Background

Exploring causal associations in HIV research requires careful consideration of numerous epidemiologic limitations. First, a primary cause of HIV, unprotected anal intercourse (UAI), is time-varying and, if it is also associated with an exposure of interest, may be on a confounding path. Second, HIV is a rare outcome, even in high-risk populations. Finally, for most causal, non-preventive exposures, a randomized trial is impossible. In order to address these limitations and provide a practical illustration of efficient statistical control via propensity-score weighting, we examine the causal association between rectal STI and HIV acquisition in the InvolveMENt study, a cohort of Atlanta-area men who have sex with men (MSM). We hypothesized that, after controlling for potentially confounding behavioral and demographic factors, the significant STI-HIV association would attenuate, but yield an estimate of the causal effect.

Methods

The exposure of interest was incident rectal gonorrhea or chlamydia infection; the outcome was incident HIV infection. To adjust for behavioral confounding, while accounting for limited HIV infections, we used an inverse probability of treatment weighted (IPTW) Cox proportional hazards (PH) model for incident HIV. Weights were derived from propensity score modeling of the probability of incident rectal STI as a function of potential confounders, including UAI in the interval of rectal STI acquisition/censoring.

Results

Of 556 HIV-negative MSM at baseline, 552 (99%) men were included in this analysis. 79 men were diagnosed with an incident rectal STI and 26 with HIV. 6 HIV-infected men were previously diagnosed with a rectal STI. In unadjusted analysis, incident rectal STI was significantly associated with subsequent incident HIV (HR (95%CI): 3.6 (1.4-9.2)). In the final weighted and adjusted model, the association was attenuated and more precise (HR (95% CI): 2.7 (1.2-6.4)).

Conclusions

We found that, controlling for time-varying risk behaviors and time-invariant demographic factors, diagnosis with HIV was significantly associated with prior diagnosis of rectal CT or GC. Our analysis lends support to the causal effect of incident rectal STI on HIV diagnosis and provides a framework for similar analyses of HIV incidence.