3-VL Monitoring.pptx presentation slides
- 1. HIV Viral Load Monitoring Viral Load Surge- Part 1
- 2. • Recall the principles and aims of VL monitoring • Recall the rationale for VL testing in S Sudan • Recall the barriers and strategies to address VL testing services Objectives
- 3. What is Viral Load? Viral load is the concentration of HIV RNA copies in blood. This is a reflection of ongoing virus replication in a person’s body. Viral load is used as an indicator of: • Response to ART and risk for clinical disease progression • Risk of transmission of HIV between sex partners • Risk of transmission of HIV from mother to child
- 4. What is CD4? Indicates the strength of the immune system • HIV kills CD4 T-cells • Low CD4 counts opportunistic infections progression towards AIDS
- 5. Viral Load during HIV Disease Acute infection: Viral load rises rapidly and often to very high levels (>1 million c/ml) 6-12 weeks after infection: Immune response reduces viral load to steady level (“set point”) Set point predicts disease progress, higher set point indicates a more rapid progression to AIDS Without ART, viral load increases over several years, gradually and then more rapidly as symptoms develop www.youngdayschool.edu.uy
- 6. Viral Load and HIV Transmission without ART HIV viral load (copies/ml) Quinn et al., NEJM 2000 Rate of transmission: 2.2 per 100 person-years Zero transmissions Rate of transmission: 23 per 100 person-years
- 7. Viral Load Measurement • Viral load can be measured using whole blood, plasma, or dried blood spots • Assays quantify HIV viral load as RNA copies/ml, also reported on a log10 scale • Lower limits of detection vary with assays (e.g.<20, 50, 400 copies/ml) • Optimal results include target not detected, or the lower limits of detection
- 8. Viral Load Result Categories <1,000 copies/ml • “Suppressed” • Results below lower limit of detection • Results up through 999 (e.g. not detected, < 20, 367 copies/ml, 934 copies/ml) >1,000 copies/ml • Includes all results greater than or equal to 1,000 copies/ml (e.g. 2,000 copies/ml, 30,000 copies/ml, 100,00 copies/ml)
- 9. Virologic Response to ART ART prevents HIV replication by inhibiting viral enzymes causing the viral load to decline The goal of treatment is a suppressed viral load: • To achieve better clinical outcomes • Lower risk of HIV transmission Persistent viral replication while taking ART can lead to resistance to one or more antiretrovirals (ARVs)
- 10. Virologic Response to ART Viral load <1000 copies/ml is considered acceptable • Risk of transmission and disease progression <1,000 copies/ml is low In most patients taking ART, the viral load should be <1000 copies/ml after 6 months of treatment Those with high baseline viral load, such as infants, may take longer to achieve suppression DHHS Guidelines, 2013; Tsibris and Hirsch, PPID 2010; Kaufmann et al., Arch Intern Med 2003 VL target: <1000 copies/ml • Better outcome • Lower risk of transmission
- 11. Immunologic and Clinical Responses to ART with Viral Suppression With viral suppression: • CD4 count increases • 50 to 150 cells/µl expected in the 1st year • 50 to 100 cells/µl expected in the 2nd year • Improved clinical status (weight gain, resolution of diarrhea, no new opportunistic infections)
- 12. Viral Load Suppression Allows for CD4 Recovery
- 13. Adherence Interventions Improve Suppression of Viral Load 53% of those with initial VL >1,000 copies/ml achieved virologic suppression after early viral load testing and a targeted intensive adherence intervention Orrell et al., Antivir Ther 2007
- 14. Enhanced Adherence Counseling Enhanced Adherence Counseling is a continual and repeated process that involves: Repeat Steps 1-4 during follow-up sessions. Step 1: A structured assessment of current level of adherence Step 2: Exploration of the specific barriers the patient must overcome Step 3: Motivating and assisting patients to identify solutions and address barriers Step 4: Develop and individualized adherence intervention plan
- 15. Achieving Good Adherence Adherence sessions should be repeated until good adherence is achieved Once good adherence is achieved, set a date for repeat viral load measurement after 3 months of good adherence and provide to patient
- 16. Viral Load is the Best Measure of Treatment Failure TIME Earliest indicator – tells us if the virus is reproducing Poor Adherence to ART Virologic Failure – VL increase Immunologic Failure – CD4 decrease Clinical Failure: specific illnesses (weak immune system) Virologic failure is currently defined as a viral load above 1000 copies/ml based on two consecutive viral load measurements 3 months apart and after an adherence intervention (WHO, 2016)
