Improvement in Cell-Mediated Immune Function during Potent Anti-Human Immunodeficiency Virus Therapy with Ritonavir plus Saquinavir

Angel, Jonathan B.; Kumar, Ashok; Parato, Karl; Filion, Lionel G.; Díaz‐Mitoma, Francisco; Daftarian, Pirouz; Pham, Ba’; Sun, Eugene; Leonard, John M.; Cameron, D W

doi:10.1086/515244

Cited by 107 publications

(78 citation statements)

References 35 publications

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“…The HAART era has changed many concepts in HIV treatment and HAART has had a dramatic effect on the prognosis of treated patients [38]. Maximal suppression of HIV replication by HAART may lead to improved and enhanced responses to IL-2.…”

Section: Immunological Effects Of Il-2 Therapy In Hiv Infectionmentioning

confidence: 99%

Effects of Subcutaneous Interleukin‐2 Therapy on Phenotype and Function of Peripheral Blood Mononuclear Cells in Human Immunodeficiency Virus Infected Patients

et al. 2000

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In the context of clinical therapy with recombinant human interleukin‐2 (IL‐2), we monitored immunological alteration in 10 human immunodeficiency virus type‐1 (HIV‐1)‐infected individuals, on stable antiretroviral therapy, who had a CD4+ cell count between 200 and 500 cells/mm3. Subcutaneous IL‐2 was prescribed thrice weekly (at a dose of 3 × 106 IU) for 24 weeks and the patients were followed‐up for 32 weeks. IL‐2 treatment induced an increase in the CD4+ percentage (P < 0.001) and CD4+ cell count (P < 0.009). Furthermore, natural killer (NK) cell activity was increased (P < 0.001) at week 8 of treatment, whereas lymphokine‐activated killer (LAK) cell activity showed a transient, nonsignificant increase at week 8 and was reduced (P < 0.001) at 32 weeks. However, the cytotoxic T‐lymphocyte (CTL) activity decreased against HIV antigens, and the proliferative response to Candida, IL‐2 and phytohaemagglutinin (PHA) declined during the first 8 weeks (P < 0.05) and returned to baseline levels after 32 weeks. The HIV RNA level did not change during IL‐2 therapy; however, after 8 weeks of follow‐up a significant increase (P < 0.001) in viral load was observed. In conclusion, continuous IL‐2 treatment to HIV‐infected individuals enhanced the CD4 count, but the in vitro lymphocyte function was impaired and an increase in viral replication occurred after treatment.

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Section: Immunological Effects Of Il-2 Therapy In Hiv Infectionmentioning

confidence: 99%

Effects of Subcutaneous Interleukin‐2 Therapy on Phenotype and Function of Peripheral Blood Mononuclear Cells in Human Immunodeficiency Virus Infected Patients

et al. 2000

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“…1 ± 9 One approach to therapy has been combinations of HIV protease inhibitors 10 and nucleoside inhibitors of HIV reverse transcriptase, which together result in partial immune reconstitution of some patients. 1 The effectiveness of these treatments suggests that the pathogenic mechanism(s) responsible for the induction of CD4 T cell loss in untreated patients are reversed by such therapies.…”

Section: Introductionmentioning

confidence: 99%

Dynamic correlation of apoptosis and immune activation during treatment of HIV infection

et al. 1999

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T cells from HIV infected patients undergo spontaneous apoptosis at a faster rate than those from uninfected patients, are abnormally susceptible to activation induced cell death (AICD), and undergo increased apoptosis in response to Fas receptor ligation. These observations have led to the hypothesis CD4 T cell apoptosis may be a mechanism of CD4 T cell depletion and the pathogenesis of AIDS. Successful treatment of HIV infected patients is accompanied by quantitative and qualitative improvements in immune function reflecting at least partial reversibility of the underlying pathogenesis of HIV. In this report we correlate improvements in markers of immune function with a decrease in apoptosis, and changes in its regulation. Therapy with nelfinavir plus saquinavir in combination with two nucleoside analogue inhibitors of reverse transcriptase dramatically reduces plasma viremia and increases CD4 T cell counts. Coincident with these improvements, CD38 and HLA-DR coexpression on both CD4 and CD8 T cells decrease, and CD45RA and CD62L coexpression increase. Furthermore, spontaneous apoptosis decreases in both CD4 and CD8 T cells (CD4 apoptosis 17.4 vs 2.6%, P=0.005; CD8 apoptosis 15.0 vs 1.0%, P50.001), as does both Fas mediated apoptosis (CD4 apoptosis 19.0 vs 3.5%, P=0.03; CD8 apoptosis 13.7 vs 1.5%, P=0.002) and CD3 induced AICD (CD4 apoptosis 13.7 vs 3.2%, P=0.001; CD8 apoptosis 29 vs 2.2%, P=0.08). Changes in apoptosis are not associated with changes in Fas receptor expression, but are significantly correlated with changes in activation marker profiles. Although this suggests a possible regulatory role for the apoptosis inhibitory protein FLIP, direct assessment did not reveal quantitative differences in FLIP expression between apoptosis resistant PBL's from HIV negative patients, and apoptosis sensitive PBL's from HIV positive patients. These findings support the hypothesis that apoptosis mediates HIV induced CD4 T cell depletion, but indicate the need for further studies into the molecular regulation of HIV induced apoptosis.

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“…C ombination antiretroviral therapy for HIV-1 infection has resulted in profound control of HIV replication in vivo, improved immune function, and significant decreases in AIDS-related morbidity and mortality (1)(2)(3)(4)(5)(6)(7)(8)(9). For many persons, however, this therapy does not provide sustained viral suppression or durable clinical benefit (10,11).…”

mentioning

confidence: 99%

HIV-1 Genotypic Resistance Patterns Predict Response to saquinavir–ritonavir Therapy in Patients in Whom Previous Protease Inhibitor Therapy Had Failed

et al. 1999

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Improvement in Cell-Mediated Immune Function during Potent Anti-Human Immunodeficiency Virus Therapy with Ritonavir plus Saquinavir

Cited by 107 publications

References 35 publications

Effects of Subcutaneous Interleukin‐2 Therapy on Phenotype and Function of Peripheral Blood Mononuclear Cells in Human Immunodeficiency Virus Infected Patients

Effects of Subcutaneous Interleukin‐2 Therapy on Phenotype and Function of Peripheral Blood Mononuclear Cells in Human Immunodeficiency Virus Infected Patients

Dynamic correlation of apoptosis and immune activation during treatment of HIV infection

HIV-1 Genotypic Resistance Patterns Predict Response to saquinavir–ritonavir Therapy in Patients in Whom Previous Protease Inhibitor Therapy Had Failed

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