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HIV and malaria

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Title: HIV and malaria


1
HIV and malaria
  • Moses R. Kamya M.B.Ch.B, M.Med, MPH, PhD
  • Associate Professor, Dept.of Medicine, Makerere
    University, Kampala, Uganda

2
Outline
  • Background (HIV/Malaria Interactions)
  • Prevention of malaria among people with HIV
  • CTX, bednets and ART
  • Treatment of malaria in people with HIV
  • Effect of HIV on response to antimalarial therapy
  • Safety of antimalarial regimens in patients
    receiving ART and/or other treatments
  • Conclusions and recommendations

3
Burden of malaria in Africa
  • Over 300 million clinical cases and 1 million
    deaths annually
  • Accounts for 25-40 of outpatient visits and
    20-50 of hospital admissions

4
Malaria incidence and HIV prevalence in selected
Sub-Saharan African countries
Brentlinger, P. E. et al. Arch Intern Med
20071671827-1836.
5
Does HIV increase the risk of malaria?
  • Early epidemiological evidence of an effect of
    HIV on malaria in children and non-pregnant
    adults found no interaction
  • 7 studies (3 children, 3 adults, 1 both)
  • All hospital or clinic based
  • Cross sectional or retrospective
  • Review in 1998 concluded no convincing nor
    consistent link between the two infections apart
    from in pregnant women

6
Rates of clinical malaria at interim visits by
HIV status, CD4 count and WHO stage (Lancet 2000)
Rates of clinical malaria per 100 person years
HIV status
CD4 count
WHO stage
7
Prevalence of HIV stratified by Age Group (Kamya
et al. JID 2005)
8
Is malaria more severe in HIV infected patients?
  • Prospective cohort study among adults presenting
    with fever in an area of unstable malaria
    transmission in South Africa (AIDS 2004)
  • 613 episodes of malaria diagnosed
  • HIV prevalence 30
  • HIV associated with an increased odds of
    severe/complicated malaria (OR2.3, 95 CI
    1.4-3.9)
  • HIV associated with an increased odds of death
    (OR7.5, 95 CI 2.2-25.1)
  • Prospective cohort study from South Africa (CID
    2005)
  • HIV-infected non-immune adults at increased risk
    for severe malaria
  • This risk associated with low CD4 count

9
What do we know about HIV and malaria in
pregnancy?
  • Pregnant women are at increased risk for malaria,
    especially in their first 2 pregnancies
  • Most pregnant women with malaria are asymptomatic
    and therefore undetected and untreated
  • Compared to HIV-uninfected pregnant women, HIV
    infected pregnant women are at increased risk of
    all of the following
  • Symptomatic malaria
  • Placental malaria
  • Maternal anemia
  • Adverse birth outcomes
  • HIV alters the typical gravidity-specific pattern
    of malaria risk by shifting the burden to all
    pregnancies
  • Estimated that the HIV epidemic results in an
    additional 500,000 to 1 million women per year
    who have malaria during pregnancy

10
Influence of malaria on HIV disease
  • Parasitemia and clinical malaria associated with
    0.25-0.89 log increase in viral load for 9 weeks
  • Treatment of malaria in HIV-infected adults
    associated with decreased viral load (190000 to
    120000 copies/ml), and increased CD4 cell count
    (297 to 447 cells/µL) after 28 days
  • Clinical malaria episodes associated with 40
    cell/year more rapid decline in CD4 cell count
  • Little information in children with HIV

Kublin, et al, Lancet 2005365233-239 ter
Kuile, et al, Am J Trop Med Hyg 20047141-54
Van Geertruyden, et al, JAIDS 200643363-7
Hoffman, et al, AIDS 199913487-495 Mermin, et
al, JAIDS 200641129-130, Brahmbhatt, et al,
AIDS 2003 17 2539-41 Ayisi, et al, AIDS 2003
17 585-94 Ned, et al, Trends Parisitol 200524
285-91
11
Ecologic impact
  • Modeling in Kisumu, Kenya, indicated a 2.1
    increase in HIV prevalence and 5.1 in malaria
    Since 1980
  • 8,500 excess HIV infections
  • 980,000 excess cases of malaria

Korenromp EL, et al, Emerg Infect Dis 2005
111410-1419 Abu-Raddad, et al, Science
20063141603-1606 Nguyen-Dinh, et al, Bull
World Health Org 198765607-613
12
Cotrimoxazole prophylaxis
  • 25-46 reduction in mortality
  • U.S., Europe, Cote dIvoire, Uganda, Zambia,
    Malawi, South Africa
  • Reductions in malaria, bacterial and Pneumocystis
    pneumonia, toxoplasmosis, diarrhea, sinusitis
  • Saved health system 2.50 per person treated

13
Malaria rates in 5 years
  • 72 reduction in malaria incidence among all
    participants (even people with CD4 cell count
    gt500)

14
Malaria incidence among HIV-infected adults
Malaria per 100 person-years
  • 95 reduction in malaria with all 3 interventions

