590 
High Risk of Neutropenia in HIV-infected Children following Treatment with Artesunate + Amodiaquine for Uncomplicated Malaria in Uganda
Moses Kamya*1, A Gasasira1, J Achan1, T Ruel2, E Charlebois2, S Staedke3, A Kekitiinwa4, P Rosenthal2, G Dorsey2, and D Havlir2
1Makerere Univ Med Sch, Kampala, Uganda; 2Univ of California, San Francisco, US; 3London Sch of Hygiene and Tropical Med, UK; and 4Mulago Hosp, Kampala, Uganda
Background: Artemisinin-based combination therapies are
rapidly being adopted for the treatment of malaria in Africa, yet data are
limited on safety and efficacy among HIV-infected populations.
Methods: We compared malaria treatment outcomes between cohorts
of HIV-infected and HIV-uninfected children in Uganda followed for 29 and 18
months, respectively. Malaria was treated with artesunate + amodiaquine (AS/AQ)
and outcomes assessed using standardized guidelines. HIV-infected children
received trimethoprim-sulfamethoxazole prophylaxis and ART according to current
guidelines.
Results: Were included 35 malaria episodes among 26 HIV-infected participants,
and 258 malaria episodes among 134 HIV-uninfected children; 12 HIV-infected
children were receiving ART, 11 of whom were receiving zidovudine. Malaria
treatment was highly efficacious in both the HIV-infected and HIV-uninfected
cohorts (28-day risk of recrudescence 0% and 3.6%, respectively) however, there
was a trend towards increased risk of recurrent malaria in the HIV-uninfected
children (2.9% vs 13.2% respectively, p = 0.08). Importantly, the risk
of neutropenia 14 days after treatment with artesunate plus amodiaquine was
higher in HIV-infected compared to HIV-uninfected children (45% vs 6%,
respectively, p <0.001). All neutropenia episodes in HIV-uninfected
children were of mild to moderate severity while 16% of neutropenia episodes in
the HIV-infected cohort were severe or life-threatening (<750/mm3).
Among HIV-infected children, the risk of neutropenia was significantly higher
in those receiving ART (75% vs 26%, p = 0.001). We compared the risk of
significant clinical events in HIV-infected children during the period of
neutropenia to HIV-infected controls not treated with AS/AQ over the same time.
There was a trend towards a higher risk of any significant clinical event in
subjects treated with AS/AQ compared to those not treated with AS/AQ (57% vs
35%, p = 0.16)
Conclusions: AS/AQ was highly efficacious for malaria
treatment in HIV-infected children, but associated with a high risk of
neutropenia, especially in the setting of concurrent ART. Our findings
highlight an urgent need for evaluation of alternative antimalarial therapies
in HIV-infected individuals.
|
