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The safety and efficacy of cidofovir gel for treatment of acyclovir-unresponsive herpes simplex virus infections in AIDS patients was evaluated in a randomized, double-blind, multicenter trial. Cidofovir (0.3% or 1%) or placebo gel was applied once daily for 5 days. Ten of 20 cidofovir-treated and none of 10 placebo-treated patients had complete healing or >50% decreased area (P = .008); 30% of cidofovir-treated patients versus 0 placebo recipients had complete healing (P = .031). Viral shedding ceased in 13 (87%) of 15 cidofovir-treated and 0 of 9 placebo-treated patients (P = .00004). For cidofovir-treated patients, median time to complete or good response was 21 days, and median time to negative viral culture was 2 days (P = .025, P = .0001, respectively). Median lesion area decreases were 58% for cidofovir-treated versus 0 for placebo-treated patients (P = .005), and mean pain score changes were -1.84 versus -0.34 (P = .042). Application site reactions occurred in 25% of cidofovir-treated and 20% of placebo-treated patients; none was dose-limiting. Cidofovir therapy provided significant benefits in lesion healing, virologic effect, and pain reduction. [ABSTRACT FROM AUTHOR]

Context: Abacavir, a nucleoside analogue, has demonstrated suppression of human immunodeficiency virus (HIV) replication alone and in combination therapy. However, the role of abacavir in a triple nucleoside combination regimen has not been evaluated against a standard protease inhibitor-containing regimen for initial antiretroviral treatment.Objective: To evaluate antiretroviral equivalence and safety of an abacavir-lamivudine-zidovudine regimen compared with an indinavir-lamivudine-zidovudine regimen.Design and Setting: A multicenter, phase 3, randomized, double-blind trial with an enrollment period from August 1997 to June 1998, with follow-up through 48 weeks at 73 clinical research units in the United States, Canada, Australia, and Europe.Patients: Five hundred sixty-two antiretroviral-naive, HIV-infected adults with a plasma HIV RNA level of at least 10 000 copies/mL and a CD4 cell count of at least 100 x 10(6)/L.Interventions: Patients were stratified by baseline HIV RNA level and randomly assigned to receive a combination tablet containing 150 mg of lamivudine and 300 mg of zidovudine twice daily plus either 300 mg of abacavir twice daily and indinavir placebo or 800 mg of indinavir every 8 hours daily plus abacavir placebo. After 16 weeks, patients with confirmed HIV RNA levels greater than 400 copies/mL were eligible to continue receiving randomized treatment or receive open-label therapy.Main Outcome Measure: Virologic suppression, defined as HIV RNA concentration of 400 copies/mL or less at week 48.Results: The proportion of patients who met the end point of having an HIV RNA level of 400 copies/mL or less at week 48 was equivalent in the abacavir group (51% [133/262]) and in the indinavir group (51% [136/265]) with a treatment difference of -0.6% (95% confidence interval [CI], -9% to 8%). In patients with baseline HIV RNA levels greater than 100 000 copies/mL, the proportion of patients achieving less than 50 copies/mL was greater in the indinavir group than in the abacavir group with 45% (45/100) vs 31% (30/96) and a treatment diference of -14% (95% CI, -27% to 0%). The 2 treatments were comparable with respect to their effects on CD4 cell count. There was no difference between groups in the frequency of treatment-limiting adverse events or laboratory abnormalities. One death in the abacavir group was attributed to hypersensitivity reaction, which occurred following rechallenge with abacavir, approximately 3 weeks after initiating study treatment.Conclusions: In this study of antiretroviral-naive HIV-infected adults, the triple nucleoside regimen of abacavir-lamivudine-zidovudine was equivalent to the regimen of indinavir-lamivudine-zidovudine in achieving a plasma HIV RNA level of less than 400 copies/mL at 48 weeks. [ABSTRACT FROM AUTHOR]

