Source: Masters Abstracts International, Volume: 47-01, page: 0341. Adviser: Luis Ostrosky. Includes bibliographical references.

There are currently an estimated 33.2 million people living with human immunodeficiency virus (HIV) worldwide. For these individuals, long-term use of combination antiretroviral therapy (cART) is not feasible for a variety of reasons including major adverse complications, multi-drug resistance, poor adherence, and high cost. Hence, development of novel therapeutic strategies that can reduce the life-long dependency on cART is highly desired. In order to develop effective therapeutic strategies such as a therapeutic vaccine, we need to have a greater understanding of the immune correlates of viral control in chronic HIV infection. In this thesis, we used treatment interruption (TI) as a tool to test the efficacy of several therapeutic approaches and immune parameters for their association with effective control of viral replication. / In Chapter 2 we showed that cART intensification and Remune vaccination resulted in reduced viral load (VL) plateau during sequential TIs. Although HIV-specific immune responses measured by interferon-gamma (IFN-gamma) enzyme-linked immunospot assay (ELISPOT) increased in the same time frame, neither their breadth nor magnitude correlated with the decrease in VL plateau. In Chapter 3 the effect of ALVAC-vCP1425 plus Remune vaccination on HIV proteome-wide HIV-specific responses was monitored using a dual color IFN-gamma/interleukin-2 (IL-2) ELISPOT assay. We observed an increase in the magnitude of HIV-specific IFN-gamma/IL-2 responses, as well as in the breadth of Gag-specific IFN-gamma responses in the vaccinated groups compared to placebo groups. A shift towards an increased contribution of Gag-specific responses to total HIV-specific vaccine induced immune response was associated with longer delay to viral rebound during TI. In Chapters 4 and 5, we examined baseline pre-TI immune parameters and their association with viral rebound and CD4 count change during TI in HIV-infected individuals in the chronic phase of infection experiencing virologic failure before TI (Chapter 4) or with different levels of VL control while on therapy prior to TI (Chapter 5). We saw that chronic antigen stimulation from persistent viremia as well as co-infections such as with cytomegalovirus are associated with T-cell senescence, which may result in less favourable clinical outcomes during TI. / Consequently, results from this thesis contribute to further understanding of immune correlates of viral control in chronic HIV infection. New therapeutic vaccines and interventions should induce polyfunctional HIV-specific immune responses, broad Gag-specific immune responses, as well as reducing chronic antigen stimulation to prevent irreversible T-cell exhaustion. Taken together, these insights could potentially lead to the development of novel treatment interventions that could effectively control viral replication off cART.

Diss. (sammanfattning) Stockholm : Karol. inst., 2005. / Härtill 5 uppsatser.

Diss. (sammanfattning) Linköping : Linköpings universitet, 2005. / Härtill 5 uppsatser.

Thesis (D.P.H.)--University of Michigan.

Thesis (M.Sc.)--Memorial University of Newfoundland, Faculty of Medicine, 2000. / Typescript. Bibliography: leaves 102-123.

Thesis (Ph.D.)--Memorial University of Newfoundland, Faculty of Medicine, 1999. / Includes bibliographical references.

Dissertation (D.P.H.)--University of Michigan.

Thesis (Ph. D.)--Curtin University of Technology, 2004. / Includes bibliographical references (p. 278-298).

