Gaps between Policy and Practice in Managing HIV disease in Asia Pacific

Transcription

1 Gaps between Policy and Practice in Managing HIV disease in Asia Pacific Dr. N. Kumarasamy Chief Medical Officer YRGCARE Medical Centre Voluntary Health Services Chief-Chennai Antiviral Research and Treatment (CART) Clinical Research Site

2 Policy and Practice- WHO Guidelines

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4 Epidemic in Asia

5 HIV Scenario in India (2017) 2 to 2.5 million infections (estimate) Heterosexual transmission ` 0.25% of adult population (1.2billion population) Growing number- MSM,PWIDs HIV-1; Subtype C 1.2 million on ART >50% decline in HIV incidence and mortality Source : NACO

6 Simulation model of HIV testing and treatment - Prevalence and Incidence in different groups - Cost of testing Conclusion: Voluntary HIV screening among National population every 5 yrs offers substantial clinical benefit and cost effective. Annual screening is cost effective among high risk population and in high prevalent districts

7 Asia misses the new infection targets

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9 In South Africa, early ART was cost-saving over a 5-year period. In both South Africa and India, early ART was projected to be very cost-effective over a lifetime. With individual, public health, and economic benefits, there is a compelling case for early ART for serodiscordant couples in resource-limited settings.

10 Evolution of the global uptake of WHO Treat All policy Low-Middle Income Countries (139) Fast Track Countries (35) mid 2016 end 2016 mid 2017 end 2017 mid 2018* * Preliminary data

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12 WHO Treatment Guidelines : What to Start in Adults FIRST-LINE REGIMENS ARV REGIMENS) TARGET POPULATION 2010 ART GUIDELINES 2013 ART GUIDELINES 2016 ART GUIDELINES HIV+ ADULTS HIV+ PREGNANT WOMEN HIV/TB CO-INFECTION HIV/HBV CO-INFECTION AZT or TDF + 3TC (or FTC) + EFV or NVP AZT + 3TC + NVP or EFV AZT or TDF + 3TC (or FTC) + EFV TDF + 3TC (or FTC) + EFV TDF + 3TC (or FTC) + EFV (as fixed dose combination) Preferred: TDF + 3TC (or FTC) + EFV (as fixed dose combination) Alternate: TDF + 3TC (or FTC) + DTG* TDF+3TC (or FTC) + EFV400mgs WHO Guidelines 2010: Accessed may WHO Guidelines 2013: Accessed May WHO Guidelines 2015: Accessed May 2016.

13 Increased Suicidality in Patients Treated With Efavirenz- Containing Regimens in ACTG Clinical Trials Retrospective analysis of 4 ACTG clinical trials Analysis of 5332 HIV-infected treatment-naive patients randomly assigned to efavirenz-containing (n = 3241) or efavirenz-free (n = 2091) initial antiretroviral therapy regimen in 1 of 4 AIDS Clinical Trials Group studies conducted between 2001 and 2010 with an approximate 3-yr median follow-up: 1 placebo-controlled study (A5095) 3 open-label studies (with respect to efavirenz assignment) (A5142, A5175, A5202)

14 Summary of Key Conclusions Among HIV-infected patients enrolled in clinical trials, 2.5-fold higher risk of attempted or completed suicide among those assigned to efavirenz vs those assigned to regimens not containing efavirenz Risk of suicidality (including suicidal thoughts) 2.3-fold higher in patients assigned to efavirenz as initial antiretroviral therapy Factors associated with suicidality in multivariate analysis included efavirenz treatment, younger age, injection drug use (IDU) history, and psychiatric history

15 Percentage with EFV/NVP Resistance Pretreatment HIV drug resistance to EFV or NVP among first-line ART initiators in selected countries 30 India -? 5-10% Thailand 7.9% 1 Indonesia 4.3% 2 Philippines 8.5% Uganda Namibia Zimbabwe Cameroon Nicaragua Guatemala Argentina Mexico Brazil Columbia Myanmar Transition to new ART in HIV program WHO July HIV Drug Resistance Report Kiertiburanakul S et al., 2016 Feb 1;11(2):e Kotaki T et al., AIDS Research and Therapy 2015:12:5 DOI /s y 3. Salvana E et al., Open Forum Infectious Diseases 2017: 4(suppl 1): S WHO Guidelines 2017: Transition to new ART in HIV program, WHO July Available at: Accessed Jan HIV Drug Resistance Report Available at: Accessed Jan 2018

