Relationships among the detection of p24 antigen, human immunodeficiency virus (HIV) RNA level, CD4 cell count, and disease progression in HIV-infected individuals with hemophilia.

The aim of this study was to assess the relationships among the detection of p24 antigen, human immunodeficiency virus (HIV) RNA level, CD4 cell count, and disease progression in 111 males with hemophilia who were infected with HIV for < or =20 years. Sixty-four individuals (58%) developed p24 antigenemia a median of 11.6 years after seroconversion. The time to first detection of p24 antigen was shorter among those who were older (P=.04) and those with a high initial HIV RNA level (P=.006). The median HIV RNA level and CD4 cell count at the time of the detection of p24 antigen were 4.95 log(10) copies/mL and 100 cells/mm(3), respectively. In univariate analyses, p24 antigenemia was associated with more-rapid progression to AIDS (relative hazard [RH], 5.50; P=.0001). The effect was reduced (RH, 1.85; P=.06) after adjusting for CD4 cell counts and HIV RNA levels during follow-up, age, and calendar year. A significant relationship between p24 antigenemia and death was nonsignificant after adjusting for CD4 cell count.

Reasons for modification and discontinuation of antiretrovirals: results from a single treatment centre.

OBJECTIVE: To describe the reasons for, and factors associated with, modification and discontinuation of highly active antiretroviral therapy (HAART) regimens at a single clinic. SUBJECTS: A total of 556 patients who started HAART at the Royal Free Hospital were included in analyses. Modification was defined as stopping or switching any antiretrovirals in the regimen, whereas discontinuation was defined as the simultaneous stopping of all antiretrovirals included in the initial regimen. Reasons were classified as immunological/virological failure (IVF) and toxicities and patient choice/poor compliance (TPC). RESULTS: The median CD4 count at starting HAART was 171 x 10(6) cells/l and viral load 5.07 log copies/ml. During a median follow-up of 14.2 months, 247 patients (44.4%) modified their HAART regimen, 72 due to IVF (29.1%) and 159 due to TPC (64.4%) and a total of 148 patients (26.6%) discontinued HAART. Older patients were less likely to modify HAART [relative hazard (RH), 0.73 per 10 years; P = 0.0008], as were previously treatment-naive patients (RH, 0.65; P = 0.0050), those in a clinical trial (RH, 0.64; P = 0.027) and those who started nelfinavir (RH, 0.57; P = 0.035). Patients who started with four or more drugs (RH, 2.21, P < 0.0001), who included ritonavir in the initial regimen (RH, 1.41; P = 0.035) or who had higher viral loads during follow-up (RH per log increase, 1.51; P < 0.0001) were more likely to modify HAART. CONCLUSIONS: There was a high rate of modification and discontinuation of HAART regimens in the first 12 months, particularly due to toxicities, patient choice or poor compliance.

The virological response to highly active antiretroviral therapy over the first 24 weeks of therapy according to the pre-therapy viral load and the weeks 4-8 viral load.

OBJECTIVES: To describe the viral response to HAART by weeks 4 and 8 in previously antiretroviral-naive patients. To assess whether the weeks 4 or 8 viral loads are useful predictors of viral suppression by week 24. DESIGN: A large clinical database including 453 antiretroviral-naive patients whose plasma viral load was monitored every 4 weeks. METHODS: Observed probabilities of achieving a viral load < or = 500 copies/ml by week 24 (days 84-168) from starting highly active antiretroviral therapy (HAART) were calculated according to viral loads at weeks 4 and 8. RESULTS: A total of 42.4% of patients (153/361) reached < or = 500 copies/ml viral load by week 4 and 70.4% (245/348) by week 8. Viral suppression below 500 copies/ml by 4-8 weeks was similar irrespective of the pre-HAART viral load. In patients with viral loads above 10000 copies/ml at week 4, 60.6% (20/33) achieved < or = 500 copies/ml by week 24. In patients with viral loads still above 10000 copies/ml at week 8, only 42.3% (11/26) achieved < or = 500 copies/ml by week 24, and only 33.3% (3/9) maintained viral suppression below 500 copies/ml to week 48. CONCLUSION: Viral loads at weeks 4 and 8 should be monitored to detect early signs of low subsequent viral suppression. For previously antiretroviral-naive patients whose viral loads after 8 weeks of HAART are still above 10000, there is an urgent need to assess adherence to therapy, drug levels and resistance, so management can be modified accordingly to reduce the rate of week 24 virological failure.

