1. Welcome to I-TECH HIV/AIDS Clinical Seminar Series October 21, 2010 Malaria/HIV Interactions: Clinical Update Paula Brentlinger, MD, MPH

2. Malaria/HIV Interactions: Clinical Update Dept. of Global Health University of Washington October 2010

3. Today’s Topics Associations between Malaria and HIV Prevention Diagnosis Treatment

4. Geographic Overlap (Source of maps: WHO, 2008 )

5. AIDS and Malaria Incidence (1) Uganda: (French et al, 2001) CD4 Malaria cases/1000 py >=500 57 200-499 93 <200140

6. AIDS and Malaria Incidence (2) Uganda (Whitworth et al 2000): % patients with symptomatic malaria, by CD4: CD4 % w malaria Cases/100py >=5000.8% 5.8 200-4992.4% 9.5 <=1994.2% 20.6 ( Lancet 2000; 356:1051-56)

7. HIV and Severity of Malaria (1) (Grimwade, 2004) HIV+HIV- Renal insufficiency27%15% Coma16% 8% Severe anemia14%11% Seizures 3% 1% Pulmonary edema 4% 1% Acidosis15% 6% Jaundice 9% 1%

8. HIV & Severity of Malaria (2) (Chalwe et al, 2009)

9. Malaria and HIV viral load (1) Malawi (Kublin et al 2005): 77 adults, HIV+, no evidence of Plasmodium infection at study entry, followed prospectively. HIV viral load changes (medians) during and 8-9 weeks after acute malaria infection: Baseline 96,215 During malaria episode: 168,901 After resolution of malaria episode: 82,058

10. Malaria and HIV viral load (2) Van Geertruyden et al 2006: Mean HIV-1 viral load, log 10 RNA copies: At enrollment (acute malaria): 4.86 28 days and 45 days after successful treatment: 0.1 log decrease (non-significant)

11. Malaria and CD4 count Van Geertruyden et al (2006, op.cit.) HIV-infected patients with acute malaria in Zambia: CD4%CD4<200 Baseline (malaria)29728.7 28 days post Tx44713.4 45 days post Tx 40313.2

12. Mathematical Modeling Abu-Raddad et al 2006 (based on Kublin et al VL increase estimates): Kisumu (Kenya), pop. 200,000, 1980-2005: 8500 additional HIV infections caused by malaria-related increases in VL 980,000 additional cases of malaria caused by increased malaria incidence in HIV

13. The Special Case of Pregnancy

14. Vertical HIV Transmission and Placental Malaria (1) (Brahmbhatt 2008)

15. Vertical HIV Transmission and Placental Malaria (2) Naniche, 2008

16. Conclusions &Recommendations(1) Malaria incidence and severity are increased in the presence of HIV infection. If your HIV-infected patients are exposed to malaria, you should have a specific plan for prevention, diagnosis, and treatment of malaria co-infection in your patient population.

17. Malaria Prevention

18. Malaria Prevention in HIV: ITNs, CTX Malaria Incidence (cases/100 person-years), HIV+ children, Uganda (Kamya et al, 2007): No CTX, no ITN: 104.6 CTX+, ITN- 64.3 ITN+, CTX- 56.0 CTX+, ITN+ 3.4

19. Malaria Prevention in HIV: Combined Interventions (Mermin, 2006)

20. Malaria Prevention in Pregnancy: CTX or IPTp? (Newman et al. 2009)

22. Malaria Prevention in Pregnancy: ITN or IPTp? (Menendez et al 2010)

23. Conclusions &Recommendations(2) Effective malaria-prevention measures are available for HIV-infected children, pregnant women, and non-pregnant adults. The combination of insecticide-treated bed nets and co-trimoxazole prophylaxis (or IPTp) appears to be more effective than either intervention alone. In pregnant women, co-trimoxazole prophylaxis may be equivalent or even superior to IPTp.

24. Clinical Issues (1): Diagnosis – Syndromic or Etiologic?

25. IMAI Acute Care, 2005

26. Malaria Rapid Tests (Mills et al 2010)

27. Prevalence of Malaria in Febrile HIV+ patients (Mills et al 2010, op. cit.)

28. Differential Diagnosis, Fever (Anglaret, 2002)

29. Malaria and.... (O’Callaghan-Gordo et al 2011)

30. Differential Diagnosis: Anemia (Lewis, 2005)

31. Conclusions &Recommendations(3) Syndromic diagnosis should be discouraged. Ensure availability and quality of microscopy or rapid tests for your patients. Anticipate comorbidity! Malaria parasitemia can coexist with other causes of morbidity (and mortality); a positive malaria test does not absolve the clinician from conducting a FULL evaluation to identify other concurrent causes of the patient’s signs and symptoms.

32. Clinical Issues (2): Treatment Treatment response in HIV Drug selection (and quandaries) Supportive treatment

33. HIV and Response to Malaria Treatment (Shah, 2006)

34. HIV and Hematologic Response to Malaria (Van Geertruyden 2009)

35. Drug Interactions (1): NNRTIs vs Antimalarials, (www.hiv- druginteractions.org)

36. Drug Interactions (2): PIs vs. Antimalarials Antimalarials with known or suspected adverse interactions with protease inhibitors: –Artemisinins, Atovaquone, Chloroquine, Mefloquine, Pentamidine, Proguanil, Pyrimethamine, Quinine, Sulfadoxine- pyrimethamine, Halofantrine, Lumefantrine. Antimalarials known to be safe if coadministered with every PI: None Source: www.hiv-druginteractions.org

37. Drug Interactions (3): TB (Sousa et al [review] 2008) Rifampin-antimalarial drug interactions: Quinine+rifampin: demonstrated 5-fold greater antimalarial treatment failure Rifampicin+mefloquine, artemisinins, lumefantrine, amodiaquine: theoretical risk of decreased antimalarial efficacy

38. Malaria and hypoglycemia (Willcox et al 2010)

39. Conclusions &Recommendations(4) As in HIV-uninfected patients, prompt diagnosis and initiation of treatment are critical. Beware of drug interactions involving antimalarials and ARVs, TB medications, and other drugs. Consult www.hiv-druginteractions.org to stay updated. Consult your national malaria and HIV programs for advice re drug selection.www.hiv-druginteractions.org

40. Conclusions &Recommendations(4) In all cases: GIVE THE MOST EFFECTIVE ANTIMALARIAL AVAILABLE TO YOU. PROVIDE ADEQUATE SUPPORTIVE CARE (FOR SEIZURES, ANEMIA, HYPOGLYCEMIA, ETC.) SEARCH CAREFULLY FOR COMORBIDITIES. MONITOR TREATMENT RESPONSE.

41. Questions? And some mini-cases if there is time.

42. Thanks, gracias, agredecimientos! In Seattle: Mark Micek, Chris Behrens, Jim Kublin, Paul Thottingal, and the Seattle Malaria Group In Mozambique: The National Malaria Control Program, the President’s Malaria Initiative, José Vallejo, Pilar Martínez, Monica Negrete, María Ruano, Florindo Mudender In Uganda: Ian Crozier, Marcia Weaver

43. Thank you! Listserv: itechdistlearning@uw.eduitechdistlearning@uw.edu Email: DLinfo@uw.edu

44. Welcome to I-TECH HIV/AIDS Clinical Seminar Series Next session: 28 October Oral Health for Primary Care Providers Leo Achembong, BDS, MPH Candidate