- 17. Drop in CD4 is Too Late TIME Poor Adherence to ART Virologic Failure – VL increase Immunological Failure – CD4 decrease Clinical Failure: specific illnesses (weak immune system) CD4 tells us just the Chance of Developing and inFection CD4 has limited sensitivity and Positive predictive value (PPV) which can lead to both delayed and inappropriate premature switching to more expensive second-line agents
- 18. Why is Viral Load the Preferred Monitoring Strategy for Patients on ART? Delayed detection of high viral load leads to: • Dropping CD4 • Weaker immune system • Development of new infections and increased morbidity and mortality To prevent unnecessary switches to second line ART • Rutherford et al: Positive predictive value of clinical and immunological criteria 29%, i.e., wrong 2 out of 3 times To reduce transmission (PMTCT and to sexual partners) by identifying those with a high viral load Allow clinicians to focus on patients with high viral load Potentially reduce frequency of clinic visits for patients with suppressed viral load To avoid development of drug resistance
- 19. VL testing benefits to ART patients Timely indication of the need for adherence support in patients who are not suppressed Reduces the chance of developing drug resistant mutations (timely switch to 2nd line ART) Reducing the risk of Opportunistic Infections Guides decision to timely switching to a more appropriate treatment regimen if treatment failure is confirmed
- 20. VL testing benefits to the program Annual VL monitoring allows for innovative service delivery models with fewer clinic visits Sub-populations at greater risk for treatment failure identified (e.g., adolescents and children) Allows for better follow-up of pregnant & breast-feeding women • Non suppressed mothers detected early for baby’s safety • Guides selection of ARVs for baby prophylaxis • Allows earlier cessation of prophylaxis in infants Cost efficiency-> only necessary 2nd line switches made • Click to edit Master text styles – Second level • Third level – Fourth level » Fifth level 11
- 21. VL in S Sudan VL is the preferred approach for monitoring ART response South Sudan started using VL for treatment monitoring in FY17 FY19, 32 out of the 41 PEPFAR-supported facilities were collecting VL from PLHIV on ART, with 13,980 individuals out of a target of 27,912 having received their VL results COP20, South Sudan will aggressively focus efforts to improve both VL coverage and VL suppression
- 22. VL in S Sudan Proposed strategies to improve VL suppression: • Finalizing TLD transition; • Providing clients with six months of drugs (MMD6); • Pediatric ARV optimization; • Fast tracking children for VL sample collection and non-suppression management; • Tracking patients for enhanced adherence counseling (EAC) and repeat VL monitoring; • Mentorship of clinic staff on EAC and non-suppressed client management; monitoring of appointment registers for patients due for VL or repeat VL testing; • Data utilization for site level quality improvement (QI) activities
- 23. FY 19 ART and VL Coverage by Counties VLC low and varies across counties (0-75%)
- 24. Who should have routine VL monitoring? All PLHIV receiving ART for 6 months or more at ALL health facilities offering ART
- 27. VL monitoring for PBFW on ART
- 28. HIV VL Cascade
- 29. VL Request Form
- 31. Summary VL predicts progression of disease in an individual, and onward transmission of HIV to sex partners or from mother to baby Viral load monitoring is the monitoring strategy of choice because: • Failure is identified earlier (than using CD4 or clinical criteria) • Resistance is less likely • Unecessary switches to second line are avoided • If virologically suppressed, transmission can be reduced At this time, VL < 1000 cp/mL indicates acceptable response to ART VL results need to be used as adherence and retention tools in suppressed patients (DSD, MMS) and as critical data for interventions (enhanced adherence counseling, 2nd line switch)
- 32. Summary Monitoring quality of care helps identify weaknesses at ART clinic and program levels associated with population-level emergence of HIVDR • Identification of quality gaps in ART service delivery (sub- optimal retention, drug stock outs, VL testing coverage, suppression, second-line ART) • Robust approach at all levels needed to identify and correct quality gaps • Rapid response at the clinic and program levels will help maximize ART service quality and preserve the durability and efficacy of ARVs
- 33. VL findings VLC and VLS suppression as an OU remains lower than other countries. The VLC and VLS rates in children and adolescents is unacceptably low (likewise VLC for PBFW).
