Maintenance Antiretroviral Therapies in HIV-Infected Subjects with Undetectable Plasma HIV RNA after Triple-Drug Therapy

Havlir, Diane V.; Marschner, Ian C.; Hirsch, Martin S.; Collier, Ann C.; Tebas, Pablo; Bassett, Roland L.; Ioannidis, John P. A.; Holohan, M.K.; Leavitt, Randi Y.; Boone, Gloria S.; Richman, Douglas D.

doi:10.1056/nejm199810293391801

Cited by 289 publications

(108 citation statements)

References 24 publications

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“…PBMCs were collected from 14 patients who participated in AIDS Clinical Trial Group (ACTG) study 343 and who rolled over to ACTG study 5025 after a median of 89 weeks. The details of these studies and the demographics of the study populations have been published elsewhere (17,18 ). Patients in ACTG 343 were antiretroviral naive or had minimal experience with AZT and received a combination of AZT, 3TC, and IDV.…”

Section: Materials and Methods Patientsmentioning

confidence: 99%

Real-Time Nucleic Acid Sequence–Based Amplification Assay to Quantify Changes in Mitochondrial DNA Concentrations in Cell Cultures and Blood Cells from HIV-Infected Patients Receiving Antiviral Therapy

Timmermans¹,

Tebas

Ruiter

et al. 2006

Clinical Chemistry

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Background:To study the clinical relevance of changes in mitochondrial DNA (mtDNA) in peripheral blood mononuclear cells (PBMCs) attributable to HIV infection and/or combination antiretroviral therapy (cART), a high-throughput molecular assay to quantify mtDNA is required. Methods:We developed a quantitative real-time duplex nucleic acid sequence-based amplification assay in which both mtDNA and nuclear DNA are simultaneously amplified in 1 tube. The assay could accurately quantify mtDNA in a range of 15-1500 copies of mtDNA per 2 genomic copies with an intrarun variation of 11% and an interrun variation of 16%. We compared this real-time assay with the lactate/pyruvate ratios in fibroblasts incubated with glucose and exposed to zalcitabine. Additionally, we studied the effects of platelet contamination and the in vivo effects of cART on mtDNA in PBMCs from a small group of patients. Results: Decreases in mtDNA preceded the increase in lactate/pyruvate ratios and vice versa when zalcitabine was eliminated from the culture. Platelets affected the mtDNA in PBMCs if >5 platelets per PBMC were present. Within 12 weeks, mtDNA increased and remained increased in PBMCs from patients on continu-

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Section: Materials and Methods Patientsmentioning

confidence: 99%

Real-Time Nucleic Acid Sequence–Based Amplification Assay to Quantify Changes in Mitochondrial DNA Concentrations in Cell Cultures and Blood Cells from HIV-Infected Patients Receiving Antiviral Therapy

Timmermans¹,

Tebas

Ruiter

et al. 2006

Clinical Chemistry

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“…Various randomized clinical trials (24)(25)(26)(27)(28)(29), have shown that 60%-90% of patients treated with HAART achieved sustained suppression of viral load below the detection limit of standard assays.…”

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Immunological and clinical progress of HIV-infected patients on highly active antiretroviral therapy in north west Ethiopia

Wabe¹,

Alemu²

2012

Gaziantep Med J

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The survival benefits of highly active antiretroviral therapy (HAART) in HIV infected patients have been studied well in the developed world. In resource poor settings like Ethiopia such treatment was started only in 2003. As a result, the existing treatment guidelines and recommendations are based on data from the developed world. The objective of this study was to determine the immunological and clinical progress in HIV/AIDS patients in one year data review of patients' card who initiated on HAART in Ethiopia. A retrospective cohort study was done based on past medical records of HIV/AIDS patients, using a structured data collection format. All patient cards of one year data with patients who initiated HAART from October 1, 2006 to November 30, 2007 were included in the study. The data collected was analyzed using SPSS for window version 16.0. The majority of the study population (383, 64.2%) were prescribed zidovudine/lamivudine/neverapine (ZDV/3TC/NVP) regimen initially. Overall functional status change showed that ability to work was increased by 31.5%, being ambulatory decreased by 93.4% and bedridden status decreased by 80%. A total of 240 (46.9%) patients have showed functional status improvement. Average mean weight change of 5.9 kg (increment by 11.9%) was seen during a one year follow-up. The patients showed immunological change from 132.883 mean CD4/mm 3 count to 335.87 mean CD4/mm 3 . About 492 (82.4%) patients present with different type of opportunistic infections (OIs) at start of therapy which dramatically dropped to only 40 (6.7%) patient after one year of receiving HAART. HAART initiation has decreased progression of the diseases and improved the patients' quality of life. Most patients have showed a significant increment in their CD4 count. The restoration of CD4 in turn has improved the clinical status of most patients. Despite the significant progression of health of patients, greater immunological and clinical success should be attained by encouraging patients for effective use of those lifesaving drugs with maximal adherence. 2) başlangıçta zidovudin/lamivudin/neverapin (ZDV/3TC/NVP) tedavisi verilmişti. Genelde fonksiyonel durum değişimi, çalışma yeteneğinin %31.5 arttığını, ayakta tedavi edilmenin %93.4 azaldığını, yatağa bağlı kalma durumunun %80 azaldığını gösterdi. Toplam 240 hasta fonksiyonel durum düzelmesi gösterdi. Bir yıllık izleme sırasında 5.9 kg ortalama ağırlık değişimi (%11.9 artma) gözlendi. Hastalar ortalama 132.883 CD4/mm 3 sayımından ortalama 335.87 CD4/mm 3 'e immünolojik değişim gösterdi. Tedavinin başlamasında farklı tipte fırsatçı enfeksiyonu bulunan yaklaşık 492 (%82.4) hasta, HAART tedavisi başlamasından bir yıl sonra dramatik olarak sadece 40'a (%6.7) düştü. HAART tedavisi başlanması hastalığın ilerlemesini azalttı ve hastaların yaşam kalitesini iyileştirdi. Hastaların çoğu CD4 sayılarında anlamlı artışlar gösterdi. CD4'deki düzelme birçok hastanın klinik durumunu iyileştirdi. Hastaların sağlığındaki anlamlı iyileşmeye karşın, hayat kurtaran bu ilaçlara d...

