didanosine and Body-Weight

Zidovudine is the initial treatment of choice in HIV-infected children. Zalcitabine or didanosine may be used in children who do not respond adequately or who are intolerant of zidovudine. Several studies of the latter agents are reviewed.. Zalcitabine at 0.005 or 0.01 mg/kg three times a day was associated with stabilization of growth and a decline in p24 antigen levels in more than 50% of treated children. In a dose-ranging study of didanosine, 30% of children showed an increase in CD4 cell counts and gained weight. There was a correlation between the plasma didanosine concentration and an improvement in IQ (Intelligence Quotient) and p24 status.. In a 12-18 month trial of zidovudine/zalcitabine in 13 children, most gained weight and more than half showed improved CD4 cell counts. The combination of various doses of didanosine with zidovudine was associated with a reduction in viral titer, a significant increase in CD4 cell counts and a trend towards increased weight in many children.. Zidovudine or placebo was administered to women throughout pregnancy and during labor and to their new-born infants up to 6 weeks of age. The infection rate for the zidovudine-treated group was 8.3% compared with 25.5% for the placebo group (P = 0.000056).. Zalcitabine and didanosine are useful drugs in the treatment of HIV-infected children. Zidovudine is associated with a reduced rate of mother to infant viral transmission.

Topics: Body Weight; Clinical Trials as Topic; Didanosine; Female; Growth; HIV Infections; Humans; Infant, Newborn; Infectious Disease Transmission, Vertical; Pregnancy; Pregnancy Complications, Infectious; Treatment Failure; Zalcitabine; Zidovudine

Nucleoside analogues such as Didanosine and Stavudine are known to cause metabolic and body habitus changes during antiretroviral therapy. The most frequently observed are lactic acidosis, hypercholesterinaemia, hypertriglyceridaemia and lipodystrophy.. Over one year we monitored a cohort of 43 patients who switched from either Stavudine, Didanosine or the combination of both to Tenofovir. A group of 11 patients was kept on their original regimen and acted as control group. Blood samples were taken every 3 months from baseline, anthropometric measurements were performed at baseline, after 6 and 12 months.. During observation the levels of lactic acid and cholesterol decreased significantly in the switch group while virologic and immunologic efficacy remained stable. Serum creatinine levels rose significantly in patients switched to Tenofovir, but remained within physiological limits. The mean skin fold thickness increased significantly by 1.8 mm in the switch group after 6 months (p < or =0.001 - p = 0.032).. These results implicate an improvement of lipid profiles, serum lactate and lipodystrophy in HIV-positive patients after switch to Tenofovir. As a moderate increase in serum creatinine levels was observed, the renal function of patients on a Tenofovir-based regimen should be monitored closely.

Topics: Adenine; Adult; Aged; Anti-HIV Agents; Body Weight; CD4 Lymphocyte Count; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Creatinine; Didanosine; Female; Glomerular Filtration Rate; Glycated Hemoglobin; Hemoglobins; HIV Infections; Humans; Lactic Acid; Male; Middle Aged; Organophosphonates; Phosphates; Skinfold Thickness; Stavudine; Tenofovir; Treatment Outcome; Triglycerides; Uric Acid; Viral Load

The objective of the present study was to develop a population pharmacokinetic model for nelfinavir mesylate (NFV) and nelfinavir hydroxy-tert-butylamide (M8), the most abundant metabolite of NFV, in infants vertically infected with human immunodeficiency virus type 1 and participating in the Paediatric European Network for Treatment of AIDS 7 study. Plasma NFV concentrations were determined during repeated NFV administrations (two to three times a day). Eighteen infants younger that age 2 years participated in this study. The doses administered ranged from 71 to 203 mg/kg of body weight/day. Pharmacokinetic parameter estimates were obtained by a compartmental approach by using a kinetic model to simultaneously fit NFV and M8 (active metabolite) concentrations. M8 was shown to be formation rate limited and was characterized by first-order rate constants of formation and elimination. Body weight was found to be a more appropriate predictor than age of the changes in (i) the rate of metabolism, (ii) the elimination rate constant of NFV, and (iii) NFV clearance. Population parameters were computed to account for the relationship between the rate of metabolism and body weight. The estimated NFV and M8 elimination half-lives were 4.3 and 2.04 h, respectively. The estimated NFV clearance was 2.13 liters/h/kg. The M8 concentration-to-NFV concentration ratio was 0.64 +/- 0.44. In conclusion, the population pharmacokinetic model describing the dispositions of NFV and M8 should facilitate the design of future studies to elucidate the relative contributions of the parent compound and M8 to the pharmacological and toxic effects of NFV therapy.

