Effect of ribavirin on intracellular and plasma pharmacokinetics of nucleoside reverse transcriptase inhibitors in patients with human immunodeficiency virus-hepatitis C virus coinfection: results of a randomized clinical study.

The intracellular triphosphorylation and plasma pharmacokinetics of lamivudine (3TC), stavudine (d4T), and zidovudine (ZDV) were assessed in a pharmacokinetic substudy, in 56 human immunodeficiency virus-hepatitis C virus (HIV-HCV) coinfected patients receiving peginterferon alfa-2a (40KD) 180 microg/week plus either placebo or ribavirin (RBV) 800 mg/day in the AIDS PEGASYS Ribavirin International Coinfection Trial. There were no significant differences between patients treated with RBV and placebo in plasma pharmacokinetics parameters for the nucleoside reverse transcriptase inhibitors (NRTIs) at steady state (weeks 8 to 12): ratios of least squares mean of area under the plasma concentration-time curve (AUC(0-12 h)) were 1.17 (95% confidence interval, 0.91 to 1.51) for 3TC, 1.44 (95% confidence interval, 0.58 to 3.60) for d4T and 0.85 (95% confidence interval, 0.50 to 1.45) for ZDV, and ratios of least squares mean plasma C(max) were 1.33 (95% confidence interval, 0.99 to 1.78), 1.06 (95% confidence interval, 0.68 to 1.65), and 0.84 (95% confidence interval, 0.46 to 1.53), respectively. Concentrations of NRTI triphosphate (TP) metabolites in relation to those of the triphosphates of endogenous deoxythymidine-triphosphate (dTTP) and deoxcytidine-triphosphate (dCTP) were similar in the RBV and placebo groups. Differences (RBV to placebo) in least squares mean ratios of AUC(0-12 h) at steady state were 0.274 (95% confidence interval, -0.37 to 0.91) for 3TC-TP:dCTP, 0.009 (95% confidence interval, -0.06 to 0.08) for d4T-TP:dTTP, and -0.081 (95% confidence interval, -0.40 to 0.24) for ZDV-TP:dTTP. RBV did not adversely affect HIV-1 replication. In summary, RBV 800 mg/day administered in combination with peginterferon alfa-2a (40KD) does not significantly affect the intracellular phosphorylation or plasma pharmacokinetics of 3TC, d4T, and ZDV in HIV-HCV-coinfected patients.

Testicular atrophy in 80 HIV-positive patients: a multivariate statistical analysis.

This retrospective study of risk factors for testicular atrophy in HIV-infected men investigates the relationship between complications of AIDS such as wasting or opportunistic illness and testicular atrophy. Microscopic sections of the right testis were evaluated for testicular atrophy by assessing the mean score in each of 80 selected HIV-infected patients who underwent an autopsy during a one-year period. A significant association was observed between testicular atrophy and body mass index (BMI) (P=0.0496). Thus, underweight patients with HIV infection were 3.52 times more likely to have testicular atrophy than those with acceptable body weight. Other significant associations between other variables were not found.

Antiretroviral prescribing patterns in the Texas prison system.

Although the prevalence of human immunodeficiency virus (HIV) infection among prison inmates is reported to be high, little is known about anti-HIV treatment patterns in correctional institutions. The present study assessed antiretroviral prescribing patterns for 2360 Texas Department of Criminal Justice (TDCJ) inmates infected with HIV. In 1998, 66.8% of all TDCJ inmates infected with HIV who had CD4 lymphocyte counts < 500 cells/mm(3) were treated with highly active antiretroviral therapy (HAART). However, no substantial differences in the use of HAART were exhibited according to the sociodemographic factors under study. While the majority of inmates receiving HAART in 1998 were prescribed a combination of 2 nucleoside reverse transcriptase inhibitors (NRTIs) and 1 protease inhibitor, 11.2% were prescribed a combination of 2 NRTIs and 1 non-NRTI. In view of the elevated rate of HIV infection in correctional settings, it will be important to continue to document the pharmacotherapy patterns among prison inmates, both during and following incarceration.

