DISCOVERY OF FALSE HIV ELITE CONTROLLERS AMONG SOUTH AFRICAN BLOOD DONORS

Transcription

1 DISCOVERY OF FALSE HIV ELITE CONTROLLERS AMONG SOUTH AFRICAN BLOOD DONORS SANBTC Sun City, South Africa 28 th 31 st August 2017 Marion Vermeulen, Karin van den Berg, Genevieve Jacobs, Brian Custer, Ronel Swanevelder, Ute Jentsch, Ravi Reddy, Lubbe Wiesner, Gary Maartens and Edward Murphy for the NHLBI Recipient Epidemiology and Donor Evaluation Study-III (REDS-III)

2 Background SANBS screens all donations for HIV, HBV & HCV using ID-NAT in parallel with serology testing This entails HIV RNA testing and HIV antibody testing Use of ID HIV antibody and RNA testing of blood donors and the high incidence of HIV infection in SA enables identification of: Donors with very early (Fiebig stage I & II) incident infection (HIV RNA+, Antibody-) Potential Elite Controllers (EC), a group who are able to control virus replications without treatment (HIV RNA-, Antibody+) Confirmed using western blot Definition of an EC is a viral load <50 copies/ml Prevalent HIV infections (HIV RNA+, Antibody+)

3 SANBS HIV+ donors according to year and Fiebig staging on index donation Year Fiebig Stage Grand Total I II III-VI ,623 EC

4 5,00% 4,50% Background Loss of Elite Control by a MATHS participant Anecdotal evidence of Elite Controllers reporting ART and therefore false EC while recruiting and enrolling donors into the MATHS cohort study Apparent increase in EC over 1-2 years and during a winter incentive campaign Antibody+, RNA- donations as a Proportion of all HIV positives Viral_Load REDS-III South Africa M ATHS Study ELITE Controllers Response to Therapy - Viral Load Loss of virologic control by an Elite controllers enrolled in MATHS* 4,00% 3,50% ,00% 2,50% 2,00% 1,50% 1,00% ,50% 0,00% Days Since Signing Consent Generated by RTI

5 Aim & Methods Aim To understand the extent of the false EC phenomenon and generate hypothesis for its genesis and prevention Methods 184 Potential EC from the period 2010 to 2016 were tested for five ARV drugs using qualitative liquid chromatography tandem mass spectrometry (sensitivity 0.02µg/mL) Nevirapine, Efavirenz, Darunavir, Atazanavir, Lopinavir Compare the frequency of false EC against blood drive characteristics, donor incentives and the temporal trend of ART rollout in South Africa using chi-square, Fisher exact and trend tests

6 ART Rollout Of 184 Potential Elite Controllers tested, 123 (67%) had evidence of ART and were therefore False Elite Controllers.

7 False Elite controllers by donation site and incentives False Elites n=123 True Elites n=61 Total n=184 Donation Site (p=0.5) Mobile Fixed Donor Incentives (p=0.1) Incentive period Non-incentive period

8 False Elite controllers by gender and Age False EC N=123 True EC N=62 Total N=184 Gender (p=0.14) Female Male Age (p=0.03)* > * For age >30 versus <=30

9 False Elite controllers by race False EC N=123 True EC N=62 Total N=184 Race (p=0.87) Asian Black Coloured Unallocated White Due to the small number of Potential ECs in non black race group we did not analyse for significance Drugs detected Drugs Atazanavir Darunavir Efavirenz Lopinavir Nevirapine Number (%) (86) 7 (5.4) 10 (8.5)

10 c o p ie s /m L Viraemia in EC s H o lo g ic /P o is s o n 9 m L C la d e B C la d e C T N0.1 D c p /m L 9 c p /m L 3 c p /m L 1 c p /m L 0.3 c p /m L E lite C o n tr o lle r TND= 0/18 reps; <0.12 set at 0.1 (1/18 reps poisson derived value 0.12) 2 7 c p /m L 9 c p /m L 3 c p /m L 1 c p /m L 0.3 c p /m L N e g a tiv e D o n o r E lite C o n tr o lle r T r e a te d " E lite C o n tr o lle r "

11 Distribution of viral load in 28 elite controllers plasmas Case number In 7/28 (25%) no HIV- RNA detectable in replicate dhiv assays HIV-RNA copies/ml Determined by probit analysis from proportion of positive samples on 30 replicate Ultrio assays against DDL HIV subtype B standard dilutions

12 Modeling the proportion of RBC and FFP transfusions from elite controllers being infectious Percent infectious (20 ml) (200 ml) Modeled on 28 elite controllers whose viral loads were determined by probit analysis against DDL HIV subtype B standard ID virions ID virions 15.5% 2.2% Likely scenario 2.2% 0.2% infectious dose (ID 50 ) in virions

13 Conclusions False EC due to undisclosed ART use, represent a large and growing proportion of potential EC in SA blood donors False EC status may be associated with older age but not with sex or race False EC status is not associated with small incentives or fixed versus mobile collection site False EC may seem to be increasing as ART coverage increases in South Africa True EC and False EC do still have viremia and therefore pose a risk to blood safety

14 Way forward Enrol False Elite controllers into a qualitative research study to determine Whether donors feel peer pressure at Mobile clinics Whether donors believe they are cured If more education is required at the treatment clinics If donors are test seeking for confirmatory purposes Whether donors donate for incentives/ small gifts Test concordant HIV NAT+/antibody+ donors especially those with low viral load - for ART to measure the extent of undisclosed ART usage in that group.

15 Acknowledgements Karin van den Berg Cynthia Nyoni Genevieve Jacobs Tinus Brits Ronel Swanevelder Ute Jentsch Coreen Barker Amisha Rama Rachel Lockyear Chris McClure Nathan Sikes South African National Blood Service Clinical HIV Research Unit (WITS) Right to Care RTI Brian Custer Edward Murphy Mars Stone Mike Busch Blood Systems Research Institute and University of California San Francisco Jennifer Norman University of Cape Town REDS-III MATHS is a NHLBI funded project