The KLEAN study of fosamprenavir-ritonavir versus lopinavir-ritonavir, each in combination with abacavir-lamivudine, for initial treatment of HIV infection over 48 weeks: a randomised non-inferiority trial
ABSTRACT Lopinavir-ritonavir is a preferred protease inhibitor co-formulation for initial HIV-1 treatment. Fosamprenavir-ritonavir has shown similar efficacy and safety to lopinavir-ritonavir when each is combined with two nucleoside reverse transcriptase inhibitors. We compared the two treatments directly in antiretroviral-naive patients.
This open-label, non-inferiority study included 878 antiretroviral-naive, HIV-1-infected patients randomised to receive either fosamprenavir-ritonavir 700 mg/100 mg twice daily or lopinavir-ritonavir 400 mg/100 mg twice daily, each with the co-formulation of abacavir-lamivudine 600 mg/300 mg once daily. Primary endpoints were proportion of patients achieving HIV-1 RNA less than 400 copies per mL at week 48 and treatment discontinuations because of an adverse event. The intent-to-treat analysis included all patients exposed to at least one dose of randomised study medication. This study is registered with ClinicalTrials.gov, number NCT00085943.
At week 48, non-inferiority of fosamprenavir-ritonavir to lopinavir-ritonavir (95% CI around the treatment difference -4.84 to 7.05) was shown, with 315 of 434 (73%) patients in the fosamprenavir-ritonavir group and 317 of 444 (71%) in the lopinavir-ritonavir group achieving HIV-1 RNA less than 400 copies per mL. Treatment discontinuations due to an adverse event were few and occurred with similar frequency in the two treatment groups (fosamprenavir-ritonavir 53, 12%; lopinavir-ritonavir 43, 10%). Diarrhoea, nausea, and abacavir hypersensitivity were the most frequent drug-related grade 2-4 adverse events. Treatment-emergent drug resistance was rare; no patient had virus that developed reduced susceptibility to fosamprenavir-ritonavir or lopinavir-ritonavir.
Fosamprenavir-ritonavir twice daily in treatment-naive patients provides similar antiviral efficacy, safety, tolerability, and emergence of resistance as lopinavir-ritonavir, each in combination with abacavir-lamivudine.
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ABSTRACT: Abacavir (ABC) is one of the more affordable antiretroviral drugs used for controlling HIV. Although with similar efficacy to current first-line drugs, its limited usage in Singapore can be attributed to its possible side effect of adverse hypersensitivity reactions (HSRs). HLA-B*5701 genotyping is a clinically relevant procedure for avoiding abacavir-induced HSRs. As patients who do not carry the risk allele are unlikely to develop HSRs, a simple rule can be developed to allow abacavir prescription for patients who are B*5701 negative. Here, we carry out a cost-effectiveness analysis of HLA-B*5701 genotyping before abacavir prescription in the context of the Singapore healthcare system, which caters predominantly to Han Chinese, Southeast-asian Malays, and South-asian Indians. In addition, we aim to identify the most cost-effective treatment regimen for HIV patients. A decision tree model was developed in TreeAge. The model considers medical treatment and genotyping costs, genotyping test characteristics, the prevalence of the risk allele, reduction in the quality of life, and increased expenditure due to side effects and other factors, evaluating independently over early-stage and late-stage HIV patients segmented by drug contraindications. The study indicates that genotyping is not cost-effective for any ethnicity irrespective of the disease stage, except for Indian patients with early-stage HIV who are contraindicated to tenofovir. Abacavir (as first-line) without genotyping is the cheapest and most cost-effective treatment for all ethnicities except for early-stage Indian HIV patients contraindicated to tenofovir. The HLA-B*5701 frequency, the mortality rate from abacavir-induced HSRs, and genotyping costs are among the major factors influencing the cost-effectiveness.Pharmacogenetics and Genomics 11/2014; 25(2). DOI:10.1097/FPC.0000000000000107 · 3.45 Impact Factor
