Antiretroviral treatment outcomes after the introduction of - - PowerPoint PPT Presentation

Antiretroviral treatment outcomes after the introduction of tenofovir in the public-sector in South Africa

Alana T Brennan, Kate Shearer, Mhairi Maskew, Prudence Ive, Ian Sanne, Matthew P Fox

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Background

• Prior to the South African National Guidelines changing in

April 2010, stavudine was the most frequently used nucleoside reverse-transcriptase inhibitor (NRTI)

• In 2010, the South African government revised its HIV

treatment guidelines to substitute stavudine with tenofovir:

▫ Initiate all newly diagnosed patients eligible for treatment on tenofovir-based regimen ▫ Patients currently on stavudine-based regimens:

 remain on stavudine if well tolerated  substitute at first sign of toxicity  substitute immediately if at high risk of toxicity:

 high body mass index, low iron levels and older females

Single-Drug Substitutions Analysis

NRTI/NtRTI stavudine  zidovudine  abacavir  tenofovir  zidovudine  abacavir zidovudine  stavudine  abacavir  tenofovir  stavudine  abacavir tenofovir  not available  stavudine  zidovudine  abacavir NNRTI efavirenz  nevirapine  nevirapine nevirapine  efavirenz  efavirenz

Investigated: Trends in single-drug substitutions from 2004 to 2011. Single-drug substitution: changing one or more drugs within first-line therapy without initiating a protease inhibitor - excluded all switches to second-line therapy.

Initiating ARV Drug Substitution 2004-2010 2010-present

Methods - Single-drug Substitution

• Prospective cohort study:

▫ Themba Lethu Clinic, Johannesburg, South Africa ▫ Included 19,699 HIV-positive adult patients:

 ART-naïve, non-pregnant, initiated standard first-line ART between April 2004 and December 2011.

• Analysis:

▫ Cox proportional hazards models to evaluate 12-month

• utcomes:

 Model 1: association of year of initiation onto ART and single-drug substitution to look at trends over time  Model 2: association of type of antiretroviral drug in first-line ART and single-drug substitutions

Methods - Sub-analysis of Stavudine (30mg) vs. Tenofovir

• Prospective cohort study:

▫ Included 4333 ART-naïve, non-pregnant, HIV-positive adult patients newly initiated on to either:

 stavudine-based first-line regimen (April 2009-March 2010) (n=2214)  tenofovir-based first-line regimen (April 2010-March 2011) (n=2219)

• Analysis:

▫ Outcomes at 24-months on ART:

 All-cause mortality (death registry)

 Cox proportional hazards model

 Lost to follow-up (at least 3-months late for the last scheduled visit)

 Fine and Gray’s regression method

 Mean CD4 change from ART initiation

 linear regression

 Detectable viral load (>400 copies/mL)

 log-binomial regression

Results – Frequency of single-drug substitutions in the first 12-months on ART by year of ART initiation

13.2% 5.8%

Results (cont.) - Single-drug Substitution

Rates / 100 pyrs Crude Hazards Ratio (95% CI) Adjust Hazards* Ratio (95% CI) MODEL 1 Year initiated onto ART 2004 vs. 2011 8.2 (6.7-9.9) 1.1 (0.9-1.4) 1.1 (0.8-1.4) 2005 vs. 2011 13.7 (12.0-15.5) 1.9 (1.5-2.3) 1.8 (1.5-2.2) 2006 vs. 2011 13.5 (12.0-15.1) 1.9 (1.6-2.3) 1.8 (1.5-2.2) 2007 vs. 2011 16.5 (14.8-18.3) 2.3 (1.9-2.8) 2.2 (1.9-2.7) 2008 vs. 2011 12.5 (11.0-14.2) 1.7 (1.4-2.1) 1.7 (1.4-2.1) 2009 vs. 2011 13.9 (12.5-15.5) 1.9 (1.6-2.3) 1.9 (1.6-2.3) 2010 vs. 2011 12.9 (11.5-14.4) 1.8 (1.5-2.2) 1.8 (1.5-2.1) MODEL 2 NRTI/NtRTI zidovudine vs. tenofovir 17.2 (14.4-20.6) 2.3 (1.9-2.9) 3.0 (2.3-3.9) stavudine (30mg) vs. tenofovir 16.3 (15.4-17.2) 2.1 (1.8-2.4) 2.8 (2.2-3.5) stavudine (40mg) vs. tenofovir 21.6 (19.6-23.7) 2.8 (2.3-3.2) 3.8 (2.9-4.8) NNRTI nevirapine vs. efavirenz 21.5 (19.1-24.2) 1.5 (1.3-1.7) 1.5 (1.3-1.7)

*Adjusted for demographic (age and gender) and clinical characteristics at ART initiation (CD4 count, hemoglobin, BMI, tuberculosis, WHO stage)

Results – Sub-analysis of Stavudine (30mg) vs. Tenofovir

Number events (%) Rates / 100 pyrs Adjusted Relative Risk (95% CI) Mortality tenofovir 128 (6.1) 3.8 (3.1-4.4) Reference stavudine (30mg) 234 (10.6) 7.3 (6.4-9.3) 1.5 (1.2, 1.9) Loss to follow-up (defined as at least 3-months late for the last scheduled visit) tenofovir 411 (19.4) 12.1 (10.9-13.3) Reference stavudine (30mg) 403 (18.2) 12.6 (11.4-13.9) 1.2 (0.95, 1.30) Detectable Viral load (unsuppressed >400 copies/mL) tenofovir 443 (20.9)

• Reference

stavudine (30mg) 504 (22.8)

• 1.1 (0.95, 1.30)

Mean Difference (95% CI) CD4 response (cells/mm

3)

stavudine (30mg) vs. tenofovir 5.4 cells/mm

3 (-6.2, 17.0)

*Adjusted for demographic (age and gender) and clinical characteristics at ART initiation (CD4 count, hemoglobin, BMI, tuberculosis, WHO stage

Conclusions

• The decline in single-drug substitutions in the first 12-months on

ART appears to be related to the introduction of tenofovir, resulting in fewer drug toxicities.

• Although comparable in regards to loss to follow-up, mean change

in CD4 count and viral load status by 24-months on ART patients initiated onto stavudine may have higher mortality than those on tenofovir.

• Despite the increased cost, the use of tenofovir could help improve

long-term treatment outcomes in HIV-positive patients.

Acknowledgments

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Funding was provided by USAID under the terms of Cooperative Agreement 674-A-00-09-00018-00 to Boston University and Cooperative Agreement 674-A-00-02-00018 and CA 674 A 00 08 0000 700 to Right to Care; INROADS USAID-674-A-12-00029 and the National Institute of Allergy and Infectious Diseases (NIAID) Award Number K01AI08309. This study is made possible by the generous support of the American people through the United States Agency for International Development (USAID) and the National Institutes of Health. The contents are the responsibility of the authors and do not necessarily reflect the views of US AID, NIH or the United States government.