- 34. What are we going to do as an OU Are there barriers, root causes that need to be addressed as an OU? • For adults and adolescents? • For children? Why are we failing as a program?
- 35. Goal To tackle low VLC in South Sudan by implementing VL catch-up surge.
- 36. Objective Problem statement: 67% VLC in South Sudan AIM statement: To increase VLC amongst PLHIV on ART in South Sudan from 67% to 85% by March 2021
- 37. Who is eligible for VL Catch-up surge Pregnant/ BF status • Already on ART (first ANC visit) • New on ART (eligible in 3 Months) All clients who have completed EAC 3 (and Extended EAC) Age < 19 (eligible every 6 months) Adults and Adolescents on ART for > 6 months • 6 months, 12 months, yearly thereafter Clients on TLD initiation/transition (eligible after 6 months on TLD)
- 38. Continuos Quality Improvement: Action Plan PrImary drivers Root Cause Aanalysis Change Ideas Responsible Timeline Comments Tools • Unavailability of VL request forms • Unavailability of VL eligibility SOP • Stock out of DBS kits • Avail and distribute VLRFs • Avail and display VL eligibility SOPs • Request and monitor inventory for DBS kits Providers Facility • Knowledge gap on VL eligibility criteria amongst providers. • Failure to request for VL sample collection • Inadequate number of phlebotomists • Access to VL services • Continue onsite supervisory and mentorship sessions; Train providers • Engage and distribute VL champions • Decentralize VL services to peripheral facilities M&E • Lack of elgibility line list from records • Poor data documentation in VL/ ART registers • Identification of eligible clients via routine query of ART database • Intensive VL data review and application of CQI methodologies Environment • Distance to facilitiy • Insecurity • Stigma and Discrimintation • Differentiated VL testing for ART sub-populations • Community-based volunteer VL-specific support • Community level advocacy and sensitization Clients • Proxy representation • Low literacy amongst clients (poor understanding of benefits of VL testing) • Community-based volunteer VL-specific support • Demand creation through patient education and community sensitization
Editor's Notes
- #5: "historically used to determine ART eligibility prior to the WHO "treat all" approach" 2016
- #6: To better understand how VL can be used for monitoring patients on ART is it helpful to briefly review the typical course of viral load trends in patients not on ART. CD4 is shown on the left side IN BLUE –go to slide 11 to define CD4 and viral load on the right IN RED with time from HIV infection to death on horizontal axis. You can see that during acute infection there are typically dramatically elevated concentrations of viral load, measured in copies of RNA per ml of plasma, and a sharp drop in CD4. Even without ART over the next 6 WEEKS there is a decline in VL due to the immune response, which allows for partial control but as you can see not total suppression of VL. The figure shows that for many PLWHIV VL can stabilize for quite a long time (up to years for some). This level of stabilization is known as “viral set point.” With no treatment the higher the set point the more rapid progression to AIDS and death. Without ART, VL increases over several years, gradually then more rapidly as symptoms develop.
