CD4 WORKSHOP REPORT JULY 22, 2017

Transcription

1 CD4 WORKSHOP REPORT JULY 22, 2017

2 TABLE OF CONTENTS Contents Introduction 1 Strengthening the interface between diagnostics and care treatment monitoring 2 Findings from the first regional CD4 workshop 4 MSF s advanced HIV disease package 5 Discussion 7

3 Introduction Rosanna Peeling, chair of the diagnostics at the London School of Hygiene & Tropical Medicine welcomed the participants to the workshop. She explained that the objective of the series of CD4 workshops organized by the International Diagnostics Centre (IDC) at the London School of Hygiene & Tropical Medicine (LSHTM) is to create awareness of the role of CD4 testing in the context of viral load (VL) scale up and in managing patients with advanced HIV disease; to share country situational analysis on viral load scale up and CD4 testing; and determine demand forecasts, funding and procurement needs for CD4 testing. Tom Denny from Duke University chaired the first session and highlighted that CD4 is an easy marker to measure and is especially critical as for staging of advanced HIV disease. He reminded the group that all tools (e.g. VL and CD4) are important for patient management. Page 1

4 Strengthening the interface between diagnostics and care treatment monitoring Lara Vojnov from the WHO provided an overview of the uses of CD4 testing. The need for CD4 testing for treatment eligibility is now less critical because of the WHO guidelines recommending all HIV positive patients initiate ART regardless of CD4 cell counts. However, priority should be given to individuals with <350 CD4 cells in order to access ART. CD4 testing to monitor treatment failure is also less critical now with the recommendation that viral load should be used to monitor treatment failure. Since 2013, viral load is the preferred method to monitor treatment failure. Where viral load is routinely available, CD4 testing can be stopped if an individual is stable on ART and virally suppressed. CD4 testing should be continued for patients who are unstable on ART. CD4 should still be used for treatment failure if viral load is not available. CD4 testing is useful for clinical management. CD4 should be performed at baseline and for those reentering care for risk assessment. Depending on the CD4 cell count, cryptococcal antigen and TB screening may be required if an individual s CD4 count is <100 cells. Simplified care can be considered for individuals who are stable and have a CD4 count of <200 cells. Even with the WHO recommending Treat All, 38% of patients who are initiating ART do so with advanced disease. This is even higher in low and middle-income countries and among men. Advanced disease is a persistent and ongoing problem - in South Africa, over 30% of people living with HIV have presented with advanced disease in the past 5 years. Advanced disease is defined as CD4 <200 cells or WHO stage 3 or 4; and all children under the age of 5. However, even though the WHO considers WHO stage 3 or 4 as advanced disease, a study from Kenya, Malawi, Zimbabwe, and Uganda found that almost half the people with CD4 cell counts <100 had WHO clinical stage 1 or 2, so clinical staging may not be very accurate in identifying individuals with advanced disease. The new WHO Advanced Disease Guidelines package of care is linked to CD4 thresholds as shown in Figure 1 below. Even with the WHO recommending Treat All, 38% of patients who are initiating ART do so with advanced disease. Advanced disease is defined as CD4 <200, yet most countries are not collecting data on CD4 thresholds. Access to CD4 testing has become increasingly difficult since countries started the treat all approach, primarily due to a lack of prioritization and funding. Page 2

5 Figure 1: CD4 thresholds and an advanced disease package of care. Most countries in sub-saharan Africa have significant capacity to continue CD4 testing to identify patients with advanced HIV disease. USAID is mapping where CD4 devices are located in order to better align diagnostic services with treatment and care. Some countries have decommissioned their traditional laboratory based CD4 devices and redistributing their point of care devices to ensure wider access. Based on the new CD4 thresholds in Figure 1, it may be time to consider a target product profile to help companies develop a cheap semi-quantitative CD4 device. There remains significant capacity for CD4 testing. Mapping exercises will help optimize diagnostic services with treatment and care. We need a cheap semi-quantitative CD4 device. Page 3

