22 research outputs found
Saquinavir trough concentration before and after switching NRTI to tenofovir in patients treated with once-daily saquinavir hard gel capsule/ritonavir 1600 mg/100 mg
No full textReduced markers of HIV persistence and restricted HIV-specific immune responses after early antiretroviral therapy in children
No full textInterruptions of tenofovir/emtricitabine-based antiretroviral therapy in patients with HIV/hepatitis B virus co-infection
No full textThai patients enrolled in STACCATO with HIV/hepatitis B virus (HBV) co-infection and tenofovir/emtricitabine-based antiretroviral therapy (ART) were randomly assigned to continuous treatment or CD4 cell count-guided interruptions. HBV replication was suppressed below detection in 15/16 patients. Structured treatment interruption increased transaminases and HBV viraemia in five of six patients; one flare was severe. Conversion to anti-hepatitis Be occurred with continuous treatment only. Tenofovir/emtricitabine-containing ART is highly effective in controlling chronic HIV/HBV co-infection but treatment should not be interrupted
Pharmacokinetics of lower doses of saquinavir soft-gel caps (800 and 1200 mg twice daily) boosted with itraconazole in HIV-1-positive patients
No full textOBJECTIVE: 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 dail
Supersensitive Viral Load Assay in Predicting CD4-Guided Treatment Failure
No full textIn HIV patients who discontinue highly active antiretroviral therapy (HAART), the degree of HIV RNA suppression at the time of treatment interruption may predict success of re-treatment after the interruption (STI). A case-control substudy of the Staccato trial in Thailand included CD4-guided STI subjects with HIV RNA > 50 copies /ml (virological failure cases, n=11) and HIV RNA < 50 copies/ml (controls, n=22) after 12-24 weeks of HAART re-treatment following a median of 2 STI cycles. Controls were matched for age, gender and pre-ART CD4 count. HIV RNA with 5 copies/ml detection limit was determined on pre-virological failure samples. HIV RNA increased in cases compared to controls with each successive STI cycle (p-trend across time-points 0.004). The last HIV RNA below 50 copies/ml was significantly higher among cases compared to controls (p=.004). Measuring HIV RNA below 50 copies/ml may be useful in predicting virological failure to STI
A Prospective, Randomized Trial of Structured Treatment Interruption for Patients with Chronic HIV Type 1 Infection
No full textBackground. Structured treatment interruption was evaluated in 74 patients who had been pretreated with antiretrovirals, consisting of 2 nucleoside reverse-transcriptase inhibitors (NRTIs) for 1 year followed by 3 years of highly active antiretroviral therapy containing a protease inhibitor. Methods. Patients with a CD4 cell count of ⩾350 cells/µL and a plasma viral load of <50 copies/mL were randomized to 3 therapy arms: (1) continuous therapy, (2) CD4 cell count—guided theory, and (3) week-on/week-off (WOWO) therapy. The efficacy and safety of structured treatment interruption and antiretroviral use were evaluated in human immunodeficiency type 1 (HIV-1)—infected patients. The study end points were percentage of patients who developed AIDS or who died and a CD4 cell count of ⩾350 cells/µL. Intergroup differences were analyzed using analysis of variance and Kruskal-Wallis tests. Results. Baseline characteristics at the start of the structured treatment interruption were similar. At week 48, no patient had died, and 1 patient in the WOWO group had an AIDS-defining condition. The proportions of patients with a CD4 cell count of ⩾350 cells/µL were 100%, 87%, and 96% in treatment arms 1, 2, and 3, respectively. The percentages of weeks of antiretroviral use were 100%, 41.1%, and 69.8% in arms 1, 2, and 3, respectively. The adverse events were not significantly different among arms (P = .27). Thirty-one percent of patients in the WOWO group experienced virological failure. Conclusion. WOWO therapy maintained a CD4 cell count of ⩾350 cells/µL in almost all patients but was associated with high virological failures rates (possibly resulting from previous dual-NRTI therapy), indicating that this strategy is less useful. Receipt of CD4 cell count—guided therapy resulted in comparable clinical outcomes to continuous therapy and may save antiretroviral-associated costs, but this needs to be confirmed by a larger tria
Highly active antiretroviral therapy (HAART) retreatment in patients on CD4-guided therapy achieved similar virologic suppression compared with patients on continuous HAART: the HIV Netherlands Australia Thailand Research Collaboration 001.4 study
