Changing clinical presentation and survival in HIV-associated tuberculosis after highly active antiretroviral therapy

OBJECTIVE: To assess changes in clinical presentation and outcome of HIV-associated tuberculosis (TB) before and after widespread implementation of highly active antiretroviral therapy (HAART). METHODS: We reviewed clinical charts of HIV-infected patients with culture-confirmed pulmonary TB in two referral clinical centers in Rome, Italy. The 67 patients diagnosed in 1995 to 1996 were compared with 51 patients diagnosed in 1997 to 1998. To analyze factors associated with survival we used a Cox model including antiretroviral therapy as a time-dependent covariate. RESULTS: Patients diagnosed in 1997 to 1998 were more likely to have TB as the first AIDS-defining illness (78% versus 58%, p <.05), to have HIV diagnosed <2 months before TB (33% vs. 7%, p <.005) and to have typical chest radiograph pattern (45% vs. 25%, p <.05), and had a higher CD4(+) count (median 105 vs. 43, p <.005). Survival at 1 year was 80% for patients diagnosed in 1997 to 1998 vs. 65% for those diagnosed in 1995 to 1996 (p by log-rank =.02). After adjusting at multivariate analysis, time period of diagnosis was not confirmed as associated with survival (hazard ratio, 1.05; 95% confidence interval, 0.39--2.81). Age, CD4+ cell count <25/mm(3), and AIDS-defining illnesses before TB diagnosis were all associated with an higher risk of death, whereas a decreased risk of death was observed in patients starting a triple combination antiretroviral therapy after TB diagnosis (hazard ratio, 0.14; 95% confidence interval, 0.03--0.57). CONCLUSIONS: Cases of HIV-associated TB occurring in patients with advanced immunosuppression and presenting with atypical radiologic appearance tend to be relatively less common in the HAART era. HAART is a major factor in prolonging survival in these patients.     

HIV-associated hematologic disorders are correlated with plasma viral load and improve under highly active antiretroviral therapy.

The relationship between HIV-1 replication and hematologic parameters was examined in two separate studies. The first study was a cross-sectional evaluation of 207 untreated patients. In this study, the proportion of patients with hematologic disorders increased with disease progression. There was a significant inverse correlation between HIV-1 plasma viral load and all hematologic values (r = -0.266 to -0.331). The second study was a longitudinal evaluation of patients on combination antiretroviral therapy (HAART) with hematologic alterations before treatment ( N = 27 with platelets <150,000/microl, 24 with hemoglobin <12 g/dl, 36 with neutrophils <2000/microl and 29 with leukocytes <3000/microl). Samples were analyzed every 3 months for 2 years. At 2 years, >50% of patients experienced a sustained virologic response, with viral loads <500 RNA copies/ml. Hematologic reconstitution occurred progressively for all blood cell lineages and became statistically significant after the sixth month of therapy ( p <.001). Mean values increased from 110 to 180 x 10(3)/microl for platelets, from 10.7 to 12.3 g/dl for hemoglobin (stabilizing finally at 11.4 g/dl), from 1,260 to 2,240/microl for neutrophils, and from 2,260 to 3,600/microl for leukocytes. In conclusion, hematologic disorders are corrected by combination antiretroviral therapy. This suggests a causative role of HIV-1 in hematologic disorders.     

Relation of lean body mass to health-related quality of life in persons with HIV

OBJECTIVE: To determine the nature and strength of the relation between lean body mass and measures of health-related quality-of-living (HRQL) including physical functioning in men and women with HIV. DESIGN: Cross-sectional analysis using 619 patients with HIV infection from two cities in the northeastern United States. MAIN OUTCOME MEASURES: Lean body mass (LBM) was assessed by bioimpedance analysis (BIA). Physical functioning, general health perceptions, energy/fatigue, and number of days spent in bed in the last month were determined by patient self-report. RESULTS: Data from 450 men and 169 women were analyzed. Mean age was 39 years, 37.6% were nonwhite, and mean CD4 counts were 352 cells/ml. In multivariable models, higher LBM was significantly associated with better physical functioning in men but not in women. In men, a 10-kg increment in LBM was associated with a 3.7 point (95% confidence interval [CI], 0.19-7.2) increment in physical functioning (0-100 scale). In similar analyses, higher LBM was significantly associated with better general health perceptions (10-kg increment in LBM associated with a 4.8 point [95% CI, 1.4-8.1] increment in general health perceptions), and fewer days in bed in the last month (10-kg increment in LBM associated with 0.9 [95% CI, -1.8-0] fewer days in bed). Lean body mass was not independently associated with energy/fatigue. CONCLUSIONS: In this diverse population of persons with HIV, LBM was significantly related to physical functioning and other measures of HQRL in men, but not in women. In men, the relation was linear but relatively weak. These data have potential implications for assessing the clinical impact of interventions aimed at increasing LBM. Even in men, increases in LBM in the ranges that are currently achievable may produce relatively small improvements in physical functioning and other measures of HRQL.     

