title: Adverse events and adherence to HIV post-exposure prophylaxis: a cohort study at the Korle-Bu Teaching Hospital in Accra, Ghana.
abstract: BACKGROUND
  There is strong evidence that post-exposure prophylaxis (PEP) with antiretroviral drugs in the timely management of occupational exposures sustained by healthcare workers decreases the risk of HIV infection and PEP is now widely used. Antiretroviral drugs have well documented toxicities and produce adverse events in patients living with HIV/AIDS. In the era of "highly active antiretroviral therapy", non-adherence to treatment has been closely linked to the occurrence of adverse events in HIV patients and this ultimately influences treatment success but the influence of adverse events on adherence during PEP is less well studied.
  
  
  METHODS
  Following the introduction of a HIV post-exposure prophylaxis program in the Korle-Bu Teaching Hospital in January 2005, the incidence of adverse events and adherence were documented in occupationally-exposed healthcare workers (HCWs) and healthcare students (HCSs). Cohort event monitoring was used in following-up on exposed HCWs/HCSs for the two study outcomes; adverse events and adherence. All adverse events reported were grouped by MedDRA system organ classification and then by preferred term according to prophylaxis regimen. Adherence was determined by the completion of prophylaxis schedule. Cox proportional regression analysis was applied to determine the factors associated with the cohort study outcomes. Differences in frequencies were tested using the Chi square test and p < 0.05 was considered statistically significant.
  
  
  RESULTS
  A total of 228 exposed HCWs/HCSs were followed up during the study, made up of 101 exposed HCWs/HCSs administered lamivudine/zidovudine (3TC/AZT) for 3 days; 75 exposed HCWs/HCSs administered lamivudine/zidovudine (3TC/AZT) for 28 days; and 52 exposed HCWs/HCSs administered lamivudine/zidovudine/lopinavir-ritonavir (3TC/AZT/LPV-RTV) for 28 days. The frequency of adverse events was 28% (n = 28) in exposed HCWs/HCSs administered 3TC/AZT for 3 days, 91% (n = 68) in exposed HCWs/HCSs administered 3TC/AZT for 28 days and 96% (n = 50) in exposed HCWs/HCSs administered 3TC/AZT/LPV-RTV for 28 days. Nausea was the most commonly reported adverse events in all three regimens. Adherence was complete in all exposed HCWs/HCSs administered 3TC/AZT for 3days, 56% (n = 42) in exposed HCWs/HCSs administered 3TC/AZT for 28 days and 62% (n = 32) in exposed HCWs/HCSs administered 3TC/AZT/LPV-RTV for 28 days. In the Cox regression multi-variate analysis, exposed HCWs/HCSs administered 3TC/AZT for 3 days were 70% less likely to report adverse events compared with exposed HCWs/HCSs administered 3TC/AZT for 28 days (Adjusted HR = 0.30 [95% CI, 0.18-0.48], p < 0.001). Exposed HCWs/HCSs administered 3TC/AZT for 3 days were 75% more likely to adhere to the schedule compared with exposed HCWs/HCSs administered 3TC/AZT for 28 days (Adjusted HR = 1.75 [95% CI, 1.16-2.66], p = 0.008).
  
  
  CONCLUSIONS
  The intolerance to adverse events was cited as the sole reason for truncating PEP, thereby indicating the need for adequate, appropriate and effective counselling, education, active follow-up (possibly through mobile /phone contact) and management of adverse events. Education on the need to complete PEP schedule (especially for exposed HCWs/HCSs on 28-day schedule) can lead to increased adherence, which is very critical in minimizing the risk of HIV sero-conversion. The present results also indicate that cohort event monitoring could be an effective pharmacovigilance tool in monitoring adverse events in exposed HCWs/HCSs on HIV post-exposure prophylaxis.
authors.affiliation: Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Universiteitsweg 99, 3584 CG, Utrecht, The Netherlands. r_niiatetteh@yahoo.com.|Pharmacy Department, Korle-Bu Teaching Hospital, P.O. Box KB 77, Korle-Bu, Accra, Ghana. r_niiatetteh@yahoo.com.
authors.forename: Raymond A
authors.initials: RA
authors.lastname: Tetteh
authors.affiliation: World Health Organisation Collaborating Centre for Advocacy and Training in Pharmacovigilance, Centre for Tropical Clinical Pharmacology & Therapeutics, School of Medicine and Dentistry, University of Ghana, P. O. Box GP 4236, Accra, Ghana. etnartey@chs.edu.gh.
authors.forename: Edmund T
authors.initials: ET
authors.lastname: Nartey
authors.affiliation: Department of Medicine, School of Medicine and Dentistry, University of Ghana, P. O. Box GP 4236, Accra, Ghana. malart38@yahoo.com.
authors.forename: Margaret
authors.initials: M
authors.lastname: Lartey
authors.affiliation: Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Universiteitsweg 99, 3584 CG, Utrecht, The Netherlands. A.K.Mantel@uu.nl.
authors.forename: Aukje K
authors.initials: AK
authors.lastname: Mantel-Teeuwisse
authors.affiliation: Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Universiteitsweg 99, 3584 CG, Utrecht, The Netherlands. H.G.M.Leufkens@uu.nl.|Medicines Evaluation Board, Utrecht, The Netherlands. H.G.M.Leufkens@uu.nl.
authors.forename: Hubert G M
authors.initials: HG
authors.lastname: Leufkens
authors.affiliation: Department of Epidemiology and Disease Control, School of Public Health, University of Ghana, P.O. Box LG 25, Legon, Accra, Ghana. prisnorts@yahoo.co.uk.
authors.forename: Priscilla A
authors.initials: PA
authors.lastname: Nortey
authors.affiliation: World Health Organisation Collaborating Centre for Advocacy and Training in Pharmacovigilance, Centre for Tropical Clinical Pharmacology & Therapeutics, School of Medicine and Dentistry, University of Ghana, P. O. Box GP 4236, Accra, Ghana. alexooo@yahoo.com.
authors.forename: Alexander N O
authors.initials: AN
authors.lastname: Dodoo
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D015331:Cohort Studies; D004338:Drug Combinations; D005260:Female; D005869:Ghana / Q000453:epidemiology; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology; D006784:Hospitals, Teaching / Q000458:organization & administration; D006801:Humans; D017758:Infectious Disease Transmission, Patient-to-Professional / Q000517:prevention & control*; D019259:Lamivudine / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D016273:Occupational Exposure / Q000009:adverse effects / Q000517:prevention & control*; D056990:Post-Exposure Prophylaxis / Q000706:statistics & numerical data*; D055815:Young Adult; D015215:Zidovudine / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D019380:Anti-HIV Agents; D004338:Drug Combinations; C109078:lamivudine, zidovudine drug combination; D019259:Lamivudine; D015215:Zidovudine