Co-trimoxazole in HIV-1 infection

Abstract

Sir—Xavier Anglaret and colleagues (May 1, p 1463) are to be commended for their important study of prophylaxis with 960 mg co-trimoxazole (sulphamethoxazole/trimethoprim 5/1) in Abidjan and their cautious discussion of policy implications. We would urge a more detailed discussion of cost-benefit, since the cost of daily prophylaxis (US$ 17.50 per annum is the figure they quote) is several times the annual expenditure on health in many resource-poor countries. Given that survival was not different, prompt outpatient treatment of illness episodes with co-trimoxazole as recommended by the WHO m i g h t be preferable. Prophylaxis should be recommended only if benefit to the individual (in a free paying setting) and to the health system (in a state-funded setting) is greater than cost. It would be interesting for Anglaret to report the effect of prophylaxis on the number of unscheduled visits and admissions to hospital. We have justified use of prophylaxis in Barbados by doing such an analysis. In 1992, shortly after the publication of the Centres for Disease Control g u i d e l i n e s , primary prophylaxis with co-trimoxazole (960 mg) was introduced. Because CD4 counts were not available, patients were started on prophylaxis on the basis of clinical judgment rather than previously established criteria. There was no attempt to recall patients to be assessed for prophylaxis. Rather, because patients returned for scheduled appointments there was a gradual but significant increase over time from 1992 to 1994 in the proportion of patients on prophylaxis (p<0·001) and in the proportion on prophylaxis who were on primary prophylaxis (p=0·01; unpublished observations). Since the introduction of primary prophylaxis was ad hoc, it was not possible to perform a survival analysis to compare two matched groups of patients, as in Anglaret and colleagues’ Abidjan study. We looked instead at the number of admissions each year during 1992–94 according to diagnostic category. There was a substantial increase in admission to hospital for non-respiratory causes from 1993 onwards, without any increase in respiratory admissions. There was an even more striking trend in inpatient d a y s . Although the most plausible explanation for the constant bed occupancy for respiratory admissions is the introduction of prophylaxis, the failure to prevent neurological admission, despite toxoplasmosis being the dominant diagnosis in our setting, is explained if greater compliance with co-trimoxazole is required, compared with prevention of respiratory admissions. We are unaware of any study on this point, but we know that there are difficulties with compliance in our population and poor compliance affects efficacy of prophylaxis for t o x o p l a s m o s i s . We found that primary prophylaxis with co-trimoxazole is justified in an island where the few cases of malaria and tuberculosis are imported and Pneumocystis carinii occurs with intermediate frequency. We would urge that future studies are large enough to analyse differential effects on the most common causes of morbidity and mortality and, if possible, compare intermittent and daily regimes. As well as saving money and being more acceptable to patients, intermittent dosing may reduce the risk of n e u t r o p e n i a .