Serum level of soluble urokinase-type plasminogen activator receptor is a strong and independent predictor of survival in human immunodeficiency virus infection.

Human immunodeficiency virus-1 (HIV-1) infection has been shown to result in up-regulation of the urokinase-type plasminogen activator receptor (uPAR/CD87) on leukocytes in vitro and in vivo. The objective of this study was to investigate whether this up-regulation is paralleled by higher serum levels of soluble uPAR (suPAR) in patients with advanced HIV-1 disease and whether the serum level of suPAR is predictive of clinical outcome. Using an enzyme-linked immunosorbent assay, the level of suPAR was measured retrospectively in serum samples from 314 patients with HIV-1 infection. By Kaplan-Meier and Cox regression analyses, the serum suPAR levels were correlated to survival with AIDS-related death as the end point. High levels of serum suPAR (greater than median) were associated with poor overall survival, and Kaplan-Meier analysis on patients stratified by suPAR level demonstrated a continuous increase in mortality rates with higher suPAR levels. After adjustment for accepted prognostic markers-including Centers for Disease Control and Prevention-defined clinical stages, CD4 counts, viral load, beta2-microglobulin, and age-the prognostic strength of suPAR remained highly significant, indicating that the serum suPAR level is a novel, strong, and independent predictor of survival in HIV-1 infection. This report is the first to demonstrate an important association between the plasminogen activator system and disease progression in HIV-1 infection.

Plasma viral load concentrations in women and men from different exposure categories and with known duration of HIV infection. I.CO.N.A. Study Group.

CONTEXT: According to recent studies, women have lower plasma HIV RNA concentrations than men. However, these studies did not take into account the duration of HIV infection. OBJECTIVES: To analyze the relationship between viral load and gender among individuals with known date of seroconversion. SETTING: Sixty infectious disease clinics in Italy. DESIGN: Cross-sectional analysis of data collected at enrollment in a cohort study. PARTICIPANTS: Injecting drug users and heterosexual contacts naive to antiretroviral therapy at enrollment (245 men; 170 women). MAIN OUTCOME MEASURES: Plasma HIV RNA concentrations, measured using quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) or signal amplification b-DNA assays before antiretroviral therapy. RESULTS: Plasma HIV RNA concentrations were similar by age and exposure category (p =.80 and p =.39, respectively). Median viral load among women was roughly half that of men (p =.002). The association between viral load and gender remained significant after fitting a two-way analysis of variance (p =.03) and after adjusting for CD4 count, modality of HIV transmission, and age at enrollment in a regression model. Viral load was 0.27 log10 copies/ml (95% confidence interval, 0.05-0.40; p =.01) lower in women (i.e., 50% lower in the raw scale). CONCLUSIONS: Plasma HIV RNA concentrations were found to be lower among women, even when considering the duration of HIV infection. Compared with men, it is possible women should be given highly aggressive antiretroviral therapy at lower HIV-RNA concentrations.

Prognostic value of single measurements of beta-2-microglobulin, immunoglobulin A in HIV disease after controlling for CD4 lymphocyte counts and plasma HIV RNA levels.

The interrelationships between the CD4 lymphocyte count, plasma viral load [human immunodeficiency virus (HIV) RNA], beta-2-microglobulin (beta2-M) and immunoglobulin A (IgA) and the mortality risk was explored in 234 HIV-infected individuals (median CD4 count 230 cells/mm3, range 1-1,247). Product-moment correlation analysis was used to study the association between beta2-M, IgA and HIV RNA. A proportional hazards Cox model was used to estimate the relative hazard (RH) of death. Both beta2-M (r = 0.49, p < 0.0001) and IgA (r = 0.42, p < 0.0001) were positively correlated with HIV RNA. High beta2-M levels were associated with an increased risk of death in both univariate Cox analysis and after adjustment for HIV RNA, CD4 lymphocyte count and age [RH = 1.16 per 100 nmol/l higher beta2-M, 95% confidence interval (CI) 1.05-1.27]. Raised IgA levels were associated with shorter survival in individuals with a CD4 count above 50 cells/mm3 in univariate analysis as well as after adjusting for age and CD4 lymphocyte count (RH = 1.19 per 10 micromol/l higher IgA, 95% CI 1.01-1.39). However, this association was no longer significant after further adjusting for HIV RNA. In conclusion, beta2-M levels provided additional prognostic information for survival to the information obtained by CD4 count and HIV RNA levels, whereas serum IgA only was a weak prognostic marker in this fairly progressed cohort.