Topics: Aging; Bayes Theorem; Body Weight; Chromatography, High Pressure Liquid; Didanosine; Drug Interactions; Half-Life; HIV Infections; HIV Protease Inhibitors; HIV-1; Humans; Infant; Infant, Newborn; Models, Biological; Nelfinavir; Reverse Transcriptase Inhibitors; Spectrometry, Mass, Electrospray Ionization; Stavudine

In this multicenter study (ISS 902), 554 previously untreated patients with <500 CD4 cells/mm3 and mildly symptomatic human immunodeficiency virus disease were randomized to receive zidovudine or didanosine (ddI). After a mean follow-up of 20 months, 80 patients (40 zidovudine, 40 ddI) had died and 146 had at least one AIDS-defining event (73 zidovudine, 73 ddI). Overall, no difference was found between treatments with respect to progression to AIDS or death. The analysis of relative risk (RR) of progression over time, however, showed an initially minor risk for zidovudine patients and an inversion in the zidovudine-ddI RR in the second and third years of follow-up. Didanosine showed a greater effect on CD4 cell count response. The two drugs confirmed the toxicity patterns already reported in other trials, with a low occurrence of pancreatitis (ddI 1.3%, zidovudine 0.4%). The overall results suggest that, in this population, zidovudine and ddI monotherapies have comparable long-term clinical efficacy and that more powerful regimens should be preferred.

Topics: Acquired Immunodeficiency Syndrome; Adult; Anti-HIV Agents; Body Weight; CD4 Lymphocyte Count; Didanosine; Disease Progression; Female; HIV Core Protein p24; HIV Infections; Humans; Male; Risk; Zidovudine

This study evaluated the efficacy of switching to didanosine in patients who were clinically or immunologically progressing despite zidovudine therapy. This multicenter, open-label study involved 400 patients with the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex (ARC), who had tolerated zidovudine for at least 12 weeks and had signs of clinical or immunological disease progression. They were randomly assigned to receive 600 mg/d of zidovudine (n=133), 500 mg/d of didanosine (n=131), or 200 mg/d of didanosine (n=136). The primary end point was a new AIDS-defining event or death. The study was prematurely terminated, after the first interim analysis, mainly owing to results of two controlled studies demonstrating that a change to didanosine was associated with an improved outcome in patients with advanced HIV-1 disease. The median duration of follow-up was 53 weeks. The primary end point rates were 41, 58, and 59 (per 100 person-years) in the didanosine 500 mg, didanosine 200 mg, and zidovudine groups (zidovudine vs. didanosine 500 mg, relative risk 1.28, 95% confidence interval, 0.88-1.86, p = 0.19; didanosine 200 vs. 500 mg, relative risk 1.24, 95% confidence interval, 0.85-1.79, p = 0.26). In subjects with a baseline CD4 count of 100/mm3 or more, the primary end point rates were 8, 29, and 25 (per 100 person-years) in the didanosine 500 mg, didanosine 200 mg, and zidovudine groups, respectively (zidovudine vs. didanosine 500 mg, relative risk 2.96, 95% confidence interval 0.91-9.62, p = 0.07). No difference was seen in survival. In the didanosine 500 mg group, more patients had a 50% increase in CD4 cells (10% vs. 1% in zidovudine group, p = 0.01) and an increase of > or = 2.5 kg in body weight (2% versus 3%). Fatal pancreatitis developed in one patient assigned to didanosine 500 mg and in one to zidovudine. Our data suggest that switching from zidovudine to currently recommended doses of didanosine in subjects with ARC or AIDS who show evidence of clinical and laboratory disease progression can be associated with improvements in clinical outcome as well as in surrogate markers of HIV disease progression. This effect tended to be greater among individuals with higher CD4 counts (>100/mm3).

