Relation Between Chemokine Receptor Use, Disease Stage, and HIV-1 Subtypes A and D

Abstract

These subtype differences in coreceptor use may partially explain the faster progression rates we have previously reported in individuals infected with subtype D compared with subtype A. Our observations may have implications for the future use of coreceptor inhibitors in this population.

Evaluation of Eight Different Bioinformatics Tools To Predict Viral Tropism in Different Human Immunodeficiency Virus Type 1 Subtypes

“…A significantly higher prevalence of X4 and X4/R5 dualtropic viruses was found in patients with lower CD4 counts, which is in agreement with previously reported observations and with the notion that these HIV-1 variants tend to be selected as immunodeficiency progresses (3,14,15,31). A higher prevalence of X4/X4R5 viruses also tended to be associated with prior exposure to antiretroviral therapy, which is also in agreement with previously reported observational data from cross-sectional surveys (11,19).…”

“…Up to 19% of these individuals carried X4/X4R5 dual-tropic viruses, with no significant differences with a control group of patients infected with clade B viruses. In other studies that included a larger number of samples from clades C and D, it was noted that clade C might less frequently harbor X4 viruses, even in late disease stages (8,16,20,24,31), while conversely, clade D could be X4 tropic more frequently (10,14). The small number of samples with these variants in our study precluded the examination of this aspect more appropriately.…”

“…Genotypic predictors of HIV-1 tropism have been developed to circumvent these disadvantages; however, the high genetic variability of HIV-1 may represent a serious obstacle to ensure their reliability. In addition to these diagnostic obstacles, it is important to better understand HIV pathogenesis and explain why some HIV-1 clades seem to be more frequently X4 tropic than others, as recently claimed for subtypes A, D, and CRF14_BG (1,10,14,17,22), since patients infected with these variants might progress faster to AIDS and will benefit less from CCR5 antagonists.…”

Molecular characterisation of newly identified HIV-1 infections in Curitiba, Brazil: preponderance of clade C among males with recent infections

“…Worldwide, clade C is responsible for about half of the epidemic, whereas clade B is the major variant in industrialised nations (Hemelaar et al 2006). HIV variability may influence the performance of laboratory tools for diagnostic, monitoring and surveillance (Koch et al 2001 (Baeten et al 2007, Kaleebu 2007 and transmission potential (Yang et al 2003, John-Stewart et al 2005 have been associated to distinct HIV clades, but the actual impact of genetic diversity in HIV disease still remains uncertain (Stebbing & Moyle 2003, Hemelaar et al 2006, Tebit et al 2007). However, some characteristics of HIV, such as tropism to either CCR5 or CXCR4 coreceptors, seem to be associated with a distinct pattern of disease progression (Shepherd et al 2008).…”

Dearth of full-length HIV-1 sequences obscures the true HIV-1 genetic subtypes distribution in sub-Saharan Africa

“…Subtypes may have an important effect on transmission of HIV-1, as the subtype B was associated with homosexual transmission and the subtype C with heterosexual transmission (van Harmelen et al, 1997;van Harmelen et al, 2001), but a heterosexually driven subtype B epidemic has been observed in Trinidad and Tobago (Cleghorn et al, 2000). Also, the subtype C is believed to be more likely to be transmitted vertically than the subtypes A and D (Blackard et al, 2001;Renjifo et al, 2001;Renjifo et al, 2003); and infection with the subtype D has been associated with faster CD4 T cell decline and a faster rate of disease progression (Alaeus et al, 1999;Kanki et al, 1999;Kaleebu et al, 2001;Vasan et al, 2006;Baeten et al, 2007;Kaleebu et al, 2007;Easterbrook et al, 2010). Subtypes could also be important in vaccine design and development (Hemelaar et al, 2011).…”