Insights into the reasons for discontinuation of the first highly active antiretroviral therapy (HAART) regimen in a cohort of antiretroviral naïve patients. I.CO.N.A. Study Group. Italian Cohort of Antiretroviral-Naïve Patients.

OBJECTIVE: To evaluate the frequency of discontinuation of the first highly active antiretroviral regimen (HAART) and the factors predictive of discontinuing for toxicity and failure in a population-based cohort of HIV-positive individuals in Italy, naïve from antiretrovirals at enrolment. METHODS: The study population consisted of individuals who initiated HAART and had at least one follow-up visit. The primary end-points were discontinuation of any component of HAART for drug toxicity and discontinuation for failure. Survival analyses were performed to identify predictive factors for reaching the two end-points. RESULTS: Eight hundred and sixty-two individuals initiated HAART; in 727 of them (84.3%) this consisted of two nucleoside reverse transcriptase inhibitors (NRTI) and one protease inhibitor (PI). Over a median follow-up of 45 weeks, 312 patients (36.2%) discontinued therapy: 182 (21.1%) discontinued due to toxicity, 44 (5.1%) due to failure. The probability of discontinuing HAART at 1 year was 25.5% [95% confidence interval (CI), 21.9-28.9] due to toxicity and 7.6% (95% CI, 4.9-1 0.3) due to failure. Independent factors associated with discontinuation for toxicity were: gender [relative hazard (RH) = 0.51; 95% CI, 0.32-0.80 for men versus women], type of treatment (indinavir-containing regimens, RH = 1.94; 95% CI, 1.10-3.41 and ritonavir-containing regimens, RH = 3.83; 95% CI, 2.09-7.03 versus hard-gell saquinavir) and time spent on treatment (RH = 0.89; 95% CI, 0.80-0.98 for each additional month). Discontinuation due to failure was independently associated with the most recent HIV-RNA (RH = 3.20; 95% CI, 1.74-5.88 for log10 copies/ml higher), and with type of treatment (indinavir-containing regimens, RH = 0.21; 95% CI, 0.06-0.78 and ritonavir-containing regimens, RH = 0.23; 95% CI, 0.04-1.26 versus hard-gell saquinavir). CONCLUSIONS: If the current HAART regimen caused no toxicity, less than 10% of naïve patients discontinue their first HAART regimen because of failure after 1 year from starting therapy.

Risk factors for HTLV-I and II in individuals attending a clinic for sexually transmitted diseases.

BACKGROUND: To date, few studies have provided information on risk factors for human t-lymphotropic viruses (HTLV) types I and II in European countries. In particular, few data are available from published studies conducted in STD centers. GOALS: To identify risk factors for HTLV-I and HTLV-II infection and to better distinguish the epidemiologic patterns of the two viruses in Italy. STUDY DESIGN: A cross-sectional study of individuals at high risk of sexually or parenterally transmitted infections attending a large STD center in an urban setting was conducted. Serologic tests for HTLV-I and II, HIV, hepatitis virus type B (HBV), hepatitis virus type C (HCV), and syphilis were performed. Information regarding at-risk behavior was collected using a specific questionnaire. RESULTS: From January 1994 to June 1996, 1,457 individuals were recruited; of them, 1,016 (69.7%) were males, 1,051 (72.4%) Italians, and 288 (19.8%) non-Europeans. One thousand seventy-five (74.8%) participants were noninjecting-drug-using heterosexuals, 285 (19.6%) were men who have sex with men, and 97 (6.6%) were injecting drug users (IDU). The mean age of the study participants was 33.6 (+/-10.5) years. Nine (0.6%) individuals were positive for HTLV-I antibodies and 9 (0.6%) for HTLV-II antibodies. The prevalence of HTLV-I among IDUs, men who have sex with men, and noninjecting-drug-using heterosexuals, was 2.1% (2/97), 1.4% (4/ 285), and 0.3% (3/1085), respectively. HTLV-II prevalence was 8.2% (8/97) among IDUs and 0.09% (1/1075) among noninjecting-drug-using heterosexuals. Among the nine HTLV-II-positive individuals, eight were Italian IDUs and one was a noninjecting-drug-using heterosexual man from India. None of the 285 men who have sex with men had HTLV-II antibodies. HTLV-infected individuals tended to be older than those who were uninfected. HTLV-I-infected individuals were more likely to be non-European and to have antibodies against Treponema pallidum. Injecting drug use tended to be independently associated with HTLV-II infection. CONCLUSIONS: The data suggest a role of sexual behavior in the spread of HTLV-I, which is more likely to be detected in individuals coming from endemic areas. Injecting drug use remains the most important risk factor for HTLV-II infection in Italy.

