Viral load as an independent risk factor for opportunistic infections in HIV-infected adults and adolescents

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Abstract
We investigated whether HIV plasma RNA (viral load; VL) predicts risk for opportunistic infections (OI) in HIV-infected persons, independent of CD4 lymphocyte count and other factors that might affect disease outcome. Among persons who had initiated antiretroviral therapy (ART), we studied the risk for OI following a VL measurement in the Centers for Disease Control and Prevention Adult and Adolescent Spectrum of HIV Disease (ASD) Project, a medical record review study of HIV-infected persons in 11 US cities. Analysis was limited to persons who had initiated ART and who had VL data, primarily from the period 1996–1999. Persons were considered at risk for OI for 1 to 6 months after a given VL; risk for OI was assessed using a Poisson multiple regression model controlling for CD4 lymphocyte count, ART, and other variables potentially associated with development of OI: history of AIDS OI, age, sex, race, HIV risk category, OI prophylaxis, and calendar year. Although decreasing CD4 count was the strongest predictor of risk for OI [relative risk (RR), 13.3 for persons with CD4 lymphocyte count < 50 × 106/l compared with persons with CD4 lymphocyte count ≥ 500 × 106/l], increasing VL was independently associated with increased risk [RR, 1.6, 1.9, 2.7, and 3.5 for VL of 7000–19 999, 20 000–54 999, 55 000–149 999, and ≥ 150 000 copies/ml (by reverse transcription–PCR), respectively, compared with VL < 400]. Similar results were obtained when the risk period was reduced to 5, 4, 3, and 2 months after VL measurement. VL is an independent risk factor for OI and should be considered in special situations, such as in decisions to discontinue primary or secondary OI prophylaxis after CD4 lymphocyte counts have increased in response to ART.