The discriminative ability of the 12-item short form health survey (SF-12) in a sample of persons infected with HIV

BACKGROUND: Self-reported health-related quality of life (HRQOL) assesses constructs that transcend laboratory-based clinical parameters. Corroboration of the hypothesized relationships between the 2 types of health indicators (ie, clinical and HRQOL) could provide evidence of the validity of an HRQOL measurement tool. OBJECTIVE: The purpose of this study was to evaluate the ability of scores on the mental component summary (MCS-12) and physical component summary (PCS-12) of the 12-Item Short Form Health Survey (SF-12) to discriminate between HIV-infected persons in predefined disease-severity groups based on surrogate markers. METHODS: This cross-sectional study involved the collection of clinical data (ie, CD4 cell count, viral load [HIV-1 RNA copies/mL]) from patients' medical records and HRQOL data from the SF-12 at 2 HIV specialty clinics. The ability of SF-12 summary scores to discriminate between patients stratified by disease severity (ie, CD4 cell count <200 vs > or = 200/mm3; HIV-1 RNA >55,000 vs < or = 55,000 copies/mL) was assessed by receiver operating characteristic curve analysis. RESULTS: Data were collected from 478 patients. The scores from the PCS-12 were able to discriminate between groups of patients stratified by disease severity based on CD4 cell count (P < 0.001) and HIV-1 RNA copies/mL (P < 0.01). MCS-12 scores did not discriminate between disease-severity groups. CONCLUSIONS: Although the SF-12 is a brief generic measure of HRQOL, these findings provide further evidence of the validity of the SF-12 and suggest that it may be a practical way to monitor health status from the perspective of the HIV-infected patient.     

A pilot case-control study of zidovudine compared with zidovudine plus didanosine in patients with advanced HIV-1 disease and no previous experience with antiretrovirals

Although zidovudine (ZDV) is effective in HIV-1-infected patients, the duration of its efficacy may be short when treatment is started in advanced HIV disease. This pilot prospective case-control study was designed to evaluate the combination of ZDV plus didanosine [ddI] compared with ZDV monotherapy as an initial therapeutic strategy. 'Control' patients (ZDV monotherapy) were matched with 'case' patients (ZDV plus ddI combination therapy) according to the presence or absence of AIDS-defining criteria at entry and CD4 cell count. The case patient group consisted of 35 consecutive HIV-1-infected individuals with < or = 300 CD4 cells/mm3, no previous experience of antiretroviral therapy and who accepted treatment with a combination of ZDV plus ddI. The control patient group consisted of 35 consecutive patients with similar characteristics, but who preferred to start treatment with ZDV alone. Control patients received 250 mg ZDV bid and case patients received ZDV at the same dose plus ddI (200 mg bid). Primary study endpoints were virological (serum HIV-1 RNA) and immunological (CD4 cell count) responses. Viral phenotype (syncytium-inducing (SI) or non-syncytium-inducing (NSI)), development of mutations at codons 215, 41 and 74 and clinical progression (new AIDS-defining event or death) were also assessed. Virological and CD4 cell count responses were significantly greater and more sustained in the group treated with ZDV plus ddI than in the control group, with peak responses of -1.2 +/- 0.7 log10 versus -0.3 +/- 0.4 log10 at 1 month (P = 0.0003) and 61 +/- 52 cells/mm3 versus 19 +/- 25 cells/mm3 at 2 months (P = 0.001), respectively. In both groups the percentage of patients developing a mutation at codon 215 was around 80 per cent at 12 months. A mutation at codon 74 was detected in 30 per cent of case patients at 12 months. Five case patients (14 per cent) versus 12 control patients (34 per cent) showed signs of clinical progression (P = 0.09). In a multivariate model, clinical progression was significantly associated with a baseline     

Predictors of clinical progression among HIV-1-positive patients starting HAART with CD4+ T-cell counts > or =200 cells/mm3

