Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. CONCISE COMMUNICATION HIV-1 envelope diversity one year after seroconversion predicts subsequent disease progression Andrea Rachinger a,1 , Neeltje A. Kootstra a,1 , Esther F. Gijsbers a , Tom L.G.M. van den Kerkhof a , Hanneke Schuitemaker a,2 and Ange ´lique B. Van ‘t Wout a,2 Objective: Recent studies have suggested that the dynamics of HIV-1 evolutionary rate reflect the rate of disease progression. We wished to determine whether viral diversity early in infection is predictive of the subsequent disease course. Design: HIV-1 envelope diversity at seroconversion (SC) and one year thereafter from 89 homosexual participants of the Amsterdam Cohort Studies on HIV infection and AIDS was correlated with clinical endpoints and markers of disease progression. Methods: Heteroduplex mobility assay (HMA) and sequencing followed by calculation of pairwise genetic distances were applied to determine HIV-1 envelope diversity. The HMA pattern (presence or absence of heteroduplexes) and sequence diversity were each tested for correlation with the clinical course of infection. Results: HMA pattern at 1 year post-SC was significantly associated with progression to AIDS and AIDS-related death, with presence of heteroduplexes associated with accel- erated disease progression. Moreover, not only this dichotomous measure of viral diversity (absence or presence of heteroduplexes), but also genetic diversity itself was associated with disease course. HMA pattern was an independent predictor of accel- erated disease progression, also when CCR5 genotype, HLA-type, viral load, CD4þ T cell counts, and coreceptor use at viral load set point were included in the analysis. Conclusions: Viral diversity early in HIV-1 infection is predictive of the subsequent disease progression. It remains to be established whether viral diversity itself plays a causal role in the increased damage to the immune system or whether it is a reflection of immune pressure or other selective forces. ß 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins AIDS 2012, 26:000–000 Keywords: disease progression, diversity, envelope, heteroduplex mobility assay, HIV a Department of Experimental Immunology, Sanquin Research, Landsteiner Laboratory, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center of the University of Amsterdam, Amsterdam, The Netherlands. Correspondence to Dr Ange ´lique B. van ’t Wout, Department of Experimental Immunology, Academic Medical Center, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands. Tel: +31 20 5668251; e-mail: a.b.vantwout@amc.uva.nl 1 These authors contributed equally to the work. 2 Present address: Crucell Holland BV, Leiden, The Netherlands. Received: 10 January 2012; revised: 7 April 2012; accepted: 18 April 2012. DOI:10.1097/QAD.0b013e328354f539 ISSN 0269-9370 Q 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins 1