Objective: To determine whether prescription patterns of hormone replacement therapy (HRT) differ in African-American, Asian, Latina, Soviet immigrant, and white women.Design: Retrospective review of computerized medical records.Setting: The general internal medicine, family medicine, and gynecology practices of an academic medical center.Patients: Women aged 50 years or older with at least one outpatient visit from January 1, 1992, to November 30, 1995.Measurements and Main Results: Use of HRT was defined as documentation of systemic estrogen use. The main predictor variable was self-identified ethnicity. Age, diagnosis (coronary heart disease, hypertension, diabetes, osteoporosis, or breast cancer), and median income were included in the analysis. Of the 8,968 women (mean age, 65.4 years) included, 50% were white, 20% Asian, 15% African American, 9% Latina, and 6% Soviet immigrants. Whites (33%) were significantly more likely to be prescribed HRT than Asians (21%), African Americans (25%), Latinas (23%), or Soviet immigrants (6.6%), p < 0.01 for each. Multivariate analysis, comparing ethnic groups and controlling for confounding variables, showed that Asians (odds ratio [OR] 0.56; 95% confidence interval [CI] 0.49, 0.64), African Americans (OR 0.70; 95% CI 0.60, 0.81), Latinas (OR 0.70; 95% CI 0.58, 0.84), and Soviet immigrants (OR 0.14; 95% CI 0.10, 0. 20) were each less likely to be prescribed HRT than were white women. Although women with osteoporosis were more likely to receive HRT (OR 2.28; 95% CI 1.71, 2.99), those with coronary heart disease were not (OR 0.88; 95% CI 0.68, 1.09).Conclusions: Physicians at this medical center were more likely to prescribe HRT for white women and women with osteoporosis. Further study is needed to address whether these differences in HRT prescribing result in different health outcomes. [ABSTRACT FROM AUTHOR]

Objective: To test the hypothesis that the therapeutic success rate of oral atovaquone is not worse than that of intravenous pentamidine in the primary treatment of mild and moderate Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome and to detect differences in the toxicity rates of the two treatments.Design: Patients were randomly assigned to receive 21 days of open-label therapy with either atovaquone, 750 mg orally with meals three times daily, or intravenous pentamidine, 3 to 4 mg per kg body weight once daily.Setting: Multicenter study including university and community treatment facilities.Patients: Patients with human immunodeficiency virus infection and clinical presentations consistent with mild or moderate P. carinii pneumonia were eligible. For efficacy and safety analyses, patients with histologically confirmed P. carinii pneumonia were emphasized.Measurements: Patients were monitored by clinical and laboratory evaluations for therapeutic efficacy and adverse events during the acute treatment phase and for 8 weeks after therapy was discontinued.Results: As initial therapy for a histologically confirmed episode of P. carinii pneumonia, 56 patients received atovaquone and 53 received pentamidine. More patients were successfully treated with atovaquone (57%) than with pentamidine (40%), a difference of 17% (95% CI, -3% to 38%; P = 0.085), but more patients failed to respond to atovaquone (29%) than to pentamidine (17%), a difference of 12% (CI, -6% to 29%; P = 0.18). Discontinuation of original therapy because of treatment-limiting adverse events was more frequent in the pentamidine group (36%) than in the atovaquone group (4%) (difference, -32%; CI, -48% to -17%; P < 0.001). Nine patients in each treatment group died during the study.Conclusions: Oral atovaquone and intravenous pentamidine have similar rates for successful treatment of mild and moderate P. carinii pneumonia, but atovaquone has significantly fewer treatment-limiting adverse events. [ABSTRACT FROM AUTHOR]

Abstract Background Low-dose ritonavir (RTV) boosts plasma amprenavir (APV) exposure. Little has been published on the efficacy, tolerability, and safety of APV 600 mg/RTV 100 mg (APV600/RTV) twice daily (BID) compared to APV 1200 mg BID (APV1200). Methods ESS40011 was a 24-week, multicenter, open-label, clinical trial in which antiretroviral therapy-naïve and -experienced HIV-1-infected adults were randomized 3:1 to receive either APV600/RTV BID or APV1200 BID, in combination with ≥ 2 non-protease inhibitor antiretroviral drugs. Non-inferiority of the APV600/RTV regimen to the APV1200 regimen was established if the 95% lower confidence limit for the difference in proportion of patients achieving HIV-1 RNA Results 211 patients were randomized, 158 to APV600/RTV and 53 to APV1200. At week 24, APV600/RTV was similar to or better than APV1200 (HIV-1 RNA P = 0.04), and greater mean reduction from baseline in HIV-1 RNA was observed (-2.21 vs -1.59 log10 copies/mL, P = 0.028). The two treatment arms were similar with respect to mean overall change from baseline in CD4+ count, frequency of drug-related grade 1–4 adverse events, and frequency of discontinuing treatment due to adverse events (most commonly nausea, diarrhea, vomiting or fatigue; 7% vs 8%), although a lower proportion of patients in the APV600/RTV arm experienced drug-related oral/perioral paresthesia (2% vs 8%). Eleven (73%) of 15 patients who had HIV-1 RNA Conclusions APV600 RTV BID was similar to or better than APV1200 BID in virologic response. Virologic results in a small number of patients who continued treatment for 24 weeks post-study suggest that virologic suppression with APV600 RTV BID is durable.

