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Prolonged control of replication-competent dual- tropic human immunodeficiency virus-1 following cessation of highly active antiretroviral therapy.

Salgado M, Rabi SA, O'Connell KA, Buckheit RW, Bailey JR, Chaudhry AA, Breaud AR, Marzinke MA, Clarke W, Margolick JB, Siliciano RF, Blankson JN - Retrovirology (2011)

Bottom Line: In addition, he does not have any known protective HLA alleles.In addition, his spouse, who transmitted the virus to him, developed AIDS.Furthermore, his CD8(+) T cells do not have potent HIV suppressive activity.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.

ABSTRACT

Background: While initiation of highly active antiretroviral therapy (HAART) during primary HIV-1 infection occasionally results in transient control of viral replication after treatment interruption, the vast majority of patients eventually experience a rebound in plasma viremia.

Results: Here we report a case of a patient who was started on HAART during symptomatic primary infection and who has subsequently maintained viral loads of < 50 copies/mL for more than nine years after the cessation of treatment. This patient had a high baseline viral load and has maintained a relatively high frequency of latently infected CD4(+) T cells. In addition, he does not have any known protective HLA alleles. Thus it is unlikely that he was destined to become a natural elite controller or suppressor. The mechanism of control of viral replication is unclear; he is infected with a CCR5/CXCR4 dual-tropic virus that is fully replication-competent in vitro. In addition, his spouse, who transmitted the virus to him, developed AIDS. The patient's CD4(+) T cells are fully susceptible to HIV-1 infection, and he has low titers of neutralizing antibodies to heterologous and autologous HIV-1 isolates. Furthermore, his CD8(+) T cells do not have potent HIV suppressive activity.

Conclusion: This report suggests that some patients may be capable of controlling pathogenic HIV-1 isolates for extended periods of time after the cessation of HAART through a mechanism that is distinct from the potent cytotoxic T lymphocyte (CTL) mediated suppression that has been reported in many elite suppressors.

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Phylogenetic Analysis: An alignment of the variable regions of env is shown for replication-competent isolates obtained from Patient 169 and his spouse. Numbering is from the first amino acid in gp120. (A). The sequences are also compared to other Clade B sequences(B). Phylogenies were estimated by using a classical approach, functioning under a maximum-likelihood (ML) optimality criterion.
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Figure 2: Phylogenetic Analysis: An alignment of the variable regions of env is shown for replication-competent isolates obtained from Patient 169 and his spouse. Numbering is from the first amino acid in gp120. (A). The sequences are also compared to other Clade B sequences(B). Phylogenies were estimated by using a classical approach, functioning under a maximum-likelihood (ML) optimality criterion.

Mentions: We next analyzed the fitness of isolates obtained from patient 169 and his spouse. For patient 169, full genome sequencing of replication-competent virus cultured from 1999 plasma and three independent replication-competent isolates obtained from CD4+ T cells in 2010 was performed. One of the isolates from 2010 (2B) was identical to the 1999 isolate with the exception of a single nucleotide difference in the HIV-1 LTR. The two other isolates from 2010 (1A, 1B) were identical although they were isolated from independent culture wells. The differences between the identical 2010 isolates and the 1999 isolate are summarized in Table 1. For the patient's spouse, full genome sequencing of two independent isolates cultured from her resting CD4+ T cells in 2010 was performed. No large deletions were found in any gene and no drug resistance mutations were found in any of the isolates obtained from either patient. Phylogenetic analysis of the env gene showed that the isolates from 169 and his spouse were more closely related to each other than to any other isolate in the Los Alamos database, confirming that the two patients were a transmission pair [Figure 2].


Prolonged control of replication-competent dual- tropic human immunodeficiency virus-1 following cessation of highly active antiretroviral therapy.

Salgado M, Rabi SA, O'Connell KA, Buckheit RW, Bailey JR, Chaudhry AA, Breaud AR, Marzinke MA, Clarke W, Margolick JB, Siliciano RF, Blankson JN - Retrovirology (2011)

Phylogenetic Analysis: An alignment of the variable regions of env is shown for replication-competent isolates obtained from Patient 169 and his spouse. Numbering is from the first amino acid in gp120. (A). The sequences are also compared to other Clade B sequences(B). Phylogenies were estimated by using a classical approach, functioning under a maximum-likelihood (ML) optimality criterion.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3293762&req=5

Figure 2: Phylogenetic Analysis: An alignment of the variable regions of env is shown for replication-competent isolates obtained from Patient 169 and his spouse. Numbering is from the first amino acid in gp120. (A). The sequences are also compared to other Clade B sequences(B). Phylogenies were estimated by using a classical approach, functioning under a maximum-likelihood (ML) optimality criterion.
Mentions: We next analyzed the fitness of isolates obtained from patient 169 and his spouse. For patient 169, full genome sequencing of replication-competent virus cultured from 1999 plasma and three independent replication-competent isolates obtained from CD4+ T cells in 2010 was performed. One of the isolates from 2010 (2B) was identical to the 1999 isolate with the exception of a single nucleotide difference in the HIV-1 LTR. The two other isolates from 2010 (1A, 1B) were identical although they were isolated from independent culture wells. The differences between the identical 2010 isolates and the 1999 isolate are summarized in Table 1. For the patient's spouse, full genome sequencing of two independent isolates cultured from her resting CD4+ T cells in 2010 was performed. No large deletions were found in any gene and no drug resistance mutations were found in any of the isolates obtained from either patient. Phylogenetic analysis of the env gene showed that the isolates from 169 and his spouse were more closely related to each other than to any other isolate in the Los Alamos database, confirming that the two patients were a transmission pair [Figure 2].

Bottom Line: In addition, he does not have any known protective HLA alleles.In addition, his spouse, who transmitted the virus to him, developed AIDS.Furthermore, his CD8(+) T cells do not have potent HIV suppressive activity.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.

ABSTRACT

Background: While initiation of highly active antiretroviral therapy (HAART) during primary HIV-1 infection occasionally results in transient control of viral replication after treatment interruption, the vast majority of patients eventually experience a rebound in plasma viremia.

Results: Here we report a case of a patient who was started on HAART during symptomatic primary infection and who has subsequently maintained viral loads of < 50 copies/mL for more than nine years after the cessation of treatment. This patient had a high baseline viral load and has maintained a relatively high frequency of latently infected CD4(+) T cells. In addition, he does not have any known protective HLA alleles. Thus it is unlikely that he was destined to become a natural elite controller or suppressor. The mechanism of control of viral replication is unclear; he is infected with a CCR5/CXCR4 dual-tropic virus that is fully replication-competent in vitro. In addition, his spouse, who transmitted the virus to him, developed AIDS. The patient's CD4(+) T cells are fully susceptible to HIV-1 infection, and he has low titers of neutralizing antibodies to heterologous and autologous HIV-1 isolates. Furthermore, his CD8(+) T cells do not have potent HIV suppressive activity.

Conclusion: This report suggests that some patients may be capable of controlling pathogenic HIV-1 isolates for extended periods of time after the cessation of HAART through a mechanism that is distinct from the potent cytotoxic T lymphocyte (CTL) mediated suppression that has been reported in many elite suppressors.

Show MeSH
Related in: MedlinePlus