The Children with HIV and Malaria Project (CHAMP)

Principal Investigators: Prof Moses Kamya, MU and Dr. Diane Havlir, UCSF

Investigators: Rukyalekere-Adeodadata Kekitiinwa, Anne Gasasira, Israel Kalyesubula, Grant Dorsey, Edwin Charlebois, Phil Rosenthal, Huyen Cao, Joseph Wong, Ted Ruel

Coordinators: Jane Achan,Carol Okello, Fred Kateera, Nestor Mbabazi, Sabrina Bakeera, Tsedal Mebrahtu

ClinicalTrials.gov Identifier: NCT00356824

Location: Mulago Hospital, Kampala, Uganda

Funded by: NIAID/NIH

Study start:  Oct 2005

Study end: May 2009

The Children with HIV and Malaria Project (CHAMP) began in 2005 with the broad aim of studying the interactions between Human Immunodeficiency Virus (HIV) infection and malaria in African children.  With a diverse team of investigators in the USA and Uganda, CHAMP brought together experts in the clinical study of HIV with the accomplished malaria research group at MU-UCSF.  A prospective cohort study, CHAMP enrolled 300 HIV-infected children ages 1 to 10 years. 

These children received care per current Ugandan guidelines for the management of HIV and malaria and were followed closely in a clinic that was open 7 days a week. 

CHAMP has led to several important discoveries about malaria and HIV.  An early and important finding was that providing trimethoprim-sulfmethoxazole prophylaxis and insecticide treated bednets to HIV-infected children was highly effective in preventing malaria, reducing the incidence to below that of HIV-uninfected children living in the same area.  Portions of this data were first presented at 2 international meetings] and then published in the journal AIDS.  Investigators went on to show that protection appears durable, even in the context of malaria stains with resistance mutations.  An additional clinically significant discovery concerned the treatment of malaria in HIV-infected children.  Thanks to the rigorous laboratory monitoring of the CHAMP protocol, investigators noted a high rate of neutropenia in the 14 days following malaria treatment with artesunate plus amodiaquine.  With mounting expertise, Ugandan members of our study team have also authored review articles and presented at regional guidelines meetings on the management of malaria in HIV-infected children.

With such close clinical follow-up, CHAMP has also provided an opportunity to better understand other aspects of the disease HIV causes in African children. CHAMP has presented data about the burden of immune reconstitution syndrome, pneumonia and other bacterial infections in this population. In 2006, the CHAMP characterized a remarkable suppression of viral replication in HIV-infected children of the cohort, reporting the analysis at an international meeting in 2007 and then publishing in the journal JAIDS. 

CHAMP has also shown that a significant number of HIV-infected African children with minimal immune-suppression, thus ineligible for ART per current guidelines, are suffering neurocognitive impairment and are at high risk for short term progression and clinical disease.CHAMP has advanced the knowledge about the levels of immune activation, a well-established factor in HIV disease progression.  We have shown that HIV-infected children have increased levels of CD4 and CD8 T-cell activation compared to HIV-negative Ugandan children, that both naïve and memoryT-cell subsets are affected, and that a decrease in activation levels is important to CD4 cell recovery in this population.  We have also examined the functional immune response to HIV in these children. 

Key Publications

1.Kamya MR, Gasasira A, Achan J, Mebrahtu T,  Kekitiinwa A, Charlebois ED, Rosenthal PJ, Havlir D, Dorsey G. The effect of co-trimoxazole prophylaxis and insecticide-treated bednets on the risk of malaria among HIV infected Ugandan children. Presented at the 55th Annual Meeting of the American Society of Tropical Medicine and Hygiene, Atlanta, November 12-16, 2006.

2.Gasasira AF, Kamya MR, Achan J, Mebrahtu T, Ruel T, Kekitiinwa A, Charlebois ED, Rosenthal PJ, Havlir D, Dorsey G. The effect of co-trimoxazole (CTX) prophylaxis and insecticide-treated bednets (ITN) on the risk of malaria among HIV infected Ugandan children. Presented at the 14th Conference on Retroviruses and Opportunistic Infections, Los Angeles, February 25-28, 2007.

3.Kamya MR, Gasasira AF, Achan J, Mebrahtu T, Ruel T, Kekitiinwa A, Charlebois ED, Rosenthal PJ, Havlir D, Dorsey G. Effects of trimethoprim-sulfamethoxazole prophylaxis and insecticide-treated bednets on the risk of malaria among HIV-infected Ugandan children. AIDS, 2007. 21(15):2059-66.

4.Gasasira A, Havlir D, Achan J, Charlebois E, Ruel T, Rosenthal P, Sandison T, Dorsey G, and Kamya M. Prophylactic effect of trimethoprim-sulfamethoxazole against malaria in HIV-infected and exposed Ugandan children living in settings of high antifolate resistance. 16th Conference on Retroviruses and Opportunistic Infections, Montreal, February 8-11, 2009

5.Gasasira A, Kamya MR, Vora N, Achan J, Charlebois E, Ruel T, Kateera F, Meya D, Havlir D, Rosenthal PJ, Dorsey, G: Effect of trimethoprim-sulfamethoxazole on the risk of malaria in HIV-infected Ugandan children living in an area of widespread antifolate resistance. (manuscript in preparation)

6.Gasasira AF, Kamya MR, Achan J, Mebrahtu T, Kalyango JN, Ruel T, Charlebois E, Staedke SG, Kekitiinwa A, Rosenthal PJ, Havlir D, Dorsey G. High risk of neutropenia among HIV-infected children following treatment with artesunate plus amodiaquine for uncomplicated malaria in Uganda. Presented at the 56th Annual Meeting of the American Society of Tropical Medicine and Hygiene, November 04-08, 2007. 

