Evolving Realities of HIV Treatment in Resource-limited Settings

Transcription

1 Evolving Realities of HIV Treatment in Resource-limited Settings Papa Salif Sow MD, MSc Department of Infectious Diseases University of Dakar, Senegal

2 Introduction: ARV access in RLS Scale-up of ART has been unprecedented ART initiation is too late: Low CD4 counts & clinical symptoms High early mortality Severe immunodeficiency/oi s Severe malnutrition Frequent co-infection with tuberculosis Frequent use of d4t in 1 st Line ARV Lack of virological tools for ARV monitoring: when and what to switch to Low access to 2 nd line ARV and Salvage ART

3 Number of people receiving ART in low- and middle-income countries, by region, Souteyrand Y. IAS 2009

4 Botswana Rwanda Papua New Guinea Burkina Faso Zambia Haiti Gabon Kenya Malawi Swaziland Cote d'ivoire Lesotho South Africa Ethiopia Cameroon Burundi Guinea Mozambique Togo Guinea-Bissau Central African Rep Zimbabwe Congo Ghana Chad Percent Coverage ART Coverage in Resource-limited Settings 100% 80% 60% 40% 20% 0%

5 CD4 count at start of ART, Comparison of the regional variation of CD4+ counts at the time ART therapy initiated Review of data from 42 countries, 176 sites; n=33,008 Median CD4+ counts at the start of therapy, by region/country North America US 187 Canada 164 South America Brazil 159 Argentina 181 Sub-Saharan Africa South Africa 87 Botswana 97 Malawi 97 Australasia India 103 Vietnam 53 Japan 192 China 163 Australia 239 Egger M, et al. 14 th CROI, Los Angeles 2007, #62

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7 Late HIV presentation at the ARV initiation Therapy.

8 High frequency of Tuberculosis in patient who initiate ARV

9 Tuberculosis & ART in RLS Interations between Tb drugs and ARV Rifabutin not available 2009 WHO recommendations Preferred option : AZT or TDF + 3TC/FTC + EFV Initiate ART as soon as possible, within the first 8 weeks after starting TB Treatment NVP or 3 NRTI acceptable options if EFV cannot be used

10 1st line regimens in Resource-Limited Countries

11 2009 WHO ART Guidelines for Adults and Adolescents When to start: All adolescents and adults with HIV infection and CD4 counts 350 cells/mm 3, including pregnant women, should be started on antiretroviral therapy (ART) immediately, regardless of whether they have clinical symptoms. Individuals with severe or advanced clinical disease (WHO clinical stage 3 or 4) should start ART irrespective of CD4 cell count. What to use in 1 st line: First-line therapy should consist of an NNRTI + two NRTIs, one of which should be AZT or tenofovir. Countries using d4t in first-line regimens should start phasing it out because of its long term toxicity (2012 the latest) Replacing d4t by TDF in RLS

12 Impact of Late Treatment in Sub-Saharan African Countries Early mortality during the first three months High frequency of IRIS Presence of Resistant Viruses +++ Treatment failure of ART

13 Early Mortality in HIV/AIDS Immunodepression Severe Malnutrition ARV High Caloric Food

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16 404 HIV patients longitudinal follow-up: patients died: incidence rate of death was 6.3/100 persons-years 47 patients died during the first year after HAART Very immunodepressed patients CD4 less than 50 Most frequent causes of death: mycobacterial infection, septicemia 33% changed ARV regimen by 7 years

17 14,352 patients were enrolled In press Overall 13,102 patients were followed up for a median of 1.8 years (IQR:( ), persons-years of followup. During the overall study period, 521 (4.0%) patients were known to be dead 2,610 (19.9%) were lost to follow-up 9,971 (76.1%) patients were still in program and remained on ART 12 months after enrollment.

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19 Retention rates in African ART Cohorts SOURCE: S Rosen, M P Fox, C J Gill PLoS 2007 Volume

20 Patients are lost to ARV programs early on More than 20% of patients are lost to follow up Mean reasons: cost of consultations; AIDS stage High cost for transport: 50% of cost in Tanzania Poverty/logistics: ART interruption driven by stock shortages (OR 3.25), binge drinking (OR 2.87), wasting symptoms (1.23). Conclusion: Food supply programs and minimization of ARV shortage may reduce ART interruptions 1 Bull World Health Organ Morris K: Marcellin F: Tropical Medicine and Int. Health, Kruk M: Tropical Medicine and Int. Health, 2008

21 Treatment Failure and Drug Resistance in Resource Limited Settings CD4 Count Virologic failure Immunologic failure Clinical failure Drug Resistance Viral Load CARE5. Kumarasamy & P Salif Sow 2008

22 -Limited HIV-RNA monitoring in RLS patients from eight cohorts and two prospective studies were analysed -Resistance at virological failure at 48 weeks: infrequently versus frequently monitored - NNRTI : 88.3 % versus 61.0% (p< 0.001) - 3TC : 80.5 % versus 40.3 % (p< 0.001) - TAM : 27.8 % versus 12.1 % (p < 0.001)

23 Probability of death 0.14 Patients remaining on failing first-line regimen Patients who switched Patients remaining on non-failing first-line regimen Time after switching, after reaching WHO criteria or after the corresponding time since starting HAART (months)

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25 HIV-2 Resistance mutations Multiclass drug resistance mutations (NRTI and PI) were detected in 30 % of patients (n= 23) 52 % had evidence of resistance to at least 1 ARV class 43 % had the M184V mutation 9 % had the K65R mutation 34% of patients had PI mutations

26 In summary :ARV Resistance in RLS Genotypic resistance at 48 weeks to 3TC and NRTI and NNRTI appears sustantially higher in less frequently monitored patients This highlights the need for cheap pointof-care viral load tests to identify early viral failures and limit the emergence of resistance.

27 Characteristics of a point-of-care viral-load test in RLS Simple to use & easy to read Independent of instrumentation or electronics Robust and able to withstand increased ambient temperatures without cold-chain shipment or storage Long shelf-life (longer than 12 months) Inexpensive (not > 2 $US) Harries Lancet ID: 2010 Jan;10(1):60-65.

28 Decentralization National VL Monitoring in RLS National Level Regional Level District Level Tertiary Laboratory : Reference Laboratory : using Nucleic Acid Testing Strategies Secondary Laboratories: Alternatives Viral Load Technologies : Non Nucleic Acid Primary Care Laboratories: sample preparation for referral

29 Conclusion : Perspectives RLS First line ART must be protected as long as possible (adults and children) Better management of co-infections HIV/TB : Rifabutin available HIV/HBV: HbSAg test before start ARV Reliable tools to diagnose ART failure (POC viral load) Easy-to use and relatively inexpensive second-line therapy has to be available

30 Demand for HIV testing still far exceeds supply