BACKGROUND: Baseline and follow-up predictors of new AIDS-defining events (ADE) or death among patients who started HAART with CD4+ T-cell counts > or =200 cells/mm3 have rarely been assessed simultaneously. METHODS: A prospective observational cohort study (1996-2002) is reported. HIV-infected patients initiating HAART with a CD4+ T-cell count > or =200 cells/mm3 were studied. Baseline and time-varying factors were tested for the prediction of new ADE/death using Cox regression models. RESULTS: A total of 896 subjects were studied over a median of 5.1 years. The incidence of a new ADE was 1.6 (95% confidence interval 1.3-2.1) per 100 person-years. Among baseline factors, higher CD4+ T-cell counts before HAART were associated with lower risk of ADE/death, but not after adjustment for time-varying factors. On a multivariable analysis including both baseline and time-varying covariates, longer delay from HIV diagnosis to HAART was an independent predictor of ADE/death (per year, hazard ratio [HR] 1.06; P = 0.025) and was independent of CD4+ T-cell count before treatment. Longer time spent with HIV RNA <400 copies/ml (per month, HR 0.96; P = 0.003) and higher latest CD4+ T-cell count (per log2 cells/mm3, HR 0.65; P < 0.001) were found to be protective. CONCLUSIONS: Patients with higher CD4+ T-cell counts before HAART initiation had a better prognosis. However, except for the delay in starting HAART, viroimmunological evolution outweighed the effect of baseline factors. Moreover, suppressing HIV replication for as long as possible could improve the clinical outcome. Prospective randomized clinical trials to assess the optimal timing of HAART initiation are both feasible and urgently needed.     

Baseline thymic volume is a predictor for CD4 T cell repopulation in adult HIV-infected patients under highly active antiretroviral therapy

The objective of the present study was to assess the impact of baseline thymic volume on the CD4 cell repopulation induced by highly active antiretroviral therapy (HAART) in HIV-infected adults. Therefore, 37 previously untreated HIV-1-infected adults were prospectively followed from August 1998 to September 2001. All patients underwent a thorax CT scan at starting HAART to measure thymic volume. The median follow-up time was 189 [87.5-498.5] days. CD4 cell repopulation was considered as an increase > or = 200 cells/mm3 above baseline count. Twenty-one (57%) patients achieved this CD4 repopulation. Baseline thymic volume was the main independent factor associated with CD4 repopulation (P = 0.016); this factor was a positive predictor (adjusted hazard ratio: 1.25 [95% confidence interval 1.1-1.4]). Although, CD4 cell count and non-AIDS diagnosis at baseline were associated with CD4 cell repopulation on the univariate analysis (P = 0.03 and P = 0.02, respectively), no statistical signification was found on the multivariate test. In summary, baseline thymic volume is a predictor of early CD4 cell repopulation in adult HIV-1-infected patients taking HAART.     

The effect of depressive symptoms at ART initiation on HIV clinical progression and mortality: implications in clinical practice

BACKGROUND: Depression is common in HIV-infected patients receiving antiretroviral therapy. However, longitudinal studies addressing the role that depression might play in HIV clinical progression and mortality remain rare. This is especially true for those studies that also consider the possible confounding influence of patient's adherence to treatment. METHODS: The ANRS CO-8 APROCO-COPILOTE cohort study enrolled 1,281 individuals at the initiation of a protease-inhibitor-containing regimen between 1997 and 1999. Adherence, depressive symptoms and other psychosocial factors were measured using self-administered questionnaires. Predictors of progression to AIDS or death were studied using Cox models. RESULTS: Out of 1,028 individuals eligible for the present analysis, 92 individuals either died or had an AIDS-defining event during a median follow up of 54 months. At baseline, 377 individuals (41%) reported depressive symptoms and 124 (12%) reported non-adherence at month 4. Depressive symptoms at baseline were associated with progression (hazard ratio [HR] 2.1; P = 0.001). Despite the association between depressive symptoms and nonadherence, depressive symptoms remained a predictor of clinical progression (adjusted HR [aHR] [95% confidence interval (CI)] 1.6 [1.0-2.5]) after adjustment for several factors: initial non-adherence (aHR [95% CI] 2.0 [1.1-3.6]), having a steady partner (aHR [95% CI] 0.5 [0.3-0.7]), older age (aHR [95% CI] 1.40 [1.12-1.74] per 10-year increment), HIV clinical stage C (aHR [95% CI] 2.5 [1.6-4.0]), plasma HIV RNA > or = 100,000 copies/ml (aHR [95% CI] 1.7 [1.1-2.87]) and more than 8 years since HIV diagnosis (aHR [95% CI] 1.8 [1.1-2.8]). CONCLUSION: Depressive symptoms and non-adherence are independent predictors of HIV clinical progression and mortality. Screening and appropriate treatment of depressive symptoms at antiretroviral treatment initiation should be included in the standard care of HIV-infected patients.     