A practical guide to applying the intention-to-treat principle to clinical trials in HIV infection.

It is recommended that randomized controlled trials be analyzed on an intention-to-treat (ITT) basis whereby patients are analyzed in the group to which they were originally assigned, irrespective of the treatment actually received. However, in trials of antiretroviral therapy, it is quite common for patients to withdraw from the trial, and information on virological or immunological endpoints may not be available. The way in which this missing information is dealt with in the analysis can have a large effect on the results of a trial and, therefore, the principle of ITT may be adhered to more closely in some studies than in others. This article describes some simple approaches commonly taken to impute missing data values and discusses the possible effects of these approaches on the results of a trial.

The spectrum of AIDS-defining diseases: temporal trends in Italy prior to the use of highly active anti-retroviral therapies, 1982-1996.

OBJECTIVE: To evaluate time trends of the spectrum of AIDS-defining diseases in Italy, 1982-1996. METHODS: Surveillance data from the Italian National AIDS Registry were used to assess temporal patterns of all AIDS-defining diseases diagnosed among adults as of December 1996. Twenty-six initial clinical manifestations of AIDS were grouped into 12 categories. Relative frequencies were calculated by year of diagnosis and stratified by age, gender, HIV-exposure category, and CD4+ cell count. A multivariate polychotomous logistic model was used to estimate the proportions of each diagnostic category over time, adjusting simultaneously for the remaining diagnostic categories and for variables of interest. RESULTS: This analysis was based on 41772 diagnoses of AIDS-defining diseases among 36 638 reported cases. Mycoses represented the most frequent condition (27.3%), followed by Pneumocystis carinii pneumonia (PCP) (21.4%) and viral infections (8.9%). Cancers accounted for less than 10% of diseases. Downward trends were observed for mycoses, PCP (in the last part of the study period), Kaposi's sarcoma (KS), and non-Hodgkin's lymphomas (NHL). Upward trends were observed for mycobacterioses, and bacterial and protozoal infections. Brain toxoplasmosis increased up to 1994, and, thereafter, it appeared to decrease. These trends were less marked when the analysis was restricted to the diseases included in the pre- 1987 AIDS definition. Trends stratified by CD4+ cell count for the period 1990-1996 were substantially consistent with the above-reported results. CONCLUSIONS: The downward temporal trends in the most recent years of the study period for PCP and for brain toxoplasmosis are likely to be related to the use of prophylactic treatment. This analysis confirms a decline in KS but suggests that this was largely over by 1990.

Bulk culture levels of specific cytotoxic T-cell activity against HIV-1 proteins are not associated with risk of death.

The ability of cytotoxic T lymphocytes (CTL) to control and influence the outcome of human immunodeficiency virus (HIV) infection is not fully understood. The association between HIV-CTL activity and disease progression was evaluated prospectively in 36 HIV-1-infected individuals with a median follow-up of 3.0 years. HIV-CTL activity was measured in a 4 h Cr* release assay using autologous target cells expressing HIV-1 BRU isolate gene products (gp-120, gag, pol, nef) and a bulk culture of autologous effector cells. The CD4 count was measured at enrolment and plasma HIV RNA was measured retrospectively. The present study failed to support the hypothesis that HIV-CTL activity, as measured using the present method, is important in reducing the risk of death in HIV-infected individuals. However, using other approaches and methods could possibly yield other conclusions, and further prospective studies are needed to examine the relationship between CTL and disease progression.

The influence of nutritional and metabolic status on progression from asymptomatic HIV infection to AIDS-defining diagnosis.