6 Findings from the first regional CD4 workshop Debi Boeras and Imelda Mahaka from the International Diagnostics Centre provided a brief update from the first Regional CD4 Workshop held on May 18-19, 2017 in Nairobi in partnership with KEMRI. Two additional Regional Workshops are planned for The next workshop will be in Lusaka, Zambia on August in partnership with CIDRZ and the last workshop is planned to coincide with ICASA in Abidjan, Cote d Ivoire on December 4 in partnership with IRESSEFF. The report from the Nairobi workshop can be found here. A questionnaire was sent to the five East African Community countries that participated in the Nairobi workshop (Burundi, Kenya, Rwanda, Tanzania and Uganda) prior to the workshop to better understand how they are currently using CD4 testing, the status of viral load scale-up, and instrument distribution and usage for both CD4 and viral load. The countries noted that the current role of CD4 testing is not clearly elucidated in the 2016 WHO Treatment Guidelines and access to CD4 testing has become increasingly difficult since countries started the treat all approach primarily due to a lack of prioritization and funding. The current CD4 instruments in country have high maintenance costs when factoring in the low utilization rates. Countries would like to see clear guidance from the WHO around advanced HIV disease and the role of CD4 testing. Additionally, countries would like to have access to tools that will help them with demand forecasting as well as data management through connectivity solutions. CHAI is currently working on a demand forecasting tool that will help formulate a more accurate global demand for CD4 testing and reagents. The forecasting will help build networks and map country needs to adapt existing networks. The tool can also be used for country budgets when discussing needs for patient management with funders and donors. An important consideration is that some of the existing devices in countries are coming to the end of their life cycle and most do not have maintenance contracts. Some countries like Kenya already have systems in place to monitor their viral load program, however most countries have very limited data on number of people with <200 CD4 cells. CD4 instruments will need to be connected in order to get these data. There was discussion on mortality rates when you do not test for CD4. It may be possible to use data from TB LAM and CrAg showing lives saved to demonstrate the benefits of CD4 testing as CD4 testing is required to determine eligibility for TB LAM and CrAg screening. Another participant felt that CD4 testing is going to be critical when dolutegravir is introduced as there will be an increased risk for immune reconstitution inflammatory syndrome (IRIS). Countries have shown lack of uptake of advanced disease tools due to lack of clear guidance for use and cost. A package of tools and services can support uptake through clearer guidance and improved pricing for bundling diagnostics with drugs. Page 4

7 MSF s advanced HIV disease package Naïve How are we going to identify patients with advanced HIV disease Well Naïve asymtomatic Need baseline CD4 and stage CD4 < 200/ 100 triggers package for advanced disease Late presenters Clinically unwell Naïve symtomatic Management of diagnosed OIs Referral as necessary Need baseline CD4 and stage If CD4 < 200/ 100 triggers package for advanced disease Emmanuel Fajardo from MSF presented on the advanced HIV disease package that they are currently using in their clinics. Median CD4 counts at ART initiation remains low, with about 30% receiving their HIV diagnosis when admitted with symptomatic disease and low CD4 cell counts. It is important to identify HIV disease earlier and HIV self-testing has increased HIV testing uptake. ART exposed Routine VL >1000 Asymptomatic Need TRIGGERED CD4 CD4 < 200/ 100 triggers package for advanced disease Treatment Failures/ interrupters symptomatic/ clinically failing Need TRIGGERED VL and CD4 CD4 < 200/ 100 triggers package for advanced disease VL > 1000 consider expedited switch if on ART for > 6 mths Data from a study in South Africa show that point of care CD4 testing accelerates ART initiation, however it did not have any effect on retention in care at 6 and 12 months. In fact, there were more people lost to follow up among people who received point of care CD4 testing. CD4 is still an important marker for people living with HIV. Baseline CD4 cell count remains the best diagnostic tool to assess a patient s immune and clinical status, the risk of opportunistic infections and guide clinical management, especially in patients with advanced disease. For patients who are ARTexperienced, CD4 testing can help guide clinical decisions if they are virologically failing ART or if they have not received treatment for some time. Data from two hospitals in Kinshasa show that people with advanced HIV disease have high mortality rates. Mortality rates were greater than 23%, with almost a third of the patients dying within two days of being admitted into the hospital. Globally, there are still about a million AIDS-related deaths a year. CD4 cell counts is especially important to screen for opportunistic infections and for the provision of cotrimoxazole prophylaxis as well as to provide adapted adherence support for people with <200 CD4 cell counts. Therefore, it is very important to identify patients with advanced disease. Several diagnostic tools are available for the management of advanced HIV disease. The TB-LAM test is a lateral flow assay and it is the only true point of care TB test on the market. It is a simple to use and inexpensive urine-based test and results are given in 25 minutes. TB-LAM has been extensively evaluated and is sensitive/specific for people with <100 CD4 cells. Uptake of TB-LAM has been extremely poor due to the lack of adoption in national guidelines and lack of interest from National TB programs. Due to the low sales of TB-LAM, production may be discontinued if uptake remains low. GeneXpert MTB/RIF provides rapid and accurate diagnosis of HIV-associated TB and rifampicin resistance TB and allows for rapid treatment initiation. Despite WHO recommendations, only a few countries are using Xpert MTB/RIF as the first test and continue to rely on sputum microscopy. Many National TB Page 5