Antiretroviral prescribing patterns in the texas prison system.

PURPOSE: Although prison inmates are reported to exhibit substantially elevated rates of HIV infection, little is known about HIV treatment patterns, particularly pharmacotherapy, in correctional institutions. The purpose of the present study, therefore, was to describe antiretroviral prescribing patterns in one of the nation's largest prison populations.METHODS: The study population consisted of all known (n = 2,360) HIV-infected inmates incarcerated in the Texas prison system in 1998. Information on medical conditions, sociodemographic factors, and pharmacotherapy was obtained from an institution-wide medical information system. Inmates who received more than one type of pharmacotherapy in 1998 were included in the appropriate number of categories.RESULTS: In 1998, 66.8 percent (95% CI = 64.0-69.4) of all HIV-infected inmates with CD4 counts below 500 were treated with highly active antiretroviral therapy (HAART); and 31.1 percent (95% CI = 29.3-33.0) were given no antiretroviral therapy. Logistic regression results showed that HAART treatment decreased monotonically as a function of patient CD4 count category.CONCLUSIONS: A substantial proportion of HIV-infected TDCJ inmates were placed on therapies that were not consistent with the generally recommended DHHS guidelines for their disease stage. It will be important to for future investigations to assess whether such patterns continue to exist among prison populations, and to assess the determinants of these patterns.

Highly active antiretroviral therapy improves survival of HIV-infected hemodialysis patients.

Human immunodeficiency virus (HIV)-infected hemodialysis (HD) patients have a very high morbidity and mortality. Reports from the last few years have suggested that highly active antiretroviral therapy (HAART) has remarkably improved the survival of HIV-infected patients. To determine whether the beneficial effects of HAART have also extended to HIV-infected HD patients, we retrospectively evaluated the survival of all HIV-infected patients who underwent chronic maintenance HD between 1992 and 1999 at our institution. Twenty-two HIV-infected patients were started on chronic maintenance HD at our institute during this period. The mean age of the patients was 36 +/- 9 (SD) years (range, 21 to 58 years). Seven patients were treated with only one or two antiretroviral drugs (patients 1 and 5 were administered two antiretroviral drugs), and the remaining 15 patients were treated with HAART (three antiretroviral drugs or more). Fifty-seven percent (4 of 7 patients) of the patients on suboptimal therapy died after a mean time on HD therapy of 13 +/- 10 months compared with only 20% (3 of 15 patients) of those on HAART after a mean period on HD therapy of 28 +/- 17 months. Plasma viral load was significantly less in patients on HAART compared with patients on suboptimal therapy (3.35 +/- 0.92 versus 4.63 +/- 1.3 log(10) copies/mL; P = 0.03). Patients with diagnoses other then HIV-associated nephropathy and those on HAART had statistically longer survival times (P = 0.02 and P = 0.04, respectively). We conclude that HAART is successful in suppressing viral load in HIV-infected HD patients, and the survival of HIV-infected HD patients on HAART is better than that of patients on suboptimal antiretroviral therapy.

Prevalence of HIV-associated nephropathy in autopsies of HIV-infected patients.

Previous studies have reported that approximately 10% of the patients with human immunodeficiency virus (HIV) infection develop HIV-associated nephropathy (HIVAN). However, over the last decade, morbidity and mortality as a result of HIV-1 infection has remarkably decreased with the availability of potent new antiretroviral drugs. We therefore determined the prevalence of HIVAN from autopsy data of HIV-infected patients in more recent years (1992 to 1997). Autopsy reports of 389 patients were reviewed. In reports suggestive of possible HIVAN, slides of renal tissue were retrieved and reviewed again to ensure appropriate classification. The criteria for the diagnosis of HIVAN were focal segmental glomerulosclerosis with collapse of the glomerular tuft in some glomeruli, extensive tubular ectasia, and significant tubulointerstitial disease. Of 389 autopsy reports, 54% of the patients were black, 35% were white, and 11% were Hispanic. Thirty-three percent of the patients had a history of intravenous drug abuse. The mean CD4 count of the patients was 54 +/- 91/microL (mean +/- SD). In 27 cases, typical features of HIVAN were found based on the criteria used, accounting for an overall HIVAN prevalence of 6.9% (27 of 389 autopsies). Because the overwhelming majority of these patients were black (93%), the prevalence in blacks was 12% (25 of 209 autopsies). We conclude that although mortality and morbidity from HIV infection is decreasing, HIVAN remains an important complication of HIV infection in blacks, even in recent years.

