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Biomedical subjects

Praphan Phanuphak

Publications and source records attributed to Praphan Phanuphak.

52 records · Page 3Linked to original sources
PubMed2003

Pharmacokinetics of indinavir/ritonavir (800/100 mg) in combination with efavirenz (600 mg) in HIV-1-infected subjects.

BACKGROUND: Addition of efavirenz (600 mg) to indinavir/ritonavir (800/100 mg) results in significant decreases in indinavir levels in healthy volunteers. This study evaluated the steady-state pharmacokinetics of indinavir/ritonavir at 800/100 mg twice daily (bid) in combination with efavirenz at 600 mg once daily (qd) in HIV-infected Thai subjects who used this nucleoside-sparing combination in The HIV Netherlands Australia Thailand Research Collaboration 009 study. METHODS: At week 4 of the study, 12-hour pharmacokinetic profiles for indinavir/ritonavir were obtained for 20 HIV-infected subjects. For efavirenz, the concentrations at 12 hours and 24 hours (Cmin) after dosing were assessed. RESULTS: All subjects (10 males and 10 females) completed the study. The geometric mean area under the concentration versus time curve, Cmin, and maximum plasma concentration of indinavir were 45.7 mg/(L. h) (95% confidence interval [CI], 39.8-52.5), 0.32 mg/L (95% CI, 0.24-0.44), and 11.1 mg/L (95% CI, 9.4-13.0), respectively. A >10-fold variation in indinavir Cmin was observed. All subjects had an indinavir Cmin that was at least comparable with the reported mean population Cmin of indinavir at 800 mg thrice daily without ritonavir (0.15 mg/L). The geometric mean concentration at 12 hours and Cmin of efavirenz were 3.1 mg/L (95% CI, 2.5-3.7) and 2.1 mg/L (95% CI, 1.6-2.6), respectively. CONCLUSIONS: Despite the known pharmacokinetic interaction between efavirenz and indinavir/ritonavir, the combination of indinavir/ritonavir at 800/100 mg bid and efavirenz at 600 mg qd results in adequate minimum concentrations of both indinavir and efavirenz for treatment-naive patients.

Acquired Immunodeficiency Syndrome↗
PubMed2003

Nucleoside analogue mutations and Q151M in HIV-1 subtype A/E infection treated with nucleoside reverse transcriptase inhibitors.

OBJECTIVES: To investigate genotypic drug resistance in HIV-1 subtype A/E infection associated with failure of double/triple-nucleoside reverse transcriptase (RT) inhibitor therapy. METHODS: Patients from HIV-NAT 002 [stavudine (d4T)/didanosine (ddI) dose reduction study] and HIV-NAT 003 (zidovudine (ZDV)/lamivudine (3TC) versus ZDV/3TC/ddI) whose HIV-1 RNA was > 1000 copies/ml at week 48 and/or week 96 were tested for genotypic resistance. In both studies, after 48 weeks, patients were switched to the other dual or triple-nucleoside RT inhibitor (NRTI) either according to randomization or to the occurrence of virological failure. RESULTS: Resistance mutations found in the d4T/ddI, ZDV/3TC, and ZDV/3TC/ddI groups: none at baseline; at week 48, nucleoside analogue mutations (NAM), 2/17 (12%), 2/10 (20%), and 1/8; Q151M complex, 3/17 (18%), 0%, and 0%; M184V, 0%, 10/10 (P < 0.001), 3/8; V75T, 3/17 (18%), 0%, and 0%; L74V, 3/7 (18%), 0%, and 0%, respectively. At week 96, among the switchers, i.e., group A d4T/ddI to ZDV/3TC, group B ZDV/3TC to d4T/ddI, and group C ZDV/3TC/ddI to d4T/3TC/abacavir: NAM, 12/21 (57%), 4/7 and 1/3; Q151M, 4/21 (19%), 0% and 1/3, respectively. Interestingly, four or more NAM were observed in a higher proportion in group A (4/17 versus none in the others). CONCLUSIONS: Multi-NRTI resistance (NAM and Q151M) and M184V (only in 3TC failure) are commonly found in HIV-1 subtype A/E infection associated with NRTI failure. Suboptimal d4T/ddI therapy led to a high incidence of V75T and L74V mutations. Switching from d4T/ddI to ZDV/3TC may be associated with a higher incidence of four or more NAM. Thus, suboptimal and dual NRTI therapy is not recommended for global application.