BACKGROUND: Changes in body weight and lean tissue increase morbidity and mortality during AIDS; however there are few data on the effect of alterations in nutrition and metabolism on disease progression at earlier stages of HIV infection. OBJECTIVES: To assess whether change in weight, lean tissue or skeletal muscle affects progression to AIDS; to assess prospectively the effects of recognized alterations in nutrition and metabolism in asymptomatic HIV-seropositive men on disease progression; and to examine prospectively changes in nutrition and metabolism at AIDS-defining diagnosis. METHODS: A group of 104 asymptomatic HIV-seropositive men were recruited and prospectively examined at 3-monthly intervals between April 1993 and September 1995. Nutritional status and metabolism were examined using indirect calorimetry, dual energy X-ray absorptiometry and urine excretion of simple sugars. Time-fixed and time-dependent Cox's proportional hazard models were fitted to calculate risks of developing a first AIDS diagnosis, weight loss or death. RESULTS: During the study period, 31 subjects had a first AIDS diagnosis of whom 26 were fully assessed. Changes in nutrition and metabolism do not affect disease progression in asymptomatic HIV infection. However, subjects with a reduction in body weight and basal metabolic index tend to have a higher risk of progression to AIDS-defining diagnosis, independent of CD4 count. There is a significant decrease in all body tissue compartments, a decrease in excretion of urinary sugars and significant increase in resting energy expenditure and fat oxidation associated with a first AIDS diagnosis. CONCLUSION: Change in metabolic and nutritional status at the asymptomatic stage of HIV infection does not influence disease progression significantly, although there is a trend suggesting weight loss has an independent effect on outcome. There is a cachectic response to AIDS-defining opportunistic infection or tumour.

The changing pattern of admissions to a London hospital of patients with HIV: 1988-1997. Royal Free Centre for HIV Medicine.

OBJECTIVE: To describe the changes over time in incidence of hospital admissions among patients with HIV, reasons for hospital admission, duration of stay, relationship with CD4 T-cell count and with antiretroviral treatment. METHODS: The incidence of hospital admissions during each calendar year from 1988 to 1997 inclusive was calculated using a person-years analysis. In addition the proportion of patient follow-up spent in hospital and the impact of changing treatment regimens among all patients with HIV aged > or = 14 years and with at least one CD4 T-cell count seen at the Royal Free Hospital, London was also described. RESULTS: A total of 1806 patients were investigated with median follow-up of 21.1 months. Among all patients, the proportion of follow-up time spent as an in-patient decreased from 3.9% in 1988 to 1.3% in 1997 (P = 0.0015; test for trend). Hospital admissions for any cause peaked during 1989 at 72.0 per 100 patient years of follow-up (PYFU) and was 28.5 per 100 PYFU during 1997 (P < 0.0001; test for trend). There was a statistically significant decline in the proportion of follow-up time spent as an in-patient among patients with CD4 T-cell counts of < 50 x 10(6)/l from > 30% before 1990 to < 5% during 1997 (P = 0.026; test for trend). Hospital admissions varied greatly according to treatment regimen; in 1996 and 1997 just 0.1% of follow-up time of patients on triple antiretroviral treatment regimens was spent as a hospital admission. CONCLUSIONS: Admissions to hospital began falling before the introduction of combination therapy and declined strikingly during 1996 and 1997 following the introduction of highly active antiretroviral therapy. These results have important implications for future allocation of resources and for patient management.

CD4 lymphocyte count as a predictor of the duration of highly active antiretroviral therapy-induced suppression of human immunodeficiency virus load.

The association between CD4 cell count and duration of virus load suppression was investigated in 558 patients in the Frankfurt HIV Clinic Cohort who had begun highly active antiretroviral therapy and who had virus load declines to 500 copies/mL; P=.0001). Baseline virus load was not associated with virus load rebound. Lower baseline CD4 cell counts were associated with increased risk of viral rebound; however, this risk was significantly reduced in persons with low baseline CD4 cell counts who experienced substantial increases in CD4 cell counts during follow-up.

Increased losses of CD4+CD45RA+ cells in late stages of HIV infection is related to increased risk of death: evidence from a cohort of 347 HIV-infected individuals.

