Effect of HIV infection and use of cotrimoxazole prophylaxis on response to chloroquine plus sulphadoxine- pyrimethamine treatment for uncomplicated malaria

Abstract

INTRODUCTION: Malaria and HIV infection contribute to significant morbidity and mortality in sub-saharan africa, any interaction between the two could lead to profound public health consquencies. HIV infected patients have an increased risk of malaria parasitaemia and clinical malaria, with the risk increasing as immunity declines. High malarial parasitaemia values are independently associated with anti-malarial treatment failure, prompting the wuestion whether the HIV epidermic may promote failure of malaria treatments and malaria-associated deaths. SIGINIFICANCE: The effect of HIV infection of response to antimalarial (Chloroquie plus Sulphadoxie pyrimethamine (CQ plus SP) treatment for un complicated malaria is not known. It is therefore important to study the response of antimalarial (CQ plus SP) treatment in HIV positive patients to be able to make recommendations on control and treatment of uncomplicated malaria in HIV positive patients. OBJECTIVES: To compare the reponse to antimalarial (CQ plus SP) treatment for uncomplicated malaria in HIV positive and negative patients aged 18 months and above at mulago national referral hospital. To compare the response of antimalarial (CQ and SP) treatment for uncomplicated malaria in HIV Positive patients aged 18 months with low (</=200/ul) CD4 counts and those with high (>200/ul) CD4 counts seen in mulago hospital. To compare the response of antimalarial (CQ and SP) treatment for uncomplicated malaria in HIV positive patients aged 18 months taking cotrimoxazole prophylaxis and those not taking cotrimoxazole prophylaxis seen in mulago hospital. METHODOLOGY: A prospective study of HIV positive patients with uncomplicated malaria as cases and historical controls were HIV negative patients with uncomplicated malaria who attended the same hospital. HIV positive patients diagnosed with uncomplicated p.falcifarum malaria seen consecutively at the paediatric and adult infectious diseased clinics of mulago hospital, kampala between 15th November 2004 and 30th may 2005 were enrolled. All subjects were treated with CQ plus SP combination and followed for 28 days of monitor treatment response. Baseline measurements included a medical history and physical examinations, and blood samples for complete blood count (cbc and CD4) counts were drawn. Subjects were evaluated o days, 0,1,2,3, 7, 14, 21 and 28 to obtain repeat blood smears for malaria slides and monitor treatmement response. Analysis compared anti-malarial treatment response among the HIV positive patients and the HIV negative historical controls treated with the same drugs and followed for the same duration. RESULTS: A total of 110 HIV positive patients (52 aged between 5 years and 18 years and 18 years and 58 and 18 years) with uncomplicated malaria were treated with CQ and SP and had a treatment outcome assigned. These were compared to 177 HIV negative patients (all aged between 5 years and 18 years) treated with CQ plus SP and had a treatment outcome assigned. The HIV positive and negative patients were comparable according to mean age (p=0.19) and mean haemoglobin level at basement (p=0.047). However, HIV positive patients had significantly higher temperature at basement (0.001) and higher parasite density (p=0.062). The risk of treatment failure was similar among positive patients and negative patients (60.9%, vs 65.5% RR 0.89, 95%, CI 0.6-1.1). Parasite density among HIV positive patients did not differ according to level of CD4 counts (p=0.11) and the risk of treatment failure was not affected by level CD4 counts (children, RR 0.9, 95% CI, 0.5-1.4, Adults RR 1.2, 95% CI, 0.4-3.4). Use of cotrimoxazole prophylaxis was higher among HIV positive children 71% compared to adults (13%) and this was associated with higher risks of treatment failure (children RR1.77 95% CI 1.04-3.05 Adults RR 2.05 95% CI 0.8-5.0) CONCLUSIONS AND RECOMMENDATIONS: This study showed high antimalarial (CQ and SP) treatment failure rates among both HIV positive and negative patients with uncomplicated malaria and there was no difference in antimalarial (CQ and SP) treatment response between HIV positive and negative. There was no difference in antimalarial (CQ and SP) treatment response when HIV positive patients with higher CD4 counts (</200/ul where compared to those with higher CD4 (>200/ul) counts. However, use of cotrimoxazole prophylaxis was associated with increased risk of treatment failure among both children (RR 2.05, 95% CI 0.8-5.0) and adults (RR 1.77, 95% C1= 1.04-3.07). Therefore, there is no evidence that antimalarial drug policy should be different for HIV positive and negative patients, however, use of cotrimoxazole prophylaxis may result in increased resistance of SP containing treatment regimens, hence the need for further research on the interactions between malaria and HIV and the use of Cotrimoxazole prophylaxis.