The results indicate that if the incidence of PCP is equal to or greater than 25%, the preferred PCP prophylaxis strategy involves administration of prophylaxis to all HIV-infected infants regardless of CD4 counts. However, if the risk of PCP among HIV-infected infants is less than 25%, it is justifiable to give prophylaxis to those infants with CD4 counts of fewer than 1500 cells/mm3. This concurs with the finding that the ‘treat some’ strategy is preferred if the proportion of infants with CD4 counts of fewer than 1500 cells/mm3 is less than 30%.
If the risk of PCP is 50%, a test used to identify HIV-infected infants at risk of PCP should have a sensitivity of greater than 98%. It is unlikely that a CD4 count of fewer than 1500 cells/mm3 would consistently achieve this desired level of sensitivity. However, if the prevalence of PCP is less than 25%, the level of sensitivity needed would be lower and could be achieved.
The fact that the ‘treat all’ option is preferred, regardless of PCP-related mortality, underscores the importance of morbidity concerns regarding PCP. In this regard, one of the psychosocial benefits in preventing PCP is the reduction of the chance of disclosure of HIV infection.
In this study, the percentage of CD4 cells was not considered in order to simplify the analyses. However, clinicians may choose to examine whether the combination of a cut-off of 20% CD4 counts and a cut-off of 1500 cells/mm3 would result in a sensitivity level of greater than 98%. Even if such a level is not achieved, the threshold analyses facilitate decision making. For example, as the sensitivity falls the probability of acquiring PCP must be lower for one to become indifferent between the ‘treat some’ option and the ‘treat all’ option ().
This study did not analyze prophylaxis options for infants with indeterminate status, rather it addressed prophylaxis options for infants who are regarded by their clinicians as being HIV-infected. The proportion of HIV-infected infants in the former group will become smaller as advanced polymerase chain reaction technology becomes more available to most Canadian centres following HIV-infected children. To implement the findings of our study, a diagnosis of HIV infection has to be made. Continued improvement in the diagnosis of perinatally-acquired HIV infection will enable the early introduction of preventive measures such as PCP prophylaxis.
Since individual preferences vary in practice, it is important to explore the effects that changes in the utility estimates have on the results. In addition, even though decision analysts may regard numerically close expected utilities as significant, thorough sensitivity analyses are performed to examine the impact of changes in probabilities on such numerically close expected utilities.
In this context, the results were not significantly affected by changes in the utility estimates, with one exception: that attributable to adverse drug reaction. The ‘treat some’ option is preferred if the disutility (1 minus utility) value for the combination of HIV-seropositivity and adverse drug reaction exceeds 0.65. However, in practice it is unlikely that the disutility associated with the combination of seropositivity and side-effects would exceed 0.65 and, hence, approach that of a less preferred option such as PCP (disutility = 0.78), or even a major but less severe disease than PCP.
In summary, we have presented an approach to arriving at a decision on PCP prophylaxis in infants less than one year of age, using the data that clinicians would use in practice. The results highlight the areas in need of further research in order to improve the degree of certainty associated with certain variables.