welcome to i-tech hiv/aids clinical seminar series october 21, 2010 malaria/hiv interactions:...
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Welcome to I-TECH HIV/AIDS Clinical Seminar Series
October 21, 2010Malaria/HIV Interactions: Clinical Update
Paula Brentlinger, MD, MPH
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Malaria/HIV Interactions:Clinical Update
Malaria/HIV Interactions:Clinical Update
Dept. of Global HealthUniversity of Washington
October 2010
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Today’s Topics
Associations between Malaria and HIV
Prevention
Diagnosis
Treatment
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Geographic Overlap (Source of maps: WHO, 2008)
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AIDS and Malaria Incidence (1)
Uganda: (French et al, 2001)
CD4 Malaria cases/1000 py
>=500 57
200-499 93
<200 140
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AIDS and Malaria Incidence (2)
Uganda (Whitworth et al 2000): % patients with symptomatic malaria, by CD4:
CD4 % w malaria Cases/100py
>=500 0.8% 5.8 200-499 2.4% 9.5 <=199 4.2% 20.6 (Lancet 2000; 356:1051-56)
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HIV and Severity of Malaria (1) (Grimwade, 2004)
HIV+ HIV-
Renal insufficiency 27% 15%
Coma 16% 8%
Severe anemia 14% 11%
Seizures 3% 1%
Pulmonary edema 4% 1%
Acidosis 15% 6%
Jaundice 9% 1%
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HIV & Severity of Malaria (2) (Chalwe et al, 2009)
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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
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Malaria and HIV viral load (2)
Van Geertruyden et al 2006:
Mean HIV-1 viral load, log10 RNA copies:
At enrollment (acute malaria): 4.86
28 days and 45 days after successful treatment: 0.1 log decrease (non-significant)
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Malaria and CD4 count
Van Geertruyden et al (2006, op.cit.)
HIV-infected patients with acute malaria in Zambia:
CD4 %CD4<200
Baseline (malaria) 297 28.7
28 days post Tx 447 13.4
45 days post Tx 403 13.2
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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
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The Special Case of Pregnancy
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Vertical HIV Transmission and Placental Malaria (1) (Brahmbhatt 2008)
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Vertical HIV Transmission and Placental Malaria (2)
Naniche, 2008
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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.
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Malaria Prevention
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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
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Malaria Prevention in HIV: Combined Interventions
(Mermin, 2006)
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Malaria Prevention in Pregnancy: CTX or IPTp? (Newman et al. 2009)
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Malaria Prevention in Pregnancy: CTX or IPTp? (Newman et al. 2009)
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Malaria Prevention in Pregnancy: ITN or IPTp? (Menendez et al 2010)
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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.
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Clinical Issues (1): Diagnosis – Syndromic or Etiologic?
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IMAI Acute Care, 2005
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Malaria Rapid Tests (Mills et al 2010)
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Prevalence of Malaria in Febrile HIV+ patients (Mills et al 2010, op. cit.)
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Differential Diagnosis, Fever (Anglaret, 2002)
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Malaria and.... (O’Callaghan-Gordo et al 2011)
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Differential Diagnosis: Anemia (Lewis, 2005)
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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.
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Clinical Issues (2): Treatment
Treatment response in HIV
Drug selection (and quandaries)
Supportive treatment
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HIV and Response to Malaria Treatment (Shah, 2006)
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HIV and Hematologic Response to Malaria (Van Geertruyden 2009)
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Drug Interactions (1): NNRTIs vs Antimalarials, (www.hiv-
druginteractions.org)
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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
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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
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Malaria and hypoglycemia (Willcox et al 2010)
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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.
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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.
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Questions?
And some mini-cases if there is time.
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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
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Welcome to I-TECH HIV/AIDS Clinical Seminar Series
Next session: 28 OctoberOral Health for Primary Care Providers Leo Achembong, BDS, MPH Candidate