RESUMO
We studied viral evolution in five human leukocyte antigen (HLA)-B*57 patients recently infected with HIV-1. Escape mutations in HLA-B*57-restricted Gag epitopes were present at study entry in all patients, but were not associated with significant increases in viremia. Conversely, no new escape mutations in HLA-B*57-restricted epitopes or known compensatory mutations were detected in patients who experienced significant increases in viremia. Thus, the development of escape mutations alone does not determine virologic outcome in recently infected HLA-B*57 patients.
Assuntos
Epitopos de Linfócito T/genética , Genes gag/genética , Infecções por HIV/genética , HIV-1/genética , Antígenos HLA-B/genética , Infecções por HIV/imunologia , Antígenos HLA-B/imunologia , Humanos , Dados de Sequência Molecular , MutaçãoAssuntos
Soropositividade para HIV/imunologia , HIV-1/imunologia , Interleucina-2/administração & dosagem , Adulto , Terapia Antirretroviral de Alta Atividade , Western Blotting , Soropositividade para HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , Humanos , Masculino , Resultado do TratamentoRESUMO
The human immunodeficiency virus type 1 (HIV-1)-specific immune responses of patients with the HLA-B*57/5801 alleles who spontaneously control viral replication serve as an important model for T cell-based HIV-1 vaccines. Determining the breadth of this response and the extent of virologic escape in primary infection in these patients is therefore critical. Here we document the development of mutations in 3 HLA-B*5801-restricted epitopes in gag, nef, and pol in an HLA-B*5801-positive patient who had a viral load of only 1159 copies/mL at day 167 after infection. A full genome sequence analysis was performed to determine the extent of mutations in HLA-B*5801-restricted epitopes, and longitudinal sequence data of specific genes were combined with enzyme-linked immunospot assay analysis of critical epitopes to determine the importance of escape mutations. Thus, relative control of viral replication can be maintained in spite of the rapid development of multiple escape mutations within cytotoxic T lymphocyte epitopes.
Assuntos
Infecções por HIV/imunologia , Infecções por HIV/virologia , HIV-1/classificação , HIV-1/imunologia , Antígenos HLA-B/imunologia , Adulto , Epitopos/genética , Evolução Molecular , Feminino , Genoma Viral , Anticorpos Anti-HIV/imunologia , Infecções por HIV/transmissão , HIV-1/genética , HIV-1/isolamento & purificação , Humanos , Immunoblotting , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Mutação de Sentido Incorreto , RNA Viral/genética , Análise de Sequência de DNA , Carga Viral , Produtos do Gene gag do Vírus da Imunodeficiência Humana/genética , Produtos do Gene nef do Vírus da Imunodeficiência Humana/genética , Produtos do Gene pol do Vírus da Imunodeficiência Humana/genéticaRESUMO
BACKGROUND: Little is known about modifications to highly active antiretroviral therapy (HAART) initiated during acute or early HIV infection. METHODS: Reasons for first modifications of HAART regimens were recorded using the AIDS Clinical Trials Group form among 363 subjects who initiated HAART within 1 year of seroconversion from 2005 in the Acute Infection and Early Disease Research Program. Modifications recorded as due to "patient choice" or "physician choice" were clarified by query to the recording site. Times to events were analyzed by Kaplan-Meier methods; significance of differences was assessed by the log-rank test. RESULTS: Two hundred five of 363 (56%) subjects modified therapy, at a median of 425 days after initiation, by changing drugs, discontinuing treatment, or removing or adding drugs. Most modifications were attributed to toxicity (n = 105, 51%), most of which was low grade; regimen simplification (n = 18, 5%); and achievement of viral suppression (n = 15, 7%). Time to first modification was shorter for those with shorter time from infection to initiation (P = 0.005) and those having higher CD4 lymphocyte count at initiation (P = 0.06). Modifications occurred sooner in subjects receiving regimens taken more than once daily (P < 0.001) or with more than 2 pills daily (P < 0.001). Most regimens were nonnucleoside reverse transcriptase inhibitor based or protease inhibitor based, and these did not differ significantly in rate and timing of modification. CONCLUSIONS: HAART initiated early in HIV infection was modified in the majority of cases, usually due to minor toxicities whose incidence was similar for protease inhibitor-based and nonnucleoside reverse transcriptase inhibitor-based regimens. Convenience of regimens (lower pill burden and dosing frequency) was associated with a lower rate of modification.
