hiv and malaria
DESCRIPTION
HIV and Malaria. Dr Jane Achan Dept of Pediatrics, Makerere University College of Health Sciences. Prof. Moses Kamya Makerere University College of Health Sciences. 6 th IAS CONFERENCE, 18 th July 2011. Burden of malaria . Over 300 million clinical cases and 1 million deaths annually - PowerPoint PPT PresentationTRANSCRIPT
![Page 1: HIV and Malaria](https://reader035.vdocument.in/reader035/viewer/2022070422/5681652c550346895dd7ae31/html5/thumbnails/1.jpg)
HIV and Malaria
Dr Jane AchanDept of Pediatrics, Makerere University
College of Health Sciences
Prof. Moses KamyaMakerere University College of Health
Sciences6th IAS CONFERENCE, 18th July 2011
![Page 2: HIV and Malaria](https://reader035.vdocument.in/reader035/viewer/2022070422/5681652c550346895dd7ae31/html5/thumbnails/2.jpg)
Burden of malaria • Over 300 million
clinical cases and 1 million deaths annually
• Accounts for 25-40% of outpatient visits and 20-50% of hospital admissions
![Page 3: HIV and Malaria](https://reader035.vdocument.in/reader035/viewer/2022070422/5681652c550346895dd7ae31/html5/thumbnails/3.jpg)
HIV and Malaria in Sub-Saharan Africa
HIV distribution Malaria distribution
![Page 4: HIV and Malaria](https://reader035.vdocument.in/reader035/viewer/2022070422/5681652c550346895dd7ae31/html5/thumbnails/4.jpg)
Epidemiological overlap: Why does this matter?
• Any interaction could be of great pubic health importance:– Malaria could accelerate HIV disease progression and facilitate
HIV transmission
– HIV infection could disrupt immune responses to malaria and may increase incidence and severity of malaria
– Routine interventions for HIV may impact upon the incidence of malaria
– Therapies for each infection may impact upon the other, leading to unanticipated effects on drug efficacy or toxicity
![Page 5: HIV and Malaria](https://reader035.vdocument.in/reader035/viewer/2022070422/5681652c550346895dd7ae31/html5/thumbnails/5.jpg)
Plausibility of interaction:Malaria affecting HIV
Antigen stimulation Immune activation
Faster disease progression
Increased viral replication
![Page 6: HIV and Malaria](https://reader035.vdocument.in/reader035/viewer/2022070422/5681652c550346895dd7ae31/html5/thumbnails/6.jpg)
HIV Viral load changes during malaria.
Hoffman et al , AIDS. 13(4):487-494, March 11, 1999.
![Page 7: HIV and Malaria](https://reader035.vdocument.in/reader035/viewer/2022070422/5681652c550346895dd7ae31/html5/thumbnails/7.jpg)
Influence of malaria on HIV disease• Increased viral load during malaria might be sustained for long enough
to increase risk of HIV transmission and accelerated disease progression.
• Parasitemia and clinical malaria are associated with 0.25-0.89 log increase in viral load for about 9 weeks
• Treatment of malaria in HIV-infected adults is associated with decreased viral load (190000 to 120000 copies/ml)
Kublin, et al, Lancet 2005;365:233-239; ter Kuile, et al, Am J Trop Med Hyg 2004;71:41-54; Van Geertruyden, et al,JAIDS 2006;43:363-7; Hoffman, et al,AIDS 1999;13:487-495; Mermin, et al, JAIDS 2006;41:129-130, Brahmbhatt, etal, AIDS 2003; 17: 2539-41; Ayisi, et al, AIDS 2003; 17: 585-94; Ned, et al, Trends Parisitol 2005;24: 285-91., tatfeng etat, J Vector Borne Dis 44, June 2007
![Page 8: HIV and Malaria](https://reader035.vdocument.in/reader035/viewer/2022070422/5681652c550346895dd7ae31/html5/thumbnails/8.jpg)
Influence of malaria on HIV disease
• Malaria associated with more rapid decline in CD4 cell count– Mean difference in CD4 cell decline per additional episode of malaria was 40
cells/µL/year (Mermin et al, JAIDS 2006;41:129-130)
• However evidence that malaria has an impact on HIV disease progression is limited
• Transient and repeated increases in HIV viral load from recurrent co-infection with malaria may contribute to promoting the spread of HIV in sub-Saharan Africa.– Modelling in Kisumu, Kenya indicated a 2.1% increase in HIV prevalence
since 1980.
