Epidemiological methods to study the interaction between HIV infection and other sexually transmitted diseases

Numerous studies performed over the past 5 years have indicated an association between HIV infection and other sexually transmitted diseases (STDs), particularly those involving genital ulceration. Such an association may be causal, indicating that STDs increase susceptibility to, or infectivity of, HIV infection or may result, in whole or in part, from the mutual dependence of HIV and STDs on patterns of sexual activity, or from an effect of HIV infection on the clinical course of STDs. In this paper we discuss the issues arising in the design and analysis of studies conducted to investigate this association. A numerical illustration is used to demonstrate non-causal associations that may arise in observational studies due to confounding and misclassification. Published cross-sectional and longitudinal studies are reviewed, and recommendations made for future studies. Special emphasis is given to the use of randomized intervention trials to overcome many of the biases associated with observational studies, and to provide information on the efficacy of intensive STD treatment programmes in reducing the transmission of HIV.