Quality of life in a clinical trial of highly active antiretroviral therapy alone or with intravenous or subcutaneous interleukin-2 administration

OBJECTIVE: To assess the impact of subcutaneous and intravenous interleukin-2 (IL-2) on health-related quality of life (HRQOL) in adults with HIV-1 receiving highly active antiretroviral therapy (HAART). DESIGN: Randomized clinical trial. SETTING: Twenty-two institutions from the Adult AIDS Clinical Trials Group. PATIENTS: One hundred forty-eight HIV-infected adults randomized, with baseline HRQOL data. METHODS: HAART (indinavir plus 2 nucleoside analogues) for 12 weeks, followed by 72 weeks of continued HAART alone, HAART plus subcutaneous IL-2, or HAART plus intravenous IL-2. OUTCOME MEASURES: Scores for 8 dimensions of HRQOL, an unweighted summary score, and a visual analogue health rating score. RESULTS: The IL-2 subcutaneous group had the best mean change in 6 of 8 dimension subscales and in the summary scale at 28 weeks (16 weeks after baseline). At 52 weeks, the IL-2 subcutaneous group had the best mean change in all the subscales and the summary scale. The differences were statistically significant for 3 subscales and the summary scale. Midcycle changes were statistically significantly worse for the subcutaneous IL-2 group for 4 subscales and the summary scale. CONCLUSIONS: We found evidence of a short-term but not long-term adverse impact of IL-2 on HRQOL and some evidence of long-term benefit for the subcutaneous group.     

Relationship between red cell mass, body weight, lean body mass, and body cell mass in growing pigs and beagles.

During growth in 55 pigs (from birth through week 12) and 42 beagles studied (from birth through year 1), there was an equally close association between red cell mass (RCM) and body weight, lean body mass (LBM) and body cell mass (BCM); the coefficients of correlation were between 0.94-0.99. The association of RCM with body weight was the result of BCM, extracellular tissue (ECT), and fat, each increasing at a constant rate relative to body weight. The primary relationship appears to be between RCM, the oxygen-delivery system, and BCM, the principla oxygen-using system; and the close association of RCM with body weight and LBM the results of the growth patterns of their components.     

Weight loss and survival in HIV-positive patients in the era of highly active antiretroviral therapy

Weight loss and wasting have long been established as strong predictors of mortality in HIV-infected patients. Today, despite the effectiveness of highly active antiretroviral therapy (HAART), there is evidence that HIV-related wasting is still an important comorbidity in many patients. We conducted a study to determine if wasting is still associated with decreased survival in patients receiving HAART and which parameter (weight, fat-free mass [FFM], body cell mass [BCM], or fat mass [FM]) is most strongly associated with mortality. The study population consisted of 678 HIV-positive participants enrolled in the Nutrition for Healthy Living study. Weight, FFM, BCM, and FM were assessed for all participants at 6-month intervals. At each follow-up visit, percent losses of each parameter were calculated from values at baseline and the previous visit. Cox proportional hazards models were used to estimate and compare the relative risks of death for each parameter, adjusting for potential confounders such as HAART use, body mass index, and CD4 cell counts. In analyses examining the parameters separately and together in the same model, weight loss emerged as the strongest independent predictor of mortality. Weight loss of >or=10% from baseline or the previous visit was significantly associated with a four- to sixfold increase in mortality compared with maintenance or gaining of weight. Even one episode of weight loss of >or=3% from baseline or >or=5% from the previous visit was predictive of mortality. In summary, despite the apparent benefits of HAART use on HIV-related survival, weight loss remains an independent predictor of mortality. In addition, FFM or BCM estimated using bioelectrical impedance analysis does not add further prognostic value over weight loss.     

