Currently, the HIV pandemic remains a major global health challenge. In order to effectively control and cure HIV-1 infection, it is necessary to perform greater research on host-HIV interactions and develop novel preventive and therapeutic approaches. The human cytidine deaminase APOBEC3G (A3G) is the first identified host restriction factor, which can serve as an initial line of defense against HIV-1 by inducing lethal mutations on proviral DNA and disrupting viral reverse transcription and integration. In order to better understand the action of A3G on HIV-1 replication, my study was focused on characterizing the interplay between A3G and HIV-1 reverse transcriptase (RT). The results indicated that A3G directly bound to RT, which contributed to A3G-mediated inhibition of viral reverse transcription. Overexpression of the RT-binding polypeptide A3G65-132 was able to disrupt wild-type A3G and RT interaction, consequently attenuating the anti-HIV effect of A3G on HIV replication. While the potent antiviral activities of A3G make it an attractive candidate for gene therapy, the actions of A3G can be counteracted by HIV-1 Vif during wild-type HIV infection. In order to overcome Vif-mediated blockage and maximize the antiviral activity of A3G, this protein was fused with a virus-targeting polypeptide (R88) derived from HIV-1 Vpr, and various mutations were then introduced into R88-A3G fusion protein. Results showed that Vif binding mutants R88-A3GD128K and R88-A3GP129A exhibited very potent antiviral activity, and blocked HIV-1 replication in a CD4+ T lymphocyte cell line as well as human primary cells. In an attempt to further determine their potential against drug resistant viruses and viruses produced from latently infected cells, R88-A3GD128K was chosen and delivered by an inducible lentiviral vector system. Expression of R88-A3GD128K in actively and latently HIV-1 infected cells was shown to be able to inhibit the replication of both drug sensitive and resistant strains of HIV-1. In conclusion, this thesis has demonstrated one of the mechanisms that how A3G can disrupt HIV-1 reverse transcription. Meanwhile, an A3G-based anti-HIV-1 strategy has been developed, which provides a proof-of-principle for a new gene therapy approach against this deadly virus.

Submitted by Ana Maria Fiscina Sampaio (fiscina@bahia.fiocruz.br) on 2013-11-26T17:48:33Z No. of bitstreams: 1 Antônio Carlos Silva Santos Junior Prevalencia... - 2002.pdf: 10555403 bytes, checksum: fc37503b147e5c2e4d6b8e5f7aa160a8 (MD5) / Made available in DSpace on 2013-11-26T17:48:33Z (GMT). No. of bitstreams: 1 Antônio Carlos Silva Santos Junior Prevalencia... - 2002.pdf: 10555403 bytes, checksum: fc37503b147e5c2e4d6b8e5f7aa160a8 (MD5) Previous issue date: 2002 / Escola Bahiana de Medicina e Saúde Pública. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Pacientes infectados pelo HIV apresentam alterações no metabolismo ósseo e mineral aparentemente relacionadas à infecção. Osteopenia tem sido associada à terapia com inibidores de protease. Porém, interação do HIV com células do esqueleto e da matriz óssea, assim como, ativação crônica de células T e produção anormal de citocínas podem afetar a função de osteoblastos e osteoclastos mesmo antes do uso de terapia. 0 objetivo deste estudo foi o de investigar a influência da infecção pelo HIV nos níveis séricos do marcador de formação óssea osteocaldna. Realizamos um estudo seccional no qual avaliamos 69 indivíduos portadores do HIV [48 homens, 21 mulheres, idade média / (sd): 33 anos ± 4] antes do uso de terapia antiretroviral. Para fins de comparação, 50 indivíduos HIV negativos foram testados como controles. Com objetivo de analisar uma possível relação entre os níveis séricos de osteocalcina e a severidade da doença o grupo HIV + foi agrupado - de acordo com seus níveis de linfócitos T CD4 - em três grupos de 23 indivíduos: Grupo 1 CD4 > que 500, Grupo 2 CD4 entre 499 e 200 e Grupo 3 CD4 < que 199. Níveis de osteocalcina foram mensurados por um ensaio imunométrico (DPC Corp., Los Angeles, CA) detectando a fração intacta da osteocalcina (1-49) com valores de referência variando variando de 3,1 a 13,7 ng/ml. Quando comparando mais de dois grupos, o teste de Kruskal-Wallis foi utilizado. Quando urna diferença estatisticamente significante