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ABSTRACT: Introduction Diarrhea poses a substantial burden for patients with human immunodeficiency virus (HIV), negatively impacting quality-of-life (QoL) and adherence to antiretroviral therapy. During the combination antiretroviral therapy (cART) era, as incidence of opportunistic infection as a cause of diarrhea decreased, incidence of noninfectious diarrhea (including diarrhea as an adverse event [AE] of cART and HIV enteropathy) increased proportionately. A literature search was conducted for information on prevalence, etiology, and treatment options for noninfectious diarrhea in patients with HIV. Results For marketed antiretroviral therapies, up to 28% of patients live with >4 loose or watery stools per day. The US Food and Drug Administration (FDA) does not require pharmaceutical manufacturers to include, within approved prescribing information, prevalence rates for all grades of diarrhea. Traditionally, noninfectious diarrhea management focused on avoiding use of diarrhea-associated cART; symptom management (nonpharmacologic and/or pharmacologic); and, as a last resort, changing cART. Examining the evidence upon which this approach is based reveals that most strategies rely upon anecdotal information and case reports. This review summarizes the literature and updates clinicians on the most recent options for management of noninfectious diarrhea in patients with HIV. Conclusion Diarrhea in patients with HIV is a significant unmet clinical need that contributes to worsening QoL and complicates medical management. Approaching management using a stepwise method of nonpharmacologic (diet), nonprescription (over-the-counter) and, finally, prescription agent changes (modification of cART or addition of an evidence-based antidiarrheal) appears reasonable, despite a lack of clear scientific evidence to support the initial two steps of this approach. If diet modifications, including psyllium and fiber introduction, fail to resolve noninfectious diarrhea in patients with HIV, loperamide followed by crofelemer should be considered. Clinicians are encouraged to review the most recent literature, not rely upon prescribing information. Continued vigilance by HIV providers to the presence of gastrointestinal AEs, even in patients taking the most recently approved antiretroviral agents, is warranted. Additional research is justified in identifying the etiology and management of HIV-associated diarrhea in patients on successful cART regimens. Electronic supplementary material The online version of this article (doi:10.1007/s40121-014-0047-5) contains supplementary material, which is available to authorized users.11/2014; 3(2). DOI:10.1007/s40121-014-0047-5
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ABSTRACT: Lopinavir/ritonavir (LPV/r) is the first ritonavir-boosted protease-inhibitor used in second-line anti-retroviral treatment (ART) in resource-limited regions. To evaluate the efficacy and safety outcomes of LPV/r in treatment-naïve and -experienced HIV-infected adults and pregnant women, we performed a meta-analysis of randomized controlled trials. Ten cohorts from 8 articles involving 2,584 ART-naïve patients, 5 cohorts from 4 articles involving 1,124 ART-experienced patients, and 8 cohorts from 7 articles involving 2,191 pregnant women were selected for the meta-analyses. For ART-naïve patients, the virologic response rate (72.3%) of LPV/r combined with tenofovir (TDF) plus lamivudine/emtricitabine (3TC/FTC) arms was significantly greater than that of LPV/r plus non-TDF-FTC arms (65.5%, p = 0.047). For ART-experienced patients, the use of LPV/r revealed a 55.7% probability of virologic success. The incidence of abnormal total cholesterol (6.9%) for ART-experienced patients was significantly lower than that for ART-naïve patients (13.1%, p < 0.001). The use of LPV/r in pregnant women revealed a mother-to-child transmission (MTCT) rate of 1.1%, preterm birth rate of 13.2%, and low birth weight rate of 16.2%. Our meta-analysis indicated that LPV/r was an efficacious regimen for ART-naïve patients and was more tolerable for ART-experienced patients. LPV/r also displayed a significant effect in preventing MTCT.Scientific Reports 02/2015; 5:8528. DOI:10.1038/srep08528 · 5.08 Impact Factor