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PubMed2002

Association of adherence to Mycobacterium avium complex prophylaxis and antiretroviral therapy with clinical outcomes in Acquired Immunodeficiency Syndrome.

High-level adherence to regimens of combination antiretroviral therapy and prophylactic medications for opportunistic infections (OIs) is crucial to their success. However, little is known about the association between adherence to these life-sustaining therapies and such clinical outcomes as progression of acquired immune deficiency syndrome (AIDS) or development of OIs. We assessed adherence to regimens of antiretroviral and Mycobacterium avium complex (MAC) prophylactic medications in 643 patients enrolled in a trial of MAC prophylaxis. By week 56 of the study follow-up, 42% of the patients reported nonadherence to MAC prophylaxis, whereas one-quarter of the patients reported nonadherence to potent antiretroviral regimens. Nonadherence to both MAC prophylaxis and antiretroviral therapy was associated with higher human immunodeficiency virus (HIV) type 1 RNA levels and a significant increase in the risk of developing an AIDS-defining complication or death. Predictors of nonadherence are presented. These results underscore the clinical significance of adherence to HIV therapy and may be helpful in designing interventions to optimize the management of HIV by improving adherence.

Acquired Immunodeficiency Syndrome↗

PubMed2005

Influence of hepatitis C virus infection on HIV-1 disease progression and response to highly active antiretroviral therapy.

OBJECTIVE: To assess hepatitis C virus (HCV) antibody prevalence in the EuroSIDA cohort, along with survival, human immunodeficiency virus (HIV)-1 disease progression, virologic response (plasma HIV-1 RNA load of < 500 copies/mL), and CD4 cell count recovery by HCV serostatus in patients initiating highly active antiretroviral therapy (HAART). RESULTS: HCV serostatus at or before enrollment was available for 5957 patients; 1960 (33%) and 3997 (67%) were HCV seropositive and seronegative, respectively. No association between an increased incidence of acquired immunodeficiency syndrome-defining illnesses or death and HCV serostatus was seen after adjustment for other prognostic risk factors known at baseline (adjusted incidence rate ratio [IRR], 0.97 [95% confidence interval {CI}, 0.81-1.16]). However, there was a large increase in the incidence of liver disease-related deaths in HCV-seropositive patients in adjusted models (IRR, 11.71 [95% CI, 6.42-21.34]). Among 2260 patients of known HCV serostatus initiating HAART, after adjustment, there was no significant difference between HCV-seropositive and -seronegative patients with respect to virologic response (relative hazard [RH], 1.13 [95% CI, 0.84-1.51]) and immunologic response, whether measured as a > or = 50% increase (RH, 0.94 [95% CI, 0.77-1.16]) or a > or = 50 cells/microL increase (RH, 0.92 [95% CI, 0.77-1.11]) in CD4 cell count after HAART initiation. CONCLUSIONS: HCV serostatus did not affect the risk of HIV-1 disease progression, but the risk of liver disease-related deaths was markedly increased in HCV-seropositive patients. The overall virologic and immunologic responses to HAART were not affected by HCV serostatus.

Adult↗

PubMed2005

CD4 lymphocyte percentage predicts disease progression in HIV-infected patients initiating highly active antiretroviral therapy with CD4 lymphocyte counts >350 lymphocytes/mm3.

BACKGROUND: The optimal timing of highly active antiretroviral therapy (HAART) in human immunodeficiency virus (HIV)-infected patients with > or = 200 absolute CD4 lymphocytes/mm3 is unknown. CD4 lymphocyte percentage could add prognostic information. METHODS: Persons who initiated HAART between 1 January 1998 and 1 January 2003, received > or = 30 days of therapy, and had baseline CD4 lymphocyte data available were included in the study. The log-rank test for time to event and Cox proportional hazards models were used to determine predictors of a new acquired immunodeficiency syndrome-defining illness or death. RESULTS: A total of 788 patients met the inclusion criteria. At baseline, subjects had a median of 225 CD4 lymphocytes/mm3 and 17% CD4 lymphocytes. Subjects with < 17% CD4 lymphocytes had earlier disease progression, compared with subjects with > or = 17%, both in the entire cohort (P<.0001) and of those subjects with > 350 absolute CD4 lymphocytes/mm3 at baseline (P=.03). CD4 lymphocyte percentage < 17% was the strongest predictor of disease progression among subjects in this latter group (hazard ratio, 3.57; P=.045). CONCLUSIONS: In this cohort, CD4 lymphocyte percentage predicted disease progression in HIV-infected subjects who initiated therapy with > 350 CD4 lymphocytes/mm3. This information may help identify persons who will derive the greatest benefit from initiation of HAART.