8 Programs consider the $10 per test to be too expensive, especially considering additional costs of service and maintenance. Cepheid, the developers of GeneXpert, has delayed the launch of the POC Omni platform until the middle of 2018 The cryptococcal antigen (CrAg) lateral flow assay is a rapid and inexpensive test and has revolutionized the management of cryptococcal meningitis (CM). This test allows for decentralizing CrAg testing as well as large-scale screening so that fluconazole prophylaxis can be administered to those who are found to be CrAg positive. While more than 20 countries have adopted CrAg screening in their national guidelines, only a few actually have large screening programs. Although the test is inexpensive if bought directly from the company, some local distributors have added high markups making the test much more expensive. In order to further reduce mortality among people with advanced HIV disease, several new diagnostic tools will be needed for other high priority opportunistic infections. One important missing rapid diagnostic test is for pneumocystis pneumonia, a common opportunistic infection, which can be fatal if left untreated. Current technologies to diagnose pneumocystis are either too expensive or require laboratory instrumentation. Diagnostic tests for toxoplamosis, a high burden disease in sub-saharan Africa, and severe bacterial infections are also urgently needed. MSF has identified a package of priority diagnostics needed for the primary health care and hospital levels. The CHAI demand forecast tool will better determine global and country needs for CD4 and can also help countries budget for the advanced disease package to provide optimal patient management. The MSF advanced HIV disease package retains a baseline CD4 cell count to assess a patient s immune and clinical status, the risk of opportunistic infections and guide clinical management. Page 6

9 Discussion It was noted that as diagnostics and the number of point of care instruments increases in countries, it becomes increasingly important that connectivity solutions be implemented to monitor and link test results for improved patient management. There are also readers for lateral flow assays that can transmit data. Most countries do not currently track mortality in their programs so it will be challenging to report on advanced disease and advocate for improved guidelines and needed diagnostics without this data. Further, there is a need to look at advanced disease as an entire package of care rather than disease specific silos and programs (CM versus TB versus PCP etc.). Many of the participants felt that there was a need to establish an Advanced Disease consortium to focus on advocacy, regulatory issues and procurement. Additionally, the consortium can support countries with the implementation of the advanced disease guidelines and reduce the barriers to implementing an advanced disease package. The group felt that a package of essential diagnostics (and drugs) is the way forward given that hospitals often have difficulties maintaining supplies of the various diagnostics and drugs with different suppliers and distributors. A number of research questions were also identified: 1. How often do we need to do CD4 testing? Should it be based on clinical signs or guidelines/country capacity? 2. Can co-trimoxazole be safely discontinued? In light of growing concerns of antimicrobial resistance, can co-trimoxazole be discontinued in low burden malaria/bacterial disease areas versus high burden malaria/bacterial disease areas. 3. How long should fluconazole prophylaxis/pre-emptive treatment be continued? Countries have shown lack of uptake of advanced disease tools due to lack of clear guidance for use and cost. A package can support uptake with clearer guidance and pricing for bundled diagnostics with drugs. Advanced Disease package needs to be an entire package of care and not individual silos for diseases or programs. Connectivity is very much need with the advanced disease package for patient management - to manage diagnostics and treatment. Need to establish an Advanced Disease consortium to focus on advocacy, regulatory issues and procurement. The consortium can support with the implementation of the AD guidelines and package. Page 7