An open-label trial of stavudine, lamivudine and efavirenz in the treatment of HIV-positive, treatment-naive patients, and implications for clinical practice

A phase II, open-label study of stavudine, lamivudine and efavirenz resulted in significant reductions in plasma HIV-1 RNA over a 24 week period in human immunodeficiency virus (HIV)-infected individuals. The trial currently has 68 patients, and this presentation covers data on the first 42 patients enrolled for 24 weeks. The mean plasma HIV-1 RNA on entry was 75858 HIV RNA copies/ml, and the mean CD4 count was 380 cells/mm3. After 24 weeks, the CD4 count increased by 169 cells/mm3 above baseline. plasma HIV-1 RNA was markedly reduced: at 24 weeks, more than 97% of patients had <50 HIV RNA copies/ml based on observed data, and 89% of patients had <50 copies/ml based on strict intent-to-treat analysis (non-completer=failure). The favourable interactions of these agents resulted in no discontinuations owing to adverse effects. This regimen provides an important first-line treatment for antiretroviral-naive patients.     

Antiretroviral therapy of late presenters with advanced HIV disease

Potent antiretroviral therapy (ART) has dramatically improved the prognosis of HIV-1-infected individuals. However, 10% to 30% of patients in Western countries still present late for care, when CD4 T cells are below 200 cells/mm(3) and symptomatic HIV disease has occurred. Clinical considerations for advanced HIV disease are paramount as morbidity and mortality are directly correlated with a low initial CD4 T cell count, which is commonly associated with the simultaneous occurrence of co-morbidities, particularly opportunistic infections. Upon start of ART, the clinical entity of immune reconstitution inflammatory syndrome may occur and, in this context, raise the question of early versus delayed ART in patients treated for opportunistic infections. Recent data clearly indicate that an earlier start of ART is warranted in this latter situation. Guidelines for specific antiretroviral treatment for late-presenting patients are lacking. Knowledge about drug-drug interactions and co-morbidities should guide treatment choices and influence the clinical management and monitoring of drug-related side effects and interactions. Importantly, the outlook of patients who present late is very much dependent upon the initial response to ART. Nevertheless, even if optimal response to treatment has been achieved, long-term prognosis may be impaired in patients who initially presented with advanced HIV disease. We encourage physicians to perform HIV testing more frequently in order to detect HIV-infected individuals in time.     

Activation of virus replication after vaccination of HIV-1-infected individuals

Little is known about the factors that govern the level of HIV-1 replication in infected individuals. Recent studies (using potent antiviral drugs) of the kinetics of HIV-1 replication in vivo have demonstrated that steady-state levels of viremia are sustained by continuous rounds of de novo infection and the associated rapid turnover of CD4+ T lymphocytes. However, no information is available concerning the biologic variables that determine the size of the pool of T cells that are susceptible to virus infection or the amount of virus produced from infected cells. Furthermore, it is not known whether all CD4+ T lymphocytes are equally susceptible to HIV-1 infection at a given time or whether the infection is focused on cells of a particular state of activation or antigenic specificity. Although HIV-1 replication in culture is known to be greatly facilitated by T cell activation, the ability of specific antigenic stimulation to augment HIV-1 replication in vivo has not been studied. We sought to determine whether vaccination of HIV-1-infected adults leads to activation of virus replication and the targeting of vaccine antigen- responsive T cells for virus infection and destruction. Should T cell activation resulting from exposure to environmental antigens prove to be an important determinant of the steady-state levels of HIV-1 replication in vivo and lead to the preferential loss of specific populations of CD4+ T lymphocytes, it would have significant implications for our understanding of and therapeutic strategies for HIV-1 disease. To begin to address these issues, HIV-1-infected individuals and uninfected controls were studied by measurement of immune responses to influenza antigens and quantitation of virion- associated plasma HIV-1 RNA levels at baseline and at intervals after immunization with the trivalent influenza vaccine. Influenza vaccination resulted in readily demonstrable but transient increases in plasma HIV-1 RNA levels, indicative of activation of viral replication, in HIV-1-infected individuals with preserved ability to immunologically respond to vaccine antigens. Activation of HIV-1 replication by vaccination was more often seen and of greater magnitude in individuals who displayed a T cell proliferative response to vaccine antigens at baseline and in those who mounted a significant serologic response after vaccination. The fold increase in viremia, as well as the rates of increase of HIV-1 in plasma after vaccination and rates of viral decline after peak viremia, were higher in individuals with higher CD4+ T cell counts.(ABSTRACT TRUNCATED AT 400 WORDS)     