OBJECTIVE: To examine changes in the distribution of CD4+CD45RA+ (naive) and CD4+CD45RO+ (memory) lymphocytes in various stages of HIV infection and the effect of these changes on disease progression. DESIGN AND METHODS: Expression of CD45RA+ and CD45RO+ on CD4+ lymphocytes was analysed by flow cytometry in a prospectively followed cohort of 300 HIV-infected individuals (median follow-up time, 2.90 years; range, 0.02-4.54 years) and in a group of 102 age- and sex-matched uninfected controls. Survival analysis was performed considering AIDS development and death as endpoints. RESULTS: The median CD4+CD45RA+/CD45RO+ ratio was 1.3 (25-75% quartiles, 0.9-2.4) in controls; it was increased to 1.8 (1.1-2.5) in 40 HIV-infected individuals with CD4+ cell counts > 500 x 10(6)/l (P < 0.05); it was similar at 1.4 (0.8-2.0) in 106 HIV-infected individuals with CD4+ cell counts of 200-500 x 10(6)/l; and it was decreased to 0.9 (0.5-1.4) in 154 HIV-infected individuals with CD4+ cell counts < 200 x 10(6)/l (P < 10[-6]). When fitted in a Cox model adjusting for the total number of CD4+ cells and age a lower concentration of CD4+CD45RA+ cells was associated with an increased risk of dying. The concentration of CD4+CD45RO+ cells was not significantly associated with AIDS or death in age- and CD4+ cell count-adjusted Cox models. CONCLUSIONS: This study confirms a selective loss of memory CD4+ cells early in HIV infection followed by increased loss of naive CD4+ cells in later stages of the infection. The loss of naive CD4+ cells seems to be important in the pathogenesis of terminal HIV infection.

Incidence and determinants of hepatitis C virus infection among individuals at risk of sexually transmitted diseases attending a human immunodeficiency virus type 1 testing program.

BACKGROUND: The role of sexual transmission of hepatitis C virus (HCV) infection is still not completely understood, partly because of the lack of longitudinal studies among cohorts of HCV-negative individuals who engage in at-risk sexual behavior. GOALS: To evaluate the incidence of HCV infection in a population at risk for human immunodeficiency virus type 1 (HIV-1) infection and other sexually transmitted diseases (STD) and to identify factors associated with HCV seroconversion. STUDY DESIGN: A retrospective longitudinal study was carried out on a cohort of consecutive attendees of a voluntary HIV-1 testing and counseling program in a large STD center in Rome. All individuals undergoing at least two consecutive tests for HCV antibodies were enrolled. Clinical data and information on individual behavior were collected for all study participants. RESULTS: Between June, 1992 and December, 1994, a total of 709 individuals (12 intravenous drug users [IDU], 244 homosexuals, and 453 heterosexual non-IDUs), initially negative for HCV antibody, were tested more than once. Among these individuals, 15 HCV seroconversions occurred. The average follow-up time was 1.25 person/years (p/y) for an incidence rate of 1.69 per 100 p/y. The incidence rates by exposure category were 39.30 per 100 p/y among IDUs, 1.37 per 100 p/y among homosexual men, and 0.97 per 100 p/y among heterosexual non-IDUs. Excluding IDUs, of the 697 STD clinic attendees engaging in at-risk sexual behavior, HIV-1-positive status tended to be associated with HCV seroconversion (relative hazard = 5.48; 95% confidence interval = 0.85-35.40). The HCV crude incidence rates among HIV-1-infected patients at enrollment was 11.5%, 4.2%, and 2.4% in those with severe, moderate, and mild levels of immunosuppression, respectively (chi-square for trend = 2.38, P = 0.1). CONCLUSIONS: In this cohort, HCV infection was confirmed to be strongly associated with intravenous drug use. Nonetheless, the occurrence of two thirds of the total HCV seroconversions in non-IDU individuals engaging in at-risk behavior suggests a role of sexual practices in the transmission of the infection. Among non-IDU individuals, the risk for development of HCV infection tended to increase in those who were HIV-1 infected.

Is there a general tendency for CD4 lymphocyte decline to speed up during human immunodeficiency virus infection? Evidence from the Italian Seroconversion Study.