16 Pre Treatment drug resistance is increasing Prevalence of NNRTI pretreatment resistance by calendar year WHO Guidelines on the public health response to pretreatment HIVDR Countries with national pretreatment HIV drug resistance to EFV or NVP greater than or equal to 10% should consider a rapid transition to DTG

17 A generic DTG regimen for 1st-line ART in India will increase survival and decrease the proportion of patients switching to more costly 2nd-line ART. At $102 (INR 6,834) per patient per year, a DTG regimen is very cost-effective and its implementation would be at no additional cost for the national HIV program in 5 years in India. DTG-based first-line ART should become the standard of care for ART initiation in India.

18 Generic DTG license for Asia

19 Monitoring- WHO 2016 Guidelines

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21 Cost Effectiveness of Viral Load in India Compare 11 alternative lab monitoring protocols using CD4 count and viral load Simulation followed a cohort of patients from initiation on first-line ART Examples of lab monitoring options Bi-annual CD4 Annual CD4 + HVL confirmation Bi-annual CD4 + HVL confirm (NACO) Annual CD4 and HVL tests Adaptive CD4 + HVL testing Adaptive HVL testing Bi-annual CD4 + adaptive HVL (WHO) Freedberg, Kumarasamy, et al., AIDS Research and Human Retroviruses CEPAC studies: VL 21

22 5 year Budget Impact HVL testing induces higher spending on labs and ART. 22

23 Generic ARVs from India/Asia NRTIs NNRTIs PIs zidovudine (AZT) didanosine (ddi) stavudine (d4t) lamivudine (3TC) abacavir (ABC) emtricitabine (FTC) Nevirapine (NVP) Efavirenz (EFV) Rilviprine (RLP) Etravirine (ETV) Nucleotide RTIs Tenofovir DF (TDF) TAF Entry Inhibitors Maraviroc (CCR5) enfuvirtide (ENF, T20) saquinavir (SQV) indinavir (IDV) ritonavir (RTV) nelfinavir (NFV) lopinavir/ritonavir (LPV/r) atazanavir (ATV) Darunavir(DRV) Post Attachment Inhibitor Ibalizumab Integrase Inhibitors Raltegravir (RAL) Elvitegravir(ELV),Bictegravir(BIC) Dolutegravir(DTG)

24 WHO Guidelines WHO Guidelines 2015: Accessed May 2016.

25 CART-Cohort study:non AIDS causes of mortality (NCDs) > 10 yrs on ART with HIV disease- 919 Median duration on ART- 10.3yrs Median latest CD4-510 % of people with suppressed viral load(<400 copies/ml)-82% % of people on 1 st line ART after 10yrs - 58% Cardiovasculardrugs,inflammation Renal- drugs,hiv Diabetes-drugs,HIV Liver-NASH Cancers Neurocognitive effectsdrugs, HIV Kumarasamy N, et al. CART Cohort study. Cell-The Lancet Translational Medicine Conf. San Francisco, Nov 3-5,2013

26 Cardiovascular disease-related mortality and factors associated with cardiovascular events in HIV-positive adults in the Asia-Pacific R Bijker 1, A Jiamsakul 1, N Kumarasamy 2, E Uy 3, R Ditango 3, R Chaiwarith 4, WW Wong 5, A Avihingsanon 6, LP Sun 7, E Yunihastuti 8, S Pujari 9, CD Do 10, TP Merati 11, S Kiertiburanakul 12, on behalf of the TREAT Asia HIV Observational Database (TAHOD) of IeDEA Asia-Pacific The study population included 7752 patients with a median followup of 6.6 (IQR ) years. Cumulative incidence of causes of death during the first ten years on ART Years since ART initiation CVD-related AIDS-related Non-AIDS-related Unknown CONCLUSIONS The development of fatal and non-fatal CVD events in patients enrolled in our cohort was associated with traditional risk factors such as older age, high blood pressure, triglycerides, total cholesterol, and BMI. The higher rate of CVD events in higher-income countries compared to lower-middle income countries may indicate under-diagnosis of CVD in resource-limited settings in the Asia-Pacific.