Abu-Raddad, et al, Science 2006;314:1603-1606;
![Page 9: HIV and Malaria](https://reader035.vdocument.in/reader035/viewer/2022070422/5681652c550346895dd7ae31/html5/thumbnails/9.jpg)
HIV and malaria in pregnancy
• Pregnant women are at increased risk for malaria, especially in their first 2 pregnancies.
• Estimated that the HIV epidemic results in an additional 500,000 to 1 million women per year who have malaria during pregnancy
● HIV infected pregnant women are at increased risk of:– Symptomatic malaria and placental malaria– Severe malaria– Maternal anemia and adverse birth outcomes
Malaria infection placental malaria low birth weight infant mortality
maternal anemia
![Page 10: HIV and Malaria](https://reader035.vdocument.in/reader035/viewer/2022070422/5681652c550346895dd7ae31/html5/thumbnails/10.jpg)
0
10
20
30
40
50
60
malaria incidence
HIV(+) HIV(-)
G1>G2
Total n = 414: Kisumu, Kenya, 1994-1996 (CDC Studies)
Gravidity-related pattern of Malaria in pregnancy is altered by HIV
![Page 11: HIV and Malaria](https://reader035.vdocument.in/reader035/viewer/2022070422/5681652c550346895dd7ae31/html5/thumbnails/11.jpg)
Gravidity-related pattern of Malaria in pregnancy ● The gravidity-related pattern of Malaria in
pregnancy is altered by HIV so that the burden is shifted from primigravidae to all pregnant women
● Possible mechanism: HIV may affect memory immune mechanism in pregnant women → parity dependent acquisition of anti-malarial immunity
![Page 12: HIV and Malaria](https://reader035.vdocument.in/reader035/viewer/2022070422/5681652c550346895dd7ae31/html5/thumbnails/12.jpg)
MTCT and Infant outcomes
• Infant Mortality Rate (IMR) increases in HIV+ pregnant women with malaria
• Mother to child transmission (MTCT) of HIV increased when women had placental Malaria • Brahmbhatt, et al, AIDS 2003; 17: 2539-41; Ayisi, et al, AIDS 2003; 17: :
585-94
• Postnatal death in infants is higher amongst HIV positive women with placental malaria compared to HIV positive women (Odds Ratio: 3 – 7.7; Bloland, Malawi .95)
![Page 13: HIV and Malaria](https://reader035.vdocument.in/reader035/viewer/2022070422/5681652c550346895dd7ae31/html5/thumbnails/13.jpg)
SP- IPT versus CTX for prevention of malaria in pregnancy
![Page 14: HIV and Malaria](https://reader035.vdocument.in/reader035/viewer/2022070422/5681652c550346895dd7ae31/html5/thumbnails/14.jpg)
“Combination prevention” for malaria in HIV infected populations.