Immunologic predictors of HIV-related survival among Texas prison inmates.

Research indicates that being incarcerated adversely affects overall health status. Because HIV-infection is a growing problem among the U.S. prison population, understanding how incarceration affects HIV-related survival holds particular clinical and public health relevance. Moreover, while the prognostic roles of CD4 and CD8 lymphocyte count have been well documented in noninstitutionalized populations, little is known about how these factors operate to predict survival among prison populations. The present study examined immunologic determinants of HIV-related survival in a cohort of 752 Texas Department of Criminal Justice (TDCJ) inmates who were treated for HIV/AIDS between 1993 and 1996 at a large south-western medical center. Survival analysis using proportional hazards modeling showed that: (1) the prognostic role of CD4 count among inmates was similar to previous findings among non-incarcerated populations; (2) the prognostic role of CD8 count was slightly weaker than that previously reported for non-incarcerated populations; and (3) inmates who exhibited high levels of both CD4 and CD8 count had a survival advantage over those who had a high score on only one of the two factors.

Role of maternal antibody in natural infection of Peromyscus maniculatus with Sin Nombre virus.

Data from naturally infected deer mice (Peromyscus maniculatus) were used to investigate vertical transmission of Sin Nombre virus (SNV) and SNV-specific antibody. The antibody prevalence in juvenile mice (14 g or less) was inversely proportional to the mass of the animal, with juvenile deer mice weighing less than 11 g most likely to be antibody positive (26.9%) and juvenile mice weighing between 13 and 14 g least likely to be antibody positive (12.9%). Although a significant sex bias in seropositivity was detected in adult deer mice, no significant sex bias in seropositivity was detected in juvenile animals. Ten juvenile deer mice were identified that had initially tested positive for SNV-specific immunoglobulin G (IgG) by enzyme-linked immunosorbent assay (ELISA) but had subsequently tested negative when recaptured as adults. SNV RNA was detected by reverse transcriptase PCR (RT-PCR) in the blood of ELISA-positive adult deer mice but not in the blood of ELISA-positive juveniles. One of the juvenile mice initially tested negative for SNV RNA but later tested positive when recaptured as an ELISA-positive adult. The RT-PCR results for that individual correlated with the disappearance and then reappearance of SNV-specific IgG, indicating that the presence of SNV RNA at later time points was due to infection with SNV via horizontal transmission. SNV-specific antibody present in both ELISA-positive juvenile and adult mice was capable of neutralizing SNV. Additionally, our data indicate that SNV is not transmitted vertically.

Is the prevalence of HIV-associated nephropathy decreasing?

