Virological and immunological responses to once-daily dosing of didanosine in combination with stavudine

Mobley, Jane E.; Pollard, Richard B.; Schrader, Shannon; Adler, Myra; Kelleher, Thomas; McLaren, Colin

doi:10.1097/00002030-199907300-00003

Cited by 26 publications

(14 citation statements)

References 3 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Preliminary information from the present study also suggests that the addition of 400 mg of didanosine once daily, a dose that appears to be an equally effective alternative to the initially approved dosage of 200 mg twice daily (16,24), does not significantly alter the pharmacokinetics of either protease inhibitor. These data, along with the increasing number of oncedaily reverse transcriptase inhibitors (including efavirenz and potentially lamivudine and emtricitabine), increases the feasibility of developing HAART regimen with once-daily dosing for all drugs in the near future.…”

Section: Discussionmentioning

confidence: 52%

Safety and Pharmacokinetics of Once-Daily Regimens of Soft-Gel Capsule Saquinavir plus Minidose Ritonavir in Human Immunodeficiency Virus-Negative Adults

Kilby

Sfakianos

Gizzi

et al. 2000

Antimicrob Agents Chemother

View full text Add to dashboard Cite

Human immunodeficiency virus type 1 (HIV-1) protease inhibitors have dramatically improved treatment options for HIV infection, but frequent dosing may impact adherence to highly active antiretroviral treatment regimens (HAART). Previous studies demonstrated that combined therapy with ritonavir and saquinavir allows a decrease in frequency of saquinavir dosing to twice daily. In this study, we evaluated the safety and pharmacokinetics of combining once-daily doses of the soft-gel capsule (SGC) formulation of saquinavir (saquinavir-SGC) and minidose ritonavir. Forty-four healthy HIV-negative volunteers were randomized into groups receiving once-daily doses of saquinavir-SGC (1,200 to 1,800 mg) plus ritonavir (100 to 200 mg) or a control group receiving only saquinavir-SGC (1,200 mg) three times daily. Saquinavir-SGC alone and saquinavir-SGC-ritonavir combinations were generally well tolerated, and there were no safety concerns. Addition of ritonavir (100 mg) to saquinavir-SGC (1,200 to 1,800 mg/day) increased the area under the concentration-time curve (AUC) for saquinavir severalfold, and the intersubject peak concentration in plasma and AUC variability were reduced compared to those achieved with saquinavir-SGC alone (3,600 mg/day), while trough saquinavir levels (24 h post-dose) were substantially higher than the 90% inhibitory concentration calculated from HIV-1 clinical isolates. Neither increasing the saquinavir-SGC dose to higher than 1,600 mg nor increasing ritonavir from 100 to 200 mg appeared to further enhance the AUC. These results suggest that an all once-daily HAART regimen, utilizing saquinavir-SGC plus a more tolerable low dose of ritonavir, may be feasible. Studies of once-daily saquinavir-SGC (1,600 mg) in combination with ritonavir (100 mg) in HIV-infected patients are underway.

show abstract

Section: Discussionmentioning

confidence: 52%

Safety and Pharmacokinetics of Once-Daily Regimens of Soft-Gel Capsule Saquinavir plus Minidose Ritonavir in Human Immunodeficiency Virus-Negative Adults

Kilby

Sfakianos

Gizzi

et al. 2000

Antimicrob Agents Chemother

View full text Add to dashboard Cite

show abstract

“…In initial small pediatric [6, 7] and adult [8, 9] studies, d4T/ddI demonstrated good antiviral activity and was well tolerated. Subsequent larger studies of adults revealed that this combination, when compared with ZDV/3TC, was associated with a significantly increased rate of lactic acidosis, peripheral neuropathy, pancreatitis, lipodystrophy, and hepatitis [10–15].…”

mentioning

confidence: 99%

Toxicities Associated with Dual Nucleoside Reverse‐Transcriptase Inhibitor Regimens in HIV‐Infected Children

