Although potent anti-HIV therapy has dramatically reduced the morbidity and mortality of HIV-1 infection in resource-rich settings [1], it continues to be associated with considerable toxicity, drug-drug interactions, difficulties in adherence, and elevated cost. Early immune deterioration, tissue compartmentalization, cellular reservoirs, masking by host components, subversion of the cytokine milieu for its own replicative advantage, and steady emergence of drug resistance and immune escape variants are major obstacles that HIV-1 poses to its eradication under the current treatment paradigm. As a result, better antiretroviral drugs and treatment strategies continue to be pursued. Small-molecule chemokine receptor antagonists are a new class of antiretrovirals (ARVs) that exert noncompetitive allosteric inhibition of the chemokine receptors CCRS and CXCR4, which are essential for HIV entry. Whereas CCR5 is the coreceptor used by macrophage-tropic viruses, CXCR4 is predominantly used by T lymphocyte-tropic variants [2, 3]. By inhibiting these coreceptors, chemokine receptor antagonists impede the release of gp41 from its metastable conformation within HIV-1 envelope, thereby blocking the fusion between the viral and the cellular membranes. Data from different cohort studies in regions affected by clade B HIV-1 demonstrate that 81/%-88% of HIV-1 variants in treatment-naive patients are CCR5 tropic and that virtually all the remaining variants are dual/mixed (D/M) tropic (i.e., are able to utilize both CCR5 and CXCR4 coreceptors). In treatment-experienced patients, 49%-78% of variants are purely CCR5 tropic, 22%-48% are D/M tropic, and 2/%-o 5% exclusively utilize CXCR4 [4-6]. A 32-bp deletion in the CCR5 gene (CCR5A32), which results in a frameshift and truncation of the normal CCR5 protein, was identified in a few persons who had remained uninfected after exposure to CCR5-tropic HIV-1 viruses [7]. This allele is common in white of European origin, with prevalence near to 10%, but is absent among East Asian, American Indian, Tamil Indian, or African ethnic groups [8, 9]. HIV infection in persons homozygous for CCR5A32 (-1% of white Northern Europeans) is extremely rare, and, when it occurs, it is caused by viral strains that utilize CXCR4 for viral entry [10]. Moreover, HIV-infected individuals who are heterozygous for CCR5A32 have slower rates of disease progression [11]. Early reports suggested that this deletion had no apparent effect on the functioning of the immune system, in spite of the deletion of a CCR5 motif that is localized intra-