ADHERENCE TO HIV POST- EXPOSURE PROPHYLAXIS (PEP) IN

Transcription

1 APPENDIX: STUDY PROTOCOL ADHERENCE TO HIV POST- EXPOSURE PROPHYLAXIS (PEP) IN VICTIMS OF SEXUAL ASSAULT: A SYSTEMATIC REVIEW AND META- ANALYSIS BACKGROUND Sexual assault is a worldwide public health concern that places victims at risk of unplanned pregnancies, psychological morbidity, and sexually-transmitted infections including HIV. HIV post-exposure prophylaxis (PEP) is a short course of antiretroviral therapy offered to individuals at risk of acquiring HIV through occupational or non-occupational routes. Current World Health Organisation (WHO) guidelines recommend a 28-day course of treatment, to be administered within 72 hours of exposure, using a combination of 2 or 3 anti-retroviral drugs. 1 Adherence to PEP is a concern, with studies from a diversity of settings indicating that PEP acceptance, completion and HIV testing rates are generally lower following sexual assault compared to consensual sexual exposures. 2-9 This protocol is for a systematic review to assess rates and determinants of PEP adherence.

2 SEARCH STRATEGY 1. Sexual Assault 2. Post-exposure Prophylaxis 3. Adherence 4. 1 AND AND AND OR 5 OR 6 The following synonyms were used across databases. Appropriate MeSH terms and truncation symbols were used as per database. Sexual Assault: Sex offense, rape, sexual violence, sexual abuse, child sexual abuse, sexual crime Post-exposure Prophylaxis: Post exposure Prophylaxis, Postexposure Prophylaxis, PEP Adherence: Adhere, compliance, comply, concordance, capacitance, conform, medication adherence, treatment compliance, patient compliance DATABASES MEDLINE <1948 to Present> EMBASE Classic + EMBASE <1947 to 2011 April 14> Health Management Information Consortium <1979 to March 2011> PsycInfo <1806 to April Week >

3 The Cochrane Library POPLINE Global Health Library INCLUSION CRITERIA Types of participants Victims of sexual assault, irrespective of age or sex Types of intervention PEP, defined as provision of 28-days antiretroviral therapy, irrespective of drug class or number Types of outcomes Primary: Adherence to 28-day course of PEP Secondary: Refusal to initiate PEP treatment Defaulting from PEP Side-effects Restrictions: No date or language restriction applied DATA EXTRACTION The following data will be extracted from papers: 10,11 Study characteristics Method of adherence measurement Number of patients that started PEP

4 Number of patients that adhered to the full course of PEP Adverse events Method of dispensing PEP PEP regimens Number lost to follow-up Primary outcomes Secondary outcomes Author s interpretation of results QUALITY ASSESSMENT The following indicators will be used as determinants of methodological quality: Study participation rate. (An arbitrary proportion of under 80% was considered poor quality) Defaulting rate from the study. (Greater than 20% was considered poor quality) 12 Were side effects reported? Were inclusion and exclusion criteria specified for patient recruitment? If the studies were experimental- were participants randomised? If studies were experimental-were participants and researchers blinded? Was a statistical analysis carried out? Handling of defaulters Were reasons for discontinuation reported? Was there any attempt to trace defaulters? Was an intention-to-treat analysis carried out?

5 Outcome measurement How was adherence defined? For this quality assessment adherence was defined as greater than or equal to 95% of PEP doses taken (based on the required minimum adherence rates for antiretroviral treatment to be maximally beneficial. 2 How was adherence measured? (Pill count is considered more accurate than self-reporting) Did the author interpret their results in view of study limitations? DATA ANALYSIS Prevalence estimates Point estimates and 95% confidence intervals will be calculated for the proportion of patients adhering to PEP at various stages in the care pathway from acceptance to end-of treatment adherence. The variance of the raw proportions will be stabilised using a Freeman-Tukey type arcsine square-root transformation Meta-analysis Estimates will be pooled using a DerSimonian-Laird random effects model for the overall proportion of adherence and defaulting. Subgroup analyses will compare studies from developed and developing countries, and studies in adults only compared to studies amongst children and/or adolescents. A p-value of <0.05 will be considered significant.

6 Heterogeneity The τ 2 statistic will be reported to assess between-study heterogeneity as this is less affected by the number of studies than the more commonly used I 2 statistic. Statistical software Analyses will be conducted using Stata (version 11, and StatsDirect (version 2.5.2). References 1. World Health Organization. Post-exposure prophylaxis to prevent HIV infection: joint WHO/ILO guidelines on post-exposure prophylaxis (PEP) to prevent HIV infection. 1. Geneva: WHO Press. Report number: 1; Myles JE, Hirozawa A, Katz MH, Kimmerling R, Bamberger JD. Postexposure prophylaxis for HIV after sexual assault. JAMA : the journal of the American Medical Association 2000 Sep 27;284(12): pp Wiebe ER, Comay SE, McGregor M, Ducceschi S. Offering HIV prophylaxis to people who have been sexually assaulted: 16 months' experience in a sexual assault service. CMAJ Canadian Medical Association Journal 2000 Mar 7;162(5): pp

7 4. Linden JA, Oldeg P, Mehta SD, McCabe KK, LaBelle C. HIV postexposure prophylaxis in sexual assault: current practice and patient adherence to treatment recommendations in a large urban teaching hospital. Academic Emergency Medicine 2005 Jul;12(7): pp Olshen E, Hsu K, Woods ER, Harper M, Harnisch B. Use of human immunodeficiency virus postexposure prophylaxis in adolescent sexual assault victims. Archives of Pediatrics and Adolescent Medicine 2006 Jul;160(7): pp Kerr E. The Haven: a pilot referral centre in London for cases of serious sexual assault Mar;110(3): pp Templeton DJ, Davies SC, Garvin AL, Garsia RJ. The uptake of HIV postexposure prophylaxis within a sexual assault setting in Sydney, Australia. International Journal of STD and AIDS 2005 Feb 2005;16(2): pp Kahn JO, Martin JN, Roland ME, Bamberger JD, Chesney M, Chambers D, et al. Feasibility of postexposure prophylaxis (PEP) against human immunodeficiency virus infection after sexual or injection drug use exposure: the San Francisco PEP Study. The Journal of infectious diseases 2001 Mar 1;183(5): pp Schechter M, do Lago RF, Mendelsohn AB, Moreira RI, Moulton LH, Harrison LH, et al. Behavioral impact, acceptability, and HIV incidence among homosexual men with access to postexposure chemoprophylaxis for HIV. Journal of acquired immune deficiency syndromes (1999) 2004 Apr 15;35(5): pp White A, Schmidt K. Systematic literature reviews. Complementary therapies in medicine 2005 Mar;13(1): pp

8 11. NICE. Methods for the development of NICE public health guidance. 2nd ed. Holborn: NICE; Schulz KF, Grimes DA. Sample size slippages in randomised trials: exclusions and the lost and wayward. Lancet 2002 Mar 2; 359(9308): pp