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Complex; AIDS-Related Opportunistic Infections; Antiviral Agents; Body Weight; CD4 Lymphocyte Count; Didanosine; Disease Progression; Female; HIV-1; Humans; Male; Pancreatitis; Zidovudine

A randomized pilot study comparing alternating and simultaneous regimens of zidovudine and didanosine (ddl) was conducted in 41 patients with AIDS or symptomatic human immunodeficiency virus (HIV) infection. Patients on each regimen received the same overall amounts of zidovudine and didanosine over time. CD4 cell counts in patients on the simultaneous regimen reached a maximum (mean +/- SE) of 108 +/- 16/mm3 above baseline (two-tailed P < or = .0001) and were significantly higher than in patients on the alternating regimen at all time points during weeks 6-45. At 54 weeks, the CD4 cell counts in the patients on the simultaneous regimen were still 40 +/- 19/mm3 above baseline. Patients on the simultaneous regimen also had significantly greater weight gain. While toxicities were generally mild and comparable between the regimens, 1 patient on the simultaneous regimen died of pancreatitis and lactic acidosis. Thus, simultaneous therapy provided more sustained elevations in CD4 cells than alternating therapy over 1 year and may be worth exploring in larger controlled trials.

Topics: Administration, Oral; Adolescent; Adult; AIDS-Related Opportunistic Infections; beta 2-Microglobulin; Body Weight; CD4-Positive T-Lymphocytes; Didanosine; Drug Administration Schedule; Drug Therapy, Combination; Female; Follow-Up Studies; HIV Core Protein p24; HIV Infections; Humans; Leukocyte Count; Male; Middle Aged; Pancreatitis; Pilot Projects; Zidovudine

Protease inhibitors (PI's) and reverse transcriptase drugs are important components of highly active antiretroviral therapy (HAART) for treating human acquired immunodeficiency syndrome (AIDS). Long-term clinical therapeutic efficacy and treatment compliance of these agents have been limited by undesirable side-effects, such as diarrhea. This study aims to investigate the effects of selected antiretroviral agents on intestinal histopathology and function in vivo and on cell proliferation and death in vitro.. Selected antiretroviral drugs were given orally over 7 days, to Swiss mice, as follows: 100 mg/kg of nelfinavir (NFV), indinavir (IDV), didanosine (DDI) or 50 mg/kg of zidovudine (AZT). Intestinal permeability measured by lactulose and mannitol assays; net water and electrolyte transport, in perfused intestinal segments; and small intestinal morphology and cell apoptosis were assessed in treated and control mice. In vitro cell proliferation was evaluated using the WST-1 reagent and apoptosis and necrosis by flow cytometry analysis.. NFV, IDV, AZT and DDI caused significant reductions in duodenal and in jejunal villus length (p < 0.05). IDV and AZT increased crypt depth in the duodenum and AZT increased crypt depth in the jejunum. NFV, AZT and DDI significantly decreased ileal crypt depth. All selected antiretroviral drugs significantly increased net water secretion and electrolyte secretion, except for DDI, which did not alter water or chloride secretion. Additionally, only NFV significantly increased mannitol and lactulose absorption. NFV and IDV caused a significant reduction in cell proliferation in vitro at both 24 h and 48 h. DDI and AZT did not alter cell proliferation. There was a significant increase in apoptosis rates in IEC-6 cells after 24 h with 70 ug/mL of NFV (control: 4.7% vs NFV: 22%) while IDV, AZT and DDI did not show any significant changes in apoptosis compared to the control group. In jejunal sections, IDV and NFV significantly increased the number of TUNEL positive cells.. The PI's, NFV and IDV, increased cell apoptosis in vivo, water and electrolyte secretion and intestinal permeability and decreased villus length and cell proliferation. NFV was the only drug tested that increased cell apoptosis in vitro. The nucleoside reverse transcriptase inhibitors, AZT and DDI, did not affect cell apoptosis or proliferation. These findings may partly explain the intestinal side-effects associated with PI's.

