HIV Type 1 Coreceptor Tropism, CCR5 Genotype, and Integrase Inhibitor Resistance Profiles in Vietnam: Implications for the Introduction of New Antiretroviral Regimens Quynh Phuong Luu, 1,2, * Jonathan Dean, 1,3, * Trinh Thi Diem Do, 1,2 Michael J Carr, 1,3 Linda Dunford, 1,3 Suzie Coughlan, 1,3 Jeff Connell, 1,3 Hien Tran Nguyen, 1,2 William W. Hall, 1,3 and Lan Anh Nguyen Thi 1,2 Abstract In Vietnam, where an estimated 280,000 people will be HIV-positive by 2012, recommended antiretroviral regimens do not include more recently developed therapeutics, such as Integrase inhibitors (INI) and coreceptor antagonists. This study examined HIV-1 coreceptor tropism and INI drug resistance profiles, in parallel with CCR5 genotypes, in a cohort of 60 HIV-positive individuals from different regions of Vietnam. No evidence of INI resistance was detected. Some 40% of individuals had X4-tropic HIV-1, making them unsuitable for treat- ment with CCR5 antagonists. We identified a novel CCR5 variant—S272P—along with other, previously re- ported variants: G106R, C178R, W153C, R223Q, and S336I. Interestingly, CCR5 variants known to affect HIV-1 infectivity were observed only in individuals harboring X4-tropic virus. Together, this study presents valuable baseline information on HIV-1 INI resistance, coreceptor tropism, and CCR5 variants in HIV-positive individ- uals in Vietnam. This should help inform policy on the future use of novel antiretrovirals in Vietnam. I t has been estimated that by 2012, 280,000 individuals in Vietnam will be HIV positive. 1 Antiretroviral therapy (ART) has been available in Vietnam since the mid 1990s and, by 2009, 53.7% of HIV-1-infected individuals had access to ART. 1 Current recommendations from the Vietnamese Min- istry of Health indicate a preferred first-line regimen com- bining two nucleoside reverse transcriptase inhibitors (NRTI) with one nonnucleoside RTI (NNRTI). However, the in- creased availability of ART may be accompanied by the emergence of antiretroviral drug resistance mutations (DRM), particularly among high-risk groups such as injecting drug users (IDU) and commercial sex workers (CSW). Indeed, we and others have recently reported rates of DRM in high-risk cohorts in Vietnam that are higher than DRM frequencies reported in cohorts with a low exposure risk. 2–5 With a high prevalence of DRM, and high rates of transmitted resistance in particular, the need for additional therapeutic options becomes greater. Recent years have seen the introduction of several new classes of antiretroviral drugs, such as integrase inhibitors (INI) and entry/fusion inhibitors, including cor- eceptor antagonists. The INI raltegravir (RAL) has been licensed for use in ART since 2007. In addition to offering a previously unexploited phase of the HIV life-cycle, and suffering from no known cross-resistance with the older ART drug classes, RAL has proven to be both potent and well-tolerated. 6 Similarly, the only currently licensed chemokine receptor antagonist, maraviroc (MVC), has demonstrated effectiveness in both treatment-experienced and treatment-naive individuals, and is also well tolerated. 7 MVC and other chemokine receptor antagonists act by binding to, and changing the conforma- tion of, the C-C chemokine receptor type 5 (CCR5) molecule, which acts as a coreceptor for the HIV gp120 molecule. Their existence follows from the discovery of natural mutations in the human CCR5 gene that confer varying degrees of resistance to HIV infection, most notably the CCR5D32 mutation. 8 Despite their relatively recent introduction to the ART ar- senal, it is still possible for HIV to demonstrate resistance to each of these new drug classes. DRM conferring INI resistance were identified even during the clinical trials that led to RAL licencing 9 and more may be discovered as use of INIs 1 Ireland Vietnam Blood-Borne Virus Initiative (IVVI), Dublin, Ireland and Hanoi, Vietnam. 2 Laboratory for Molecular Diagnostics, Department of Immunology and Molecular Biology, National Institute of Hygiene and Epide- miology, Hanoi, Vietnam. 3 National Virus Reference Laboratory, University College Dublin, Belfield, Dublin, Ireland. *These authors contributed equally to this work. AIDS RESEARCH AND HUMAN RETROVIRUSES Volume 28, Number 10, 2012 ª Mary Ann Liebert, Inc. DOI: 10.1089/aid.2011.0396 1344