Increased body mass index does not alter response to initial highly active antiretroviral therapy in HIV-1-infected patients

BACKGROUND: Body mass index (BMI) can influence drug metabolism, thus affecting efficacy and risk for toxicities. Hypothesizing that persons with an increased BMI and larger volumes of distribution may experience a suboptimal response to highly active antiretroviral therapy (HAART), we evaluated the effect of BMI on virologic and immunologic response in previously ART-naive patients initiating therapy. METHODS: Using data from the HIV Outpatient Study, we analyzed the statistical association of BMI and other selected demographic variables with achieving an undetectable viral load and experiencing a CD4 cell count increase of more than 100 cell/microL after 3 to 9 months of therapy among antiretroviral-naive patients initiating HAART. RESULTS: Among 711 patients included in analysis, 43% had a BMI of more than 25 (overweight-obese). Higher BMI was associated with being female, having black or Hispanic race/ethnicity, being heterosexual, and using injection drugs (all P<0.001). The patients in BMI groups did not differ significantly by baseline CD4 cell count or the duration of the initial HAART regimen. Although median baseline viral loads were significantly lower in obese participants (P=0.008), overweight or obese BMI did not significantly alter the likelihood of achieving an undetectable viral load and a CD4 cell count increase of more than 100 cells/microL compared with normal weight persons. CONCLUSION: A substantial proportion of HIV-infected outpatients in this cohort were overweight or obese. Increased BMI was not associated with decreased virologic and immunologic responses to initial HAART. Responses were equivalent and within expected ranges between normal weight patients, overweight patients, and obese patients at 3 to 9 months of observation.     

Effects of depressive symptoms and mental health quality of life on use of highly active antiretroviral therapy among HIV-seropositive women

This study examines the effects of depressive symptoms and mental health quality of life on utilization of highly active antiretroviral therapy (HAART) among HIV-seropositive women. Data were collected biannually from 1996 through 1998 in a prospective cohort study. Women reported use of antiretroviral therapy, health and mental health status, demographics, and social and behavioral factors; CD4 count and viral load also were assessed. Random effects regression models estimated the longitudinal effects of depressive symptoms and mental health quality of life on the probability of HAART utilization, controlling for clinical indicators (CD4 count, viral load, symptom presence), demographics (race, age, education), behavioral factors (drug/alcohol use, clinical trials participation), service features (insurance status, mental health service utilization), and study site. High levels of depressive symptoms and poor mental health quality of life were found, and they significantly reduced the probability of HAART utilization. Receiving mental health services significantly increased the probability of utilizing HAART. HIV-seropositive women characterized as being in poor mental health were less likely to use HAART, whereas those receiving treatment of mental health difficulties were more likely to use HAART. These findings suggest that efforts to enhance women's access to psychological treatment may increase their use of the latest HIV therapies.     

Excessive body weight is associated with additional loss of quality of life in children with asthma

BACKGROUND: Asthma and excessive body weight frequently coexist, whereas the exact relationship between the 2 diseases is unknown. OBJECTIVE: To study whether asthma combined with excessive body weight has a greater effect on quality of life in children than the separate effects of asthma or excessive body weight alone. METHODS: In a cross-sectional design, 1758 school children (age 7-10 years) participated: 4 study groups were composed of children with asthma and with/without excessive body weight, and healthy controls with/without excessive body weight. Diagnosis of asthma was defined by either a doctor's diagnosis or by core questions of the International Study of Asthma and Allergies in Childhood questionnaire in combination with either reversible airway obstruction or bronchial hyperresponsiveness. Excessive body weight was defined by using international cutoff points for body mass index. Quality of life was evaluated by the Pediatric Asthma Quality of Life Questionnaire. RESULTS: For all domains of quality of life, children with both asthma and excessive body weight had lower scores than children with either asthma alone or excessive body weight alone. Compared with healthy controls, the score was 25% lower in children with asthma and excessive body weight, 14% lower in children with asthma and normal weight, and only 1% lower in overweight controls. CONCLUSION: Excessive body weight is associated with an additional decrease in quality of life in children with asthma. CLINICAL IMPLICATIONS: Clinicians should be aware of the interaction between asthma and excessive body weight and the effect on quality of life and should give extra attention to children with both conditions.     

Changes in body habitus and serum lipid abnormalities in HIV-positive women on highly active antiretroviral therapy (HAART).

