Anton Pozniak

Bio: Anton Pozniak is an academic researcher from Imperial College London. The author has contributed to research in topics: Ritonavir & Viral load. The author has an hindex of 53, co-authored 241 publications receiving 13079 citations. Previous affiliations of Anton Pozniak include Oxleas NHS Foundation Trust & Bristol-Myers Squibb.

Efficacy and safety of tenofovir DF vs stavudine in combination therapy in antiretroviral-naive patients: a 3-year randomized trial.

Abstract: ContextTenofovir disoproxil fumarate (DF) is a once-daily nucleotide analogue reverse transcriptase inhibitor.ObjectiveTo evaluate the efficacy and safety of tenofovir DF compared with stavudine in antiretroviral-naive patients.Design, Setting, and ParticipantsA prospective, randomized, double-blind study conducted at 81 centers in the United States, South America, and Europe from June 9, 2000, to January 30, 2004. A total of 753 patients infected with HIV who were antiretroviral naive were screened and 602 patients entered the study.InterventionPatients were randomized to receive either tenofovir DF (n = 299) or stavudine (n = 303), with placebo, in combination with lamivudine and efavirenz.Main Outcome MeasureProportion of patients with HIV RNA levels of less than 400 copies/mL at week 48.ResultsIn the primary intent-to-treat analysis in which patients with missing data or who added or switched antiretroviral medications before week 48 were considered as failures, the proportion of patients with HIV RNA of less than 400 copies/mL at week 48 was 239 (80%) of 299 in patients receiving tenofovir DF and 253 (84%) of 301 in patients receiving stavudine (95% confidence interval, −10.4% to 1.5%), exceeding the predefined −10% limit for equivalence. However, equivalence was demonstrated in the secondary analyses (HIV RNA <50 copies/mL) at week 48 and through 144 weeks. Virologic failure was associated most frequently with efavirenz and lamivudine resistance. Through 144 weeks, the K65R mutation emerged in 8 and 2 patients in the tenofovir DF and stavudine groups, respectively (P = .06). A more favorable mean change from baseline in fasting lipid profile was noted in the tenofovir DF group at week 144: for triglyceride levels (+1 mg/dL for tenofovir DF [n = 170] vs +134 mg/dL for stavudine [n = 162], P<.001), total cholesterol (+30 mg/dL [n = 170] vs +58 mg/dL [n = 162], P<.001), direct low-density lipoprotein cholesterol (+14 mg/dL [n = 169] vs +26 mg/dL [n = 161], P<.001), and high-density lipoprotein cholesterol (+9 mg/dL [n = 168] vs +6 mg/dL [n = 154], P = .003). Investigator-reported lipodystrophy was less common in the tenofovir DF group compared with the stavudine group (9 [3%] of 299 vs 58 [19%] of 301, P<.001). The number of bone fractures and the renal safety profile were similar between the 2 groups.ConclusionsThrough 144 weeks, the combination of tenofovir DF, lamivudine, and efavirenz was highly effective and comparable with stavudine, lamivudine, and efavirenz in antiretroviral-naive patients. However, tenofovir DF appeared to be associated with better lipid profiles and less lipodystrophy.

Tenofovir DF, Emtricitabine, and Efavirenz vs. Zidovudine, Lamivudine, and Efavirenz for HIV

Abstract: background Durable suppression of replication of the human immunodeficiency virus (HIV) depends on the use of potent, well-tolerated antiretroviral regimens to which patients can easily adhere. methods We conducted an open-label, noninferiority study involving 517 patients with HIV infection who had not previously received antiretroviral therapy and who were randomly assigned to receive either a regimen of tenofovir disoproxil fumarate (DF), emtricitabine, and efavirenz once daily (tenofovir–emtricitabine group) or a regimen of fixed-dose zidovudine and lamivudine twice daily plus efavirenz once daily (zidovudine–lamivudine group). The primary end point was the proportion of patients without baseline resistance to efavirenz in whom the HIV RNA level was less than 400 copies per milliliter at week 48 of the study. results Through week 48, significantly more patients in the tenofovir–emtricitabine group reached and maintained the primary end point of less than 400 copies of HIV RNA per milliliter than did those in the zidovudine–lamivudine group (84 percent vs. 73 percent, respectively; 95 percent confidence interval for the difference, 4 to 19 percent; P = 0.002). This difference excludes the inferiority of the tenofovir DF, emtricitabine, and efavirenz regimen, indicating a significantly greater response with this regimen. Significant differences were also seen in the proportion of patients with HIV RNA levels of less than 50 copies per milliliter (80 percent in the tenofovir– emtricitabine group vs. 70 percent in the zidovudine–lamivudine group; 95 percent confidence interval for the difference, 2 to 17 percent; P = 0.02) and in increases in CD4 cell counts (190 vs. 158 cells per cubic millimeter, respectively; 95 percent confidence interval for the difference, 9 to 55; P = 0.002). More patients in the zidovudine–lamivudine group than in the tenofovir–emtricitabine group had adverse events resulting in discontinuation of the study drugs (9 percent vs. 4 percent, respectively; P = 0.02). In none of the patients did the K65R mutation develop. conclusions Through week 48, the combination of tenofovir DF and emtricitabine plus efavirenz fulfilled the criteria for noninferiority to a fixed dose of zidovudine and lamivudine plus efavirenz and proved superior in terms of virologic suppression, CD4 response, and adverse events resulting in discontinuation of the study drugs. (ClinicalTrials. gov number, NCT00112047.)

