ITREMA is a collaborative project between several universities in The Netherlands and South Africa and Ndlovu Care Group.

Transcription

1 ITREMA is a collaborative project between several universities in The Netherlands and South Africa and Ndlovu Care Group. Objective: To do research into the best way to use viral load testing to ensure that ARV s are working well

2 HIV in South Africa South Africa has largest number of HIV-infected people worldwide Over half of HIV-infected patients now on ART Monitoring of patients during ART poses a major challenge to the public health system

3 Monitoring of antiretroviral treatment (ART) After start of ART, viral load testing is done at 6 months, 12 months, then annually As long as the patient has a viral load <1000 copies/ml, no additional interventions are recommended by the SA guidelines

4 targets

5 Research question 1: What is the treatment success rate in South Africa

6 Question 1: Methods We sourced data from 57 South African HIV treatment facilities Primary health care centers, CHC s, hospitals Gauteng, North-West, Mpumalanga, Limpopo provinces Urban, Urban-rural mixed, rural We included data from patients on first-line ART: Observational cohort We studied viral load data during ART from these patients

7 Question 1: Results The treatment programme is very successful At any point in time: 90% of patients has a last viral load <1000 copies/ml 80% of patients has a last viral load <50 copies/ml Hermans et al. CROI 2018

8 We observed low-level viremia (LLV) in many patients Low-level viremia between copies/ml

9 Research question 2: What are the risks of having low-level viremia in SA patients?

10 Question 2: Methods Same observational cohort of patients (57 clinic, patients) Stratified patients with low-level viremia into three groups Viral load copies/ml Viral load copies/ml Viral load copies/ml Precise statistical research question: For patients with low-level viremia, what is the chance that their next viral load is above 1000 copies/ml (= viral rebound)

11 Question 2: Results Low-level viremia was associated with an increased failure risk Patients with a last VL of copies/ml are five times more likely to have treatment failure Low level viremia treatment success and should be a call for action Hermans et al, Lancet ID, 2018

12 Research question 3: What happens after patients develop viral rebound?

13 SA/WHO monitoring algorithm

14 Question 3: Methods Same observational cohort of patients (57 clinic, patients) We studied follow-up of all patients with a first viral load >1000 copies/ml on first-line ART (= viral rebound) We measured the time from rebound to the second (confirmatory) viral load and to switch

15 Question 3: Results

16 Question 3: Results Viral load is repeated multiple times after rebound Switch is often postponed or not performed at all

17 To switch or not to switch to second-line ART? Switch Best option if resistance is present Unnecessary if resistance is absent No switch One pill per day Limited toxicity Preserve first-line ART Accumulation of resistance if present Clinicians need better insight in why patients have a high viral load! Is there drug resistance to the first line, or is the patient simply not adherent?

18 Research question 4: How can we improve insight into the cause of a high viral load?

19 Question 4: Methods Collaboration with National Health Laboratory Service (NHLS) Study of 497 patients with confirmed virological failure on secondline ART with LPV/r (= Aluvia) All patients had a drug resistance test requested We performed drug level testing on the sample sent for drug level testing

20 Question 4: Results 47.3% of patients had a negative LPV level Negative LPV level Positive LPV level 5.9% chance of PI-resistance 45.4% chance of PI-resistance Sens: 89% [83-94] NPV: 94% [90-97] Spec: 61% [55-66] PPV: 45% [39-52] N = 497 LPV drug test POSITIVE LPV drug test NEGATIVE LPV-resistance PRESENT LPV-resistance ABSENT 23.9% (119) 28.8% (143) 52.7% (262) 2.8% (14) 44.5% (221) 47.3% (235) 26.8% (133) 73.2% (364) 100% (497)

21 Next steps In collaboration with two universities Ndlovu Medical Centre is developing as a rural research facility We want to strive towards implementation of drug level testing in clinical practice These tests are currently being field tested at Ndlovu Medical Centre

22 Please visit

23 THANKS TO PHILADELPHIA HOSPITAL FOR ALLOWING US TO PRESENT AND FOR YOUR ATTENTION!

24 Acknowledgments RCT investigator team Annemarie Wensing Monique Nijhuis Rob Schuurman Mirjam Kretzschmar Kiki Tesselaar Sigrid Vervoort Hugo Tempelman Project collaborators Sergio Carmona Kim Steegen Ndlovu Research Consortium Francois Venter John de Wit David Burger Rob ter Heine Advisory board Douglas Richman Elliot Raizes Andy Gray Osama Hamoudah Jonathan Schapiro Annelies van der Vorm All participants, clinical and research staff at Ndlovu Care Group Supported by The Netherlands Organisation for Scientific Research (ZonMW) and NOW-WOTRO Science for global development