It has been suggested that the rate of CD4 cell decline accelerates in parallel with decreasing numbers of cells; however, the statistical literature suggests the opposite. CD4 cells were counted about every 6 months in a cohort of 1264 human immunodeficiency virus-infected subjects (the Italian Seroconversion Study cohort). Kaplan-Meier analysis was used to estimate the time for CD4 cells to decline by 100 cells/mm3, conditional on reaching predefined levels. In addition, CD4 cell counts were modeled as a function of time since seroconversion in individuals with > or = 5 counts. Kaplan-Meier survival times for a 100 cell/mm3 decrease in CD4 cells increased as lower counts were reached (log rank test, P < .001). The shape of the overall fitted curve of the CD4 cell counts does not suggest an increasing rate of decline. Data from the Italian Seroconversion Study cohort do not show a general tendency for accelerating CD4 cell decline in association with lower counts.

Energy balance in asymptomatic HIV infection.

OBJECTIVES: Body weight is regulated by the balance between energy intake and energy expenditure, but the influence of HIV infection on energy balance has not been fully examined. The main objectives of this study were (1) to assess the effect of HIV on energy balance, (2) to examine the relationship of parameters of immunodeficiency to energy balance, and (3) to examine the interrelationship of different components of energy balance in asymptomatic HIV-seropositive men. DESIGN: A cross-sectional study of nutrition and metabolism in asymptomatic HIV-seropositive men METHODS: Components of energy balance were examined in 104 asymptomatic HIV-seropositive men (CD4 count 4-482 x 10(6)/l) and 57 age-matched HIV-seronegative male controls. Energy and protein intake were measured using 5-day diaries, and small bowel absorption and permeability was assessed using four sugar probes. Resting energy expenditure was calculated from indirect calorimetry and nitrogen loss estimated from 24 h urine collection. Four methods were used to assess the effect of HIV infection on body composition (anthropometry, dual energy X-ray absorptiometry, bioelectrical impedance and 24 h urine creatinine). RESULTS: Resting energy expenditure per kilogram of fat-free mass was raised (P < 0.0001), fat mass was decreased (P = 0.001), fat-free mass was increased (P = 0.05), energy intake was higher (P = 0.05), absorption of L-rhamnose (P = 0.01) and 3-O-methyl-D-glucose was decreased (P = 0.003), and small bowel permeability was increased (P < 0.0001) in HIV-seropositive men compared with HIV-seronegative controls. HIV-seropositive subjects with a CD4 count less than 100 x 10(6)/l had decreased absorption of L-rhamnose (P < 0.05), D-xylose (P < 0.05) and 3-O-methyl-D glucose (P < 0.05) compared with HIV-seropositive subjects at higher CD4 counts, and had a similar resting energy expenditure to HIV-seronegative controls. Protein intake, carbohydrate, fat and protein oxidation. 24 h nitrogen excretion and appendicular muscle mass were similar in HIV-seropositive men and controls. CONCLUSION: HIV infection exerts a direct effect on parameters of energy balance that varies with the severity of immunosuppression.

Category of exposure to HIV and age in the progression to AIDS: longitudinal study of 1199 people with known dates of seroconversion. HIV Italian Seroconversion Study Group.

OBJECTIVES: To determine whether rate of development of AIDS is affected by category of exposure to HIV and whether the more rapid development found in older subjects persists for each exposure category. DESIGN: Longitudinal study of people with known date of seroconversion to HIV. SETTING: 16 HIV treatment centres throughout Italy. SUBJECTS: 1199 people infected with HIV through use of injected drugs, homosexual sex, or heterosexual sex. MAIN OUTCOME MEASURES: AIDS as defined by 1987 definition of Centers for Disease Control (including and excluding neoplasms) and by 1993 European definition. RESULTS: 225 subjects (18.8%) progressed to AIDS (Centers for Disease Control 1987 definition) during median follow up of 5.8 years. Univariate analyses showed more rapid progression to AIDS for older subjects compared with younger subjects and for homosexual men compared with other exposure categories. The age effect was of similar size in each exposure category and in men and women. In a bivariate model with age and exposure categories simultaneously included as covariates, differences by exposure category disappeared for use of injected drugs and heterosexual sex compared with homosexual sex (relative hazards 1.02 (95% confidence interval 0.71 to 1.45) and 1.07 (0.70 to 1.64) respectively), while the age effect remained (relative hazard 1.55 (1.32 to 1.83) for 10 year increase in age). Analyses using the other definitions for AIDS did not appreciably change these results. CONCLUSIONS: There was no evidence of differences in rate of development of AIDS by exposure category, while there was a strong tendency for more rapid development in older subjects for all three groups. This supports the view that external cofactors do not play major role in AIDS pathogenesis but that age is of fundamental importance.