The NIQ of lopinavir is predictive of a 48-week virological response in highly treatment-experienced HIV-1-infected subjects treated with a lopinavir/ritonavir-containing regimen

OBJECTIVE: To investigate the normalized inhibitory quotient (NIQ) of lopinavir (LPV) as a predictor of 48-week virological responses to a lopinavir/ritonavir (LPV/RTV)-containing regimen in highly treatment-experienced patients. DESIGN: We calculated the NIQ for 59 patients who completed 48 weeks' treatment and assessed the factors predicting a week-48 virological response. METHODS: The NIQ was calculated by dividing each subject's IQ (LPV Ctrough/fold change in LPV susceptibility, as assessed by VirtualPhenotype) by a reference IQ (mean population LPV Ctrough/fold change in LPV IC50, as assessed by VirtualPhenotype). HIV-1 RNA was assessed by NASBA (quantification limit: 80 copies/ml). The general linear model and multiple logistic regression, respectively, were used to estimate the independent predictors of a change in viral load and HIV-1 RNA <80 copies/ml. RESULTS: The median (interquartile range) baseline levels of CD4+ cells and HIV-1 RNA were 251 (141-385) cells/microl and 4.85 (4.49-5.23) log10 copies/ml, respectively. The median NIQ was 2.2 (0.5-14). At week 48, the median decrease in HIV-1 RNA was 1.4 (0.59-2.79) log10 copies/ml (P<0.0001), with 24 subjects (41%) reaching <80 copies/mi. Baseline HIV-1 RNA (P=0.001), CD4+ cells (P=0.002) and NIQ (P=0.0006) independently predicted the week-48 change in viral load, whereas baseline CD4+ cells (P=0.011) and NIQ (P=0.009) independently predicted a week-48 HIV-1 RNA level of <80 copies/ml. CONCLUSION: The LPV NIQ independently predicts virological responses to an LPV/RTV-containing regimen in highly treatment-experienced HIV-1-infected patients.     

Acyclovir in combination with zidovudine does not prolong survival in advanced HIV disease

The aim of this study was to evaluate the association between acyclovir use and survival in HIV-infected patients. To achieve this, we used survival analysis in an observational cohort of HIV-infected patients enrolled in primary care at an urban HIV clinic. We measured survival in a cohort of HIV-infected patients who had CD4 cell counts < or = 500/mm3 and who enrolled for care at a single urban HIV clinic between December 1988 and April 1995. We compared survival in users of acyclovir alone, zidovudine alone, and acyclovir and zidovudine in combination with the survival of those using neither drug. Factors associated with improved survival were identified using Cox proportional hazards analysis. Among the 1408 patients enrolled, there were no significant differences in overall survival between acyclovir users and non-users. After adjustment for CD4 cell count, the use of other antiretroviral agents, race, transmission risk and a history of herpesvirus infection, acyclovir use alone was independently associated with a relative hazard (RH) of death of 1.008 (P = 0.969); zidovudine use alone with a RH of 0.559 (P < 0.001); and combination use of acyclovir and zidovudine associated with a RH of 1.062 (P = 0.788). Therefore we conclude that the use of acyclovir is not associated with prolonged survival in this cohort of HIV-infected patients.     

