Inhibition of tolbutamide 4-methylhydroxylation by a series of non-steroidal anti-inflammatory drugs in V79-NH cells expressing human cytochrome P4502C10.
We compared biological outcomes in antiretroviral-naive patients with viral load (VL) > 5,000 copies/ml starting combivir-based, three-drug highly active antiretroviral therapy regimens in 2001-2002 according to the third component, namely abacavir (ABC), nelfinavir (NFV), indinavir/ritonavir (IDV/r), lopinavir/ritonavir (LPV/r), nevirapine (NVP) or efavirenz (EFV).
For the last several years, the combination of ddI (didanosine, Videx) and d4T (stavudine, Zerit) as a backbone of three-drug therapy has been popular both in treatment and in research. Together, the two nucleoside analog reverse transcriptase inhibitor (NARTI) drugs offered relatively high strength and fairly simple use. Despite this, some researchers have long questioned the wisdom of the combination as it violates one of the key rules of combining drugs: combine only drugs with different side effect profiles. Both drugs are associated with the development of peripheral neuropathy and pancreatitis. Pancreatitis is more commonly seen with ddI and neuropathy with d4T, but both occur to a significant degree with each drug and to a higher degree than was seen with other drugs of their class. However, few if any studies were run comparing the ddI/d4T combination to alternatives such as AZT/3TC (Combivir) or even 3TC/d4T. Both ddI and d4T come from the same company, Bristol Myers Squibb.
In order to evaluate long-term toxicity of Combivir, we retrospectively reviewed clinical records of HIV-1 infected cases under treatment with Combivir-containing regimen and we analyzed the clinical data compared to other NRTIs-containing regimens.
Once-a-day HAART with ddl+3TC+EFV is a safe and effective alternative to twice-a-day regimens. Once-a-day therapy, with its simple daily schedule, may be proposed as one of the first choice treatments in HIV infection.
Multicenter open-label pilot study. Clinical and biological assessments were performed at baseline and at weeks 2, 4, 8, 16, 24, 32, 40, 48.
A 25-year-old HIV-infected woman participating in a study of the effects of hormonal contraception on HIV disease progression was started on antiretroviral therapy-Combivir & Nevirapine (NVP) on May 27, 2004. NVP was 200mg daily initially for two weeks to be increased to 200mg bid thereafter. On day twelve, she presented with a mild skin rash on the trunk, purulent conjunctivitis, pharyngitis and fever. She was treated symptomatically and sent home. The following day she returned with a generalized erythematous eruption. She was admitted to JCRC (Joint Clinical and Research Centre) on June 14 and was diagnosed with Stevens - Johnson syndrome (SJS). Antiretroviral therapy was stopped. By July 05, 2004, she had improved and was discharged. After recovery she was restarted on Combivir and Efavirenz and is subsequently doing well on this regimen.
An open-label, noninferiority study was carried out. Antiretroviral therapy (ART)-naïve patients with CD4 count ≤ 350 cells/μL and HIV-1 RNA >30000 copies/mL (n=207) were treated with zidovudine/lamivudine and lopinavir/ritonavir. After achieving HIV-1 RNA <50 copies/mL on two consecutive occasions between weeks 12 and 24 after baseline, 120 patients (baseline: median HIV-1 RNA 5.19 log10 copies/mL; median CD4 count 180 cells/μL) were randomized to receive abacavir/lamivudine/zidovudine (ABC/3TC/ZDV) (n=61) or to continue the PI-based ART (n=59).
Of 50 participants recruited (23 to LPVr/ZDV/3TC), 48 started therapy, and 37 participants (19 on LPVr/ZDV/3TC) enrolled in the substudy. At 36 months, the LPVr/ZDV/3TC group had significantly lower limb fat [6.4 kg (0.26) versus 7.3 kg (0.31), P = 0.017] and a trend toward lower abdominal SAT compared to the LPVr/NVP group [131 cm (6.86) versus 146 cm (6.33), P = 0.097]. Over 36 months, mtDNA declined in the LPVr/ZDV/3TC group [mtDNA region 1: -190 (95) copies/cell, P = 0.053, region 2: -269 (106) copies/cell, P = 0.016] but not within the LPVr/NVP group [region 1: +28 (99) copies/cell, P = 0.78, region 2: +51 (111) copies/cell, P = 0.65, between-group difference P < 0.01 for both measurements]. mtDNA was significantly lower in the LPVr/ZDV/3TC group at 36 months.
Three prospective cohort studies reported outcomes of children given zidovudine (ZDV) plus lamivudine (3TC) as a 2-drug PEP regimen. The proportion of children completing the full 28-day course of PEP was 64.0% (95% confidence interval [CI], 41.2%-86.8%), whereas the proportion discontinuing due to adverse events was 4.5% (95% CI, .4%-8.6%). One randomized trial compared abacavir (ABC) plus lamivudine (3TC) and ZDV+3TC as part of a dual or triple first-line antiretroviral therapy regimen; this study showed better efficacy in the ABC-containing combinations and no difference in the time to first serious adverse event. Three randomized trials compared lopinavir/ritonavir (LPV/r) to nevirapine (NVP) for antiretroviral therapy and showed a lower risk of treatment discontinuations associated with LPV/r vs NVP (hazard ratio, 0.56 [95% CI, .41-.75]) but no difference in drug-related adverse events. The overall quality of the evidence was rated as very low.