15
MU-UCSF Study Design and Objectives
  • We compared malaria incidence between two
    parallel cohorts
  • HIV infected children
  • community-based cohort of healthy children
  • Objectives
  • To estimate the protective efficacy of CTX and
    ITNs on the incidence of malaria in HIV infected
    children
  • To investigate the prevalence of molecular
    markers associated with antifolate resistance in
    incident malaria cases.
  • (Kamya et al. AIDS 2007)

16
Proportion of patients with fever diagnosed with
malaria
17
Effect of TMP/SMX prophylaxis and ITN use on
malaria incidence
18
Baseline characteristics of malaria episodes
19
High malaria risk in high transmission settings
despite CTX
Following randomization only- CTX
groupControl- RR0.36 (p0.13)
Controlling for breastfeeding
20
Strategic use of HIV PIs may be justified to
prevent malaria
  • Antiretroviral protease inhibitors (PIs) exert
    antimalarial activity in vitro and in animal
    models
  • HIV PIs may protect against malaria.
  • Clinical evidence is lacking

21
Malaria Treatment in HIV Infected Populations- 3
messages
  • Effective regimens are efficacious for treatment
    of malaria in HIV-infected and uninfected
    populations
  • new infections are higher in HIV but
    recrudescence is similar between HV HIV-
  • Increased treatment failure among HIV-infected
    with low CD4 cell counts
  • Lower risk of recurrent malaria due to
    re-infection among HIV-infected on CTX prophylaxis

22
To assess the effect of HIV infection on response
to antimalarial therapy
  • The trials, conducted between 2002 and 2004 at 7
    sites and included the following treatment arms
  • Sulfadoxine-pyrimethamine (SP) chloroquine
  • SP amodiaquine (AQ)
  • AQ Artesunate

23
Associations between HIV and treatment failure
following antimalarial therapy (Kamya et al. JID
2005)
Controlling for age and treatment group
24
Increased treatment failure among HIV-infected
with low CD4 cell counts
  • HIV associated with delayed clearance time of P.
    falciparum by artemisinin
  • HIV with CD4 lt200-300 treated with SP have a
    higher risk of treatment failure compared to
    CD4gt200-300 or HIV-

Birku Y et al. Ethiop Med J 2002 40 Suppl
117-26. Shah SN et al. J Infect Dis 2006
1941519-28. . Van geertruyden JP et al J Infect
Dis 2006 194917-25
25
Better response in HIV on TMP/SMX
26
Safety of antimalarial regimens in patients
receiving ART, TMP/SMX etc?
  • Elevated LFTs in healthy volunteers given AQAS
    and EFV
  • AQ levels (AUC, Cmax and half life) were elevated
    with EFV exposure

27
Time course for abnormalities in liver-associated
enzyme levels ALT (alanine aminotransferase) AST
(aspartate aminotransferase) ULN (upper limit of
normal) Bars, duration of study drug
administration AQ/AS (amodiaquine artesunate)
EFV (efavirenz)
28
Risk of new of worsening adverse events within 14
days of AQAS therapy
29
Risk factors for new or worsening adverse events
due to neutropenia
30
Conclusions (HIV/malaria interactions)
  • HIV-infected adults and children have higher
    rates of clinical malaria and in non-malaria
    endemic areas more severe disease
  • Advanced immune suppression is associated with an
    increased incidence of malaria
  • Malaria episodes are associated with short term
    increases in viral load and decreases in CD4 cell
    count and may have long-term effects on CD4 cell
    count
  • HIV is associated with increased placental
    malaria and poor birth outcomes

31
Conclusions/Recommendations 1
  • Use of TMP/SMX prophylaxis and ITNs substantially
    reduce the risk of malaria in HIV infected
    children and adults despite a high prevalence of
    molecular markers of antifolate resistance
  • No evidence to support differential antimalarial
    treatment policies for HIV infected and
    uninfected patients with uncomplicated malaria
  • Effective regimens must be used
  • Severely immunosuppressed patients should be
    closely followed for Rx failure

32
Conclusions/Recommendations 2
  • Among HIV infected people receiving TMP/SMX and
    using ITNs, malaria is rarely the cause of fever,
    and the empiric treatment of all fevers as
    malaria would be misguided.
  • Provide routine HIV testing for people with
    malaria

33
Conclusions/Recommendations 3
  • Malaria prevention programs should target HIV
    infected individuals, HIV prevention and
    treatment programs offer an opportunity to
    deliver malaria prevention
  • Integrated interventions for both HIV and malaria
  • Joint programme planning

34
Future Research
  • Need to monitor surveillance of higher level
    antifolate resistance-- may impact of the
    protective efficacy of TMP/SMX
  • Do ARV drugs prevent malaria in vivo?
  • Continued research is needed to establish the
    safety and efficacy of ACT regimens in patients
    receiving ART (PK studies, pharmacovigilance)
  • Interactions between malaria and HIV in children,
    the population at greatest risk of malaria, need
    further study

35
Thank You
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