Topics: Animals; Anti-Retroviral Agents; Apoptosis; Body Weight; Cell Membrane Permeability; Cell Proliferation; Didanosine; HIV Protease Inhibitors; Indinavir; Intestinal Absorption; Intestinal Mucosa; Male; Mice; Models, Animal; Necrosis; Nelfinavir; Reverse Transcriptase Inhibitors; Survival Rate; Water-Electrolyte Balance; Zidovudine

Topics: Adolescent; Anti-HIV Agents; Body Weight; Child; Child, Preschool; Delayed-Action Preparations; Didanosine; Dosage Forms; Drug Approval; Drug Labeling; HIV Infections; Humans; Infant; Infant, Newborn; Reverse Transcriptase Inhibitors; United States; United States Food and Drug Administration

To examine the effect of antiretroviral agents and clinical factors on the development of tenofovir-associated kidney dysfunction.. Observational cohort study of HIV-infected patients receiving tenofovir in an HIV clinic population. Patients' kidney function prior to initiating and while receiving tenofovir was evaluated in relation to other antiretroviral medications and demographic and clinical characteristics. Decline in kidney function was assessed by the glomerular filtration rate (GFR) as estimated by the Cockcroft-Gault (CG) equation, which incorporates weight. Logistic regression analysis was used to examine factors associated with GFR of > 90, 60-90, 30-60, and < 30 ml/min per 1.73 m(2) while on tenofovir. Secondary analyses used the simplified Modification of Diet in Renal Disease (MDRD) equation.. Among the 445 patients initiating tenofovir, 51 (11%) developed a decline in kidney function. In multivariate analysis, there was a significant association between decline in kidney function and concurrent use of amprenavir [odds ratio (OR) 3.6; P = 0.045] and didanosine (OR, 3.1; P = 0.006), age over 50 years (OR, 4.4; P = 0.03), and lower baseline weight (OR, 0.95/kg; P < 0.001). Patients identified with kidney dysfunction by the MDRD equation did not fully overlap with those identified by the CG equation.. Didanosine and amprenavir use, increased age, and lower baseline weight were significantly associated with risk for kidney dysfunction among patients receiving tenofovir. GFR results using the MDRD equation were inconsistent with those using CG, which highlights the impact of including weight in the estimation of GFR among HIV-infected patients.

Topics: Adenine; Adult; Age Factors; Analysis of Variance; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Body Weight; Carbamates; Creatinine; Didanosine; Drug Interactions; Female; Furans; Glomerular Filtration Rate; HIV Infections; HIV-1; Humans; Kidney; Linear Models; Male; Middle Aged; Organophosphonates; Sulfonamides; Tenofovir; Time Factors