Anti-HIV Agents↗
PubMed2003

Recurring thrombocytopenia associated with structured treatment interruption in patients with human immunodeficiency virus infection.

In a structured treatment interruption (STI) trial, 3 of 23 patients in a CD4 cell count-guided treatment arm developed recurring thrombocytopenia associated with the interruption of antiretroviral therapy. All 3 patients had slightly low or normal platelet counts before initiating antiretroviral therapy. STI may play a role in inducing thrombocytopenia in patients with human immunodeficiency virus infection.

Adult↗
PubMed2003

Pharmacokinetics of once-daily saquinavir hard-gelatin capsules and saquinavir soft-gelatin capsules boosted with ritonavir in HIV-1-infected subjects.

OBJECTIVE: To investigate the pharmacokinetics of once-daily saquinavir (SQV) hard-gelatin capsule (HGC)/ritonavir (RTV), 1600/100 mg, compared with once-daily SQV soft-gelatin capsule (SGC)/RTV, 1600/100 mg. METHODS: We evaluated 13 randomly selected HIV-1-infected subjects taking once-daily SQV SGC/RTV, 1600/100 mg, plus dual nucleoside reverse transcriptase inhibitors (NRTIs) in this pharmacokinetic (PK) substudy. Subjects took 1 week of SQV HGC/RTV and NRTIs, followed by steady-state SQV PK determinations. Subjects then changed to SQV SGC/RTV and NRTIs for 1 week, followed again by steady-state SQV PK determinations. Area under the plasma concentration versus time curve (AUC), maximum concentration (C(max)), minimum concentration (C(min)), time to C(max), and elimination half-life were calculated. RESULTS: There was no significant difference in AUC values between HGCs and SGCs, with a median (plus interquartile range [IQR]) of 50.0 (42.6-71.5) versus 35.5 (28.0-50.2) mg/L/h, respectively ( =.056). Intersubject variability resulted in 4 of 13 subjects on the SQV SGCs and 2 of 13 subjects on the SQV HGCs having a C(min) below the minimum effective concentration of 0.05 mg/L. CONCLUSION: Once-daily SQV HGCs, 1600 mg, boosted with once-daily RTV, 100 mg, resulted in PK parameters that were similar to those observed with 1600 mg of SQV SGC/100 mg RTV once daily. Once-daily SQV HGC/RTV, 1600/100 mg, may be easier to use in developing countries and may increase access where drug costs can be less, the capsule size is smaller, and the need for refrigeration is lessened.

Administration, Oral↗
PubMed2003

Pharmacokinetics of lower doses of saquinavir soft-gel caps (800 and 1200 mg twice daily) boosted with itraconazole in HIV-1-positive patients.

OBJECTIVE: The pharmacokinetics of 800 mg and 1200 mg of saquinavir soft-gel caps (SQV-SGC) twice daily plus 100 mg itraconazole once daily were compared to 1400 mg SQV-SGC twice daily without itraconazole. METHODS: The pharmacokinetics of SQV were determined in 17 randomly selected patients on 1400 mg twice daily SQV-SGC without itraconazole and after 2 weeks with lower SQV-SGC doses plus itraconazole. SQV plasma concentrations were determined by HPLC. Pharmacokinetic parameters were calculated by a non-compartmental model. RESULTS: Median (+IQR) area under plasma concentration-versus-time curve (AUC0-12h) were 3.33 (1.96-7.34), 4.29 (3.14-7.67) and 4.07 (2.76-4.49) mg/l x h for SQV 1400 mg without itraconazole, SQV 1200 mg with itraconazole and SQV 800 mg with itraconazole, respectively. These differences were not statistically significant. The median Cmin was above the proposed minimum effective concentration of 0.05 mg/l for all three regimens. CONCLUSION: SQV-SGC 800 mg or 1200 mg twice daily boosted with 100 mg of itraconazole once daily resulted in adequate SQV pharmacokinetics not significantly different from SQV-SGC 1400 mg twice daily.

Adult↗
PubMed2002

Dose-escalating study of the safety and pharmacokinetics of nelfinavir in HIV-exposed neonates.