2008

View full text Add to dashboard Cite

Background Human immunodeficiency virus (HIV) therapy includes a backbone of nucleoside reverse-transcriptase inhibitors (NRTIs). Toxicities associated with NRTIs are not fully defined in children. Methods We studied 2233 children ≤13 years of age who were perinatally infected with HIV and were receiving ≥2 NRTIs, to determine the relative toxicities of the 5 most common NRTI pairs: zidovudine (ZDV)/lamivudine (3TC), ZDV/didanosine (ddI), stavudine (d4T)/3TC, d4T/ddI, and ddI/3TC. Incidence rates for clinical and laboratory toxicities were estimated, and NRTI pairs were compared with regard to the time to the first toxicity. Results The most common clinical toxicities noted were hepatitis, peripheral neuropathy, lipodystrophy/lipoatrophy, and pancreatitis, whereas the most common laboratory toxicities were an elevated anion gap, an increased total amylase level, neutropenia, and thrombocytopenia. Overall, regimens containing ZDV were associated with a significantly lower rate of clinical toxicities than were those containing d4T (adjusted hazard ratio [HR], 0.49; P = .02); regimens containing ddI were associated with a significantly lower rate of laboratory toxicities than were those containing 3TC (adjusted HR, 0.78; P = .04). ZDV/3TC was associated with a lower rate of clinical toxicities than were d4T/ddI and ddI/3TC and with a higher rate of laboratory toxicities than was ZDV/ddI. ZDV/ddI was associated with a lower rate of clinical toxicities than was d4T/3TC. Conclusions In children, regimens containing ZDV have less toxicity than do those containing d4T, thereby supporting their use in first-line regimens. D4T/3TC, d4T/ddI, and ddI/3TC have similar toxicity rates and are appropriate for second-line therapy.

show abstract

“…Two antiviral medications are currently available as once-aday drugs-efavirenz, a nonnucleoside reverse transcriptase inhibitor, and didanosine [6][7][8][9]. Emtricitabine (2 ,3 -dideoxy-5-fluoro-3 -thiacytidine [FTC]) is a new nucleoside reverse transcriptase inhibitor that currently is being developed as a oncea-day drug [10][11][12][13].…”

mentioning

confidence: 99%

Once‐Daily Combination Therapy with Emtricitabine, Didanosine, and Efavirenz in Human Immunodeficiency Virus–Infected Patients

et al. 2000

View full text Add to dashboard Cite

The safety and efficacy of a once-daily regimen that combines emtricitabine, didanosine, and efavirenz was studied among 40 previously untreated human immunodeficiency virus (HIV)-infected patients. The median plasma HIV RNA level was 4.77 log(10) copies/mL at baseline and decreased by a median of 3.5 log(10) copies/mL at 24 weeks, with 98% and 93% of patients achieving plasma HIV RNA levels <400 and <50 copies/mL, respectively. The median CD4 cell count was 373 cells/microL at baseline and increased by a median of 159 cells/microL at week 24. The most common treatment-related adverse events were mild to moderate central nervous system symptoms (73% of patients), diarrhea (33%), rashes (10%), and biochemical abnormalities. Adverse reactions led to permanent drug discontinuation in only 1 patient. The once-daily combination therapy of emtricitabine, didanosine, and efavirenz was safe and demonstrated strong antiviral and immunologic effects that lasted for the 24-week period of the study.

show abstract

Virological and immunological responses to once-daily dosing of didanosine in combination with stavudine

Abstract: Once-daily ddI plus d4T and twice-daily ddI plus d4T were similarly effective in reducing plasma HIV-1 RNA levels and increasing CD4 cell counts over 12-24 weeks of therapy.

Cited by 26 publications

References 3 publications

Safety and Pharmacokinetics of Once-Daily Regimens of Soft-Gel Capsule Saquinavir plus Minidose Ritonavir in Human Immunodeficiency Virus-Negative Adults

Safety and Pharmacokinetics of Once-Daily Regimens of Soft-Gel Capsule Saquinavir plus Minidose Ritonavir in Human Immunodeficiency Virus-Negative Adults

Toxicities Associated with Dual Nucleoside Reverse‐Transcriptase Inhibitor Regimens in HIV‐Infected Children

Once‐Daily Combination Therapy with Emtricitabine, Didanosine, and Efavirenz in Human Immunodeficiency Virus–Infected Patients

Contact Info

Product

Resources

About