Adolescent↗

PubMed1998

Use of changes in plasma levels of human immunodeficiency virus type 1 RNA to assess the clinical benefit of antiretroviral therapy.

Data from 1330 human immunodeficiency virus type 1 (HIV-1)-infected patients enrolled in seven antiretroviral treatment trials were analyzed to characterize the clinical benefit of treatment-mediated reductions in plasma HIV-1 RNA levels. The risk of a new AIDS-defining event or death was reduced proportionally to the magnitude of the reduction of the HIV-1 RNA level during the first 6 months of therapy. Pretherapy HIV-1 RNA levels were prognostic independently of on-therapy levels. In addition, the reduction in risk associated with any given reduction of the level of HIV-1 RNA did not vary by pretherapy level. Having either a reduction in HIV-1 RNA level or an increase in CD4+ lymphocyte count, or both, was associated with a delay in clinical disease progression. This indicates that patient prognosis should be assessed using both HIV-1 RNA and CD4+ lymphocyte responses to therapy.

Acquired Immunodeficiency Syndrome↗

PubMed1998

Variability and prognostic values of virologic and CD4 cell measures in human immunodeficiency virus type 1-infected patients with 200-500 CD4 cells/mm(3) (ACTG 175). AIDS Clinical Trials Group Protocol 175 Team.

Virologic measurements are increasingly used to evaluate prognosis and treatment responses in human immunodeficiency virus (HIV) type 1 infection. Markers of HIV-1 replication, including infectious HIV-1 titer from peripheral blood mononuclear cells, serum HIV-1 p24 antigen, plasma HIV-1 RNA, CD4 cell numbers, and viral syncytium-inducing (SI) phenotype, were determined in 391 virology substudy participants in AIDS Clinical Trials Group study 175. The subjects had 200-500 CD4 cells/mm3. All markers of viral replication significantly correlated with one another and were inversely related to CD4 cell number. Disease progression to an AIDS-defining event or death or loss of >50% of CD4 cells was associated with infectious HIV-1 titer (P < .001), HIV-1 RNA (P < .001), and HIV-1 p24 antigen (P = .007). In multivariate proportional hazards models, p24 antigen was never significant when HIV-1 RNA level was included. In a model containing infectious HIV-1 titer (P = .038), HIV-1 RNA (P < .001), SI phenotype (P < .001), and CD4 cell number (P = .18), only the virologic parameters remained significantly associated with progression.

CD4 Lymphocyte Count↗

PubMed1997

Evaluation of pharmacokinetics, safety, tolerance, and activity of combination of zalcitabine and zidovudine in stable, zidovudine-treated pediatric patients with human immunodeficiency virus infection. AIDS Clinical Trials Group Protocol 190 Team.

A double-blind phase II trial compared zalcitabine (0.03 mg/kg/day) in combination with zidovudine (720 mg/m2/day) and zidovudine monotherapy in 250 clinically stable, previously zidovudine-treated, human immunodeficiency virus-infected children. The combination was well-tolerated except for an increased incidence of neutropenia (14%) compared with that in children receiving monotherapy (5%). No differences were noted for time to first AIDS-defining illness or death, neuropsychologic status, or weight Z scores. In patients in the combination arm, the CD4 cell count decline was slower (13% per year) than in patients receiving monotherapy (25% per year) (P = .03), and quantitative peripheral blood mononuclear cell virus load remained lower at all time points (P = .08). Deaths were fewer in patients receiving combination therapy (4) compared with those in patients receiving monotherapy (10) (P = .083). Thus, administration of zidovudine with zalcitabine to children with prior zidovudine treatment did not result in a significant increase in toxicity compared with that resulting from zidovudine monotherapy and demonstrated improvement in immunologic and virologic surrogate markers.

AIDS-Related Opportunistic Infections↗

PubMed2001

Do HIV type 1 RNA levels provide additional prognostic value to CD4(+) T lymphocyte counts in patients with advanced HIV type 1 infection?