The pharmacokinetics of nelfinavir (NFV) in neonates younger than 4 weeks of age was assessed. Three cohorts of HIV-exposed neonates were enrolled in cohorts to receive 15, 30, and 45 mg of NFV/kg twice daily in combination with stavudine and didanosine for 4 weeks after birth. Trough NFV concentrations (C(min)) were measured at 1 and 7 days of age. Intensive pharmacokinetic evaluations were performed at 14 and 28 days of age. The median NFV C(min) values in the 15 mg/kg (6 patients), 30 mg/kg (5), and 45 mg/kg (11) cohorts at 1, 7, 14, and 28 days of age were 0.19, 1.21, 0.51, and 0.33; 1.02, 3.18, 0.73, and 0.55; and 0.67, 3.21, 0.70, and 0.73 mg/L, respectively. The median area under the plasma concentration-versus-time curve values over 12 hours in the three cohorts at 14 and 28 days of age were 14.4 and 8.7, 19.4 and 15.8, and 23.4 and 18.5 (h. mg)/L, respectively. No serious adverse events were observed. In conclusion, the systemic exposure of NFV decreased after 7 days of age, possibly because of hepatic enzyme maturation, autoinduction of NFV metabolism, and/or changes in NFV absorption. The highly variable systemic exposure observed in the study indicates that therapeutic drug monitoring seems warranted to ensure adequate NFV dosing in this population.

Adult↗
PubMed2002

Simplifying protease inhibitor therapy with once-daily dosing of saquinavir soft-gelatin capsules/ritonavir (1600/100 mg): HIVNAT 001.3 study.

OBJECTIVE: To determine the feasibility of switching therapy for HIV-1-infected patients with plasma viral loads of <50 HIV-1 RNA copies/mL who are receiving twice-daily saquinavir soft-gelatin capsules (SQV-SGC) plus dual nucleoside reverse transcriptase inhibitors (NRTIs) to a regimen containing once-daily SQV-SGC/ritonavir (RTV). DESIGN: Therapy for patients with plasma viral loads of <50 copies/mL after 2 years of treatment with twice-daily SQV-SGC (1400 mg) plus zidovudine/lamivudine or didanosine/stavudine was switched to once-daily SQV-SGC/RTV (1600/100 mg) with continuing NRTI treatment. METHODS: Safety and efficacy (determined by plasma viral load and CD4 cell count) were evaluated (week 24). For 12 patients, steady-state plasma pharmacokinetics of SQV was determined (week 4). RESULTS: Once-daily SQV-SGC/RTV was well tolerated. No patient changed regimens. After 24 weeks, 64 (93%) of 69 patients had plasma viral loads of <50 copies/mL (the remaining 5 patients had plasma viral loads of <300 copies/mL). The median CD4 cell count increased from 534/mL at the start of once-daily SQV-SGCs/RTV to 695/mL after 24 weeks (p <.001). Compared with the preceding 24 weeks of treatment with twice-daily SQV-SGC, the CD4 cell count improved significantly during once-daily SQV-SGC/RTV therapy (p <.001). All patients maintained SQV trough concentrations (C(24h)) of >0.05 mg/L. Median values for the area under the plasma concentration-versus-time curve from 0 to 24 hours (AUC(0-24h)), maximal concentration (C(max)), and C(24h) for SQV were 48.1 (h.mg)/L, 6.98 mg/L, and 0.17 mg/L, respectively. Body weight was inversely correlated with SQV AUC(24h) and C(24h) (p <.01). CONCLUSIONS: Clinical and pharmacokinetic data support once-daily SQV-SGC/RTV (1600/100 mg) with two NRTIs as a convenient and safe therapeutic regimen to maintain viral suppression and immune function in HIV-1-infected patients with plasma viral loads of <50 copies/mL.

Adult↗
PubMed2002

Potential benefit and limitations of a broad access to potent antiretroviral therapy in developing countries.

In industrialised countries, highly active antiretroviral therapy (HAART) has drastically reduced HIV mortality. Only few developing countries have introduced HAART on a large scale, leaving millions of HIV-infected individuals without life-saving therapy. Although HAART appears to be economically viable for middle income countries, it remains unaffordable for many of the poorest and worst affected nations. In response, significant discounts for antiretrovirals and debt relief have been granted. Apart from economic problems, other important issues need to be addressed before antiretroviral therapy can be optimally utilised, including the logistics of drug supply, HIV education for hospital staff and patients, and laboratory facilities that allow clinicians to assess the efficacy of HAART.

