Impact of HIV‐1 viral subtype on disease progression and response to antiretroviral therapy

Easterbrook, Philippa; Smith, Mel; Mullen, Jane; O’Shea, Siobhan; Chrystie, I. L.; Ruiter, Annemiek de; Tatt, Iain; Geretti, Anna María; Zuckerman, Mark

doi:10.1186/1758-2652-13-4

Cited by 132 publications

(133 citation statements)

References 50 publications

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“…In this study, some viral and host characteristics of HIV/viral hepatitis-coinfected patients were evaluated in order to gain further knowledge about this issue. Furthermore, the results of the present study are in accord with previous investigations, that most HIV-1 subclade F1 strains circulating in Brazil may contain recombinant genomes 16 .…”

Section: Discussionsupporting

confidence: 82%

Profile of HIV subtypes in HIV/HBV- and HIV/HCV-coinfected patients in Southern Brazil

Avanzi

Vicente

Beloto

et al. 2017

Rev. Soc. Bras. Med. Trop.

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Introduction: HIV and viral hepatitis infections are major causes of chronic disease worldwide and have some similarities with regard to routes of transmission, epidemiology, front barriers faced during access of treatment, and strategies for a global public health response. The objective was to describe the HIV-1 subtypes, viral tropism and single-nucleotide polymorphisms (SNPs) of interleukin 28B (IL28B) from a case series of HIV/viral hepatitis coinfected patients from southern Brazil. Methods: Clinical and epidemiological data were evaluated by a review of medical records. Periodic blood draws were taken to determine the viral and host characteristics. Results: This study included 38 patients with HIV/HBV or HIV/HCV coinfection; the median age was 49 years. Thirty-seven (97.4%) were on antiretroviral therapy, 32 (84.2%) had an undetectable viral load, a median CD4 + T-cell count of 452 cells/mm 3 . HIV-1 subtyping showed 47.4 and 31.6% of patients with subtypes C and B, respectively. Analysis of viral co-receptor usage showed a predominance of the R5 variant (64.7%), with no significant difference between the subtypes. Twenty patients with HIV/HCV coinfection were eligible to receive HCV therapy with pegylated-interferon-alpha plus ribavirin, and 10/20 (50%) of them achieved sustained virological response. SNPs of IL28B were evaluated in 93.3% of patients with HIV/ HCV coinfection, and 17 (60.7%) presented the CC genotype. Conclusions: In the present case series, a higher frequency of HIV subtype C was found in coinfected patients. However such findings need to be prospectively evaluated with the inclusion of data from regional multicenter analyses.

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Section: Discussionsupporting

confidence: 82%

Profile of HIV subtypes in HIV/HBV- and HIV/HCV-coinfected patients in Southern Brazil

Avanzi

Vicente

Beloto

et al. 2017

Rev. Soc. Bras. Med. Trop.

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“…There is also evidence that recombinant forms have a higher rate of progression to AIDS than does subtype A (10,14), although this was not observed in another study (12). There are conflicting reports regarding the rate of disease progression of subtype C relative to that of other subtypes (12,(15)(16)(17)(18). While there is general agreement that subtype C has a transmissibility rate at least equal to those of other M group subtypes (19,20), some studies have reported increased transmissibility of subtype C compared to subtypes A and D (21)(22)(23).…”

mentioning

confidence: 79%

Subtype-Specific Differences in Gag-Protease-Driven Replication Capacity Are Consistent with Intersubtype Differences in HIV-1 Disease Progression