7.Gasasira AF, Kamya MR, Achan J, Mebrahtu T, Kalyango, J, Ruel T, Charlebois E, Staedke SG, Kekitiinwa A, Rosenthal P, Havlir D, and Dorsey G. High risk of neutropenia in HIV-infected children following treatment with artesunate plus amodiaquine for uncomplicated malaria in Uganda. CID 2008.46:985-991.

8.Kateera F, Dorsey G, Achan J, Ruel T, Charlebois E, Havlir D, Rosenthal P, Kamya MR, Gasasira A. Efficacy, safety and tolerability of amodiaquine-artesunate verses artemether-lumefantrine for the treatment of uncomplicated malaria in HIV-infected children in Kampala, Uganda. Malaria Initiative Meeting (MIM), Nairobi, November, 2009. 

9.Achan J, Gasasira AF, Aweeka F, Havlir D, Rosenthal PJ, Kamya, MR. Prophylaxis and treatment of Malaria in HIV infected populations. (in press, Future Medicine)

10.Achan J, Ruel T, Kateera F, Kalyango J, Akello C, Gasasira A, Charlebois E, Dorsey G, Rosenthal P, Kekitiinwa A, Havlir D, Kamya M. Reconstitution Inflammatory Syndrome in the first 6 months of antiretroviral therapy in HIV-infected Ugandan children. XVII International AIDS Conference, August 03-08, 2008, Mexico City.

11.Achan J, Gasasira A, Ruel T, Kateera F, Kalyango J, Akello Caroline, Charlebois E, Dorsey G, Rosenthal P, Kamya M, Havlir D. A high risk of pneumonia in HIV infected African children persists up to six months after initiation of antiretroviral therapy (ART). 16th Conference on Retroviruses and Opportunistic Infections, Montreal, February 8-11, 2009.

12.Gasasira A, Ruel T, Charlebois E, Achan A, Akello C, Kateera F, Rosenthal P, Dorsey G, Kamya M, Havlir D. Burden of significant bacterial infections in HIV-infected Ugandan children receiving trimethoprim-sulfamethoxazole prophylaxis. XVII International AIDS Conference, August 03-08, 2008, Mexico City.

13.Ruel TD, Achan J, Gasasira AF, Charlebois ED, Rosenthal PJ, Dorsey G, Kamya MR, Kekitiinwa A, Wong J, Havlir D, and the CHAMP Team. Dramatic reductions in HIV RNA among HIV-infected children with acute measles in Uganda. Presented at the 14th Conference on Retroviruses and Opportunistic Infections, Los Angeles, February 25-28, 2007.

14.Ruel T, Achan J, Gasasira AF, Charlebois ED, Mebrahtu T, Rosenthal PJ, Dorsey G, Kamya MR, Kekitiinwa A, Wong J, Havlir DV. HIV RNA suppression among HIV-infected Ugandan Children with Measles. JAIDS. 2008. 48(2):225-227.

15.Ruel T, Boal HE, Bangirana P, Akello C, Rosenthal PJ, Kamya MR, Charlebois ED, Havlir, DV, Boivin, MJ, Wong, JK, and Children with HIV and Malaria Project (CHAMP). Neurocognitive Impairment in HIV+ African Children Not Yet Eligible for Antiretroviral Therapy (ART). 16th Conference on Retroviruses and Opportunistic Infections, Montreal, February 8-11, 2009.

16.Charlebois ED, Ruel T, Cao H, Gasasira A, Achan J, Kateera F, Akello C, Dorsey G, Wong J, Rosenthal P, Kamya M, Havlir D. Risk of short-term progression in Ugandan children not yet eligible for antiretroviral therapy (ART). XVII International AIDS Conference, Mexico City, August 3-8, 2008.

17.Ssewanyana I, Elrefaei M, Dorsey G, Ruel T, Jones NG, Gasasira A, Kamya M, Nakiwala J, Achan J, Charlebois E, Havlir D, Cao H. Profile of T Cell Immune Responses in HIV Infected Children from Uganda. JID 2007:196.

18.Ssewanyana I, Baker CAR, Ruel T, Bousheri S, Kamya M, Dorsey G, Rosenthal PJ, Charlebois E, Havlir D, Cao H. The distribution and immune profile of T cells subsets in HIV infected children from Uganda. AIDS Res Hum Retroviruses. 2009. 25(1):65-71

19.Ruel T, Ssewanyana I, Achan J, Gasasira A, Kamya M, Adeodata Kekitiinwa A, Wong J, Cao H, Havlir D, Charlebois E. Dynamics of T-cell activation accompanying CD4 recovery in antiretroviral treated HIV-infected Ugandan children. 15th Conference on Retroviruses and Opportunistic Infections, Boston, 2008.

20.Ruel T, Ssewanyana I, Achan J, Gasasira A, Kamya MR, Kekitiinwa A, et al. Dynamics of T cell activation accompanying CD4 recovery in antiretroviral treated HIV-infected Ugandan children. Clinical Immunology. 2009.131:410-414. 21.Ssewanyana, I. Distinct profile of immune response and effector responses in HIV positive Ugandan children. Poster presented at Immunology Research in Africa, December 7-8, 2006.