Correlation between HIV disease and lipid metabolism in antiretroviral-na?ve HIV-infected patients in Japan

Antiretroviral therapy alters lipid metabolism in HIV-infected patients. However, interpreting the impact of HIV infection on lipid metabolism is difficult because of various associated factors, including antiretroviral drugs and demographic characteristics. A few studies have associated HIV infection with lipid metabolism in antiretroviral-na?ve HIV-infected patients. Because there were no data in this regard from Japan, the present study examined the impact of HIV infection, as well as demographic and clinical features, on lipid metabolism in antiretroviral-na?ve HIV-infected patients in Japan. We performed a cross-sectional study to examine the impact of HIV disease, demographic and clinical characteristics on lipid metabolism among 168 HIV-infected Japanese men who were antiretroviral na?ve and who did not have hemophilia, including patients who took medication for dyslipidemia. The mean age of the patients was 45.7 years; 0.6% of the patients took medication to dyslipidemia. The mean CD4 lymphocyte count was 289/μL, the mean baseline log10 HIV viral load was 4.2 HIV-1 RNA copies/mL, and 22% of the patients had a history of AIDS-defining events. A higher HDL-C concentration was associated with a higher CD4 lymphocyte count (p = 0.043). Also, a higher LDL-C concentration was associated with a higher CD4 lymphocyte count (p = 0.003). Infection with HIV was associated with dyslipidemia in antiretroviral-na?ve patients. More advanced HIV disease was associated with less favorable lipid homeostatic profiles. These results are similar to findings from other countries.     

Identification of dynamically distinct subpopulations of T lymphocytes that are differentially affected by HIV.

We examined the effects of human immunodeficiency virus infection on the turnover of CD4 and CD8 T lymphocytes in 17 HIV-infected patients by 30 min in vivo pulse labeling with bromodeoxyuridine (BrdU). The percentage of labeled CD4 and CD8 T lymphocytes was initially higher in lymph nodes than in blood. Labeled cells equilibrated between the two compartments within 24 h. Based on mathematical modeling of the dynamics of BrdU-labeled cells in the blood, we identified rapidly and slowly proliferating subpopulations of CD4 and CD8 T lymphocytes. The percentage, but not the decay rate, of labeled CD4 or CD8 cells in the rapidly proliferating pool correlated significantly with plasma HIV RNA levels for both CD4 (r = 0.77, P < 0.001) and CD8 (r = 0.81, P < 0.001) T cells. In six patients there was a geometric mean decrease of greater than 2 logs in HIV levels within 2 to 6 mo after the initiation of highly active antiretroviral therapy; this was associated with a significant decrease in the percentage (but not the decay rate) of labeled cells in the rapidly proliferating pool for both CD4 (P = 0.03) and CD8 (P < 0.001) T lymphocytes. Neither plasma viral levels nor therapy had an effect on the decay rate constants or the percentage of labeled cells in the slowly proliferating pool. Monocyte production was inversely related to viral load (r = -0.56, P = 0.003) and increased with therapy (P = 0.01). These findings demonstrate that HIV does not impair CD4 T cell production but does increase CD4 and CD8 lymphocyte proliferation and death by inducing entry into a rapidly proliferating subpopulation of cells.     

Effects of hepatitis C virus infection on the pharmacokinetics of ritonavir-boosted atazanavir in HIV-1-infected patients

Most antiretrovirals are metabolized in the liver, and overexposure could be more common in human immunodeficiency virus (HIV)-infected patients with hepatic impairment. Careful monitoring of potential drug-related liver injury in clinical practice is necessary. The aim of our study was to analyze the trough concentrations (C (trough)) of atazanavir (ATV) in the plasma of HIV/hepatitis C virus (HCV)-co-infected patients and to compare the values with those of a HIV-infected control population. C (trough) values (22-26 h after last intake) of atazanavir, following the administration of atazanavir/ritonavir 300/100 mg once daily as part of antiretroviral therapy, were assessed by HPLC. We also collected data on dosing of atazanavir, and on demographic (age, gender, and ethnicity), physiological (weight and body mass index), and clinical parameters (CD4+ cell count, HIV-RNA viremia, co-medication, and hepatitis C co-infection). A total of 28 Caucasian HIV-infected adults were studied, of whom 13 were HIV/HCV co-infected. No baseline characteristics differed between the two cohorts, except statistically significant differences regarding ALT, AST, and total bilirubin. The median (range) plasma ATV C (trough) levels were 0.62 (0.05-3.22) μg/ml in HIV patients and 0.32 (0.04-3.37) μg/ml in HIV/HCV patients. Thus, there was no significant difference in plasma trough levels of atazanavir in the two cohorts. In our patients with mild impairment of hepatic function caused by HCV infection, atazanavir C (trough) was comparable in HIV-infected and HIV/HCV-co-infected patients.     