Initial reports have suggested that approximately 10% of patients with HIV-infection develop HIV-associated nephropathy (HIVAN). It has also been predicted that by the end of the decade, HIVAN is likely to become a third leading cause of end-stage renal disease (ESRD) in African-Americans between the ages of 20-64 years. As the morbidity and mortality from HIV-infection has decreased in the last few years, it is possible that prevalence of HIVAN is also changing. We therefore screened HIV-1-infected patients followed in our hospital for HIVAN. A screening urinalysis was performed in 557 HIV-1-infected adult patients between March and May 1998. Of these, 252 were outpatients and 305 were Texas Department of Criminal Justice inmates (TDCJI). Demographic and laboratory data of these patients was obtained from the HIV patients' database. Fifty percent of the patients were African-American, 36.6% were Caucasian and 12. 7% were Hispanic. The mean age of patients was 37 +/- 8 years. Seventy-nine percent of the patients were males and a history of intravenous drug abuse (IVDA) was present in 28%. Twenty-three percent of the patients were concomitantly infected with hepatitis C virus, 4.1% were positive for hepatitis B surface antigen, and rapid plasma reagin test for syphilis was positive in 9.1%. In 38 patients who had more than 100 mg/dl (2+) proteins on screening urinalysis, total urinary proteins were quantitated by collecting 24 h urine specimens. Fifteen of these patients had urinary proteins more than 1.5 g/day (12 patients >3.5 g/24 h and 3 patients >1.5 g/24 h). A renal biopsy was done in 14 of these patients and clinical diagnosis of HIVAN was made in one patient who refused biopsy. Renal biopsies revealed HIVAN [9], diabetic nephropathy [2], membranoproliferative glomerulonephritis [2], Fibrillary glomerulonephritis [1]. All 10 patients (5 TDCJI and 5 outpatients) with HIVAN were African-American. Two of these 10 patients had a history of IVDA and another two were concomitantly infected with hepatitis C virus. The plasma viral load (Pvl) and total CD4 count was not different in patients with or without HIVAN [(Pvl log 10.05 +/- 1.39 vs. 9.9 +/- 2.18 copies/ml, p = 0.78) (CD4: 187 +/- 192 vs. 288 +/- 249 cells/microl, p = 1.17) mean +/- SD]. We conclude that in our HIV-infected population HIVAN exclusively affected African-Americans and the prevalence in them was 3.5%.

Immunological predictors of HIV-related survival.

While the prognostic role of CD4 lymphocyte count is well established, little is known about how other immunological factors are associated with HIV-related survivorship. CD8 lymphocyte count is reported to inhibit growth of HIV in vitro and to deter the development of cytomeglovirus infections. Scarce information exists, however, on its association with HIV-related survivorship. The objective of the present study therefore was to assess whether survival estimation could be improved by including CD8 lymphocyte count as a prognostic factor. The study sample consisted of 904 adult HIV-infected patients who were treated between 1992 and 1997 at a large southwestern academic medical centre in the US. Survival analysis using proportional hazards modelling showed that baseline CD4 lymphocyte was highly and positively predictive of HIV-related survival. By contrast, baseline CD8 count was not predictive of survival in the study cohort. While the interaction between CD4 and CD8 was not statistically significant in the present study sample, decomposition of this effect indicates that these factors may operate synergistically to predict survival. In conclusion, these findings suggest that clinicians may improve their prognostic accuracy by relying on both CD4 and CD8 lymphocyte counts rather than relying exclusively on CD4 counts.

Determinants of survival in HIV-positive patients.

Variation in the clinical stage at which AIDS is diagnosed has hindered the ability of investigators to generate survival estimates which are stable across study cohorts. As a result, little is known about how clinical and sociodemographic factors are associated with survival, independent of AIDS diagnosis stage. By estimating survival following seroconversion while adjusting for baseline CD4 lymphocyte count, the present study generated survival determinants which were unconfounded by time-related changes in AIDS diagnosis. This study's findings indicate that the following factors were associated with significant decreases in HIV-related survival: older age; self-report of no known HIV transmission risk factors; and presence of cytomegalovirus, Mycobacterium avium complex, and Pneumocystis carinii pneumonia. Furthermore, survival decreased in a monotonic fashion with decreases in baseline CD4 count and with increases in calendar period. While this study's findings are consistent with previous investigators' reports of AIDS survival determinants, it will be important for future investigators to refine and update estimates of HIV-related survival determinants as clinical care for HIV-infected patients continues to improve.

Risk factors for colonization or infection due to methicillin-resistant Staphylococcus aureus in HIV-positive patients: a retrospective case-control study.