Our objective was to assess whether HIV-1 RNA levels provide additional prognostic information beyond CD4(+) T lymphocyte counts in the prediction of subsequent HIV-1 disease progression among patients with advanced HIV-1 disease. In a nested case-control study conducted in patients with baseline CD4(+) T lymphocyte counts < 300 cells/mm(3) and receiving nucleoside reverse transcriptase inhibitors, 102 patients who progressed to an AIDS-defining event or death were matched within 10 CD4(+) T lymphocyte cells/mm(3) to patients who did not progress. The relationship between plasma HIV-1 RNA levels and HIV-1 disease progression was studied using conditional logistic regression analysis, which adjusts for the matching by baseline CD4(+) T lymphocytes. We observed a 0.10 log(10) copies/ml difference in baseline HIV-1 RNA levels between cases and their matched controls (p = 0.027). The relative risk for HIV-1 disease progression increased with increasing baseline HIV-1 RNA levels (odds ratio [OR] for a 3-fold higher HIV-1 RNA level, 1.42; 95% confidence interval [CI], 1.08--1.86), and remained important when also controlling for clinical status at baseline and CD4(+) T lymphocytes at 2 months (p = 0.038). Higher baseline HIV-1 RNA levels were associated with HIV-1 disease progression among patients with a baseline CD4(+) T lymphocyte count of 100 cells/mm(3) or greater (OR, 1.80; 95% CI, 1.15--2.81), but not among patients with a baseline CD4(+) T lymphocyte count < 100 cells/mm(3) (OR, 1.09; 95% CI, 0.73--1.63). We concluded that HIV-1 RNA levels predict subsequent HIV-1 disease progression independent of CD4(+) T lymphocyte counts. The magnitude and importance of the prognostic information contained in the HIV-1 RNA levels appear to depend on the CD4(+) T lymphocyte counts.

Adult↗

PubMed1999

Modeling the long-term outcomes and costs of HIV antiretroviral therapy using HIV RNA levels: application to a clinical trial.

A model was developed to gain insight into the potential clinical and economic impact of antiretroviral therapy for HIV-infected patients. Observed HIV RNA levels and CD4 cell counts are used in the model to estimate the probability that an individual progresses from asymptomatic infection to the first AIDS-defining illness and death and to estimate the total net cost of care and long-term cost-effectiveness of antiretroviral therapy. The model was applied to patients in a clinical trial (Merck protocol 035) that compared the surrogate marker response to triple therapy with indinavir (IDV; 800 mg every 8 hr) plus zidovudine (ZDV; 200 mg every 8 hr) plus lamivudine (3TC; 150 mg twice a day) to double therapy with ZDV+3TC. The model projected that for an individual without AIDS who received triple therapy the progression to AIDS and death would be delayed more than for a patient who received double therapy with ZDV+3TC if no other treatment options were offered. Because of this delay in disease progression, the total discounted cost over the initial 5-year period was projected to be $5100 lower for patients who received triple therapy compared with double therapy if suppression with triple therapy lasts up to 3 years. If suppression with triple therapy lasts up to 5 years, costs were projected to be higher with the triple combination, but 81% of the cost is offset by lower disease costs as a result of fewer patients progressing to AIDS. Over 20 years, total discounted cost was projected to be higher for the triple-therapy regimen primarily because of a longer estimated survival time. At 20 years, the incremental cost per life-year gained by adding IDV to a ZDV+3TC regimen was estimated at $13,229, which is well within the range of other widely accepted medical interventions.

Anti-HIV Agents↗

PubMed2001

Involvement of p38 in apoptosis-associated membrane blebbing and nuclear condensation.

The stress-activated protein kinase p38 is often induced by cytotoxic agents, but its contribution to cell death is ill defined. In Rat-1 cells, we found a strong correlation between activation of p38 and induction of c-Myc-dependent apoptosis. In cells with deregulated c-Myc expression but not in control cells, cis-diamminedichloroplatinum induced p38 activity and typical features of apoptosis, including internucleosomal DNA degradation, induction of caspase activities, and both nuclear (nuclear condensation and fragmentation) and extranuclear (cell blebbing) morphological alterations. The pan-caspase inhibitor N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone did not block p38 activation and the p38 inhibitor SB203580 had no detectable effect on the activation of caspases or the in vivo cleavage of several caspase substrates, suggesting that p38 and caspase activation can contribute distinct features of apoptosis. Accordingly, we found that cell blebbing was independent of caspase activity and, rather, depended on p38-sensitive changes in microfilament dynamics likely mediated by heat shock protein 27 phosphorylation. Furthermore, p38 activity contributed to both caspase-dependent and caspase-independent nuclear condensation and fragmentation, suggesting a role in an early event triggering both mechanisms of apoptosis or sensitizing the cells to the action of both types of apoptosis executioners. Inhibiting p38 also resulted in a significant enhancement in cell survival estimated by colony formation. This capacity to modulate the sensitivity to apoptosis in cells with deregulated c-Myc expression suggests an important role for p38 in tumor cell killing by chemotherapeutic agents.