27 ACTG REPRIEVE/ NIH Randomized Clinical Trial Pitavastatin vs Placebo Enrolling in Chennai, Bangkok, Chiangmai

28 Oral PrEP global roll-out, 2018 National roll-out- Australia, Belgium, Brazil, Canada, Kenya, New Zealand, Norway, Scotland NHS, South Africa (?US) Other implementation (e.g. demonstration projects, pharmacy access, DREAMS) Feasibility/Demonstration projects underway. (Clinic vs Community based)

29 Improved Survival in HIV treatment Programmes in Asia-TAHOD/IeDEA In a study who initiated ART between (n=16 546), from seven sites across six Asia-Pacific countries. The survival probabilities at 4 years follow-up for those initiating ART in was 92.1%, was 94.3% and was 94.5% (p<0.001). Concurrent with improved survival was increased tenofovir use, ART initiation at higher CD4 counts, and greater monitoring of CD4 and HIV viral load. CONCLUSION: This is likely a consequence of improvements in treatment and, patient management and monitoring over time. De La Mata NL, Kumarasamy N, Khol V, et al. Antiviral Therapy 2016

30 TARGET POPULATION (ARV-NAIVE) Recommendations in WHO ART 2010 ART GUIDELINES Guidelines 2013 ART GUIDELINES HIV+ CD4 500 cells/mm 3 (CD4 ASYMPTOMATIC CD4 350 cells/mm cells/mm 3 as a priority) HIV+ SYMPTOMATIC WHO clinical stage 3 or 4 regardless of CD4 cell count PREGNANT AND No change 2016 ART GUIDELINES Will avert 21 million AIDS-related deaths and will CD4 350 cells/mm BREASTFEEDING 3 Regardless of CD4 cell count prevent or 28 million WOMEN WITH HIV or new WHO clinical infections stage by 2030 ALL WHO clinical stage 3 or 4 ALL ALL HIV/TB CO- INFECTION HIV/HBV CO- INFECTION HIV+ PARTNERS IN SD COUPLE Presence of active TB disease, regardless of CD4 cell count Evidence of chronic active HBV disease, regardless of CD4 cell count No recommendation established No change Evidence of severe chronic HBV liver disease, regardless of CD4 cell count Regardless of CD4 cell count or WHO clinical stage ALL ALL ALL WHO Guidelines 2010: Accessed may WHO Guidelines 2013: Accessed May WHO Guidelines 2015: Accessed May 2016.

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32 90/90/90 CASCADE PROGRESS VARIES AMONG REGIONS KNOWLEDGE OF HIV STATUS, TREATMENT COVERAGE AND VIRAL LOAD SUPPRESSION, BY REGION, 2016 Comparison of HIV testing and treatment cascades by region reveals different patterns of progress. Western and central Europe and North America are approaching global targets. Latin America and eastern and southern Africa show high levels of achievement across the cascade. Eastern Europe and central Asia, the Middle East and North Africa, and western and central Africa are clearly on track. Source: UNAIDS special analysis, 2017; see annex on methods for more details. 1 Cascade for the western and central Europe and North America region is for 2015.

33 Cascade in Asia Source : UNAIDS 2017

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35 Conclusions Progress on scale-up of ART in Asia has been extraordinary- > 2.4 millions on ART ( 47%) out of 5.1 million estimated Decrease in morbidity and mortality Declining incidence of HIV Sustainability of ARVs- Stock outs had happened.this will require forward-looking policies, more effective and innovative approaches, together with further investments Prevention of transmission of resistance strains Prevention and management of NCDs PrEP need to be implemented in Asia soon. Cost Effectiveness studies and Need for Program Managers training

36 HIV/HCV Prevalence in India PWIDU Established Epidemics Large Cities Emerging Epidemics (documented Lancet Infect Dis 2014 Emerging Epidemics (anecdotal)

37 Kenneth Mayer Treat Asia colleagues Marco Vitoria-WHO CHAI Thuy Le Acknowledgment