1 / 13

Journal Club

Journal Club. “Implementing a Tenofovir -Base First-Line Regimen in Rural Lesotho: Clinical Outcomes and Toxicities After Two Years” JAIDS 2011 Bygrave et al. Background. - Stavudine (d4T) was the most commonly used backbone drug in resource limited settings (RLS)

lillians
Download Presentation

Journal Club

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Journal Club “Implementing a Tenofovir-Base First-Line Regimen in Rural Lesotho: Clinical Outcomes and Toxicities After Two Years” JAIDS 2011 Bygrave et al

  2. Background -Stavudine (d4T) was the most commonly used backbone drug in resource limited settings (RLS) -Based on RCT’s by Gallant et al in JAMA 2004 (TDF vs d4T) and in NEJM 2006 (TDF/FTC + EFZ vs AZT/3TC + EFZ) the WHO guidelines of 2009 recommended TDF or AZT in favor of d4T -Lesotho adopted these recommendations before the release of these guidelines

  3. Background -Pop. ~ 2 million, 40% below poverty line, GDP around 6 bi $ (wiki) -Almost ¼ of the population is HIV + (UNAIDS) -HIV co-infections: 35.5 % (28.9-42.6) HbCAg +, 5.5% (2.8-9.6%) HbSAg +, 0.5% (0-2.8%) HCV + (Rebenau et al Sex TransmDis 2010) -In US: MMWR 2011 survey on Armed Forces> HIV/HBV: 1.6% HIV/HCV: 1.4% -MSF established a RN run clinic at the Scott Health Service Area in rural Lesotho in 2006

  4. Study Outline -Goal: evaluate real life application of WHO guidelines -Design: Retrospective cohort outcomes study -Setting: RN run rural clinic -Participants: Adults starting HAART from Jan 1 2008 to Dec 31 2008, follow up until Dec 31 2009. Exclusion criteria: GFR < 30 ml/min or no Cr or CD4 at baseline -Data collection: extraction from files by a team of 3 clinicians -End points: (1) death (2) loss for follow up {defined by missing an appointment for > 90 days} (3) 1st toxicity driven switch

  5. Study Outline -TDF prescribed to all non pregnant adults with GFR> 50ml/mim -AZT is pregnant or GFR < 50 ml/min -d4T: excluded from d4T and Hb < 8 g/dl -All on triple Rx with 3TC + nevirapine or efavirenz -HAART started when CD4 < 350 or WHO stage 3 or 4

  6. Study Outline -Nelson Aalen cumulative hazards estimative method to calculate cumulative hazards for regimen change using Cox regression for the following confounders: Age, gender, TB at HAART initiation, pregnancy at HAART initiation, CD4 baseline, and GFR -Nelson Aalen is used to estimate cumulative hazards (vs survival Kaplan-Meier) (wikipedia)

  7. Results

  8. Results -Mortality: 6.5 per 100 patient-years (5.3-7.9) -Non significant trend for higher mortality on non-TDF regimens: TDF CI (3.8-7.0), AZT CI (5.0-11.1), and d4T CI (5.8-11.7) -Trend was sustained on multivariate analysis -Difference of loss for follow up non statistically significant

  9. Results Switch rates • TDF (2.0-4.5) “renal toxicity” • AZT (5.4-12.1) “severe anemia” • d4T (14.8-24.1) “severe neuropathy” “lipodystrophy” -This was sustained in the multivariate analysis

  10. Strengths -Feasible study design in a setting the is very different from where RCT’s were done -No blinding: switches are not protocol driven. Allows us to understand why providers or patients elect to switch between regimens when they are aware of the medication used. -Nurse managed: realistic to RSL settings

  11. Weaknesses -Retrospective -No validation system for data collection mentioned -Death in Lesotho -Side effects vs loss for follow up -Anemia not included in multivariate analysis: bias against d4T?

  12. Weaknesses -HBV status? This data is not included in the pivotal TDF trial, but given HBV as much more prevalent in Lesotho than in US, this could have introduced bias. -Definition of toxicity?

  13. Weaknesses -How often can they measure Cr? Can they check proteinuria? What about phosphate? -Is Lesotho ready to deal with CKD? -LDL? To they care about dyslipidemia as much as we care?

More Related