● Cotrimoxazole prophylaxis (CTX)
● Insecticide treated bed nets (ITNs)
● ART
![Page 15: HIV and Malaria](https://reader035.vdocument.in/reader035/viewer/2022070422/5681652c550346895dd7ae31/html5/thumbnails/15.jpg)
Malaria incidence among HIV-infected adults
● 95% reduction in malaria with all 3 interventions
0
10
20
30
40
50
60
Cotrim Cotrim and ART Cotrim, ART, andbednets
Malaria per 100 person-years
![Page 16: HIV and Malaria](https://reader035.vdocument.in/reader035/viewer/2022070422/5681652c550346895dd7ae31/html5/thumbnails/16.jpg)
Effect of CTX and ITN use on malaria incidence (Kamya et al. AIDS 2007)
Exposure Group IRR (95% CI) P-value
No CTX, No ITN Reference group
CTX prophylaxis alone 0.65 (0.27-1.57) 0.34
ITN alone 0.56 (0.45-0.70) <0.001
Both CTX and ITN 0.03 (0.01-0.11) <0.001
![Page 17: HIV and Malaria](https://reader035.vdocument.in/reader035/viewer/2022070422/5681652c550346895dd7ae31/html5/thumbnails/17.jpg)
Protective efficacy of CTX in Kampala over time
Time period Malaria incidence (PPY) Protective efficacy IRR (95% CI)*
No TS TS
Aug 06-Jan 07 0.11 0.71 0.16 (0.09-0.27)
Feb 07-Jul 07 0.14 0.51 0.28 (0.16-0.46)
Aug 07 – Jan 08 0.09 0.38 0.24 (0.13-0.46)
* Test for trend: p-value = 0.35
![Page 18: HIV and Malaria](https://reader035.vdocument.in/reader035/viewer/2022070422/5681652c550346895dd7ae31/html5/thumbnails/18.jpg)
Prophylactic effect of CTX against malaria in contrasting transmission settings
Site CTX use
Episodes of malaria
Person time
Incidence of malaria
(PPY)
IRR(95% CI)
Kampala*
No CTX
389 727 0.540.20
(0.13-0.30)CTX 49 423 0.12
Tororo‡
No CTX
121 44.1 2.740.27
(0.19 -0.40)CTX 45 66.3 0.68
*low-medium transmission site; ‡ very high transmission site
![Page 19: HIV and Malaria](https://reader035.vdocument.in/reader035/viewer/2022070422/5681652c550346895dd7ae31/html5/thumbnails/19.jpg)
Clinical implications
● Malaria is rarely the cause of fever in individuals receiving CTX
● Malaria accounted for only 4% of febrile episodes in an HIV- infected cohort compared to 33% in the HIV- uninfected cohort (p < 0.0001). Kamya et al, AIDS, 2007
● Presumptive therapy for malaria in these groups should be avoided and careful evaluation for other causes of fever should be done
![Page 20: HIV and Malaria](https://reader035.vdocument.in/reader035/viewer/2022070422/5681652c550346895dd7ae31/html5/thumbnails/20.jpg)
Are we creating resistance?
020406080
100
mutations
Kampala No TS Kampala TS Tororo No TS Tororo TS
![Page 21: HIV and Malaria](https://reader035.vdocument.in/reader035/viewer/2022070422/5681652c550346895dd7ae31/html5/thumbnails/21.jpg)
HIV and Malaria Interactions
DON’T FORGET THE DRUGS!
![Page 22: HIV and Malaria](https://reader035.vdocument.in/reader035/viewer/2022070422/5681652c550346895dd7ae31/html5/thumbnails/22.jpg)
AQ/AS
AL
AQ Exposure ¹Liver Function Tests ¹
Moderate to severe neutopenia ²
HIV Infected Children
Antiretrovirals(nucleosideanalogues)
On going study
Healthy Volunteers Efavirenz
Efavirenz
Healthy Volunteers
Lopinavir / ritonavir
Healthy Volunteers
Lumefantrine ³Exposure(200%)
¹ German, etal CID, 2007² Gasasira, etal CID, 2008³ German, etal 15th Croi, 2008
![Page 23: HIV and Malaria](https://reader035.vdocument.in/reader035/viewer/2022070422/5681652c550346895dd7ae31/html5/thumbnails/23.jpg)
Conclusions
● Significance of the impact of malaria on HIV disease progression remains to be determined especially in this era of malaria preventive strategies.
● Malaria prevention in pregnancy is critical to minimize adverse pregnancy outcomes.
● There is strong evidence for the impact of combination prevention against malaria in HIV infected populations
● Attention to drug-drug interactions is critical as new antimalarial and antiretroviral drugs are rolled out.
![Page 24: HIV and Malaria](https://reader035.vdocument.in/reader035/viewer/2022070422/5681652c550346895dd7ae31/html5/thumbnails/24.jpg)
Acknowledgements● Makerere University-University of California San
Francisco (MU-UCSF) Research Collaboration:– Diane Havlir– Edwin Charlebois– Grant Dorsey– Philip J Rosenthal
● Sponsors: NIH, NICHD, CFAR
● Staff, Patients and caretakers that contribute to these studies
![Page 25: HIV and Malaria](https://reader035.vdocument.in/reader035/viewer/2022070422/5681652c550346895dd7ae31/html5/thumbnails/25.jpg)
Thank You