Background Here we report 96- and 144-week follow-up data from VERxVE, which demonstrated that NVP XR (400 mg QD) was non-inferior to NVP IR (200 mg BID), each on a backbone of emtricitabine/tenofovir at 48 weeks. Methods VERxVE was a double-blind, double-dummy, non-inferiority study in adults with screening viral-load (VL) >1000 copies/mL and CD4+ cell count <400 cells/mm3 (males) and <250 cells/mm3 (females). Randomization was stratified by baseline VL (copies/mL), ≤100,000 or >100,000. Primary endpoint was confirmed virologic response (<50 copies/mL) at Week 48. Cochran's statistic incorporating baseline-VL strata tested non-inferiority of XR efficacy to IR. Secondary endpoints included 144-week sustained virologic response and safety. Results 1011 patients were randomized and treated; 736 (NVP XR: 378, NVP IR: 358) completed 144 weeks. Virologic response was 63.6% for NVP XR and 58.5% for NVP IR (adjusted difference of 4.8% [95% CI: −1.1%, 10.8%] favoring NVP XR). No significant differences were seen in changes in CD4+ T cell counts from baseline, virologic failures, and total discontinuation rates between treatment arms regardless of demographic or baseline characteristics. [ABSTRACT FROM AUTHOR]

Purpose of the study The primary Week 48 analysis of this ongoing, randomized, double-blind, double-dummy, active-controlled Phase 3 international trial of elvitegravir/cobicistat/emtricitabine/tenofovir DF (Quad) in treatment-naïve patients demonstrated that Quad was non-inferior to atazanavir boosted by ritonavir (ATV/r) + FTC/TDF with a differentiated safety profile. We report the Week 96 interim data. Methods Key eligibility criteria included HIV-1 RNA≥5,000 c/mL and eGFR≥70 mL/min. Virologic success (HIV-1 RNA <50 c/mL) at Week 96 was assessed per snapshot algorithm. Adverse events and laboratory data were collected prospectively. Bone mineral density (BMD) was assessed by DEXA scan in a subgroup of patients. Results 708 patients (90% male, 74% white, 41% with HIV-1 RNA >100,000 c/mL) were randomized and treated. At Week 48, Quad was non-inferior to ATV/r+FTC/TDF (90% vs 87%, difference 3.0%, 95% CI −1.9% to 7.8%). High rates of virologic success were maintained at Week 96 (83% vs 82%, difference 1.1%, 95% CI −4.5% to 6.7%). Subgroup analysis revealed similar rates of virologic success in patients with baseline HIV-1 RNA >100,000 c/mL (82% vs 80%). Mean CD4 cell increases (cells/mm3) were 256 vs 261 at Week 96. Emergent resistance was infrequent (2% vs<1%). Rates of study drug discontinuation due to adverse events (AEs) were low and comparable (4% vs 6%). Rates of study drug discontinuation due to renal reasons remained low and similar through Week 96 (3 [0.8%] vs 2 [0.6%]); since Week 48, 1 patient in each group discontinued study drug due to serum creatinine (Cr) increase without features of proximal renal tubulopathy. Median increases from baseline in serum Cr (µmol/L [mg/dL]) in Quad vs ATV/r+FTC/TDF at Week 96 (10.6 vs 7.1 [0.12 vs 0.08]) were similar to those at Week 48 (10.6 vs 7.1 [0.12 vs 0.08]). Quad continued to have smaller increases (mmol/L [mg/dL]) in triglycerides (0.06 vs 0.18 [5 vs 16], P=0.012); Quad had greater increases in total cholesterol (0.36 vs 0.21 [14 vs 8], P=0.046) at Week 96 only; changes in LDL and HDL cholesterol were similar. Quad had smaller mean decreases (%) in BMD (hip: −3.16 vs -4.19, P=0.069, spine: −1.96 vs −3.54, P=0.049). Conclusions At Week 96, Quad demonstrated high rates of virologic suppression with low rates of resistance and a differentiated safety and tolerability profile relative to ATV/r+FTC/TDF. These results support the durable efficacy and long-term safety of Quad in HIV-1 infected patients. [ABSTRACT FROM AUTHOR]