Amino Acid Chloromethyl Ketones↗

PubMed2003

Essential roles for GPI-anchored proteins in African trypanosomes revealed using mutants deficient in GPI8.

The survival of Trypanosoma brucei, the causative agent of Sleeping Sickness and Nagana, is facilitated by the expression of a dense surface coat of glycosylphosphatidylinositol (GPI)-anchored proteins in both its mammalian and tsetse fly hosts. We have characterized T. brucei GPI8, the gene encoding the catalytic subunit of the GPI:protein transamidase complex that adds preformed GPI anchors onto nascent polypeptides. Deletion of GPI8 (to give Deltagpi8) resulted in the absence of GPI-anchored proteins from the cell surface of procyclic form trypanosomes and accumulation of a pool of non-protein-linked GPI molecules, some of which are surface located. Procyclic Deltagpi8, while viable in culture, were unable to establish infections in the tsetse midgut, confirming that GPI-anchored proteins are essential for insect-parasite interactions. Applying specific inducible GPI8 RNAi with bloodstream form parasites resulted in accumulation of unanchored variant surface glycoprotein and cell death with a defined multinuclear, multikinetoplast, and multiflagellar phenotype indicative of a block in cytokinesis. These data show that GPI-anchored proteins are essential for the viability of bloodstream form trypanosomes even in the absence of immune challenge and imply that GPI8 is important for proper cell cycle progression.

Amino Acid Sequence↗

PubMed2001

Efficacy of a nurse-led multidimensional preventive programme for older people at risk of functional decline. A randomized controlled trial.

OBJECTIVE: To verify the efficacy of a multidimensional preventive programme on functional decline of older people. DESIGN: Randomized controlled trial. SETTING: Community of Sherbrooke City, Quebec, Canada. SUBJECTS: A representative sample of individuals aged over 75 living at home and identified to be at risk of functional decline by postal questionnaire (n = 503). INTERVENTION: Subjects randomized to the study group (n = 250) were assessed at home by a nurse on 12 dimensions (including medication, depressive mood, risk of falls, hearing). A report of the assessment was sent to the general practitioner with recommendations for interventions. A monthly telephone contact was carried out by the nurse for surveillance and to verify if the recommendations had been applied. METHODS: The primary outcome--functional decline--was defined as either death, admission to an institution or increase of > or = 5 points on the disability score of the Functional Autonomy Measurement System (SMAF) scale during the reference year. Secondary outcomes were functional autonomy (on the SMAF), well-being (General Well-being Schedule), perceived social support (Social Provisions Scale) and use of health care services. RESULTS: Of the 494 subjects who completed the study, 48 (19.6%) of 245 in the study group and 49 (19.7%) of 249 in the control group had functional decline (relative risk 1.00; 95% confidence interval 0.82-1.23). There were no differences between the groups in all secondary outcomes. CONCLUSIONS: This study confirms the inefficacy of multidimensional programmes for preventing functional decline in the older population. More effort should be devoted to improving the efficacy of specific interventions for conditions causing functional decline.

Aged↗

PubMed2006

Obesity and cardiovascular events in patients with established coronary disease.

AIMS: To explore the association between obesity and major adverse coronary events (MACE) in patients with established coronary artery disease (CAD). METHODS AND RESULTS: The Prevention of Events with Angiotensin Converting Enzyme-Inhibition (PEACE) Trial randomized 8290 patients with stable CAD and left ventricular (LV) ejection fraction (EF) (LVEF) > or =0.40 to trandolapril or placebo and followed them for a median of 4.8 years. In PEACE patients who were non-diabetic at baseline (5693 men and 1171 women), we used proportional hazards models to conduct a post hoc analysis to examine whether obesity, defined as a body mass index (BMI) > or =30 kg/m(2), is an independent risk factor for the composite endpoint of MACE, defined as cardiovascular death, non-fatal myocardial infarction, coronary revascularization, or stroke. The analysis was conducted separately for men and women. The baseline prevalence of obesity was 28.5% in men and 28.9% in women. After adjusting for significant confounders, obesity was associated with MACE in men [hazard ratio (HR) = 1.28, 95% CI 1.13-1.46, P < 0.01], but not in women (HR = 0.96, 95% CI 0.70-1.31, P = 0.77). Further categorization of BMI showed a J-shaped association between BMI and MACE in the men, and no association in the women. CONCLUSION: In the presence of established CAD, obesity is associated with risk for MACE in men, but there is no support of an association in women. This finding requires further evaluation.