era encontrada o teste U, Mann-Whitney foi usado para determinar as diferenças entre cada par de grupos. Coeficientes de correlação foram calculados utilizando o teste de Spearman. Valores de P foram considerados significantes quando < 0,05. Redução de níveis séricos de osteocalcina foram encontrados em 43,5 % dos individuos HIV positivos e em 16% dos controles [P=0,00G1; odds ratio (OR) 4,04; intervalo de confiança 95% 1,68-9,69]. Não houve diferença estatisticamente significante nos níveis de osteocalcina, quando comparada nos grupos HIV positivos. Os níveis de osteocalcina apresentaram uma correlação positiva com a contagem de células CD4 [r=0,067 ; P=0,587] e uma correlação negativa com a carga virai [r=- 0,228; P=0,06]. Pacientes HIV positivos apresentaram acentuado decréscimo nos níveis séricos da osteocalcina. As hipóteses - de que 0 osteoblasto pode servir de reservatório para o HIV, de que a ativação sistêmica de células T aumenta a osteoclastogenese e que a osteopenia pode ser devida a toxicidade de mitocôndrias - podem explicar a interação da infecção pelo HIV e as alterações do metabolismo ósseo e mineral. Uma densidade mineral óssea reduzida já foi descrita em pacientes HIV+ e para comprovarmos que alterações nos níveis plasmáticos da osteocalcina podem levar a redução da massa óssea necessitamos de estudos prospectivos. / HIV-infected patients have been sliown to have alteration in bone mineral metabolism that appears to be related to the infection. Osteopenia has been associated with protease inhibitor (PI) therapy. However, direct interaction of HIV with cells of the bone, and bone marrow microenviroment, chronic T cell activation, and abnormal cytokine production affecting osteoblast and osteoclast function had been described in HIV-infected patients, before the use of antiretroviral therapy. The aim of this study is to investigate the influence of HIV infection on the serum osteocalcin levels. A cross-sectional study was performed on 69 HIV-infected patients [48 men, 21 women, mean age / (SD) 33 years (+-4)] pre-antiretroviral therapy. Fifty healthy seronegative adults matched by age, and sex served as controls.To analyze the possible relationship between the serum osteocalcin levels and disease severity the HIV-infected group, was, stratified according to CD4 cell count into three groups of 23 patients: Groupl CD4 cell count >500, Group 2 CD4 cell count in between 499-200, Group 3 CD4 cell count less than 199. Osteocalcin levels were measured by an immunometric assay (DPC Corp., Los Angeles, CA) detecting Intact osteocalcin (1-49) with a reference range of 3.1 -13.7 ng/ml. When comparing more than two groups, the Kruskal-Wallis test was used. If a significant difference was found, the Mann-Whitney U test (two tailed) was used to determine the differences between each pair of groups. Coefficients of correlation were calculated by the Spearman rank test. Data are given as medians and 25-75th percentiles if not otherwise quoted. P values are two-sided, and considered significant when <0,05. Serum osteocalcin levels reduction was present in 43,5% of HIV infected patients and in 16% of controls [P=0,0001;odds ratio (OR) 4,04; 95% Cl 1,68-9,69].No statistical significant difference on osteocalcin levels were found in HIV-Infected patients, irrespective of the CD4 cell count and viral load however serum osteocalcin concentration had a positive correlation with CD4 cell count [r=0,067 ; P=0,587], and a negative correlation with viral load [r=-0,228; P=0,06]. The HIV-infected patients showed marked decrease in serum osteocalcin concentration compared with non-HIV patients.The hypothesis that osteoblasts could act on as local HIV-1 reservoirs, the systemic activation of T cells in vivo leads an osteoprotegerin ligand- mediated increase in osteoclastogenesis and the hypothesis that osteopenia could result from mitochondrial toxicity, may explain the interaction of HIV infection, and alteration in bone mineral metabolism. Decreased bone mineral density has previously been reported in HIV-infected patients, and although the clinical consequences of our findings with disturbed osteocalcin levels remain unclear, it is conceivable that if these abnormalities persist over time, they may well lead to clinically significant bone loss.