Kiguoya

Mann

Chopera

et al. 2017

J Virol

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There are marked differences in the spread and prevalence of HIV-1 subtypes worldwide, and differences in clinical progression have been reported. However, the biological reasons underlying these differences are unknown. Gag-protease is essential for HIV-1 replication, and Gag-protease-driven replication capacity has previously been correlated with disease progression. We show that Gag-protease replication capacity correlates significantly with that of whole isolates (r ϭ 0.51; P ϭ 0.04), indicating that Gag-protease is a significant contributor to viral replication capacity. Furthermore, we investigated subtype-specific differences in Gag-proteasedriven replication capacity using large well-characterized cohorts in Africa and the Americas. Patient-derived Gag-protease sequences were inserted into an HIV-1 NL4-3 backbone, and the replication capacities of the resulting recombinant viruses were measured in an HIV-1-inducible reporter T cell line by flow cytometry. Recombinant viruses expressing subtype C Gag-proteases exhibited substantially lower replication capacities than those expressing subtype B Gag-proteases (P Ͻ 0.0001); this observation remained consistent when representative Gag-protease sequences were engineered into an HIV-1 subtype C backbone. We identified Gag residues 483 and 484, located within the Alix-binding motif involved in virus budding, as major contributors to subtype-specific replicative differences. In East African cohorts, we observed a hierarchy of Gag-protease-driven replication capacities, i.e., subtypes A/C Ͻ D Ͻ intersubtype recombinants (P Ͻ 0.0029), which is consistent with reported intersubtype differences in disease progression. We thus hypothesize that the lower Gagprotease-driven replication capacity of subtypes A and C slows disease progression in individuals infected with these subtypes, which in turn leads to greater opportunity for transmission and thus increased prevalence of these subtypes.IMPORTANCE HIV-1 subtypes are unevenly distributed globally, and there are reported differences in their rates of disease progression and epidemic spread. The biological determinants underlying these differences have not been fully elucidated. Here, we show that HIV-1 Gag-protease-driven replication capacity correlates with Citation Kiguoya MW, Mann JK, Chopera D, Gounder K, Lee GQ, Hunt PW, Martin JN, Ball TB, Kimani J, Brumme ZL, Brockman MA, Ndung'u T. 2017. Subtype-specific differences in Gagprotease-driven replication capacity are consistent with intersubtype differences in HIV-1 disease progression. J Virol 91:e00253-17.

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“…However, a more extensive survey would be needed to establish an influence of G153 on clade D or CRF02_AG envelopes. Of note, clade D viruses have been associated with faster disease progression (1,14,19,20,45) and a higher frequency of dementia (40). In addition, CXCR4 tropism was common among CRF02_AG viruses, a sign of a mature HIV epidemic (15).…”

Section: Discussionmentioning

confidence: 99%

A Conserved Determinant in the V1 Loop of HIV-1 Modulates the V3 Loop To Prime Low CD4 Use and Macrophage Infection

Musich

Peters

Dueñas-Decamp

et al. 2011

J Virol

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The CD4 binding site (CD4bs) on the HIV-1 envelope plays a major role in determining the capacity of R5 viruses to infect primary macrophages. Thus, envelope determinants within or proximal to the CD4bs have been shown to control the use of low CD4 levels on macrophages for infection. These residues affect the affinity for CD4 either directly or indirectly by altering the exposure of CD4 contact residues. Here, we describe a single amino acid determinant in the V1 loop that also modulates macrophage tropism. Thus, we identified an E153G substitution that conferred high levels of macrophage infectivity for several heterologous R5 envelopes, while the reciprocal G153E substitution abrogated infection. Shifts in macrophage tropism were associated with dramatic shifts in sensitivity to the V3 loop monoclonal antibody (MAb), 447-52D and soluble CD4, as well as more modest changes in sensitivity to the CD4bs MAb, b12. These observations are consistent with an altered conformation or exposure of the V3 loop that enables the envelope to use low CD4 levels for infection. The modest shifts in b12 sensitivity suggest that residue 153 impacts on the exposure of the CD4bs. However, the more intense shifts in sCD4 sensitivity suggest additional mechanisms that likely include an increased ability of the envelope to undergo conformational changes following binding to suboptimal levels of cell surface CD4. In summary, we show that a conserved determinant in the V1 loop modulates the V3 loop to prime low CD4 use and macrophage infection.

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Impact of HIV‐1 viral subtype on disease progression and response to antiretroviral therapy

Cited by 132 publications

References 50 publications

Profile of HIV subtypes in HIV/HBV- and HIV/HCV-coinfected patients in Southern Brazil

Profile of HIV subtypes in HIV/HBV- and HIV/HCV-coinfected patients in Southern Brazil

Subtype-Specific Differences in Gag-Protease-Driven Replication Capacity Are Consistent with Intersubtype Differences in HIV-1 Disease Progression

A Conserved Determinant in the V1 Loop of HIV-1 Modulates the V3 Loop To Prime Low CD4 Use and Macrophage Infection

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