Efficacy of short-term monotherapy with maraviroc, a new CCR5 antagonist, in patients infected with HIV-1.

Abstract: We assessed the efficacy and safety of 10-d monotherapy with the orally administered CCR5 antagonist maraviroc in 63 HIV-1-positive individuals prescreened for the absence of CXCR4-using virus Maximum reduction in viral load occurred at a median of 10-15 d, with a mean reduction of >or=16 log(10) copies/ml at all twice daily doses >or=100 mg These results provide proof of concept that CCR5 antagonism is a viable antiretroviral therapeutic approach

European AIDS Clinical Society (EACS) guidelines for the clinical management and treatment of HIV-infected adults

Abstract: A working group of the European AIDS Clinical Society (EACS) have developed these guidelines for European clinicians to help them in the treatment of adults with HIV infection. This third version of the guidelines includes, as new topics, the assessment of patients at initial and subsequent clinic visits as well as post-exposure prophylaxis. A revision of the 2005 guidelines based on current data includes changes in the sections on primary HIV infection, when to initiate therapy, which drug combinations are preferred as initial combination regimens for antiretroviral-naive patients, how to manage virological failure and the treatment of HIV during pregnancy. In Europe, there is a wide range of clinical practices in antiretroviral therapy depending on various factors such as drug registration, national policies, local availability, reimbursement and access to treatment. These can vary greatly from one country to another, especially in Central and Eastern parts of Europe. These guidelines are intended to help clinicians achieve the best care for their patients. In some countries, particularly where the quality of and access to care are not optimal, these guidelines should help AIDS societies and physicians or patient group organizations to negotiate with their national health authorities with a view to implementing what should be the standard of care for HIV-infected patients all over Europe.

Preexposure Chemoprophylaxis for HIV Prevention in Men Who Have Sex with Men

Abstract: The study subjects were followed for 3324 person-years (median, 1.2 years; maximum, 2.8 years). Of these subjects, 10 were found to have been infected with HIV at en rollment, and 100 became infected during follow-up (36 in the FTC–TDF group and 64 in the placebo group), indicating a 44% reduction in the incidence of HIV (95% confidence interval, 15 to 63; P = 0.005). In the FTC–TDF group, the study drug was detected in 22 of 43 of seronegative subjects (51%) and in 3 of 34 HIV-infected subjects (9%) (P<0.001). Nausea was reported more frequently during the first 4 weeks in the FTC–TDF group than in the placebo group (P<0.001). The two groups had similar rates of serious adverse events (P = 0.57). Conclusions Oral FTC–TDF provided protection against the acquisition of HIV infection among the subjects. Detectable blood levels strongly correlated with the prophylactic effect. (Funded by the National Institutes of Health and the Bill and Melinda Gates Foun dation; ClinicalTrials.gov number, NCT00458393.)

The growing burden of tuberculosis: global trends and interactions with the HIV epidemic.

Abstract: BACKGROUND: The increasing global burden of tuberculosis (TB) is linked to human immunodeficiency virus (HIV) infection. METHODS: We reviewed data from notifications of TB cases, cohort treatment outcomes, surveys of Mycobacterium tuberculosis infection, and HIV prevalence in patients with TB and other subgroups. Information was collated from published literature and databases held by the World Health Organization (WHO), the Joint United Nations Programme on HIV/Acquired Immunodeficiency Syndrome (UNAIDS), the US Census Bureau, and the US Centers for Disease Control and Prevention. RESULTS: There were an estimated 8.3 million (5th-95th centiles, 7.3-9.2 million) new TB cases in 2000 (137/100,000 population; range, 121/100,000-151/100,000). Tuberculosis incidence rates were highest in the WHO African Region (290/100,000 per year; range, 265/100,000-331/100,000), as was the annual rate of increase in the number of cases (6%). Nine percent (7%-12%) of all new TB cases in adults (aged 15-49 years) were attributable to HIV infection, but the proportion was much greater in the WHO African Region (31%) and some industrialized countries, notably the United States (26%). There were an estimated 1.8 million (5th-95th centiles, 1.6-2.2 million) deaths from TB, of which 12% (226 000) were attributable to HIV. Tuberculosis was the cause of 11% of all adult AIDS deaths. The prevalence of M tuberculosis-HIV coinfection in adults was 0.36% (11 million people). Coinfection prevalence rates equaled or exceeded 5% in 8 African countries. In South Africa alone there were 2 million coinfected adults. CONCLUSIONS: The HIV pandemic presents a massive challenge to global TB control. The prevention of HIV and TB, the extension of WHO DOTS programs, and a focused effort to control HIV-related TB in areas of high HIV prevalence are matters of great urgency.