No Brasil vÃrios estudos demonstraram prevalÃncia de coinfecÃÃo pelos vÃrus linfotrÃpico de cÃlulas T humanas â HTLV e vÃrus da imunodeficiÃncia humana â HIV, dentre grupos especÃficos de indivÃduos, que variou de 0,58% a 11,4%. O CearÃ, segundo dados anteriores, representa dentre os Estados do Nordeste, uma Ãrea de baixa endemicidade para a infecÃÃo pelos vÃrus HTLV. Este estudo tem por objetivo estudar aspectos clÃnicos e epidemiolÃgicos da coinfecÃÃo por HTLV e HIV, em Hospital de referÃncia para tratamento de pacientes com HIV do CearÃ. Este estudo à descritivo, do tipo transversal, realizado no perÃodo de maio de 2001 a outubro de 2002. Foram colhidas 420 amostras de sangue de pacientes soropositivos ao HIV, confirmados por Elisa e Western Blot que posteriormente foram testadas para HTLV-I/II, no Centro de Hematologia do Cearà â HEMOCE. Entrevistou-se 337 pacientes e pesquisou-se 165 prontuÃrios mÃdicos para obtenÃÃo de informaÃÃes referentes à dados sÃcio-econÃmicos, fatores de risco para HTLV, prÃticas sexuais e aspectos clÃnicos. Os resultados revelaram valor de soroprevalÃncia geral de 0,95%, distribuÃdos em 0,23% de HIV-HTLV-I e 0,47% de HIV-HTLV-II, seguido de 01 (0,23%) amostra com sorologia indeterminada. NÃo foi evidenciada concomitÃncia de infecÃÃo pelos vÃrus HTLV-I e HTLV-II. A populaÃÃo estudada concentrou maior nÃmero de pacientes na faixa etÃria de 30 a 39 anos, era predominantemente de baixa renda (67,6%), menor grau de escolaridade (44,8%) e constituÃda na sua maioria por heterossexuais (67,8%). Quanto Ãs manifestaÃÃes clÃnicas pesquisadas em 119 indivÃduos, 105 (88,2%) manifestaram doenÃa intercorrente e 14 (11,8%) foram assintomÃticos, sendo 111 (93,27%) com definiÃÃo para diagnÃstico de AIDS. Um percentual elevado dos entrevistados amamentou (38,5%), sendo baixa a exposiÃÃo ao uso de tatuagem (12,2%) e a transfusÃo de sangue (15,9%). Foi notada que a escassez no uso de drogas intravenosas (4,8%), um menor nÃmero de negros (5,6%) e maior nÃmero de preferÃncia heterossexual (67,8%), poderiam ser os principais fatores apontados como responsÃveis pela baixa prevalÃncia encontrada em nosso Estado. / Several studies carried out in Brazil have shown a serum-prevalence rate of HIV / HTLV (Human Immunodeficiency - virus / Human T-Lymphotropic virus) co-infection of 0.58% to 11.4% among specific groups of individuals. Based on previous data, the State of Cearà is considered an area of low HTLV prevalence in the northeastern Brasil. This study evaluated the clinical and epidemiological aspects of the HIV / HTLV co-infection in a reference hospital for the treatment of HIV infected patients in CearÃ. A descriptive, cross sectional study was performed, in the period of May of 2001 to October of 2002. Blood samples were randomly collected from 420 HIV-positive patients, through Elisa and Western Blot tests, that later were serologically tested for HTLV-I/II in the Hematological Center of Cearà - HEMOCE. Interviews were done in 337 patients and 165 files were searched for socio-economic, risk factors for HTLV, sexual practice and clinical aspects. The results confirmed a general seroprevalence value of 0.95%, distributed as 0.23% of HIV-HTLV-I and 0.47% of HIV-HTLV-II, followed by one (0.23%) sample of undetermined serology. Concomitant infection was not evidenced by the viruses HTLV-I and HTLV-II. The population studied was more frequently 30 to 39 years old, had predominantly lower income (67.6%) and educational (44.8%) levels and were heterosexual mainly (67,8%). In 119 patients evaluated, 105 (88.2%) complained of HIV-related diseases, 14 (11.8%) were asymptomatic and 111 (93.3%) were diagnosed with AIDS. An elevated percentage was breast fed (38.5%), few had had tattoos (12.2%), and also did receive blood products (15,9%). The scarce use of intravenous drugs (4.8%), the few numbers of black individuals (5.6%) and higher numbers of heterosexuals (67.8%), were pointed as possible reasons for the low HTLV prevalence found in this research.