Zidovudine and didanosine are antiretroviral drugs used for human immunodeficiency virus (HIV)-infected children with dose recommendations based on body surface area calculations. Although weight and height can both be measured, it may be impractical to expect providers in resource-limited settings to estimate accurately body surface area.. We developed an antiretroviral dosing chart based on authoritative sources for brand name drugs in weight bands (ie, 5-6.9, 7-9.9, 10-11.9, 12-14.9, 15-16.9, 17-19.9, 20-24.9, 25-29.9, 30-34.9 and 35-40 kg) to assist proper dosing of antiretrovirals for HIV-infected children in resource-limited settings. For drugs dosed by body surface area, we estimated likely weights and heights for age using standardized US growth charts for girls from which doses in weight bands were calculated. For this analysis, we calculated the difference between weight-based doses and body surface area-based doses for zidovudine 10 mg/mL oral solution, zidovudine 100-mg capsules, and didanosine 25, 50 and 100-mg chewable tablets using actual heights and weights from HIV-infected children in Africa and Romania.. We used 1752 observations from 826 HIV-infected children (48% girls) from 9 countries. A total of 454 observations were in children <20 kg and 1298 > or =20 kg. For those <20 kg, the median difference of the weight-based dose as compared with the body surface area-based dose for zidovudine solution was -6.4% (range, -22.6, +13.7), zidovudine capsules +3.1% (range, -38.8, +44.7), didanosine chewable tablets +0.7% (range, -24.4, +22.5); for those > or =20 kg for zidovudine solution was 0.0% (range, -16.4, +11.8), zidovudine capsules +7.6% (range, -16.4, +36.9) and didanosine chewable tablets +1.2% (range, -16.4, +14.1). The dose precision for children <20 versus > or =20 kg was different for zidovudine solution (P < 0.001) and zidovudine capsules (P < 0.001), but not didanosine chewable tablets. The frequency that weight-based dose was more than 20% less than the body surface area-based dose for those <20 kg was 1.3% for zidovudine solution, 27.2% for zidovudine capsules and 4.9% for didanosine chewable tablets. For those > or =20 kg, the weight-based dose was never more than 20% less than the body surface area-based dose.. Dosing zidovudine and didanosine by weight band provides reasonably precise dosing as compared with body surface area-based doses. However, use of zidovudine capsules in children <20 kg results in under dosing by >20% in many instances. Didanosine chewable tablets allow for higher dosing precision compared with zidovudine capsules because of increased flexibility in the dosage form. Solid dosage forms of antiretroviral medications designed specifically for children are urgently needed.

Topics: Adolescent; Anti-HIV Agents; Body Surface Area; Body Weight; Child; Child, Preschool; Didanosine; Dosage Forms; Female; HIV Infections; Humans; Infant; Male; Zidovudine

Although adverse events in HIV patients taking tenofovir are relatively rare, postmarketing reports of nephrotoxicity have alerted physicians to other potentially serious outcomes. We present a series of 40 patients who developed hypokalemia associated with tenofovir. Identified risk factors included concomitant ritonavir or didanosine use, a lower weight and longer duration of tenofovir use. Recovery or improvement was seen in the majority of patients (66%) after the discontinuation of tenofovir; however, four deaths occurred. The associated consequences of tenofovir-related hypokalemia may be profound and life-threatening.

Topics: Adenine; Adolescent; Adult; Body Weight; Child; Didanosine; Drug Therapy, Combination; Female; HIV Infections; HIV Protease Inhibitors; Humans; Hypokalemia; Kidney Diseases; Male; Middle Aged; Organophosphonates; Reverse Transcriptase Inhibitors; Risk Factors; Ritonavir; Tenofovir; Time Factors

(i) To investigate whether protease inhibitor (PI) (nelfinavir)-containing highly active antiretroviral therapy (HAART) affects body composition differently in HIV-infected and AIDS patients without wasting syndrome. (ii) To delineate the changes in resting energy expenditure (REE) under PI therapy, and to determine whether sustained reductions in HIV RNA would decrease REE.. Prospective longitudinal cohort study with individually matched healthy controls.. Tertiary care centre at a University Hospital.. HIV-seropositive (n = 20) and AIDS patients (n = 17) with a plasma viral load of at least 10000 copies/ml and 37 healthy volunteers were enrolled. All participants were weight stable, free of acute opportunistic infections, and naive to PI therapy. Patients underwent testing of bioelectrical impedance analysis (BIA), indirect calorimetry and food intake, shortly before the initiation of HAART and 24 weeks thereafter.. Both patient groups gained weight, body mass index (BMI), and fat-free mass (FFM) (P < 0.05 versus baseline), whereas only AIDS patients gained fat mass. Increases were more pronounced in the AIDS group. REE was elevated compared with corresponding controls at baseline, and decreased similarly in HIV and in AIDS patients during PI therapy (P < 0.05). The reduction in the viral burden preceded the decrease in REE by several weeks.. Body composition and metabolic parameters improved during PI therapy in HIV-infected and AIDS patients without wasting. Although an early reduction in viral load as a result of HAART does not seem to influence REE directly, sustained viral load suppression may promote a decrease in energy expenditure.