Dissertação (mestrado)-Universidade de Brasília, Instituto de Ciências Biológicas, 2010. / Submitted by Fernanda Weschenfelder (nandaweschenfelder@gmail.com) on 2010-11-10T19:06:21Z No. of bitstreams: 1 2010_EduardoLourencodaSilva.pdf: 1331200 bytes, checksum: 0fc919ee04504d9f27bbc0833663f8f3 (MD5) / Rejected by Daniel Ribeiro(daniel@bce.unb.br), reason: Copiar abstract. Foi coladado errado. on 2010-12-03T00:46:09Z (GMT) / Submitted by Fernanda Weschenfelder (nandaweschenfelder@gmail.com) on 2010-12-06T20:01:59Z No. of bitstreams: 1 2010_EduardoLourencodaSilva.pdf: 1331200 bytes, checksum: 0fc919ee04504d9f27bbc0833663f8f3 (MD5) / Approved for entry into archive by Daniel Ribeiro(daniel@bce.unb.br) on 2010-12-08T21:34:12Z (GMT) No. of bitstreams: 1 2010_EduardoLourencodaSilva.pdf: 1331200 bytes, checksum: 0fc919ee04504d9f27bbc0833663f8f3 (MD5) / Made available in DSpace on 2010-12-08T21:34:12Z (GMT). No. of bitstreams: 1 2010_EduardoLourencodaSilva.pdf: 1331200 bytes, checksum: 0fc919ee04504d9f27bbc0833663f8f3 (MD5) / A Síndrome da Imuno-Deficiência Adquirida (AIDS), causada pelo vírus da imunodeficiência humana (HIV), caracteriza-se por ser uma infecção em que se observa uma alta taxa de mutações na formação das estruturas proteicas de seu agente etiológico, o que dificulta a terapia antibiótica e a resposta imunológica natural do indivíduo infectado. Desta forma, o conhecimento sobre a variabilidade genética humana e a análise da possível resistência deste à infecção pelo HIV é tão importante quanto o estudo da etiologia e dos ciclos biológicos do vírus para a correta aplicação da terapêutica e para a melhor orientação das pesquisas na busca por medicamentos mais eficientes. O presente estudo visou à caracterização genética populacional do hospedeiro do HIV em uma população do Distrito Federal. Para tal, foi realizada uma avaliação da distribuição gênica e genotípica de uma deleção de 32 pares de base no gene CCR5, CCR5*Δ32, e dos marcadores microssatélites TNFc, TNFd e TNFe associados aos genes do fator de necrose tumoral – TNFα e TNFβ -, que são marcadores genéticos associados à resistência ao HIV, em uma amostra de indivíduos nascidos no Distrito Federal. A frequência para a deleção de 32 pares de base neste estudo foi de 5,5% com a existência de um indivíduo homozigoto para a mutação e nove heterozigotos. O alelo 2 de TNFc foi encontrado com uma frequência de 9%, o que é muito abaixo em relação ao relatado para outras populações brasileiras e em africanos e europeus. TNFd teve o alelo 3 como mais frequente e o marcador TNFe apresentou o alelo 3 como o mais frequente. O haplótipo formado pelos alelos TNFc*1, TNFd*3 e TNFe*3 apresentou-se como o mais comum. Desta forma, o conhecimento da frequência do alelo CCR5*Δ32 no Distrito Federal fortalece a proposta de um gradiente associado com a presença de ancestralidade europeia e corrobora com os dados bibliográficos de que a população do Centro-Oeste é como um resumo da população brasileira. A descrição da distribuição alélica para os loci TNFc, d e e contribui para o melhor conhecimento da distribuição desses marcadores no Brasil. _________________________________________________________________________________ ABSTRACT / AIDS, the Acquired Immune Deficiency Syndrome, caused by the human immunodeficiency virus, HIV, is characterized as an infection where there has been found a high mutation rate in the formation of protein structures of its etiologic agent, troubleling the antibiotic therapy and natural immune response of the infected person. Therefore, knowledge of human genetic variability and analysis of the possible resistance of the HIV infection are so important as the study of the etiology and biological cycles of the virus to the correct application of therapy and for better targeting of research for more effective drugs. This study aimed to characterize the population genetics of the HIV´s host in Distrito Federal population. By reason of, an assessment of gene and genotypic distribution of a deletion of 32 base pairs in the CCR5 gene, CCR5*Δ32, and microsatellite markers TNFc, TNFd and TNFe genes associated with tumor necrosis factor - TNFα and TNFβ -, which are genetic markers associated with resistance/susceptibility to HIV in a sample of individuals born in Distrito Federal. The frequency of 32 base pairs deletion in this study was 5.5% with the existence of an individual homozygous for the mutation and nine heterozygotes. The allele 2 of TNFc was found with a frequency of 9%, which is much lower than previously reported for other populations in Brazil and in Africa and Europe. TNFd had the allele 3 as the most frequent and TNFe marker allele 3 showed the most frequent. The haplotype formed by alleles TNFc *1, TNFd *3 and TNFe *3 was the most common. Consequently, knowledge of the frequency of the CCR5 * Δ32 in the Distrito Federal has supported the proposal of a gradient associated with the presence of European ancestry and corroborates the view that the population of Distrito Federal and also from this geographical region is a brief of the brasilian population. The description of the distribution of alleles for loci TNFc, TNFd and TNFe contributes to a better understanding of the distribution of these markers in Brazil.