Antiretroviral Therapy, Highly Active↗
PubMed2002

Significant differences between plasma HIV-1 RNA assays in HIV-1 subtype E infected patients treated with antiretroviral therapy.

UNLABELLED: A total of 72 HIV-1 infected Thai patients treated with didanosine (ddI) or stavudine (d4T) plus ddI at the time of interim analysis were analyzed. Sixty patients (83%) carried subtype E documented by HIV-1 V3 serotyping. HIV-1 RNA levels were measured using three commercial viral load assays. At baseline (n = 57), Quantiplex 2.0 and NucliSens 2.0 showed mean log10 HIV-1 RNA of 0.7 log10 or 5 fold lower than Amplicor 1.5 (mean 4.29 versus 5.0 log10, respectively, p < 0.001). At week 20 of treatment (n = 29), HIV-1 RNA levels were detected in 55.2%, 31%, and 33.5% of subjects tested by Amplicor 1.5, Quantiplex 2.0, and NucliSens 2.0, respectively. IN CONCLUSION: plasma HIV-1 RNA analyses showed comparable values with Quantiplex 2.0 and NucliSens 2.0 assays. In contrast, Amplicor 1.5 resulted in approximately 5 folds higher HIV-1 RNA levels and a 25% higher rate of detection of plasma HIV-1 RNA as compared to the other two assays. As the current goal of therapy is to suppress plasma viral load below the detection limit of the assays, the significant differences between the assays may influence antiretroviral efficacy evaluation and management.

Adult↗
PubMedDate not supplied

HIV/AIDS in Asia.

HIV (ie, HIV-1) epidemics in Asia show great diversity, both in severity and timing. But epidemics in Asia are far from over and several countries including China, Indonesia, and Vietnam have growing epidemics. Several factors affect the rate and magnitude of growth of HIV prevalence, but two of the most important are the size of the sex worker population and the frequency with which commercial sex occurs. In view of the present state of knowledge, even countries with low prevalence of infection might still have epidemics affecting a small percentage of the population. Once HIV infection has become established, growing needs for care and treatment are unavoidable and even the so-called prevention-successful countries of Thailand and Cambodia are seeing burgeoning care needs. The manifestations of HIV disease in the region are discussed with the aim of identifying key issues in medical management and care of HIV/AIDS. In particular, issues relevant to developing appropriate highly active antiretroviral treatment programmes in the region are discussed. Although access to antiretroviral therapy is increasing globally, making it work effectively while simultaneously expanding prevention programmes to stem the flow of new infections remains a real challenge in Asia. Genuine political interest and commitment are essential foundations for success, demanding advocacy at all levels to drive policy, mobilise sufficient resources, and take effective action.

AIDS Vaccines↗
PubMedDate not supplied

V-1 Immunitor.

Explore the source record for details and available documents.

AIDS Vaccines↗
PubMedDate not supplied

Beneficial effect of macrophage activating agent NK-4 on Thai HIV-infected patients.

BACKGROUND: We examined the effect of NK-4 (4,4'-[3-[2-(1-ethyl-4(1H)-quinolinylidene) ethylidene] propenylene] bis(-ethylquinolinium iodide)) on the clinical course of Thai HIV-infected patients receiving antiretroviral drugs. PATIENTS AND METHODS: Twelve subjects with CD4 count < 500/mm3 were enrolled to receive 0.5 mg of NK-4 orally once daily for 8 weeks and then twice daily during the follow-up. RESULTS: Most patients showed vitality, increased appetite, stable body-weight, increased CD4 counts and no serious adverse effects due to viral load. We suggest that the increased CD4 counts are due to the macrophage activating effect of NK-4. The patients with increased CD4 counts showed lower alpha-N-acetylgalactosaminidase (alpha-NaGalase) activity than those with decreased CD4 counts. CONCLUSION: These results suggest that the macrophage activating agent NK-4, as an inexpensive and safe drug for HIV-infected patients, may play a beneficial role in the clinical treatment of HIV-infected patients.

Adult↗