Topics: Acquired Immunodeficiency Syndrome; Adult; Basal Metabolism; Body Composition; Body Weight; Case-Control Studies; Cohort Studies; Didanosine; Energy Metabolism; Female; HIV Infections; HIV Protease Inhibitors; Humans; Longitudinal Studies; Male; Middle Aged; Nelfinavir; Prospective Studies; Stavudine; Viremia

2',3'-dideoxyinosine (ddI) is one of several purine analogues used for the treatment of HIV and the acquired immunodeficiency syndrome (AIDS). These nucleoside analogues are promising in their inhibition of viral reverse transcriptase and termination of DNA synthesis. However, each of these drugs has toxicity associated with its use. A previous immunotoxicological evaluation of 2',3'-dideoxyadenosine (ddA), the parent compound of ddI, showed that ddA suppresses humoral immunity. These studies were undertaken to determine the potential for immunotoxicity due to treatment with ddI. This evaluation included an assessment of innate and acquired immunity after exposure to ddI (100, 250, 500, and 1000 mg/kg/day) for 14, 28 or 180 days. There were no overt signs of toxicity related to treatment with ddI except for a decrease in body weight in the group treated with the highest dose of ddI for 180 days. Overall, 6 months of treatment with ddI showed minimal effects on specific organs with the exception of the spleen and thymus. ddI selectively targets the immune system, with assays that challenge humoral immunity being more affected than those testing cell-mediated immunity. Innate immunity was unaffected by ddI treatment. Cell-mediated immunity, as measured by proliferative response to allogeneic cells (MLR) and the T cell mitogen (Concanavalin A), was moderately suppressed. There were no ddI associated effects on NK function or macrophage function as measured by the vascular clearance rate and phagocytic uptake of the tissue macrophages. The most sensitive indicator of ddI-induced immunotoxicity is suppression of the response to the T-dependent antigen, sheep red blood cells (sRBC). The No Observable Adverse Effect Level (NOAEL) for toxicity to the immune system following 14 days of exposure to ddI is 250 mg/kg. A suppression of the humoral immune response was seen at the lowest dose tested after treatment for 28 and 180 days. Thus, the NOAEL for both of these treatment periods is below 100 mg/kg/day.

Topics: Animals; Anti-HIV Agents; Body Weight; Bone Marrow Cells; Cell Division; Didanosine; Female; Immune System; Mice; Mice, Inbred Strains; Organ Size; Reverse Transcriptase Inhibitors; Spleen

One hundred and fifty-one patients intolerant to zidovudine (AZT) received didanosine (ddI) to a maximum dose of 12.5 mg/kg/day. Patient response was assessed using changes in CD4+ lymphocyte subset count, HIV p24 antigen, weight, and quality of life. Seventy patients developed major opportunistic infections whilst on therapy; this was the first AIDS diagnosis in 17. Only minor changes in CD4+ lymphocyte subset count were observed in AIDS patients, although a more significant rise occurred in those with earlier stages of disease. Of those positive for p24 antigen at the commencement of the study 67% showed a positive response, and this was most likely in those with CD4+ lymphocyte subset counts above 100 mm3. A positive weight response was seen in 16% of patients. Most patients showed improvement in individual parameters and global score of quality of life. Adverse reactions possibly attributable to didanosine were common. The most common side-effect was diarrhoea, which resulted in cessation of therapy in 19 individuals. Peripheral neuropathy occurred in 12 patients and pancreatitis in six. Thirteen patients developed a raised serum amylase without abdominal pain. Seven patients developed glucose tolerance curves characteristic of diabetes but these were mild, did not require treatment and returned to normal on ceasing didanosine.

