A Pharmacovigilance Study of Adults on Highly Active Antiretroviral Therapy; South Africa: 2007-2011

Background: Of the 1.6 million South African people infected with human immunodeficiency virus (HIV); approximately 970;000 (55) have been initiated on HAART. Despite these numbers; very little has been published about the safety profile of antiretroviral (ARV) medicines in the country. This study was performed at the Medunsa National Pharmacovigilance Centre and aimed to describe the demographic characteristics of patients enrolled in the pharmacovigilance surveillance study; highly active antiretroviral therapy (HAART) initiation regimen patterns; reasons for regimen changes; and adverse effects of ARV medicines. Methods: A cohort study of HIV-infected individuals aged 15 years or older who were on ARV medicines was conducted at four sentinel sites. Results: After HAART initiation; with an average lapse of 17.8 months (range: 0 - 83.8 months); 2;815 patients were enrolled into the study. Results show that patients were observed for 1;606.2 person-years for pharmacy visits (collection of ARV medicines) and 817.1 person-years for clinical visits (consultation with the doctor). Females constituted 69.6 (1;958/2;815) of the study population. Almost all patients initiated HAART on first-line regimens (2;801/2;815). Some patients (6.7; 190/2;815) dropped out of the study after HAART initiation. Reasons for regimen changes were not recorded for 2.5(22/891) of the patients who changed regimens. The primary reason for regimen changes was drug-related toxicity (76.1; 678/891); mostly evident in patients taking first-line regimens. Adverse effects experienced by patients were polyneuropathy (24.0; 163/678); lipodystrophy (23.9; 162/678); neuropathy (10.6; 72/678); and suspected lactic acidosis (3.8; 26/678). Conclusion: The majority of prescribers complied with the HAART guidelines and initiated most patients on first-line regimens. However; adverse effects are evident in patients taking first-line regimens. We recommend that the Department of Health should introduce less toxic first-line ARV regimens. Future efforts will aim to initiate patients on HAART and enrol them into the study simultaneously to determine early risk profiles of ARV medicines

Effects of tegaserod and erythromycin in upper gut dysmotility: a comparative study.

Objectives Tegaserod may enhance upper gut transit, but, its prokinetic effects on antral/small bowel motility and how this compares with erythromycin is unknown. We prospectively assessed and compared the effects of tegaserod and erythromycin on upper gut motility. Methods In an open label, non-crossover study, 22 patients (M/F=4/18; mean age=37 years) with symptoms of upper gut dysmotility underwent 24-hour ambulatory antroduodenojejunal manometry with a six-sensor solid state probe. The effects of 12 mg oral tegaserod were compared with 125 mg intravenous erythromycin by quantifying pressure wave activity and assessing motor patterns. Results Motor activity increased (p<0.05) in antrum, duodenum and jejunum with both drugs when compared to baseline period. The motor response with tegaserod was higher (p<0.05) in jejunum and occurred during the second or third hours, whereas with erythromycin, it was higher (p<0.05) in antrum and occurred within 30 minutes. After tegaserod, a ‘fed-response’ like pattern was seen whereas after erythromycin, large amplitude (>100 mmHg) antral contractions at 3 cycles per minute were seen. Following tegaserod and erythromycin, phase III MMCs occurred in 12 (55%) and 8 (36%) patients respectively (p>0.05). Conclusions Both drugs increase upper gut motility and induce MMC’s, but exert a differential response. Tegaserod produces a more sustained prokinetic effect in the duodenum/ jejunum, whereas erythromycin predominantly increases antral motor activity.