Capacity of neutrophils and monocytes from human immunodeficiency virus-infected patients and healthy controls to inhibit growth of Mycobacterium bovis

We compared the differences in growth inhibition of Mycobacterium bovis by monocytes and neutrophils from human immunodeficiency virus (HIV)-infected persons (n = 12; mean CD4 count = 451/mm(3)) and healthy controls (n = 6). Phagocytes from all HIV-infected patients were incubated with or without exogenous granulocyte-macrophate colony-stimulating factor (GMCSF; 500-1000 U/mL). In two of the HIV-infected patients, phagocytes were incubated with or without interleukin (IL)-2 or IL-8 (500-1000 U/mL). Compared with that in HIV-infected patients, the reduction of M. bovis growth at 24 hours was 81% greater among monocytes and 69% greater among neutrophils from healthy controls (P =.03 and.04, respectively). Among HIV-infected patients, we noted greater mycobacterial reduction in monocytes (49%, P =.04) and neutrophils (42%, P =.05) from the early-stage patients (mean CD4 count = 760/mm(3)) compared with that in late-stage patients (mean CD4 count = 172/ mm(3)). Incubation with GM-CSF, IL-2, or IL-8 did not augment mycobactericidal activity. These findings suggest that the capacity of neutrophils and monocytes from HIV-infected patients to inhibit the growth of M. bovis is impaired, and this impairment is more pronounced in later stages of HIV infection.     

非小细胞肺癌合并人类免疫缺陷病毒阳性患者29例的外科治疗分析

目的评价手术治疗非小细胞肺癌(NSCLC)合并人类免疫缺陷病毒(HIV)阳性患者的临床效果。方法回顾性分析收集1998年9月至2006年4月莫桑比克马普托中心医院胸外科手术治疗的NSCLC合并HIV阳性患者29例(HIV阳性组),并选择同期34例HIV检测呈阴性NSCLC患者作为对照组(HIV阴性组)。分析两组患者的手术时间、术中出血量、术后引流量、手术后胸腔引流量、手术后肺部和伤口感染率、手术后住院日、HIV阳性组CD4计数,并随访生存时间等临床指标。结果两组患者手术在死亡率上的差异没有统计学意义;HIV阳性组手术后肺部感染发生率比HIV阴性组高(31.03%vs5.88%,P=0.009),前者发生手术后肺部感染的危险比后者增加7倍以上(OR=7.200;95%可信区间(1.409,36.779));HIV阳性患者不同CD4计数手术后肺部感染发生率的差异有统计学意义(P=0.040),CD4计数与手术后肺部感染发生率呈负相关(r=-0.501;P=0.014);HIV阳性组与HIV阴性组患者在生存时间上差异无统计学意义(P=0.248)。结论 NSCLC合并HIV阳性患者手术后并发肺部感染危险增加且与患者CD4细胞计数呈负相关,但不会增加手术死亡率;伴随高效抗逆转录病毒治疗(HAART)的实行,其手术后生存期与HIV阴性者相似。对于非艾滋病发作期的该类患者,均应考虑积极地治疗。     

Priming of human CD4+ antigen-specific T cells to undergo apoptosis by HIV-infected monocytes. A two-step mechanism involving the gp120 molecule.

The study of the pathology of HIV-1 infection in chimpanzees supports the idea of the crucial role of HIV-infected monocytes in the pathogenesis of AIDS, although viral mechanisms that lead to T cell dysfunction and deletion during HIV infection are still unclear. We show here that HIV-1-infected antigen-presenting monocytes (APCs) are able to prime in vitro non-HIV-infected antigen-specific CD4+ T cell lines or peripheral blood CD4+ T cells to undergo apoptosis after antigen-specific restimulation. The priming of T cells for apoptosis occurs in the absence of HIV replication in the T cells. Priming for apoptosis required two concomitant signals present on the same APC, an antigenic stimulus and a second signal provided by the HIV gp120 protein as demonstrated by the use as APCs of EBV-LCLs infected with different recombinant deleted proviruses or transfected with different HIV proteins. These results provide a mechanism for the priming for apoptosis of T cells in HIV-infected patients, implicating a role for HIV-infected APCs in the induction of T cell dysfunction and depletion in AIDS.