Dissertação (mestrado)—Universidade de Brasília, Instituto de Química, 2011. / Submitted by Shayane Marques Zica (marquacizh@uol.com.br) on 2011-10-03T20:18:34Z No. of bitstreams: 1 2011_CarlosEduardodeMeloSalvador.pdf: 2899436 bytes, checksum: c55960ffbf36e6c5a421c9438d2c5e0a (MD5) / Approved for entry into archive by Leila Fernandes (leilabiblio@yahoo.com.br) on 2011-10-18T11:14:20Z (GMT) No. of bitstreams: 1 2011_CarlosEduardodeMeloSalvador.pdf: 2899436 bytes, checksum: c55960ffbf36e6c5a421c9438d2c5e0a (MD5) / Made available in DSpace on 2011-10-18T11:14:20Z (GMT). No. of bitstreams: 1 2011_CarlosEduardodeMeloSalvador.pdf: 2899436 bytes, checksum: c55960ffbf36e6c5a421c9438d2c5e0a (MD5) / Aproximadamente após 25 anos da implantação da terapia anti-retroviral, a pesquisa em HIV/SIDA encontra-se em uma encruzilhada marcada pelo surgimento de novos paradigmas, entre os quais se destacam o aparecimento de variantes resistentes a inibidores presentes no coquetel anti-retroviral; a permanência de reservatórios virais latentes; a presença de efeitos tóxicos colaterais causados pelo tratamento e o alto custo das drogas disponíveis no mercado. Diante deste quadro, a pesquisa de mecanismos básicos de patogêneses, assim como a identificação de novos alvos terapêuticos, volta a desempenhar um papel crucial no desenvolvimento de novas drogas anti-retro virais. A diminuição da expressão do receptor CD4 na superfície das células infectadas é um dos mais importantes eventos durante a infecção pelo HIV-1. A identificação de inibidores desta função de Nef é de grande valia no tratamento da infecção pelo HIV. Para atingir este objetivo, foram sintetizados, com base em cálculos teóricos de modelagem molecular, três compostos (I, 15 e 18) que se demonstraram relevantes para futuros testes farmacológicos como possíveis inibidores da degradação de CD4 pela Nef. _______________________________________________________________________________ ABSTRACT / Approximately after 25 years of the implantation of the anti-retroviral therapy, the research in HIV, aids is at a crossroad marked for the sprouting of new paradigms: the emergence of variants resistant to protease inhibitors present in the anti-retroviral cocktail; the persistence of latent viral reservoirs, and the presence of collateral toxic effect caused by the treatment and the high cost of the available drugs in the market. Because of this situation, the research of basic mechanisms of pathogenesis and the identification of new therapeutic targets should play a crucial role in the development of new anti-retro viral drugs. Decrease in the expression of receiver CD4 on the surface of the infected cells is one of the most important events during the infection by HIV-1. The identification of inhibitors through function of Nef is very important to the treatment of HIV infection. To achieve this goal, three compounds (I, 15 and 18) were synthesized based on theoretical calculations of molecular modeling, which proved to be relevant for future pharmacological tests as potential inhibitors of the degradation of CD4 by Nef.