- #7: These are results of an observational study conducted prior to availability of ART in Uganda which assessed rates of HIV transmission in serodiscordant couples based on the HIV+ partners’ viral load. Among those with low viral load (<400) NO transmission was observed, and with increasing viral load the rate of transmission had a corresponding increase and those in the highest VL category (>50K) had transmission rate of 23 per 100 person years.
- #8: In addition to content on the slide can say: Assays quantify HIV VL by means of cycles of amplification then detection with indicator primers that target viral enzymes
- #9: WHO defines HIV viral suppression as VL<1000 copied/ml Viral load result reports may vary in appearance, here we discuss the different categories relevant to patient management We use the term “suppressed” for VL <1000 because WHO is currently using that cut off. Traditionally this term has been used for when the VL is below the lower limit of detection. Ongoing studies are examining this cut off and we will have an increased understanding of the risk of regimen failure with VL > 50 < 1000 cp/mL, there may be changes In definition of VF, but at this time current WHO guidelines still use > 1000 copies
- #10: Now that we have reviewed how VL is measured and what the typical natural history of VL is over the course of infection without treatment I want to describe briefly what the desired and expected VL response is when ART are given. ART prevents HIV replication by inhibiting viral enzymes causing the viral load to decline. The goal of treatment is to achieve an undetectable viral load: associated with better clinical outcomes lower risk of HIV transmission.
- #11: While the goal of treatment is an undetectable viral load, VL <1000 copies/ml is considered acceptable given that risk of transmission and disease progress are low at this level. You can see from the curve here that in most patients on ART, VL will decline to below 1000 copies/ml after 6 months of treatment. Those with high baseline VL such as infants may take longer to reach viral load <1000 copies/ml.
- #12: Once viral suppression is achieved, we see measurable improvement to the immune system and in clinical signs and symptoms
- #13: While trajectories vary, suppression of VL with ART allow for immunologic recovery and improvements even normalization of CD4 count. Those who start at very low CD4 counts however may not achieve robust CD4 recovery. Here is plot of a single individual patient in which you can see over the course of 2 years following initiation of ART and persistently suppressed VL, an improved CD4 from low 400’s to sustained above 500.
- #14: Why do enhanced adherence counseling? This study from S. Africa looked at the effect of early viral load testing and adherence interventions on viral load suppression and preservation of first line regimens. VL was checked every 4 months while on ART and if the result was above 1000 copies/ml, participants received intensive adherence interventions including home visits and then the VL was repeated 6-8 weeks after the adherence interventions From the graph here it can be seen that the early VL result and intensive adherence interventions (pill box, dosing diary, home visits, education sessions) resulted in half of those with initial VL >1000 shown with the dashed line, subsequently achieving full suppression. The solid line shows those whose second VL remained above 1000 copies/ml
- #16: Once good adherence is achieved based on calculating adherence using the table, a date for follow up viral load testing is set and given to the patient. Adherence support may need to continue on a monthly basis to maintain good adherence until the viral load drops to 1000 copies/ml or less. Remember it will takes some months for vl to decline once good adherence achieved so starting counting the 3-6 m interval from time good adherence has begun
- #17: If patients are not taking their medications correctly and /or the virus has developed some resistance to the medication, the early or first change that we can measure in the blood is an increase in the HIV viral load
