Clinically significant cognitive dysfunction in medically asymptomatic human immunodeficiency virus-infected (HIV+) individuals?

No single-tablet antiretroviral (ARV) regimens (STRs) are approved for patients with human immunodeficiency virus (HIV) and end-stage renal disease (ESRD) on hemodialysis (HD). Based on known pharmacokinetic (PK) properties, abacavir (ABC)/lamivudine (3TC)/dolutegravir (DTG) STR may represent a promising option. This case series presents the safety and efficacy of ABC/3TC/DTG STR in patients with HIV and ESRD on HD. Patients were included if they were HIV-positive, maintained on intermittent HD for ESRD, switched to an ARV regimen containing ABC/3TC/DTG, and had at least one set of virologic data before and after the switch. Average age (±standard deviation) was 59 (±8) years. The majority of patients were cis-gender male and non-Hispanic Black. Only one demonstrated clinically significant resistance at baseline. All were on multiple-tablet regimens prior to the switch. Five patients (83%) achieved undetectable HIV-RNA after the switch while only four patients (46%) were undetectable immediately prior. No decline in immune function was noted. ABC/3TC/DTG STR was well tolerated. Only one patient self-reported an adverse event (nausea), which resolved without drug discontinuation. Based on these data, it appears that ABC/3TC/DTG may be a safe and effective ARV-STR option for patients with HIV and ESRD on HD. A larger trial including a PK analysis is needed to confirm these findings.

Download Full-text

Acid Dissociation Increases the Sensitivity of p24 Antigen Detection for the Evaluation of Antiviral Therapy and Disease Progression in Asymptomatic Human Immunodeficiency Virus-Infected Persons

The Journal of Infectious Diseases ◽

10.1093/infdis/165.5.913 ◽

1992 ◽

Vol 165 (5) ◽

pp. 913-916 ◽

Cited By ~ 32

Author(s):

R. C. Bollinger ◽

R. L. Kline ◽

H. L. Francis ◽

M. W. Moss ◽

J. G. Bartlett ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Antiviral Therapy ◽

Disease Progression ◽

Antigen Detection ◽

Acid Dissociation ◽

Immunodeficiency Virus ◽

P24 Antigen ◽

Asymptomatic Human Immunodeficiency Virus

Download Full-text

Multidose Pharmacokinetics of Ritonavir and Zidovudine in Human Immunodeficiency Virus-Infected Patients

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.42.7.1788 ◽

1998 ◽

Vol 42 (7) ◽

pp. 1788-1793 ◽

Cited By ~ 16

Author(s):

Allen Cato ◽

Jiang Qian ◽

Ann Hsu ◽

Benjamin Levy ◽

John Leonard ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Adverse Event ◽

Dosage Adjustment ◽

Elimination Rate ◽

Time Curve ◽

Safety And Efficacy ◽

Concentration Time ◽

Immunodeficiency Virus ◽

Asymptomatic Human Immunodeficiency Virus

ABSTRACT The effect of coadministration of ritonavir and zidovudine (ZDV) on the pharmacokinetics of these drugs was investigated in a three-period, multidose, crossover study. Eighteen asymptomatic, human immunodeficiency virus-positive men were assigned randomly to six different sequences of the following three regimens: ZDV (200 mg every 8 h [q8h]) alone for 4 days, ritonavir (300 mg q6h) alone for 4 days, and ZDV with ritonavir for 4 days. Ritonavir pharmacokinetics were unaffected by coadministration with ZDV. However, ZDV exposure was reduced by about 26% (P < 0.05) in the presence of ritonavir. The maximum concentration in (C max) of ZDV plasma decreased from 748 ± 375 (mean ± standard deviation) to 546 ± 296, and area under the concentration-time curve from 0 to 24 h (AUC0–24) decreased from 3,052 ± 1,007 to 2,261 ± 715 when coadministered with ritonavir. In contrast, the ZDV elimination rate constant was unaffected by ritonavir, suggesting that there was no change in ZDV systemic metabolism. Correspondingly, differences in ZDV-glucuronide C max and AUC were not statistically significantly different between regimens (P > 0.31). Also, there were no apparent differences in the formation of 3′-amino-3′-deoxythymidine or in the adverse event profiles between the regimens. The lack of change in ritonavir pharmacokinetics suggests that dosage adjustment of ritonavir is unnecessary when it is administered concurrently with ZDV. The clinical relevance of a 26% reduction in ZDV exposure when ZDV is administered with ritonavir is unknown. In addition to other multidrug regimens, the long-term safety and efficacy of coadministration of ritonavir and ZDV is being investigated.

Download Full-text

Randomized study of didanosine monotherapy and combination therapy with zidovudine in hemophilic and nonhemophilic subjects with asymptomatic human immunodeficiency virus-1 infection. AIDS Clinical Trial Groups

Blood ◽

10.1182/blood.v85.9.2337.bloodjournal8592337 ◽

1995 ◽

Vol 85 (9) ◽

pp. 2337-2346 ◽

Cited By ~ 9

Author(s):

MV Ragni ◽

DA Amato ◽

ML LoFaro ◽

V DeGruttola ◽

C Van Der Horst ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Combination Therapy ◽

Cd4 Count ◽

High Dose ◽

Immunodeficiency Virus ◽

Dose Combination ◽

Hiv 1 ◽

Asymptomatic Human Immunodeficiency Virus ◽

Human Immunodeficiency Virus 1 ◽

Asymptomatic Hiv

To evaluate the safety and efficacy of didanosine (ddl) monotherapy and three different combinations of zidovudine (ZDV) and ddl in asymptomatic human immunodeficiency virus-1 (HIV-1) infection, we conducted an open-label, phase I/II study in 126 asymptomatic HIV-1-infected hemophilic and nonhemophilic subjects with a CD4 count of 200 to 500/mm3 stratified for prior zidovudine treatment and baseline CD4 count. Study arms included arm A, low-dose combination (ZDV 150 mg and ddl 134 mg, daily); arm B, moderate-dose combination (ZDV 300 mg and ddI 334 mg, daily); arm C, high-dose combination (ZDV 600 mg and ddl 500 mg, daily), and arm D, ddl monotherapy (ddl 500 mg, daily). Earlier, more frequent hepatotoxicity was experienced by hemophilic subjects (P = .008), but there were no differences in toxicity between treatment arms (P = .51), nor were there any differences in the rate of development of clinical endpoints by treatment (P = .41). Smaller median CD4 increases occurred over the first 12 weeks for arms A and D, 44/mm3 and 42/mm3, than arms B and C, 105/mm3 and 114/mm3, respectively, (P = .015). Hemophilia status (P = .0004) and prior ZDV experience (P = .044) independently predicted weaker CD4 responses during the first 12 weeks of treatment. Using a regression model and adjusting for hemophilia status, prior ZDV treatment, and baseline CD4, there was a significant reduction in quantitative viral load from baseline by week 12 for all treatment arms combined (P = .0001), with significantly lower median percent reduction for arm A (56.3%) than arms B, C, and D (94.6%, 98.5%, and 91.9%, respectively, P = .015). Although greater hepatoxicity and weaker CD4 responses occur in hemophilic subjects, didanosine monotherapy and combination therapy with zidovudine are safe and effective in asymptomatic HIV-1-infected patients.

Download Full-text