A dissertation submitted to the Faculty of Health Sciences, Umversity of the Witwatersrand, Johannesburg, for the degree of Masters of Science in Medicine (Virology). Johannesburg, 2001 / This dissertation examines HIV-1 subtype C nucleotide and amino acid Nef sequences from South African recently-infected (n=12) and chronically-infected individuals (n=9) and from AIDS patients (n=ll). The overall aim is to determine which regions of subtype C Nef are variable and which are conserved and to associate these regions with targeting by the immune system. Phylogenetic analysis and sequence alignments showed that there was no association of Nef variations with stage of disease. Nef amino acid alignments of 32 sequences showed a high degree of conservation in areas of functional and structural importance. The mean intrasubtype variation from these isolates was 15.8%, with sequences from the AIDS cohort being significantly (p<0.05) more variable than those from recent or chronic infection / IT2019

No description available.

Human immunodeficiency virus type 1 (HIV-1) and Mycobacterium tuberculosis (Mtb) coinfection remains a major global health threat. Both pathogens synergistically drive pathogenesis of the other. The risk of developing active tuberculosis (TB) is increased in people living with HIV-1, even in those receiving antiretroviral therapy (ART), whilst TB was responsible for 15 % of HIV-related deaths in 2020. Mtb co-infection increases the likelihood of transcriptionally activating HIV-1 replication potentially due to bioactive Mtb lipids engaging macrophage surface receptors, thus triggering signaling pathways which activate human transcriptional factors (hTF) and production of inflammatory cytokines capable of activating HIV-1 transcription. This work investigated the hypothesis that clinical Mtb strains with single nucleotide polymorphisms (SNP) in lipid-metabolizing genes, required for cell wall lipid biosynthesis, differentially affect HIV-1 replication and human macrophage inflammatory response during Mtb-HIV-1 co-infection in vitro. Monocyte derived macrophages (MDM) were the predominant model used to investigate this phenomenon. Infections, in the presence or absence of HIV-1 co-infection, were performed using either lineage 2 or lineage 4 clinical strains with non-synonymous SNP in polyketide synthase 2 (pks2) required for sulfolipid 1 (SL-1) biosynthesis and compared to control infections using phylogenetically close clinical strains without the SNP of interest and canonical lineage 2 and 4 laboratory strains (H37RvP1939/T605, CDC1551WT and HN878WT). Secreted cytokines and chemokines were measured in supernatant (SN) by Luminex. The effect of Mtb on HIV-1 viral production was assessed by measuring HIV-1 Gag p24 in the SN of co-infected MDM or SN of HIV-1 infected MDM incubated with conditioned media from Mtb-infected MDM. The influence of Mtb on HIV-1 transcriptional activity was measured using a transgenic cell line (TZM-bl) with Luciferase reporter under HIV-1 long terminal repeat (LTR) expression. The impact of incubating TZM-bl cells in Mtb-induced conditioned media before or after HIV-1 infection was assessed. One pair of phylogenetically close clinical strains with and without a pks2 SNP of interest (EX30Q1939/A605 and MRC16P1939/A605) with interesting lipid and inflammatory phenotypes, and H37RvP1939/T605 as a lineage 4 control, were subject to single nucleotide mutagenesis using recombineering to either revert SNP of interest to match the alleles of H37Rv or introduce the SNP of interest into the control strains. The wild-type and mutant strains were used in a trans-well assay to infect MDM in the presence of HIV-1 co-infection in the top chamber, while simultaneously mimicking the bystander effect of cytokine-mediated HIV-1 regulation in the bottom chamber which was only infected with HIV-1. Results demonstrate there was increased cytokine production by MDM infected with MRC16P1939/A605 in both the presence and absence of HIV-1 co-infection compared to its phylogenetically close paired strain EX30 Q1939/A605. The data shows that there was no difference in LTR activity in TZM-bl cells co-incubated with inflammatory environment between the strains of interests, however co-incubation of TZM-bl cells with Mtb-induced inflammatory environment generally increased LTR activity during HIV-1; a proxy for HIV-1 replication. In the trans-well co-infection assay, a significant positive association between production of HIVp24 and secretion of CCL2 was observed, whilst IL-1β secretion showed a significant negative relationship with the production of HIVp24, with donor variability in baseline cytokine production also associated with the extent of HIVp24, CCL2, IL-1β and IL-8 production. Introduction of the pks2 T605A SNP into H37RvP1939/T605 and reversion in EX30Q1939/A605T significantly modified their inflammatory phenotype. Together these results support the hypothesis that Mtb clinical stains with genetic variation in cell wall lipid biosynthesis impacts the inflammatory milieu and, subsequently, HIV-1 replication during co-infection. The outcome of Mtb-HIV co-infection is therefore not homogenous but contingent on the phenotype of infecting Mtb strain and individual.