Body Mass Index↗

PubMed1996

Virologic and immunologic benefits of initial combination therapy with zidovudine and zalcitabine or didanosine compared with zidovudine monotherapy. Wellcome Resistance Study Collaborative Group.

A randomized controlled study was done to determine whether initial combination therapy with zidovudine and zalcitabine or zidovudine and didanosine would delay the emergence of zidovudine-resistant virus. Human immunodeficiency virus (HIV)-1-infected patients with <300 CD4 cells/mm3 and <4 weeks of prior zidovudine therapy were randomized to zidovudine, zidovudine plus zalcitabine, or zidovudine plus didanosine. Combination therapy did not delay the emergence of zidovudine-resistant virus isolates. However, combination therapy resulted in a significant increase in CD4 cells through 72 weeks compared with zidovudine monotherapy and a greater and more sustained decline in serum HIV-1 RNA. Although this trial was not designed as a clinical end-point study, patients assigned to zidovudine plus didanosine combination therapy experienced a significant delay in time to first AIDS-defining event or death compared with those assigned to zidovudine monotherapy.

Adult↗

PubMed1995

The prognostic value of exercise testing early after myocardial infarction in patients treated with thrombolytics.

Exercise testing early post AMI was evaluated as a predictor of reinfarction in patients treated with thrombolytics. AMI patients exercise-tested prior to discharge were included in the study (n = 178). The patients were followed for 2.9 +/- 0.9 years (mean +/- 1 SD) for the development of new cardiac events defined as cardiac death or reinfarction. Cox regression analysis of clinical and exercise test variables showed that there was significant predictive value of treating heart failure with drugs from two or more therapeutic groups (P < 0.001; hazard ratio 9.4 (3.1-28.2) (estimate and 95% confidence interval)), such as those with a previous history of myocardial infarction (P = 0.001; hazard ratio 4.0 (1.7-9.6)) and of significant ST depression (P = 0.029; hazard ratio 2.5 (1.1-5.7)). Significant ST depression could be substituted by the delta ST/delta HR index (P = 0.042; hazard ratio 2.8 (1.2-6.8)). The exercise test had independent but limited prognostic value in AMI patients treated with thrombolytics. The delta ST/delta HR index did not improve the predictive value of the exercise test.

Aged↗

PubMed2005

Autoactive alleles of the flax L6 rust resistance gene induce non-race-specific rust resistance associated with the hypersensitive response.

L6 is a nucleotide binding site-leucine rich repeat (NBS-LRR) gene that confers race-specific resistance in flax (Linum usitatissimum) to strains of flax rust (Melampsora lini) that carry avirulence alleles of the AvrL567 gene but not to rust strains that carry only the virulence allele. Several mutant and recombinant forms of L6 were made that altered either the methionine-histidine-aspartate (MHD) motif conserved in the NBS domain of resistance proteins or exchanged the short domain C-terminal to the LRR region that is highly variable among L allele products. In transgenic flax some of these alleles are autoactive; they cause a gene dosage-dependent dwarf phenotype and constitutive expression of genes that are markers for the plant defense response. Their effects and penetrance ranged from extreme to mild in their degree of plant stunting, survival, and reproduction. Dwarf plants were also resistant to flax rust strains virulent to wild-type L6 plants, and this nonspecific resistance was associated with a hypersensitive response (HR) at the site of rust infection. The strongest autoactive allele, expressed in Arabidopsis from an ethanol-inducible promoter, gave rise to plant death dependent on the enhanced disease susceptibility 1 (EDS1) gene, which indicates that the mutant flax (Linaceae) L6 gene can signal cell death through a defined disease-resistance pathway in a different plant family (Brassicaceae).

Alleles↗

PubMed2001

Electrocardiographic exercise stress testing for cardiac risk assessment in patients undergoing noncardiac surgery.