OBJECTIVE: To determine the risk factors for colonization or infection with methicillin-resistant Staphylococcus aureus in human immunodeficiency virus (HIV)-infected patients. DESIGN: Retrospective matched-pair case-control study. SETTING: Continuity clinic and inpatient HIV service of a university medical center. POPULATION: Patients with HIV infection from the general population of eastern and coastal Texas and from the Texas Department of Criminal Justice. DATA COLLECTION: Patient charts and the AIDS Care and Clinical Research Program Database were reviewed for the following: age, race, number of admissions, total hospital days, presence of a central venous catheter, serum albumin, total white blood cell count and absolute neutrophil count, invasive or surgical procedures, any cultures positive for S. aureus, and a history of opportunistic illnesses, diabetes, or dermatologic diagnoses. Data also were collected on the administration of antibiotics, antiretroviral therapy, steroids, cancer chemotherapy, and subcutaneous medications. RESULTS: In the univariate analysis, the presence of a central venous catheter, an underlying dermatologic disease, lower serum albumin, prior steroid therapy, and prior antibiotic therapy, particularly antistaphylococcal therapy or multiple courses of antibiotics, were associated with increased risk for colonization or infection with methicillin-resistant S. aureus. Multivariate analysis yielded a model that included presence of a central venous catheter, underlying dermatologic disease, broad-spectrum antibiotic exposure, and number of hospital days as independent risk factors for colonization or infection with methicillin-resistant S. aureus. CONCLUSIONS: In our HIV-infected patient population, prior hospitalization, exposure to broad-spectrum antibiotics, presence of a central venous catheter, and dermatologic disease were risk factors for acquisition of methicillin-resistant S. aureus.

Determinants of HIV-related survival among Texas prison inmates.

Research indicates that being incarcerated adversely affects disease progression and overall health status. Because HIV infection is a growing problem among prison populations in the United States, understanding how incarceration affects HIV-related survival patterns is critical. The present study examined determinants of HIV-related survival in a cohort of 2380 Texas Department of Criminal Justice (TDCJ) inmates who were treated for HIV/AIDS, dating from January 1, 1992 and June 31, 1997. Assessment of the study factors indicated that there were no substantial violations of the assumptions of the Cox's proportional hazards (PH) model in the present study population. Furthermore, to address the potential problem of censoring-related bias, mortality information was collected on all inmates who were paroled on the basis of disease status. The present study's findings indicate that the following factors were associated with significant decreases in HIV-related survival in the TDCJ prison population: male gender, older age, self-report of no known HIV transmission risk factors, and presence of cytomegalovirus (CMV), Mycobacterium avium complex (MAC), and Pneumocystis carinii pneumonia. Moreover, survival decreased in a monotonic fashion with decrease in baseline CD4 count. While the majority of the present study's findings were consistent with those reported for non-incarcerated populations, it will be important for investigators to assess whether these findings persist among future cohorts of prison inmates.

Temporal trends in AIDS-related survival.

Although research indicates that AIDS-related survival has improved over calendar time, studies of temporal AIDS-related survival patterns are often confounded by the stage of AIDS diagnosis. The objective of the present study was therefore to assess temporal trends in AIDS-related survival from clinical indicators other than point of AIDS diagnosis. The study sample consisted of 2126 adult HIV-positive patients who were treated between 1987 and 1996 at a large southwestern academic medical center. Proportional hazards analyses indicate that survival from each of the following clinical baselines improved in a linear fashion over calendar period: first CD4 count, first CD4 count of 200 or greater, first CD4 count less than 200, and diagnosis of Pneumocystis carinii pneumonia, cytomegalovirus, and Mycobacterium avium complex. These findings indicate that previously estimated survival trajectories have persisted through the mid-1990s, even when defining survival from clinical indicators other than AIDS diagnosis.

Characterization of La Crosse virus RNA in autopsied central nervous system tissues.

