ABSTRACT
OBJECTIVES: TMC125-C227, an exploratory phase II, randomized, controlled, open-label trial, compared the efficacy and safety of TMC125 (etravirine) with an investigator-selected protease inhibitor (PI) in nonnucleoside reverse transcriptase inhibitor (NNRTI)-resistant, protease inhibitor-naïve, HIV-1-infected patients. METHODS: Patients were randomized to TMC125 800 mg twice a day (bid) (phase II formulation; n=59) or the control PI (n=57), plus two nucleoside reverse transcriptase inhibitors (NRTIs). RESULTS: In an unplanned interim analysis, patients receiving TMC125 demonstrated suboptimal virological responses relative to the control PI. Therefore, trial enrolment was stopped prematurely and TMC125 treatment discontinued after a median of 14.3 weeks. In this first-line NNRTI-failure population, baseline NRTI and NNRTI resistance was high and reduced virological responses were observed relative to the control PI. No statistically significant relationship was observed between TMC125 exposure and virological response at week 12. TMC125 was better tolerated than a boosted PI for gastrointestinal-, lipid- and liver-related events. CONCLUSIONS: In a PI-naïve population, with baseline NRTI and NNRTI resistance and NRTI recycling, TMC125 was not as effective as first use of a PI. Therefore the use of TMC125 plus NRTIs alone may not be optimal in PI-naïve patients with first-line virological failure on an NNRTI-based regimen. Baseline two-class resistance, rather than pharmacokinetics or other factors, was the most likely reason for suboptimal responses.
Subject(s)
HIV Infections/drug therapy , HIV Protease Inhibitors/administration & dosage , HIV-1 , Pyridazines/administration & dosage , Reverse Transcriptase Inhibitors/administration & dosage , Adult , Antiretroviral Therapy, Highly Active/methods , CD4 Lymphocyte Count , Drug Administration Schedule , Drug Resistance, Viral/drug effects , Epidemiologic Methods , Female , HIV Protease Inhibitors/adverse effects , HIV Protease Inhibitors/pharmacokinetics , Humans , Male , Middle Aged , Nitriles , Pyridazines/adverse effects , Pyridazines/pharmacokinetics , Pyrimidines , RNA, Viral , Reverse Transcriptase Inhibitors/adverse effects , Reverse Transcriptase Inhibitors/pharmacokinetics , Viral Load , Young AdultABSTRACT
Coronary heart disease (CHD) is still relatively uncommon in the black population of South Africa. We embarked on a study to determine the prevalence of risk factors leading to CHD in the black population of Durban. The study sample was selected from patients attending a dental clinic at a hospital. A total of 458 Zulus (age range 16-69 years) were studied. The prevalence of CHD was 2.4%. The prevalence percentage of selected risk factors were: hypertension (SBP > or = 140 mmHg and/or a DBP > or = 90 mmHg) was 28%, males 31.9%, females 25.4%; protective levels of high density lipoprotein cholesterol/total cholesterol (HDLC/TC) (> or = 20%) were 81.3%; diabetes, males 4.9%, females 2.9%; smoking > or = ten cigarettes per day, males 28.1%, females 3.4%; obesity, males 3.7%, females 22.6%. We have found the Minnesota Coding System for ECG changes of CHD and Rose questionnaire to be unreliable for eliciting CHD in Blacks. Hypercholesterolaemia is less common and this may explain the low incidence of CHD in Blacks. Epidemics of CHD as seen in the Indian, 'mixed' and white South Africans can still be prevented in the black population but preventive measures must be instituted rapidly.
Subject(s)
Black People , Coronary Disease/ethnology , Coronary Disease/epidemiology , Adult , Female , Humans , Male , Prevalence , Risk Factors , South Africa/ethnology , Urban HealthABSTRACT
Coronary heart disease (CHD) is still relatively uncommon in the black population of South Africa. We embarked on a study to determine the prevalence of risk factors leading to CHD in the black population of Durban. The study sample was selected from patients attending a dental clinic at a hospital. A total of 458 patients (age range 16-69 years) was studied. The prevalence of CHD was 2.4%. The percentage prevalences of selected risk factors were: hypertension (blood pressure > or = 140 mmHg systolic and/or > or = 90 mmHg diastolic) 28% (31.9% for males, 25.4% for females); protective levels of high-density lipoprotein/total cholesterol > or = 20%, 81.3%; diabetes mellitus 4.9% for males, 2.9% for females; smoking > or = 10 cigarettes per day 28.1% for males, 3.4% for females; obesity 3.7% for males 22.6% for females. We found the Minnesota Coding System for electrocardiographic changes of CHD and the Rose questionnaire to be unreliable for eliciting CHD in blacks. Hypercholesterolaemia is less common, and this may explain the low incidence of CHD in blacks. Epidemics of CHD as seen in Indian, coloured and white South Africans can still be prevented in the black population, but preventive measures must be instituted rapidly.
