The impact of protease inhibitor-containing highly active antiretroviral therapy on progression of HIV disease and its relationship to CD4 and viral load

Miller, Veronica; Sabin, Caroline; Phillips, Andrew; Rottmann, Carsten; Rabenau, Holger F.; Weidmann, Eckard; Rickerts, Volker; Findhammer, Stephan; Helm, E. B.; Staszewski, Schlomo

doi:10.1097/00002030-200009290-00009

Cited by 40 publications

(18 citation statements)

References 23 publications

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“…The finding of an independent treatment benefit is in agreement with findings in prior studies [7,8,10,16,17], indicating a clinical and/or immunologic benefit to continuing treatment despite virologic failure and (possibly) viral drug resistance. This treatment effect could be due to a residual activity of the regimen in spite of decreased drug susceptibility, changes in virus characteristics due to accumulation of drug resistance-associated mutations (decreased fitness or replicative capacity and/or changes in pathogenicity), or to nonantiviral effects of the inhibitors.…”

Section: Discussionsupporting

confidence: 91%

“…Because the level of immunosuppression or immunocompetence determines disease progression, CD4 cell count may be a better predictor for progression than plasma HIV-1 RNA levels for patients receiving HAART. On the other hand, a treatment benefit independent of both CD4 cell count and virus load was observed when patients receiving protease inhibitors (PIs) were compared with patients not receiving PI-containing therapies, although both virus load and CD4 cell count remained significant independent factors associated with disease progression [10]. Furthermore, treatment discontinuation in patients with virologic failure leads to rapid increases in virus load and declining CD4 cell count, which provides further evidence of a treatment benefit despite virologic failure [11,12].…”

mentioning

confidence: 99%

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Association of Virus Load, CD4 Cell Count, and Treatment with Clinical Progression in Human Immunodeficiency Virus–Infected Patients with Very Low CD4 Cell Counts

Miller¹,

Phillips²,

Clotet³

et al. 2002

J INFECT DIS

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This study prospectively assessed the impact of treatment modality, virus load, and CD4 cell count of <50 cells/mm(3) on human immunodeficiency virus disease progression. The incidence rate of new AIDS disease or death was 54.8 (95% confidence interval, 48.7-59.9) per 100 person-years of follow-up. Independent predictors related to progression were latest CD4 cell count (relative risk [RR], 0.84/10 mm(3) higher; P<.0001), latest hemoglobin level (RR, 0.79/g/L higher; P<.0001), Pneumocystis carinii pneumonia prophylaxis (RR, 0.49; P<.0001), latest body mass index (RR, 0.93/kg/m(2) higher; P=.002), latest virus load (RR, 1.11/log(10) higher; P=.03), and intensity of treatment (RR, 1.82, P=.004; RR 2.27, P<.0001; RR 2.46, P=.0001; RR 2.33 P<.0006; 5.10, P<.0001, respectively, for 4, 3, 2, 1, or no drugs vs. >or=5 drugs). Although reverse causality cannot be excluded, more intense antiviral treatment appears to decrease the risk of progression in immunocompromised patients.

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Section: Discussionsupporting

confidence: 91%

mentioning

confidence: 99%

Association of Virus Load, CD4 Cell Count, and Treatment with Clinical Progression in Human Immunodeficiency Virus–Infected Patients with Very Low CD4 Cell Counts

Miller¹,

Phillips²,

Clotet³

et al. 2002

J INFECT DIS

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“…Three different methods of modelling CD4 cell count between two consecutive measurements were examined. Based on the three methods used in this study, as in other studies in both sub-Saharan Africa [14,15] and elsewhere [16,17], the highest incidence rates occurred in the lowest CD4 cell count stratum. The incidence rates of opportunistic infections and death were lower in the higher CD4 cell count strata, except for mild malaria.…”

Section: Discussionmentioning

confidence: 66%

Estimates of opportunistic infection incidence or death within specific CD4 strata in HIV-infected patients in Abidjan, Côte d’Ivoire: impact of alternative methods of CD4 count modelling

et al. 2007

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CD4 lymphocyte count is an important surrogate marker of HIV disease progression, but it is often unavailable at the time of clinical events. We analysed data from the Cotrame cohort (1999-2004) and the Trivacan Structured Treatment Interruption trial (2002-2005) to estimate the incidence of opportunistic infections and death within specific CD4 strata in HIV-infected patients receiving highly active antiretroviral therapy (HAART) in sub-Saharan Africa. We used three methods of CD4 modelling: the first assumed that CD4 cell count remained constant until the next measurement; the second assumed that it changed immediately to the level of the subsequent measurement; and the third assumed that it followed a linear function between two consecutive CD4 measurements. The cohort used in this analysis consisted of 981 patients. The incidence rates of opportunistic infections were highest in the lower CD4 strata and decreased in the higher CD4 count strata. The incidence rates of mild opportunistic infections and severe bacterial infections, however, remained high in the highest CD4 stratum. Although all confidence intervals overlapped among the three methods, the incidence rate estimates showed differences of up to 74% in the lowest CD4 stratum. Different methods of estimating CD4 counts at the time of clinical events led to minor differences in incidence rates, except in the CD4 stratum <50 cells/mm(3), where the follow-up time was shorter. All of the models indicate that the overall incidence of opportunistic infections under HAART in sub-Saharan Africa is high. This suggests that prophylaxis against opportunistic infections may be needed even for patients receiving HAART.

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“…[1][2][3][4][5] Once HAART has been initiated, these parameters are monitored regularly to assess patient response to therapy. The initial response is generally determined at 6 months.…”

mentioning

confidence: 99%

Response to Highly Active Antiretroviral Therapy at 6 Months and Long-Term Disease Progression in HIV-1 Infection

Grabar

Moing²,

Goujard³

et al. 2005

JAIDS Journal of Acquired Immune Deficiency Syndromes

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The impact of protease inhibitor-containing highly active antiretroviral therapy on progression of HIV disease and its relationship to CD4 and viral load

Cited by 40 publications

References 23 publications

Association of Virus Load, CD4 Cell Count, and Treatment with Clinical Progression in Human Immunodeficiency Virus–Infected Patients with Very Low CD4 Cell Counts

Association of Virus Load, CD4 Cell Count, and Treatment with Clinical Progression in Human Immunodeficiency Virus–Infected Patients with Very Low CD4 Cell Counts

Estimates of opportunistic infection incidence or death within specific CD4 strata in HIV-infected patients in Abidjan, Côte d’Ivoire: impact of alternative methods of CD4 count modelling

Response to Highly Active Antiretroviral Therapy at 6 Months and Long-Term Disease Progression in HIV-1 Infection

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