A reverse transcription-PCR (RT-PCR) technique was used to detect La Crosse (LAC) virus RNA in the central nervous system (CNS) tissues of two patients who died of LAC encephalitis in 1960 and 1978. Viral RNA was readily detected by RT-PCR although the tissues had been stored frozen for up to 37 years. LAC virus was detected in the cerebral cortex but not in other CNS tissues. RT-PCR allowed detection of replicative forms of the virus, indicating that the virus was actively replicating in the specific CNS tissues. The small (S) RNA segments of the viruses from the CNS samples were demonstrated to be genetically similar by single-strand conformation polymorphism analyses. These S RNA segments were then sequenced; only two base changes were demonstrated between the 1960 and the 1978 samples, suggesting that LAC virus is genetically stable in areas of endemicity. The RT-PCR analyses of analyte directly from CNS tissues allows study of the virus without passage in cell culture.

Mycobacterium kansasii osteomyelitis presenting as a solitary lytic lesion of the ulna: fine-needle aspiration findings and morphologic comparison with other mycobacteria.

A 35-yr-old woman, with acquired immunodeficiency syndrome, presented with right arm pain, erythema, and swelling. A lytic lesion of the ulna was found by radiograph. Ultrasonic and fluoroscopic guided fine-needle aspiration (FNA) yielded a neutrophilic and histiocytic exudate admixed with abundant long, bacillary forms that appeared as negative images on Papanicolaou stain and as very coarsely beaded acid-fast bacilli, resembling candy canes, on Kinyoun stain. These morphologic features permitted a preliminary diagnosis of mycobacteriosis, possibly of M. kansasii (MK) etiology. Appropriate therapy was initiated and resulted in not only marked symptomatic improvement of osteomyelitis and cellulitis, but resolution of chronic pulmonary infiltrates, presumed to be caused by fibrosis. Culture confirmed MK infection 3 wk after FNA. MK is one of the few mycobacteria that has a sufficiently characteristic morphology to permit presumptive diagnosis by smear. Culture, however, still remains the definitive method of speciation.

Sorivudine versus acyclovir for treatment of dermatomal herpes zoster in human immunodeficiency virus-infected patients: results from a randomized, controlled clinical trial. Collaborative Antiviral Study Group/AIDS Clinical Trials Group, Herpes Zoster Study Group.

The present randomized, double-blind, placebo-controlled, multicenter clinical trial was designed to compare the efficacy and tolerability of sorivudine [1-beta-D-arabinofuranosyl-E-(2-bromovinyl)uracil] and acyclovir for the treatment of dermatomal herpes zoster in human immunodeficiency virus (HIV)-seropositive patients. A total of 170 HIV-seropositive adults presenting with herpes zoster (confirmed by direct fluorescent-antigen testing and/or viral culture) were enrolled and randomized to receive a 10-day course of orally administered sorivudine (40 mg once daily plus acyclovir placebos) or acyclovir (800 mg five times daily plus sorivudine placebo). Patients were monitored daily to document the events of cutaneous healing, pain, zoster-related complications, and drug-related adverse events. Patients were reassessed on days 21 and 28 and then once monthly for 1 year. The primary efficacy endpoint was time to the cessation of new vesicle formation. Secondary efficacy endpoints included times to other events of cutaneous healing, resolution of pain, and frequency of dissemination and zoster recurrence. In a multivariate analysis, sorivudine was superior to acyclovir for reducing the times to the cessation of new vesicle formation (relative risk [RR] = 1.54, 95% confidence interval [CI] = 1.00 to 2.36; P = 0.049) and total lesion crusting (RR = 1.48, 95% CI = 1.07 to 2.04; P = 0.017). In a univariate analysis, there was a trend favoring sorivudine for the cessation of new vesicle formation (median of 3 versus 4 days; P = 0.07) and a significant advantage for time to total lesion crusting (median of 7 versus 8 days; P = 0.02). The time to the resolution of zoster-associated pain, the frequency of dissemination, and the frequency of zoster recurrence were not different between the two treatment groups. Both drugs were well tolerated. Sorivudine is an effective drug for the treatment of herpes zoster in HIV-infected patients and results in accelerated cutaneous healing when compared with acyclovir therapy.

Pulmonary lymphomatoid granulomatosis in acquired immunodeficiency syndrome: lesions with Epstein-Barr virus infection.

