Structured Treatment Interruption in Patients with Multidrug-Resistant Human Immunodeficiency Virus

Lawrence, Jody; Mayers, Douglas L.; Hullsiek, Katherine Huppler; Collins, Gary; Abrams, Donald I.; Reisler, Ronald B.; Crane, Lawrence R.; Schmetter, Barry; Dionne, Thomas J.; Saldanha, Jennifer M.; Jones, M. C.; Baxter, John D.

doi:10.1056/nejmoa035103

Cited by 216 publications

(134 citation statements)

References 15 publications

(16 reference statements)

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“…6,7 Studies evaluating CD4-guided treatment interruption and structured treatment interruptions have had mixed results and have not demonstrated consistent benefits to subjects. [8][9][10][11][12][13] Results of studies of short-cycle therapy, the interruption of therapy for 2 to 7 days only, have demonstrated mixed results. Dybul and colleagues demonstrated good initial results of a study in adults of 7 days on=7 days off therapy with sustained viral control and stable CD4 þ T cell counts.…”

Section: Introductionmentioning

confidence: 99%

Short-Cycle Therapy in Adolescents after Continuous Therapy with Established Viral Suppression: The Impact on Viral Load Suppression

Rudy

Sleasman

Kapogiannis

et al. 2009

AIDS Research and Human Retroviruses

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This was a proof-of-principle study to evaluate the impact of short cycle therapy (SCT; 4 days on=3 days off) in adolescents and young adults with good viral suppression on a protease inhibitor-based antiretroviral regimen. Subjects were recruited by the Adolescent Trials Network for HIV=AIDS Interventions and the Pediatric AIDS Clinical Trials Group. Subjects were infected either through perinatal=early childhood transmission or later via risk behaviors. All subjects were required to have at least 6 months of documented viral suppression below 400 copies=ml plus a preentry value below 200 copies=ml and an entry CD4 þ T cell count above 350 cells=mm 3 . Of the 32 subjects enrolled, 12 (37.5%) had confirmed viral load rebound >400 copies, with 18 subjects (56%) coming off for any reason. The majority of subjects resuppressed when placed back onto continuous therapy using the same agents. Although no difference was found in virologic rebound rates between the early and later transmission groups, those infected early in life had higher rates of coming off SCT for any reason. There was no impact of SCT on the CD4 þ T cell counts in those who remained on study or those who came off SCT for any reason. Subjects demonstrated good adherence to the SCT regimen. This study suggests that further evaluation of SCT may be warranted in some groups of adolescents and young adults infected with HIV.

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Section: Introductionmentioning

confidence: 99%

Short-Cycle Therapy in Adolescents after Continuous Therapy with Established Viral Suppression: The Impact on Viral Load Suppression

Rudy

Sleasman

Kapogiannis

et al. 2009

AIDS Research and Human Retroviruses

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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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“…On the other hand, it also has been shown that interruption of HAART can convert a resistant virus population to wild-type virus [24][25][26][27]. Although this strategy has been harmful in the patients receiving salvage therapy [28], the situation may be different in immunologically intact patients infected with HIV resistant to NRTIs but treated successfully with HAART. Indeed, major HIV mutations present after dual-NRTI therapy and before HAART had disappeared after STI.…”

Section: Discussionmentioning

confidence: 99%

Development of HIV with Drug Resistance after CD4 Cell Count--Guided Structured Treatment Interruptions in Patients Treated with Highly Active Antiretroviral Therapy after Dual--Nucleoside Analogue Treatment

Nüesch

Ananworanich

Sirivichayakul

et al. 2005

Clinical Infectious Diseases

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Structured Treatment Interruption in Patients with Multidrug-Resistant Human Immunodeficiency Virus

Abstract: In patients infected with multidrug-resistant HIV, structured interruption of treatment was associated with greater progression of disease and did not confer immunologic or virologic benefits or improve the overall quality of life.

Cited by 216 publications

References 15 publications

Short-Cycle Therapy in Adolescents after Continuous Therapy with Established Viral Suppression: The Impact on Viral Load Suppression

Short-Cycle Therapy in Adolescents after Continuous Therapy with Established Viral Suppression: The Impact on Viral Load Suppression

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

Development of HIV with Drug Resistance after CD4 Cell Count--Guided Structured Treatment Interruptions in Patients Treated with Highly Active Antiretroviral Therapy after Dual--Nucleoside Analogue Treatment

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