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Advanced HIV: Diagnosis, Treatment, and Prevention

This article discusses the clinical considerations, natural history, immune reconstitution syndrome, and diagnosis of advanced HIV disease. It also explores the treatment options and prevention strategies for individuals with advanced HIV.

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Advanced HIV: Diagnosis, Treatment, and Prevention

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  1. Advanced HIV Disease-Clinical considerations Dr. N. KumarasamyChief & Director VHS- Infectious Diseases Medical Centre Director/Site Leader-Chennai Antiviral Research and Treatment (CART) Clinical Research Site Clinical Advisor-Clinton Health Access Initiative Chennai, India

  2. Natural History of HIV disease in Resource limited settings HIV RNA copies/ml CD4 count cells/ul Acute HIV HIV antibodies 10^6 10^2 800 200 asymptomatic Virologic set-point Varies from patient to patient Opportunistic infections † • 3 about 6mths // 5 10 yrs Kumarasamy, et al. Clin Infect Dis 2003

  3. Natural History of Human Immunodeficiency Virus Disease in Southern India 80% had one or more AIDS defining opportunistic infection when presented for care

  4. Co-factors relating to progression of patients with HIV disease:Kumarasamy et al., CID Jan 2003

  5. TREAT ALL Cohen MS, Chen YQ, McCauley M, Gamble T, Hosseinipour MC, Kumarasamy N et al, NEJM, 2011 INSIGHT Study group.Initiation of ART in early asymptomatic HIV infection. NEJM 2015

  6. Proportion of people with advanced HIV disease starting ART by sex and country income group, 2010–2015 Globally, in 2015, 37% of people starting ART did so at CD4 cell count <200 cells/mm3 IeDEA-COHERE: Results based on 951 855 adults from 55 countries after imputation of missing data Does not include “re-starters” after interruption

  7. WHO Guidelines

  8. Immune reconstitution syndrome Case Definition: A paradoxical deterioration in clinical status after initiating highly active antiretroviral therapy (HAART) attributable to the recovery of the immune response to latent or subclinical infectious or non-infectious processes Other Nomenclature Immune reconstitution inflammatory syndrome (IRIS) Immune restoration/restitution/recovery disease immune rebound illness

  9. Incidence of Immune Reconstitution Syndrome

  10. When to start ART in TB? Havilr- NEJM 2011, Blanc- NEJM 2011, AbdoolKarim, NEJM, 2011

  11. Cryptococcal Meningitis and Antiretroviral Therapy • Randomized clinical trial in Zimbabwe; ART started within 72 hours vs. 8 weeks after initiation of fluconazole alone for treatment of CM(Makadzange C, et al. Clin Infect Dis 2010) • Trial stopped by the DSMB due to increased HR for death (HR 2.85) in the early ART arm • Randomized clinical trial in Uganda, South Africa (COATS) in patients with CM • After 7-11 days of treatment with amphotericin B + fluconazole, patients were randomized to start ART within 48 hours or > 4 weeks • Trial stopped by the DSMB due to increased mortality in the early ART arm

  12. Diagnosis: Overview Lumbar puncture facilitate CSF examination and controlling of intracranial pressure http://apps.who.int/iris/bitstream/handle/10665/260399/9789241550277-eng.pdf?sequence=1

  13. WHO recommendations: Treatment of HIV associated CM Induction therapy: Preferred regimen 1 week: - Amphotericin B deoxycholate (1.0mg/kg/day) - Flucytosine (100mg/kg/day divided into four doses) Followed by 1 week of fluconazole 1200mg/kg/day: Adults 12mg/kg/day (Maximum 800 daily): Children and adolescents ART should be deferred by 6 weeks from the initiation of antifungal treatment http://apps.who.int/iris/bitstream/handle/10665/260399/9789241550277-eng.pdf?sequence=1

  14. Cytomegalovirus (CMV) vitritis following ART-IRIS

  15. REMSTART resultsMfinanga S. Lancet 2015;385:2173-82 • There was a 28.4% reduction in mortality with community support and CrAg screening (18% versus 13%) • 34% of all mortality occurred in the first month • About half of the reduction in mortality was from community support and half from pre-emptive treatment of cryptococcal antigenemia Patients with a positive CrAg had much higher mortality (32% versus 13%), even with preemptive fluconazole.

  16. REALITY Trial – enhanced prophylaxisHakim J. NEJM 2017;377:233-45 • Research study in Uganda, Zimbabwe, Malawi and Kenya • Adults and children >5 years with CD4 <100 cells randomized to receive • Routine care with cotrimoxazole and ART, or • Enhanced prophylaxis with ART • INH/B6/cotrimoxazole FDC • Fluconazole • Azithromycin • Albendazole • Although the median CD4 was only 37 cells, almost half were asymptomatic

  17. REALITY resultsHakim J. NEJM 2017;377:233-45 There was a reduction in mortality, from 12.2% to 8.9%, at 24 weeks with enhanced prophylaxis Mortality Weeks since randomization The main mortality benefit for prophylaxis was for reductions in mortality from cryptococcus infections and “unknown”. It was felt that most of the “unknown” causes of death were severe bacterial infections, which caused death at home where diagnosis was not possible.

  18. The new Unitaid/CHAI AHD initiative will reduce morbidity and mortality and improve cost efficiencies by accelerating access to affordable, optimal AHD products

  19. Advanced HIV: diagnosis, treatment and prevention

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