Topics: Acquired Immunodeficiency Syndrome; Adult; Aged; AIDS-Related Complex; Body Weight; Diarrhea; Didanosine; Female; HIV Core Protein p24; Humans; Leukocyte Count; Lymphocyte Subsets; Male; Middle Aged; Pancreatitis; Peripheral Nervous System Diseases; Quality of Life; Risk Factors; Zidovudine

A pilot study was initiated to explore a sequential combination antiretroviral regimen in 21 patients with AIDS or advanced human immunodeficiency virus (HIV) infection, who had received little or no prior anti-HIV therapy. The mean entry CD4 cell count was 184/mm3. Patients received 3-week cycles consisting of zidovudine plus acyclovir, dideoxyinosine, and dideoxycytidine for 1 week each. Overall, the regimen was well tolerated for up to 3 years. The principal toxicities were anemia, nausea, and vomiting; 1 patient developed retinal lesions. The mean CD4 cell count reached a peak of 64 cells/mm3 above baseline at week 8 (P = .005 compared to baseline) and remained above baseline for > 40 weeks. Patients also gained weight and had decreases in serum HIV p24 antigen. Eight patients developed opportunistic infections or tumors. Only 4 patients died during 3 years of follow-up. This regimen appears to be generally tolerable and to have anti-HIV activity. Additional studies will be needed, however, to learn how to best combine the available agents in patients with HIV infection.

Topics: Acquired Immunodeficiency Syndrome; Acyclovir; Adult; AIDS-Related Complex; Antigens, CD; Biomarkers; Body Weight; CD4 Antigens; Didanosine; Drug Administration Schedule; Drug Therapy, Combination; HIV Core Protein p24; Humans; Male; Middle Aged; Pilot Projects; T-Lymphocyte Subsets; Time Factors; Zalcitabine; Zidovudine

To determine if suppression of human immunodeficiency virus (HIV) replication during antiretroviral therapy correlates with clinical outcome, serial quantitative serum cultures and HIV p24 antigen measurements were made in patients with advanced HIV disease treated with didanosine. Twenty-one (78%) of 27 had viremia detected, and in 14 (67%) viral titer decreased by fivefold or more. Compared with those with no decrease, patients who had a decrease in titer were more likely to achieve a > or = 5% increase in body weight (8/12 vs. 0/7, P = .013) and had a significantly greater mean increase in body weight during treatment months 1-5. Occurrence of new AIDS-defining illnesses and survival were not significantly different between groups. Changes in p24 antigenemia did not correlate with any parameter of clinical outcome examined. Changing serum HIV titer is a marker of the virologic effect of didanosine therapy that correlates with the early clinical benefit as reflected by weight gain. However, correlation of this marker with long-term clinical benefit is uncertain.

Topics: Acquired Immunodeficiency Syndrome; Body Weight; Didanosine; HIV; HIV Core Protein p24; Humans; Survival Rate; Viremia

The acute cardiotoxic potential of single dosages of FddA (2'-fluoro-2',3'-dideoxyadenosine) and FddI (2'-fluoro-2',3'-dideoxyinosine) was investigated in 6- to 9-week-old rats. Both nucleoside analogs were administered orally at 1000 and 2000 mg/kg and intravenously at 500 or 1000 mg/kg. For comparative purposes, additional groups of rats received 2'-deoxyadenosine or the 2-fluororibose moiety common to both the FddA and FddI molecules. The effects of two adenosine receptor antagonists, caffeine and theophylline, on the cardiotoxicity induced by FddA were also investigated. Deaths occurred within a few hours to a few days in FddA-treated rats given 2000 mg/kg orally or 500 mg/kg intravenously and in FddI-treated rats given 1000 mg/kg intravenously. Microscopic examination of the hearts revealed myocardial degeneration and necrosis for all rats that died and myocardial fibrosis for many survivors. No deaths or cardiac lesions were observed after administration of 2'-deoxyadenosine or the 2-fluororibose moiety. FddA was more cardiotoxic than FddI in rats at equivalent dosages administered either orally or intravenously. Based on the anatomic findings, all deaths were attributed to cardiac lesions. The administration of high, oral dosages of caffeine and theophylline accentuated the acute cardiotoxicity of FddA in rats.

Topics: Administration, Oral; Animals; Antiviral Agents; Behavior, Animal; Body Weight; Didanosine; Dideoxyadenosine; Dose-Response Relationship, Drug; Heart Diseases; Injections, Intravenous; Male; Myocardium; Necrosis; Rats; Rats, Sprague-Dawley; Xanthines