No description available.

Thesis (Ph. D.)--University of Washington, 2005. / Vita. Includes bibliographical references (leaves 112-127).

HIV-1 is a global pandemic with about 39 million people infected. In India, 2.9 million people are infected and about 2 lakh new infections have been reported last year. To date, there is no cure for HIV/AIDS. Current treatment, which is associated with serious side effects, only delays the onset of AIDS and death. Thus, HIV/AIDS is responsible for a global health concern imposing significant healthcare costs, especially in low- and middle-income regions such as India and Africa, and a marked loss of quality of life to infected individuals. Understanding factors impacting vaccine design and drug development via mathematical modelling of HIV-1 transmission, evolution and pathogenesis and discerning the subtype and region specific differences are a crucial part of the overall strategy of reducing the burden of HIV/AIDS. The strain dominant in India is HIV-1 subtype C (HIV-1C). Treatment guidelines have largely been based on studies on HIV-1 subtype B (HIV-1B), dominant in the west. In this thesis, we have attempted to understand the dynamics of the spread of HIV-1C, leading to new guidelines and intervention strategies applicable to India. We have for the first time estimated the basic reproductive ratio, R0, of HIV-1 subtype C (HIV-1C), a proxy for its fitness and virulence, using clinical data of infected patients from India. We employed measurements of viral load decay dynamics during treatment and estimated R0, and the critical efficacy, εc, for successful treatment of HIV-1C infection. Clinical data showed that the viral load in patients in India was significantly higher than in the west. Yet, in 6 months following the start of treatment, 87.5% had undetectable viral load, indicating an excellent response to ART, comparable to the west. We analyzed the clinical data using a mathematical model and estimated the median R0 to be 5.3. The corresponding εc was ∼0.8. These estimates of R0 and εc are smaller than current estimates for HIV-1B, suggesting that HIV-1C exhibits lower in vivo fitness compared to HIV-1B, which allows successful treatment despite high baseline viral loads. New treatment guidelines thus emerge that are less stringent than in the west. HIV-1C is far more prevalent globally than HIV-1B. This is surprising in light of our findings above of a lower fitness of HIV-1C than HIV-1B. To understand this observation, we next developed a mechanistic paradigm of HIV-1 transmission. HIV-1 has been hypothesized to optimize its transmission potential (TP) in an infected population by modulating its steady state viral load (VSS), a robust marker of virulence. The mechanism of this optimization is paradoxical and poorly understood given that HIV-1 mutates rapidly in vivo in response to selection pressure by the host immune system. We hypothesize that the HIV-1 TP is not solely a function of VSS as proposed earlier, but a function of two variables - VSS and R0, which function such that R0 is optimized within an infected individual in response to the immune system while VSS is optimized across individuals such that transmission is optimized. On this TP(VSS, R0) landscape, we find that HIV-1C lies closer to the optimum than HIV-1B, suggesting an explanation for the global spread of HIV-1C. This leads to the intriguing implication that the lower virulence of HIV-1C may be because it has evolved more along the TP(VSS, R0) landscape than HIV-1B. Lastly, we examined the role of recombination on HIV-1 adaptation. Following transmission, HIV-1 adapts in the new host by acquiring mutations that allow it to escape from the host immune response at multiple epitopes. It also reverts mutations associated with epitopes targeted in the transmitting host but not in the new host. Moreover, escape mutations are often associated with additional compensatory mutations that partially recover fitness costs. It is unclear whether recombination expedites this process of multi-locus adaptation. To elucidate the role of recombination, we constructed a detailed population dynamics model that integrates viral dynamics, host immune response at multiple epitopes through cytotoxic T lymphocytes, and viral evolution driven by mutation, recombination, and selection. Using this model, we computed the expected waiting time until the emergence of the strain that has gained escape and compensatory mutations against the new host’s immune response, and reverted these mutations at epitopes no longer targeted. We found that depending on the underlying fitness landscape, shaped by both costs and benefits of mutations, adaptation proceeds via distinct dominant pathways with different effects of recombination, in particular distinguishing escape and reversion. Specifically, recombination tends to delay adaptation when a purely uphill fitness landscape is accessible at each epitope, and accelerate it when a fitness valley is associated with each epitope. Our study points to the importance of recombination in shaping the adaptation of HIV-1 following its transmission to new hosts, a process central to T cell-based vaccine strategies.