Cotrimoxazole better at preventing malaria than standard preventive treatment in pregnant women with HIV

Daily cotrimoxazole treatment significantly reduced malaria parasitaemia and anaemia in pregnant women with HIV infection when compared to intermittent preventive treatment with sulfadoxine-pyrimethamine, a study in Malawi has found.

The findings are published in advance online by the Journal of Infectious Diseases, and the study was carried out by researchers associated with the Malawi-Liverpool Wellcome Clinical Research Programme and Médècins sans Frontières, with support from the University of North Carolina-Chapel Hill.

Cotrimoxazole, a cheap antibiotic that is widely available as an essential medicine in regions affected by malaria, is recommended as a prophylaxis against bacterial infections and against pneumocystis carinii pneumonia in HIV-infected people.

Cotrimoxazole has also been shown to have a protective effect against malaria, which is a major cause of illness and death in pregnant women (and in their offspring, who may acquire placental malaria if their mother suffers an attack of malaria during pregnancy).

Women with HIV have greater vulnerability to developing clinical malaria during pregnancy than other women, and have a higher risk of developing anaemia, particularly more severe forms of anaemia. Infants of mothers with HIV who developed malaria are also more likely to have a low birth-weight. (Ter Kuile). There is conflicting evidence about the extent to which malaria during pregnancy increases the risk of mother-to-child HIV transmission.

For women without HIV infection, the standard way of preventing malaria during pregnancy is to take intermittent therapy with sulphadoxine-pyrimethamine (SP).

However the World Health Organization does not recommend SP for pregnant women with HIV already taking cotrimoxazole due to an increased risk of sulpha drug adverse reactions (both drugs are sulphonamide-type antibiotics).

Although cotrimoxazole is known to protect against malaria in adults and children with HIV, its efficacy and safety for malaria prevention in pregnant women with HIV have not been established.

The study conducted in Malawi was a cross-sectional analysis of responses to cotrimoxazole or SP in pregnant women with HIV. Women had not been randomised; the cross-sectional analysis arose from confusion amongst medical staff at one hospital over the implementation of new government guidelines recommending cotrimoxazole prophylaxis for pregnant women with HIV in 2007. Prior to this time, pregnant women had received intermittent SP.

Researchers were thus able to compare two groups of women who received different treatment, sampled at the same time in another cross-sectional study evaluating the effect of iron supplementation in HIV-infected pregnant women on maternal illness. The study sampled women attending the hospital’s antenatal service who were at least 34 weeks pregnant.

Due to the cross-sectional nature of the study the outcomes evaluated were laboratory markers rather than malarial morbidity. The study evaluated malarial parasitaemia and anaemia.

The study recruited 1142 pregnant women with a median age of 27 years and median CD4 cell count of 427 cells/mm³. Sixty per cent were using bed nets to reduce the risk of mosquito bites (insecticide-treated bed nets are recommended for all pregnant women in Malawi).

48.5% were already receiving antiretroviral therapy according to Malawi’s national treatment guidelines, which recommended treatment for all pregnant women with WHO stages 3 or 4 HIV disease, or with CD4 cells counts below 250 cells/mm³.

Data were available on cotrimoxazole and SP usage for 98.2% of women, of whom 49.7% received intermittent SP (three doses) only), 29.8% received cotrimoxazole only, and 15.4% received cotrimoxazole and intermittent SP. Five per cent received no prophylaxis.

The investigators found that after adjusting for age, CD4 count bed net use, number of antenatal visits and number of pregnancies, women who received cotrimoxazole were significantly less likely to have malaria parasitaemia (odds ratio 0.43, 95% confidence interval 0.19 – 0.97), as were those who received both cotrimoxazole and intermittent SP (OR 0.09, 95% CI 0.01-0.66), when compared to those who received intermittent SP alone.

Prevalence of parasitaemia was also lower in women who took cotrimoxazole for more than 30 days (p=0.002).

Similarly, women who received cotrimoxazole were significantly less likely to have anaemia (haemoglobin < 11g/dL) (cotrimoxazole alone OR 0.67, cotrimoxazole and SP OR 0.72). The prevalence of anaemia was not affected by the duration of cotrimoxazole prophylaxis, although haemoglobain concentrations were significantly lower in women who took cotrimoxazole for less than 30 days when compared to women who took the drug for more than 60 days. This is despite the fact that both cotrimoxazole and SP can increase the risk of anaemia.

The investigators suggest that cotrimoxazole may have proved more effective in preventing malaria because of the greater frequency of dosing.

They note that one limitation of the study is that it recruited only women in the third trimester of pregnancy, and relied on self-report of drug exposure to assess the effectiveness of treatment.

“Our study demonstrated the challenges that resource-limited countries such as Malawi face when changing drug policies. Proper planning and timely training of health personnel should always precede implementation, especially in settings where frequent policy changes do take place,” the investigators write.

The authors say that a randomised trial should be conducted to evaluate whether cotrimoxazole and SP are more effective than cotrimoxazole alone in preventing malaria in pregnant women with HIV.