With an estimated 33 million persons living with HIV-1, 2.1 millions deaths from AIDS in 2007, and 2.5 million new HIV-1 infections per year worldwide, the global impact of HIV-1 and AIDS continues to be overwhelming, despite advances in treatment of chronic HIV-1 infection and improved access to treatment in developing countries Even in the United States, whose epidemic is dwarfed by that in developing countries, HIV-1 infection has had major health and social impacts: an estimated 1.3 million persons were living with HIV-1 infection and 56,000 people were newly infected in 2007[1,2]. Virologic and immunologic data germane to development of biomedical preventative strategies such as vaccines is critically important. 3.1 Viral Correlates of Sexual Transmission of HIV-1. The strongest viral correlate of sexual transmission has been plasma HiV-1 RNA levels[3,4]. HIV RNA levels in plasma and genital secretions correiate[5,6] and seminal plasma have been correlated with transmission probability[7,8]. More recent data suggest that distinct viral variants may be enriched in genital secretions compared with blood plasma although data are conflicting [9-12]. Many studies of sexual transmission over the years have shown that infections with HIV-1 subtype B typically (current estimates are ??70-80[13,14,15]) originate from single virus founders. However, data from heterosexual African women and men who had recently acquired HIV-1 subtypes A or D demonstrated that 20 of 32 women had multiple viral variants whereas all 10 of the men studied had a single variant^^. These data suggest that sex of the Infected individual or viral subtype might modify the characteristics of the transmitted virus. Other studies have suggested that other viral characteristics such as such as env glycoprotein N-llnked glycosylation or env lengths may impact transmissibility^^'^^, though again this may be subtype-specific[2021] (see Projects 1 and 3 for more detailed discussions).

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Stekler, Joanne D; McKernan, Jennifer; Milne, Ross et al. (2015) Lack of resistance to integrase inhibitors among antiretroviral-naive subjects with primary HIV-1 infection, 2007-2013. Antivir Ther 20:77-80
Liu, Yi; Rao, Ushnal; McClure, Jan et al. (2014) Impact of mutations in highly conserved amino acids of the HIV-1 Gag-p24 and Env-gp120 proteins on viral replication in different genetic backgrounds. PLoS One 9:e94240
Kulkarni, Viraj; Valentin, Antonio; Rosati, Margherita et al. (2014) Altered response hierarchy and increased T-cell breadth upon HIV-1 conserved element DNA vaccination in macaques. PLoS One 9:e86254
Sunshine, Justine; Kim, Moon; Carlson, Jonathan M et al. (2014) Increased sequence coverage through combined targeting of variant and conserved epitopes correlates with control of HIV replication. J Virol 88:1354-65
Kahle, Erin; Campbell, Mary; Lingappa, Jairam et al. (2014) HIV-1 subtype C is not associated with higher risk of heterosexual HIV-1 transmission: a multinational study among HIV-1 serodiscordant couples. AIDS 28:235-43
Melhem, Nada M; Smith, Kellie N; Huang, Xiao-Li et al. (2014) The impact of viral evolution and frequency of variant epitopes on primary and memory human immunodeficiency virus type 1-specific CD8? T cell responses. Virology 450-451:34-48
Kulkarni, Viraj; Valentin, Antonio; Rosati, Margherita et al. (2014) HIV-1 conserved elements p24CE DNA vaccine induces humoral immune responses with broad epitope recognition in macaques. PLoS One 9:e111085
Grant, Igor; Franklin Jr, Donald R; Deutsch, Reena et al. (2014) Asymptomatic HIV-associated neurocognitive impairment increases risk for symptomatic decline. Neurology 82:2055-62
Herbeck, Joshua T; Mittler, John E; Gottlieb, Geoffrey S et al. (2014) An HIV epidemic model based on viral load dynamics: value in assessing empirical trends in HIV virulence and community viral load. PLoS Comput Biol 10:e1003673
Rolland, Morgane; Manocheewa, Siriphan; Swain, J Victor et al. (2013) HIV-1 conserved-element vaccines: relationship between sequence conservation and replicative capacity. J Virol 87:5461-7

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