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“…One of the implicit hopes accompanying strategies designed to suppress viral activity is that, at some point, the host's immune system might be able to maintain this suppression either in the absence of, or at least after a de-intensification of, the current medications (8)(9)(10)(11)(12). Unfortunately, with the exception of occasional anecdotal reports of sustained suppression, fairly prompt virologic relapse after discontinuation of HAART has been the predominant pattern observed thus far (13)(14)(15)(16).…”

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HIV-1 and T cell dynamics after interruption of highly active antiretroviral therapy (HAART) in patients with a history of sustained viral suppression

Davey

Bhat

Yoder

et al. 1999

Proc. Natl. Acad. Sci. U.S.A.

755

523

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Identifying the immunologic and virologic consequences of discontinuing antiretroviral therapy in HIV-infected patients is of major importance in developing long-term treatment strategies for patients with HIV-1 infection. We designed a trial to characterize these parameters after interruption of highly active antiretroviral therapy (HAART) in patients who had maintained prolonged viral suppression on antiretroviral drugs. Eighteen patients with CD4 ؉ T cell counts > 350 cells͞l and viral load below the limits of detection for >1 year while on HAART were enrolled prospectively in a trial in which HAART was discontinued. Twelve of these patients had received prior IL-2 therapy and had low frequencies of resting, latently infected CD4 cells. Viral load relapse to >50 copies͞ml occurred in all 18 patients independent of prior IL-2 treatment, beginning most commonly during weeks 2-3 after cessation of HAART. The mean relapse rate constant was 0.45 (0.20 log 10 copies) day ؊1 , which was very similar to the mean viral clearance rate constant after drug resumption of 0.35 (0.15 log 10 copies) day ؊1 (P ‫؍‬ 0.28). One patient experienced a relapse delay to week 7. All patients except one experienced a relapse burden to >5,000 RNA copies͞ml. Ex vivo labeling with BrdUrd showed that CD4 and CD8 cell turnover increased after withdrawal of HAART and correlated with viral load whereas lymphocyte turnover decreased after reinitiation of drug treatment. Virologic relapse occurs rapidly in patients who discontinue suppressive drug therapy, even in patients with a markedly diminished pool of resting, latently infected CD4 ؉ T cells.HIV-1 infection ͉ antiretroviral drugs ͉ viral load ͉ relapse ͉ CD4

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Maintenance Antiretroviral Therapies in HIV-Infected Subjects with Undetectable Plasma HIV RNA after Triple-Drug Therapy

Abstract: The suppression of plasma HIV RNA after six months of treatment with indinavir, zidovudine, and lamivudine is better sustained by the continuation of these three drugs than by maintenance therapy with either indinavir alone or zidovudine and lamivudine.

Cited by 289 publications

References 24 publications

Real-Time Nucleic Acid Sequence–Based Amplification Assay to Quantify Changes in Mitochondrial DNA Concentrations in Cell Cultures and Blood Cells from HIV-Infected Patients Receiving Antiviral Therapy

Real-Time Nucleic Acid Sequence–Based Amplification Assay to Quantify Changes in Mitochondrial DNA Concentrations in Cell Cultures and Blood Cells from HIV-Infected Patients Receiving Antiviral Therapy

Immunological and clinical progress of HIV-infected patients on highly active antiretroviral therapy in north west Ethiopia

HIV-1 and T cell dynamics after interruption of highly active antiretroviral therapy (HAART) in patients with a history of sustained viral suppression

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