BACKGROUND: The value of exercise electrocardiography in the prediction of perioperative cardiac risk has yet to be defined. This study was performed to determine the predictive value of exercise electrocardiography as compared with clinical parameters and resting electrocardiography. METHODS: A total of 204 patients at intermediate risk for cardiac complications prospectively underwent exercise electrocardiography before noncardiac surgery. Of these, 185 were included in the final evaluation. All patients underwent follow-up evaluation postoperatively by Holter monitoring for 2 days, daily 12-lead electrocardiogram, and creatine kinase, creatine kinase MB, and troponin-T measurements for 5 days. Cardiac events were defined as cardiac death, myocardial infarction, minor myocardial cell injury, unstable angina pectoris, congestive heart failure, and ventricular tachyarrhythmia. Potential risk factors for an adverse event were identified by univariate and multivariate logistic regression analysis. RESULTS: Perioperative cardiac events were observed in 16 patients. There were 6 cases of myocardial infarction and 10 cases of myocardial cell injury. The multivariate correlates of adverse cardiac events were definite coronary artery disease (odds ratio, 8.8; 95% confidence interval [CI], 1.1--73.1; P = 0.04), major surgery (odds ratio, 4.7; 95% CI, 1.3--16.3; P = 0.02), reduced left ventricular performance (odds ratio, 2.0; 95% CI, 1.1--3.8; P = 0.03), and ST-segment depression of 0.1 mV or more in the exercise electrocardiogram (odds ratio, 5.2; 95% CI, 1.5--18.5; P = 0.01). A combination of clinical variables and exercise electrocardiography improved preoperative risk stratification. CONCLUSIONS: This prospective study shows that a ST-segment depression of 0.1 mV or more in the exercise electrocardiogram is an independent predictor of perioperative cardiac complications.

Adult↗

PubMed1995

Estimating standardized mortality odds ratios with national mortality followback data.

Proportionate mortality analyses are often used to study cause-specific mortality when population denominators are not available. The purpose of this paper is to present an extension of published proportionate mortality ratio logistic regression methods used to analyze such data. This paper describes methods used to estimate standardized mortality odds ratios (SMORs) with numerator data and the problems encountered when external standard rates are not available for all strata of interest. This paper focuses on the case where one has representative mortality followback data. These data are based on a large, representative sample of deaths from a defined population for whom numerous covariates about the decedents are collected from surviving family members. With these data, one may use logistic regression methods to generate fully standardized estimates of risk, SMORs, with numerator data. It is also possible to generate SMORs that allow for effect modification. Mortality followback data are also a more flexible data source from which one may generate substitutes for external standard mortality rate ratios to be used with previously developed SMOR methods. An application of the methods is provided using logistic regression.

Heart Diseases↗

PubMed2000

Clinical progression of HIV-1 infection according to the viral response during the first year of antiretroviral treatment. Groupe d'Epidémiologie du SIDA en Aquitaine (GECSA).

OBJECTIVE: To compare HIV-disease progression according to changes of plasma HIV RNA observed in the year following initiation of a new antiretroviral treatment. DESIGN: Prospective cohort treated with two nucleoside analogues or a triple combination including a protease inhibitor. METHODS: A Cox model was used to estimate the effect of viral response during the first year after initiation of treatment on the subsequent occurrence of new AIDS-defining events or death. Viral response was fitted either as HIV RNA reduction during the initial 4-12 months of treatment or reduction during the first month. RESULTS: Among 773 patients (47% with triple drug combination) followed for a median period of 27 months, 62 patients experienced a clinical event. Poor viral responders (at least two measurements > 3.7 log10 copies/ml during 4-12 months of treatment) had a higher risk of disease progression than good responders (RNA < 2.7 log10 copies/ml) after adjustment [hazard ratio (HR), 2.24; 95% confidence interval (CI), 1.1 7-4.29]. Intermediate responders (2.7 < or = RNA < or = 3.7 log10 copies/ml) had a risk of progression comparable with that of good responders (HR, 1.43; 95% CI, 0.64-3.22). A large initial viral reduction was also a protective factor for clinical progression (HR, 0.51 for 1 log10 copies/ml increase of the reduction; 95% CI, 0.31-0.85) and was associated with the viral response during the subsequent 4-12 month period. No patient with a reduction < 0.5 log10 copies/ml in the first month was classified as a good responder in the subsequent 4-12 month period (P < 0.01). CONCLUSIONS: A sustained HIV RNA > 3.7 log10 copies/ml should suggest a prompt change of treatment. When the reduction in HIV RNA is < 0.5 log10 after 1 month of treatment, this action should be anticipated. A sustained HIV RNA level between 2.7 and 3.7 log10 copies/ml may permit the deferral of a change of drug regimen according to the patient's history and therapeutic options.

Adult↗