No full textOBJECTIVE: To assess the safety of 2 intermittent treatment strategies compared with continuous therapy for patients with virologic suppression on highly active antiretroviral therapy (HAART) at baseline. DESIGN: Seventy-four nucleoside reverse transcriptase inhibitor (NRTI) and protease inhibitor (PI) pretreated patients with an HIV RNA level <50 copies at screening were randomized to continuous treatment, CD4-guided treatment, or week-on-week-off treatment with 2 NRTIs plus 1600 mg/100 mg of saquinavir/ritonavir once daily. At week 96 (end of the randomized phase of the study), all patients were given continuous HAART for 12 weeks to week 108. Primary outcomes were the proportion of patients with a CD4 count >350 cells/microL and HIV RNA level <400 copies/mL at week 108. METHODS: Patients were followed up every 12 weeks for CD4 count, HIV RNA level, and clinical and laboratory toxicities. In the CD4-guided arm, treatment was stopped and restarted using a CD4 count threshold (above or below 350 cells/microL or reduction of 30%). RESULTS: Seventy-four patients were enrolled with a median CD4 count of 644 cells/microL before the structured treatment interruption (STI). The week-on-week-off arm (n=26) was discontinued at week 72 because of high rates (46%) of HIV RNA rebound above 50 copies/mL. In the continuous arm, 25 (100%) of 25 patients and 24 (96%) of 25 patients had an HIV RNA level <400 copies/mL and <50 copies/mL, respectively, at week 108, and 96% had a CD4 count above 350 cells/microL, with a median CD4 count of 661 cells/microL. Patients in the CD4-guided arm had a significantly lower median CD4 count (489 cells/microL) than the patients in the continuous arm (P=0.03), but all had a CD4 count above 350 cells/microL and 1 had a new HIV-related illness. At week 108, 21 (91%) of 23 patients and 13 (57%) of 23 patients had an HIV RNA level <400 copies/mL and <50 copies/mL, respectively. Those who did not achieve an HIV RNA level <50 copies/mL had a higher HIV RNA load before retreatment, and 4 of 5 patients subsequently achieved viral suppression after an additional 12 weeks of HAART (week 120). Therefore, 17 (94%) of 18 evaluable CD4-guided arm patients achieved viral suppression after retreatment. Antiretroviral (ARV) side effects were similar in all arms. CD4-guided treatment had a 54% ARV cost savings. CONCLUSIONS: This pilot study suggests that CD4-guided HAART is a well-tolerated and cost-saving treatment strategy for patients with high pre-ARV and pre-STI CD4 counts. Week-on-week-off treatment had a high virologic failure rate and was discontinued. The HIV RNA suppression rate was similar in patients treated with continuous HAART and in those retreated with 12 to 24 weeks of HAART after CD4-guided therapy
Pharmacokinetics and pharmacodynamics of indinavir with or without low-dose ritonavir in HIV-infected Thai patients
No full textObjectives: To describe the pharmacokinetics and pharmacodynamics of indinavir with or with-out low-dose ritonavir in human immunodeficiency virus (HIV)-infected Thai patients. Patients and methods: Thirty-six HIV-1-infected patients who participated in HIV-NAT 005 study gave informed consent to record a pharmacokinetic curve 4 weeks after starting a regimen con-taining either indinavir 800 mg every 8 h (n = 19) or indinavir 800 mg + ritonavir 100 mg every 12 h (n = 17). Indinavir plasma concentrations were measured by HPLC. Pharmacokinetic parameters were calculated by non-compartmental methods. Results: The median (interquartile range; IQR) body weight of the 36 patients (11 females and 25 males) was 60 (54–72) kg. Median and IQR values for indinavir AUC, Cmax and Cmin were 20.9 (13.1–27.0) mg⋅h/L, 8.1 (6.6–9.4) mg/L and 0.13 (0.09–0.27) mg/L, respectively, for indinavi
Neurocognitive impairment in patients randomized to second-line lopinavir/ritonavir-based antiretroviral therapy vs. lopinavir/ritonavir monotherapy
No full textWe compared rates of neurocognitive impairment (NCI) among 93 Thai adults failing non-nucleoside reverse transcriptase inhibitor (NNRTI)-based combination antiretroviral therapy (cART) before and after switching to lopinavir/ritonavir monotherapy (mLPV/r) vs. tenofovir/lamivudine/LPV/r (TDF/3TC/LPV/r). Participants completed the Color Trails 1 and 2, Digit Symbol, and Grooved Pegboard at weeks 0, 24, and 48. We calculated z-scores using normative data from 451 healthy HIV-negative Thais. We defined NCI as performance of <-1 SD on ≥2 tests. The Thai depression inventory was used to capture depressive symptoms. Lumbar puncture was optional at week 0 and 48. At baseline, median (IQR) age was 36.9 (32.8-40.5) years, and 46 % had primary school education or lower. The median CD4 count was 196 (107-292) cells/mm(3), and plasma HIV RNA was 4.1 (3.6-4.5) log(10) copies/ml. Almost all (97 %) had circulating recombinant CRF01_AE. At baseline, 20 (47 %) of the mLPV/r vs. 22 (44 %) of TDF/3TC/LPV/r arms met NCI criteria (p = 0.89). The frequency of NCI at week 48 was 30 vs. 32 % (p = 0.85) with 6 vs. 7 % (p = 0.85) developing NCI in the mLPV/r vs. TDF/3TC/LPV/r arms, respectively. Having NCI at baseline and lower education each predicted NCI at week 48. Depression scores at week 48 did not differ between arms (p = 0.47). Cerebrospinal fluid HIV RNA of <50 copies/ml at 48 weeks was observed in five out of seven in mLPV/r vs. three out of four in TDF/3TC/LPV/r arm. The rates of NCI and depression did not differ among cases failing NNRTI-based cART who received mLPV/r compared to LPV/r triple therapy
Pharmacokinetics of once-daily saquinavir hard-gelatin capsules and Saquinavir soft-gelatin capsules boosted with Ritonavir in HIV-1-infected subjects
No full textOBJECTIVE: 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 lessene
