Cotrimoxazole prophylaxis reduces the risk of death in TB patients

Theo Smart
Published: 03 February 2005

Cotrimoxazole prophylaxis reduces the risk of death in TB patients in a setting with high HIV seroprevalence according to the results of a large South African study reported in the January 28th issue of AIDS. Offering cotrimoxazole to all adults with TB at the onset of anti-TB treatment could be an effective, simple, and safe way to reduce mortality, especially in settings where HIV coinfection is common.

Background

Patients coinfected with TB and HIV have a high risk of death not only because of TB but because of increased susceptibility to pneumonia and other infections.

Cotrimoxazole is a medication widely used for its activity against a variety of microorganisms. Early in the AIDS epidemic, cotrimoxazole was shown to reduce fatalities caused by pneumocystis jiroveci pneumonia (PJP) (previously known as pneumocystis carinii pneumonia or PCP), toxoplasmosis and other infections.

More recently, two major clinical trials in West Africa found that cotrimoxazole reduces mortality in HIV and TB coinfected adults. Since PJP and toxoplasmosis are uncommon in this population, the benefit was attributed to cotrimoxazole’s protective effects against bacterial infections and malaria.

However, there were concerns that the same findings might not extend to other parts of the world where there is a lower risk of malaria and where many bacteria have developed resistance to cotrimoxazole.

One such setting is South Africa, where the burden of malaria is low but bacterial resistance to cotrimoxazole is common. Nevertheless, the government of South Africa provides cotrimoxazole prophylaxis to any of its citizens who tests positive for HIV.

Uptake has been low though because the programme only reaches those people who go through the voluntary HIV testing and counseling process— which, in South Africa, is only a small proportion of the patients who might actually benefit from the drug.

One way to reach them might be to offer the drug to all patients with TB since many patients with TB in South Africa are also HIV-infected.

The study

British and South African researchers designed this study to evaluate whether cotrimoxazole benefits TB patients irrespective of HIV status, in a setting where the malaria risk is low and where bacterial resistance to cotrimoxazole is common.

The study was conducted in TB patients from a rural area of KwaZulu Natal, South Africa. Data from 1321 adults treated for TB between June 2001 and June 2002 — in combination with cotrimoxazole prophylaxis (960 mg once daily for 6 months during TB treatment) were compared to a historical control group of 2004 patients treated for TB between 1998 and 2000. There were no significant differences in the baseline characteristics of each group except that HIV seroprevalence was likely to have been higher in the group that received cotrimoxazole.

Results

At the end of six months, mortality was 29% lower in the patients treated with cotrimoxazole than in the historical controls (p < 0.001). Only twenty four patients needed to be treated with cotrimoxazole to prevent one death.

Adherence problems

The survival benefit might have been even greater had patients been more adherent to cotrimoxazole treatment. 58% (743 patients) were adherent to cotrimoxazole at 3 months, and 43% (523) patients at 6 months. Adherence to cotrimoxazole prophylaxis at three months was highly predictive of survival at the end of six months. Only 12 (1.8%) of the adherent patients were dead at 6 months versus 27 (6%) of non-adherent patients (P < 0.001).

The adherence problems were not due to side effects — cotrimoxazole was generally well tolerated with few adverse reactions identified. The most commonly identified reasons patients did not take their cotrimoxazole related to problems collecting the medication from the clinic: “financial, transport or physical constraints; or clinics were too far away to attend monthly to pick up tablets.”

After the six months of TB treatment, very few patients continued the cotrimoxazole treatment — despite the fact that many had received a diagnosis of HIV. Not surprisingly, there was no difference in mortality rates in the two groups between 6 and 12 months.

Implications

The study authors believe adherence could be improved “by linking the distribution of tablets to TB treatment, either providing tablets via the DOTS supervisor or providing all drugs together for the duration of TB treatment.” They also believe the community could benefit from educational campaigns explaining the concept of preventative treatment.

One of the study team’s original goals had been to encourage TB patients to also seek out voluntary HIV counseling and testing (VCT). However, they found that uptake of those services was often low perhaps because of a fear of getting two bad diagnoses at once.

However, they believe that offering cotrimoxazole to all TB patients would not only provide them with the benefits of cotrimoxazole immediately, it could also “act as an incentive for HIV testing by linking prophylaxis to a complete package of care for newly identified infected individuals that would include antiretroviral treatment.”

References

Grimwade K et al. Effectiveness of cotrimoxazole prophylaxis on mortality in adults with tuberculosis in rural South Africa. AIDS 19:163–168, 2005.