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Cited by 112HIV/AIDS drug development and treatmentHIV Research and TreatmentHIV/AIDS Research and Interventions

HIV-1 coreceptor use in triple-class treatment-experienced patients: Baseline prevalence, correlates, and relationship to enfuvirtide response

Melby, Tom, DeSpirito, Michael, DeMasi, Ralph, Heilek‐Snyder, Gabrielle, Greenberg, Michael L., Graham, Neil·2006·The Journal of Infectious Diseases
DOI 10.1086/504693
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Abstract

OBJECTIVE: We wished to assess, in heavily treatment-experienced patients, the prevalence of and baseline characteristics associated with HIV-1 coreceptor use and their relationship to responses to enfuvirtide treatment. METHODS: Samples were obtained from participants in phase 3 studies of enfuvirtide. Multiple logistic regression and analysis of covariance were performed on data for baseline coreceptor use, virological and immunological response, and changes in coreceptor use during treatment. RESULTS: Baseline envelopes were phenotyped for 724 patients; 50% harbored R5 strains, 48% harbored dual/mixed (D/M) strains, and 2% harbored X4 strains. D/M strains were associated with significantly lower CD4(+) cell counts but comparable viral loads, compared with R5 strains (P=.0005). Virological and immunological responses to enfuvirtide-based treatment showed no correlation with baseline coreceptor use. Changes in virus tropism from D/M to R5 strains during treatment were common, particularly in patients who received enfuvirtide (27%, vs. 14% who received no enfuvirtide; P<.05). CONCLUSION: At baseline, D/M strains were associated with lower CD4(+) cell counts but similar viral loads, compared with R5 strains, and were common across CD4(+) cell count strata. The comparable virological and immunological responses and bias toward shifts from D/M to R5 strains in patients who received enfuvirtide support its use in triple-class treatment-experienced patients and its study as a therapeutic partner for coreceptor-binding inhibitors.

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  • Once HIV-1 infection is established, it is able to choose CXCR4 as an alternative co-receptor.

    “However, once HIV-1 infection is established, it is able to choose CXCR4 as an alternative co-receptor [47,48].”

    From Newer Gene Editing Technologies toward HIV Gene Therapy (2013) · cites this paper as [47]

  • CCR5 serves as the predominant co-receptor for HIV entry during initial transmission and through the early stages of infection.

    “Generally, CCR5 serves as the predominant co-receptor for HIV entry during initial transmission and through the early stages of infection.”

    From Newer Gene Editing Technologies toward HIV Gene Therapy (2013) · cites this paper as [47]

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Research works printed but not linked: 6

  1. Koot M, Keet IPM, Vos AHV, et al. Articles: prognostic value of HIV- 1 syncytium-inducing phenotype for rate of CD4+ cell depletion and progression to AIDS. Ann Intern Med 1993; 118:681-8.
  2. Greenberg M, Melby T, Sista P, et al. Baseline and on-treatment sus- ceptibility to enfuvirtide seen in TORO 1 and TORO 2 through 24 weeks [abstract 141]. In: Program and abstracts of the 10th Conference on Retroviruses and Opportunistic Infections (Boston). Alexandria, VA: Foundation for Retrovirology and Human Health, 2003.
  3. Melby T, DeMasi R, Kuritzkes D, Heilek-Snyder G, Salgo M, Greenberg M. Analyses of virological response and enfuvirtide resistance through 48 weeks in the TORO 1 and 2 studies [abstract 165]. In: Program and abstracts of the XIIIth International Drug Resistance Workshop (Tenerife Sur-Costa Adeje, Canary Islands, Spain). London: Interna- tional Medical Press, 2004:S181.
  4. Demarest J, Bonny T, Vavro C, et al. HIV-1 co-receptor tropism in treatment naive and experienced subjects [abstract H-1136]. In: Pro- gram and abstracts of the 44th International Conference on Antimi- crobial Agents and Chemotherapy (Washington, DC). Washington, DC: American Society for Microbiology, 2004.
  5. Lazzarin A, Clotet B, Cooper D, et al. Efficacy of enfuvirtide in patients infected with drug-resistant HIV-1 in Europe and Australia. N Engl J Med 2003; 348:2186-95.
  6. Sista P, Melby T, Greenberg M, et al. Subgroup analysis of baseline (BL) susceptibility and early virological response to enfuvirtide in the combined TORO studies [abstract 55]. In: Program and abstracts of the XIIth International HIV Drug Resistance Workshop (Los Cabos, Mexico). London: International Medical Press, 2003:S60.

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Authors
Melby, T., DeSpirito, M., DeMasi, R., Heilek‐Snyder, G., Greenberg, M. L., & Graham, N.
Corresponding author
Melby, Tom
ORCID
Venue
The Journal of Infectious Diseases
Publisher
Oxford University Press (OUP)
Published
2006-07-15
Volume
194
Issue
2
Pages
238-246
ISSN
  • 0022-1899 (ISSN-L)
  • 1537-6613
DOI
10.1086/504693
OpenAlex
W2102690771
Cited by
112
References
44
Citations by year
2026: 1 · 2022: 1 · 2020: 1 · 2019: 1 · 2018: 4 · 2017: 2 · 2016: 3 · 2015: 3 · 2014: 4 · 2013: 13 · 2012: 9
FWCI
10.74
Type
journal article
Language
en
Open access
closed
Locations
  • The Journal of Infectious Diseases (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Infectious Diseases › HIV/AIDS drug development and treatment
  • Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
  • Health Sciences › Medicine › Infectious Diseases › HIV/AIDS Research and Interventions
Keywords
enfuvirtide, R5-tropic HIV-1, X4-tropic HIV-1, treatment-experienced patients, CD4 count, viral load, virological response, immune response, CCR5
MeSH terms
Enfuvirtide, Adult, Female, Humans, Male, Middle Aged, Peptide Fragments, RNA, Viral, Time Factors, HIV Infections, HIV Envelope Protein gp41, Receptors, HIV, Prevalence, Treatment Outcome, CD4 Lymphocyte Count, Anti-HIV Agents, Viral Load

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