Twenty-one women (propositi) who expressed serious concerns about changes in body habitus during highly active antiretroviral therapy (HAART) were evaluated by thorough physical examination, anthropometric measurements, and serum lipid and endocrine assays. The same evaluations were carried out in a comparison group of 21 women who received HAART but did not complain of changes in habitus. No significant demographic differences were found between the propositi and the comparison group, nor were there significant differences in CD4 count or plasma viral load (PVL) between the two groups. Lipid analyses were also performed on plasma obtained prior to HAART from 12 of the women. The frequency of changes reported by the 21 propositi were increase in abdominal size (90%), increase in breast size (71%), weight gain of >5 kg (43%), peripheral fat wasting (43%), buttock fat wasting (38%) and development of cervicodorsal fat pad (19%). A subset of patients in the comparison group experienced increase in abdominal size (29%) and weight gain >5 kg (19%), but none experienced clinically detectable peripheral or buttock fat wasting, increased breast size, or development of cervicodorsal fat pads. Mean waist circumference, waist-to-hip ratios (WHR), body fat, and body mass index (BMI) were above the desirable range for women in both propositi and the comparison group. Levels of total cholesterol, triglycerides, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol associated with increased cardiovascular risk were found in 48%, 62%, 45%, and 33%. respectively, of the propositi, with similar findings in the comparison group. Fasting insulin levels were elevated in 4 propositi and 6 of the comparison group; mean insulin levels were within the normal range for both groups. In the comparison of lipids for the subset of patients before and after HAART therapy, HAART was associated with significant increases in total cholesterol, apolipoprotein B, and HDL cholesterol. Changes in body habitus caused by redistribution of fat occur commonly in women receiving HAART. Serum lipid abnormalities also are common during HAART and appear to be as frequent in women who do not experience clinically apparent body fat redistribution as in those who do. The observed changes in body fat distribution and in serum lipid levels are alterations that have been strongly correlated with increased risk for cardiovascular disease. Therefore, an understanding of the basis of these phenomena, and the risks with which they may be associated in this population, will be important for therapeutic decision making in women with HIV disease.     

Impact of adherence and highly active antiretroviral therapy on survival in HIV-infected patients

OBJECTIVES: To assess the effect of antiretroviral therapy (ART) adherence on survival in HIV-infected patients. DESIGN: Cohort study at a single hospital in Barcelona, Spain. METHODS: Data on HIV-infected patients older than 18 years of age who began ART during the period 1990 to 1999 were analyzed. Patients were considered nonadherent if the total dose of antiretroviral drug was less than 90% of that prescribed. Adherence was assessed through self-report and hospital pharmacy appointments. Cox regression with time-dependent variables was used. RESULTS: A total of 1219 patients were included. The first ART was with monotherapy in 23.7% of cases, with two drugs in 30.5%, and with triple therapy in 45.8%. In multivariate analysis, the variables that presented significant differences with respect to mortality were clinical stage at the beginning of treatment (AIDS: relative hazard (RH) = 2.97; 95% confidence interval [CI]: 2.14-4.13), CD4 cell count (<200 cells/microL: RH = 5.89; CI: 3.44-10.10), type of treatment (monotherapy: RH = 9.76; CI: 4.56-20.90; bi-therapy: RH = 9.12; CI: 4.23-19.64), and adherence (nonadherence: RH = 3.87; CI: 1.77-8.46). CONCLUSIONS: The modifiable factors most strongly associated with survival were type of treatment and adherence. It would be desirable to accompany therapy with intervention strategies intended to improve adherence.     

Presence of HIV-specific CD4+ T-cell responses in HIV-infected subjects with sustained virologic control after highly active antiretroviral therapy

HIV-specific CD4+ T-helper cell responses in 40 subjects with chronic infection (CI) who had virus suppression after highly active antiretroviral therapy (HAART) were compared with those in 34 subjects treated during primary infection (PI). A CD4+ T-cell proliferative response to HIV p24 protein was present in 50% of these subjects compared with 79% of subjects treated during PI. The existence of a proliferative response in CI subjects was associated with a higher CD4+ T-cell count at initiation of HAART, a longer duration of virus suppression, and a higher CD4+ T-cell count at the time of analysis. These results show that an HIV-specific proliferative response is preferentially observed in treated CI subjects with CD4+ T-cell counts of >200/microL. However, in treated CI subjects with a significant degree of CD4+ T-cell depletion (<200/microL), it may also be observed in 35% provided that the duration of virus suppression is long enough, which may have implications for future therapeutic strategies.