- #18: Only after the viral load has been elevated for some time does this lead to a drop in the CD4 ( immunological failure ) Finally as the CD4 declines and the patient is not able to fight off infections clinical failure can occur Because of the low sensitivity of immunologic criteria, a substantial number of failures are missed, potentially resulting in accumulation of resistance mutations. In addition, specificity and predictive values are low, which may result in large numbers of unnecessary ART switches. Monitoring solely by immunologic criteria may result in increased costs because of excess switches to more expensive ART and development of drug-resistant virus. References World Health Organization. Transaction prices for antiretroviral medicines and HIV diagnostics from 2004 to September 2008. Summary report from the global price reporting mechanism [Internet]. 2008 [cited 2014 Jan 13]. Available from: http://www.who.int/hiv/amds/GPRMsummaryReportOct2008.pdf Lynen L, Van Griensven J, Julian E. Monitoring for treatment failure in patient on first-line antiretroviral treatment in resource-constrained settings. Curr Opin HIV AIDS. 2010;5(1):15. Mee P, Fielding KL, Charalambous S, Churchyard GJ, Grant AD. Evaluation of the WHO criteria for antiretroviral treatment failure among adults in South Africa. AIDS. 2008;22(15):19717. Reynolds SJ, Nakigozi G, Newell K, Ndyanabo A, Galiwongo R, Boaz I, et al. Failure of immunologic criteria to appropriately identify antiretroviral treatment failure in Uganda. AIDS. 2009;23:697700. Keiser O, Tweya H, Boulle A, Braitstein P, Schecter M, Brinkhof MW, et al. Switching to second-line antiretroviral therapy in resource-limited settings: comparisons of programmes with and without viral load monitoring. AIDS. 2009;23:186774. Ferreyra C, Yun O, Eisenberg N, Alonso E, Khamadi AS, Mwau M. Evaluation of clinical and immunological markers for predicting virological failure in a HIV/ AIDS treatment cohort in Busia, Kenya. PLoS One. 2012;7(11):e49834. doi: 10.1371/journal.pone.0049834 Kanapathipillai R, McGuire M, Mogha R, Szumilin E, Heinzelmann A, Pujades-Rodrı´guez M. Benefit of viral load testing for confirmation of immunological failure in HIV patients treated in rural Malawi. Trop Med Int Health. 2011;16(12):1495500. Rawizza HE, Chaplin B, Meloni ST, et al. Immunologic criteria are poor predictors of virologic outcome: implications for HIV treatment monitoring in resource-limited settings. Clin Infect Dis 2011;53(12):1283-90.
- #19: Viral load has been chosen as the preferred strategy for a number of reasons As shown previously delayed detection of a high viral load will lead to a drop in CD4 , reduced immunity and eventually new infections with the risk of increased morbidity and mortality for the patient In addition, by identifying a patient with a high viral load and intervening early if there are adherence problems, it may avoid future development of resistance. If a high viral load is acted upon with adherence interventions or a switch to second line, transmission both to sexual partners and from mother to child can be reduced Finally, knowing someone is suppressed and doing fine on their ART provides reassurance and the potential for the patient to receive extended refills of ART or enter into alternative refill strategies such as fast track or community based refill groups
- #22: PEPFAR will continue to prioritize interventions in all the supported counties by working closely with stakeholders, including MOH in order to scale-up viral load testing in priority counties and sites for FY20 and FY21
- #23: VL also related to other key areas s/a case identification- will hear more about index testing focus on clients with HVL (and newly diagnosed) BLUF: Retention and VLS paramount goals
- #30: replace
- #34: VLC and VLS suppression as an OU remains lower than other countries. The VLC and VLS rates in children and adolescents is unacceptably low (likewise VLC for PBFW). What are we going to do as an OU. Are there barriers, root causes that need to be addressed as an OU? know on adult front optimizing ART with TLD What about children? Why are we failing as a program? -> consider more RCA, driver diagram from OU perspective Don’t think 3rd bullet’s true
- #35: VLC and VLS suppression as an OU remains lower than other countries. The VLC and VLS rates in children and adolescents is unacceptably low (likewise VLC for PBFW). What are we going to do as an OU. Are there barriers, root causes that need to be addressed as an OU? know on adult front optimizing ART with TLD What about children? Why are we failing as a program? -> consider more RCA, driver diagram from OU perspective Don’t think 3rd bullet’s true
- #36: Tackling low VLC
- #37: Refine problem and AIM statement Problem statement: xx% VLC and S in South Sudan AIM statement: To increase VLC/S amongst PLHIV on ART in South Sudan from X to Y% in 3 months Would use a shorter time frame Specify for all populations From X to Y%