We report the clinicopathologic characteristics of pulmonary lymphomatoid granulomatosis (LYG) in 11 patients (identified from a series of 330 consecutive patients who underwent autopsy between 1984 and 1995 at the University of Texas Medical Branch at Galveston, Texas) with a diagnosis of acquired immunodeficiency syndrome (AIDS). We used immunohistochemical stains, RNA in situ hybridization (ISH), and gene rearrangement studies to identify the immunophenotype and the presence or absence of Epstein-Barr virus (EBV) infection. All of the patients were men ranging in age from 27 to 65 years (mean age, 38.6 yr). Autopsy lungs of 21 age-matched controls were examined for EBV using ISH; these included 9 patients with AIDS who did not have pulmonary lesions and 12 HIV-negative individuals who died accidentally (mean age, 38.6 yr). All of the 11 pulmonary lesions showed the gross and microscopic characteristics of LYG, with zonal necrosis and prominent angioinvasion. The tumor nodules consisted of a mixture of atypical large lymphocytes, with vesicular nuclei and prominent nucleoli and with a background of small and intermediate-size lymphocytes, histiocytes, and plasma cells. The large lymphocytes were CD20 positive, consistent with a B-cell phenotype. Ten of the 11 cases demonstrated EBV1-encoded RNA and CD20 positivity in the large, atypical lymphocytes by double labeling. One patient showed EBV positivity in CD20-negative, CD45RO-positive large cells, but these cells were CD3 negative and showed a monoclonal heavy chain gene rearrangement by polymerase chain reaction, indicating that these were of B-cell origin. Aberrant CD43 coexpression was identified in four cases. EBV latent membrane protein was demonstrated in 9 of 11 cases by immunohistochemical stains. The lungs of all of the 21 control patients were negative for EBV by ISH. We conclude that, in our series, AIDS-associated LYG is a B-cell neoplasm and that it has a strong association with EBV infection.

A randomized, placebo-controlled study of the immunogenicity of human immunodeficiency virus (HIV) rgp160 vaccine in HIV-infected subjects with > or = 400/mm3 CD4 T lymphocytes (AIDS Clinical Trials Group Protocol 137).

Immune responses provoked by human immunodeficiency virus (HIV) infection ultimately are insufficient to control the disease and do not include strong lymphocyte-proliferative responses to HIV antigens or antibodies to many viral epitopes. A randomized double-blind, placebo-controlled trial evaluated the immunogenicity of recombinant HIV envelope vaccine (rgp160) in HIV-infected subjects with > or = 400/mm3 CD4 T cells. Controls received hepatitis B vaccine. Of subjects receiving rgp160, 98% developed lymphocyte-proliferative responses to the immunogen, 33% to a different envelope protein, and 56% and 60% to p24 and p66, respectively. All doses of vaccine (20, 80, 320, 1280 microgram) induced new responses. New antibodies to epitopes on rgp160 developed only in recipients of higher doses of rgp160. CD4 T cell percentages declined less rapidly in recipients of rgp160 than in controls. Vaccination of HIV-infected subjects with rgp160 results in cellular and humoral immune responses to HIV that infection itself had not stimulated.

Massive hepatic steatosis and lactic acidosis in a patient with AIDS who was receiving zidovudine.

Massive steatosis has recently been described among a few human immunodeficiency virus-seropositive patients who were receiving antiretroviral therapy. Although clinical and light-microscopic pathological findings were carefully described, no ultrastructural studies of the liver were performed in these cases. We report the light-microscopic and ultrastructural findings at autopsy of a 35-year-old woman with AIDS who developed severe lactic acidosis and hepatic failure. The patient had been receiving standard doses of zidovudine for 5 months when she was hospitalized because of the rapid onset of abdominal pain, nausea, and vomiting. The most significant findings at autopsy were massive hepatomegaly and steatosis. Ultrastructural examination of the liver and skeletal muscle showed slightly enlarged mitochondria in the liver but no mitochondrial changes in the skeletal muscle. The pathogenesis of mitochondrial toxicity associated with antiviral therapies is briefly discussed.