiretroviral regimen.…”

mentioning

confidence: 99%

Evolution of HIV Resistance Mutations in Patients Maintained on a Stable Treatment Regimen After Virologic Failure

Goetz¹,

Ferguson²,

Han³

et al. 2006

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Objective-We compared the rate of emergence of thymidine analogue mutations (TAMs) and major protease inhibitor mutations in adherent patients who remained on stable treatment with a thymidine analogue and/or protease inhibitor after the onset of virologic failure.Design-Follow-up genotypic resistance testing was done using archived plasma obtained from patients having 0 or 1 TAM and/or 0 or 1 major protease inhibitor resistance mutation at the onset of virologic failure.Results-The median duration of observed failure was 691 days. There were 41 thymidine analogue regimens and 34 protease inhibitor regimens; concomitant ritonavir was used 4 times. New major protease inhibitor mutations emerged more rapidly than did new TAMs (P = 0.0019); new TAMs emerged more rapidly in thymidine analogue regimens that did not include lamivudine (P = 0.0073). The emergence of TAMs and major protease inhibitor mutations did not differ if lamivudine was not part of the thymidine analogue regimen. The evolution of CD4 + cell counts and plasma viral loads (pVLs) during virologic failure was similar regardless of whether or not a new TAM or major protease inhibitor mutations emerged or, for thymidine analogue-containing regimens, whether lamivudine was or was not used.Conclusions-Major protease inhibitor mutations arose more frequently and rapidly than did TAMs in patients with sustained virologic failure who received lamivudine.

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mentioning

confidence: 99%

Evolution of HIV Resistance Mutations in Patients Maintained on a Stable Treatment Regimen After Virologic Failure

Goetz¹,

Ferguson²,

Han³

et al. 2006

JAIDS Journal of Acquired Immune Deficiency Syndromes

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“…It has been reported that the use of boosted protease inhibitors (Boosted PI) is associated with multiple clinical benefits, including higher efficacy against resistant HIV strains [28], lower rates of resistance emergence at highadherence levels [29] and a lack of PI-associated resistance mutations after virologic failure in treatment-naïve patients [30]. As well, studies have shown that Boosted PI offers a marginal independent protective effect on disease progression [23,31]. As the prevalence of HIV drug resistance accumulates in China, the need for scaling up second-line therapy is clear and must be a priority in China's efforts to control HIV/AIDS.…”

Section: Discussionmentioning

confidence: 99%

Effect of Viral Load and Drug Resistance on Mortality among Chinese HIV-Infected Patients Receiving Antiretroviral Treatment

Wang¹,

Xing²,

Ruan³

et al. 2012

J Antivir Antiretrovir

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Background: The Chinese National Free Antiretroviral Treatment Program (NFATP) for HIV-infected patients has saved lives. However, there is no data on the effect of HIV drug resistance on mortality among Chinese patients receiving antiretroviral treatment. Methods:We linked patient records from two national databases: baseline HIV drug resistance and viral load data were obtained from four national drug resistance surveys in 2004, 2005, 2006 and 2009, and all-cause mortality was ascertained in a prospective way in NFATP database. Factors associated with death were identified by Cox regression model.

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“…Both non-adaptive and adaptive STI strategies have been studied in individuals with chronic infection (Katlama et al, 2004;Lawrence et al, 2003;Ruiz et al, 2000;Ruiz et al, 2003;El-Sadr and Neaton, 2006), based on several rationales for interrupting therapy in these patients (Hirschel, 2001). One is to provide "drug holidays," breaks from the burden and side effects of antiretroviral therapy (while hopefully not negating the benefits).…”

Section: Hiv Therapy and Structured Or Supervised Treatment Interruptionmentioning

confidence: 99%

“…These observations have led to the hypothesis that an interruption in therapy eliminates drug pressure, resulting in reversion of viral populations to a more susceptible viral quasi-species, thus improving chances that subsequent salvage regimens will be effective. Although studies have demonstrated that virus harboring genotypic mutations can revert back to wild-type quasi-species and may improve virologic outcome (Katlama et al, 2004), clinical benefit of treatment interruption in chronically-infected patients leads has not been established (Antinori et al, 2005;Ghosn et al, 2005;Yeni et al, 2004).…”

Section: Hiv Therapy and Structured Or Supervised Treatment Interruptionmentioning

confidence: 99%

Using mathematical modeling and control to develop structured treatment interruption strategies for HIV infection

Rosenberg

Davidian

Banks

2007

Drug and Alcohol Dependence

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The goal of this article is to suggest that mathematical models describing biological processes taking place within a patient over time can be used to design adaptive treatment strategies. We demonstrate using the key example of treatment strategies for human immunodeficiency virus Type-1 (HIV) infection. Although there has been considerable progress in management of HIV infection using highly active antiretroviral therapies, continuous treatment with these agents involves significant cost and burden, toxicities, development of drug resistance, and problems with adherence; these latter complications are of particular concern in substanceabusing individuals. This has inspired interest in structured or supervised treatment interruption (STI) strategies, which involve cycles of treatment withdrawal and re-initiation. We argue that the most promising STI strategies are adaptive treatment strategies. We then describe how biological mechanisms governing the interaction over time between HIV and a patient's immune system may be represented by mathematical models and how control methods applied to these models can be used to design adaptive STI strategies seeking to maintain long-term suppression of the virus. We advocate that, when such mathematical representations of processes underlying a disease or disorder are available, they can be an important tool for suggesting adaptive treatment strategies for clinical study.

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Benefit of treatment interruption in HIV-infected patients with multiple therapeutic failures

Abstract: Treatment interruption was beneficial for treatment-experienced HIV-infected patients with advanced HIV disease and multidrug-resistant virus.

Cited by 79 publications

References 29 publications

Evolution of HIV Resistance Mutations in Patients Maintained on a Stable Treatment Regimen After Virologic Failure

Evolution of HIV Resistance Mutations in Patients Maintained on a Stable Treatment Regimen After Virologic Failure

Effect of Viral Load and Drug Resistance on Mortality among Chinese HIV-Infected Patients Receiving Antiretroviral Treatment

Using mathematical modeling and control to develop structured treatment interruption strategies for HIV infection

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