The Experts below are selected from a list of 35838 Experts worldwide ranked by ideXlab platform

Joseph D Tucker - One of the best experts on this subject based on the ideXlab platform.

  • reframing the interpretation of Sex Worker health a behavioral structural approach
    The Journal of Infectious Diseases, 2011
    Co-Authors: Joseph D Tucker, Astrid S Tuminez
    Abstract:

    Expanding Sexually transmitted infection (STI) epidemics in many parts of Asia increase the importance of effective human immunodeficiency virus (HIV)/STI prevention programs for female Sex Workers. Designing Sex Worker health research and programs demands a well-stated conceptual approach, especially when one is interpreting the relationship between local policy environments and Sex Worker health. However, the core principles of the 2 most common conceptual approaches used in Sex Worker health programs—abolitionism and empowerment—have frequently divergent assumptions and implications. The abolitionist approach sees major aspects of the Sex industry as fundamentally coercive and exploitative of women and supports dismantling all or parts of the Sex sector. The empowerment approach strengthens Sex Workers’ agency and rights in order to build collective self-efficacy and have women invested in implementing their own HIV/STI prevention programs. This review compares these approaches using implication analysis and empirical cases from Asia. The misperception of an unresolvable gap between the 2 approaches ignores common ground that forms the basis of a new behavioral–structural conceptual framework. Explicitly accounting for the interaction between female Sex Worker behaviors and larger structures and policies, a behavioral–structural approach may provide a solid foundation for Sex work research and programs.

  • female Sex Worker social networks and sti hiv prevention in south china
    PLOS ONE, 2011
    Co-Authors: Joseph D Tucker, H Peng, K Wang, H Chang, L G Yang, Sen Miao Zhang, B Yang
    Abstract:

    Background: Reducing harm associated with selling and purchasing Sex is an important public health priority in China yet there are few examples of sustainable successful programs to promote Sexual health among female Sex Workers. The limited civil society and scope of nongovernmental organizations circumscribe the local capacity of female Sex Workers to collectively organize advocate for their rights and implement STI/HIV prevention programs. The purpose of this study was to examine social networks among low-income female Sex Workers in South China to determine their potential for Sexual health promotion. Methods/Principal Findings: Semi-structured interviews with 34 low-income female Sex Workers and 28 health outreach members were used to examine how social relationships affected condom use and negotiation STI/HIV testing and health-seeking behaviors and dealing with violent clients. These data suggested that Sex Workers laoxiang (hometown social connections) were more powerful than relationships between women selling Sex at the same venue in establishing the terms and risk of commercial Sex. Female Sex Workers from the same hometown often migrated to the city with their laoxiang and these social connections fulfilled many of the functions of nongovernmental organizations including collective mobilization condom promotion violence mitigation and promotion of health-seeking behaviors. Outreach members observed that Sex Workers accompanied by their laoxiang were often more willing to accept STI/HIV testing and trust local Sexual health services. Conclusions/Significance: Organizing STI/HIV prevention services around an explicitly defined laoxiang social network may provide a strong foundation for Sex Worker health programs. Further research on dyadic interpersonal relationships between female Sex Workers group dynamics and norm establishment and the social network characteristics are needed.

  • p2 s2 10 Sex Worker collective organization in the absence of ngos a qualitative analysis of female Sex Worker hometown social networks in south china
    Sexually Transmitted Infections, 2011
    Co-Authors: Joseph D Tucker, H Peng, K Wang, H Chang, L G Yang, S Zhang, B Yang
    Abstract:

    Background Reducing harm associated with selling and purchasing Sex is an important public health priority in China, yet there are few examples of sustainable, successful programs to promote Sexual health among female Sex Workers. Programs focusing on empowering Sex Workers using a rights-based framework have been effective in India and other regions, but have been challenging to replicate in China. The limited civil society and scope of nongovernmental organizations circumscribe the local capacity of female Sex Workers to collectively organise, advocate for their rights, and implement STI/HIV prevention programs. The purpose of this study was to examine social networks among low-income female Sex Workers in South China to determine their potential for Sexual health promotion. Methods Semi-structured interviews with 34 low-income female Sex Workers and 28 outreach members were used to examine how social relationships affected condom use and negotiation, STI/HIV testing and health-seeking behaviours, and dealing with violent clients. Results These data showed that Sex Worker9s hometown social connections were more powerful than relationships between women selling Sex at the same venue in establishing the terms and risk of commercial Sex. Female Sex Workers from the same hometown often migrated to the city with their hometown sisters and these social connections fulfilled many of the functions of non-governmental organizations, including collective mobilisation, condom promotion, violence mitigation, and promotion of health-seeking behaviours. Outreach members observed that Sex Workers accompanied by their hometown sisters were often more willing to accept STI/HIV testing and trust local Sexual health services. Conclusions Organising STI/HIV prevention services around an explicitly defined hometown social network may provide a strong foundation for Sex Worker health programs. Further research on dyadic interpersonal relationships between low-income female Sex Workers, group dynamics and norm establishment, and the social network characteristics are needed. Hometown social networks may represent a powerful force for organising STI/HIV prevention among low-income Sex Workers in China and other regions with limited civil society.

  • Sex Worker incarceration in the people s republic of china
    Sexually Transmitted Infections, 2008
    Co-Authors: Joseph D Tucker, X. Ren
    Abstract:

    Tens of thousands of commercial Sex Workers in China are administratively detained each year in female re-education through labor (RTL) centres for moral education and vocational training. Recent increases in syphilis and heteroSexual HIV make tailored HIV prevention efforts for Sex Workers increasingly important in many regions of China. However, RTL centres focused on detaining commercial Sex Workers have not traditionally been linked to Sexually transmitted infections (STI)/HIV programmes. The stigma of being incarcerated and selling Sex complicates STI/HIV prevention for these women. Incarcerated Sex Workers represent a particularly marginalised HIV risk group that has been excluded from domestic and international HIV programmes to date. Although several laws and administrative decrees provide a legal mandate for Sex Worker STI/HIV testing, treatment and rights, there is still substantial variation in how laws are implemented. Creating devoted medical services and legal aid for incarcerated Sex Workers is important in curbing the spread of heteroSexual HIV and other STIs in China. Recent legal and social developments suggest that China’s RTL system will be transformed in the near future, gaining momentum for reform that could improve the Sexual and human rights of incarcerated Sex Workers.

  • Sex Worker incarceration in the People’s Republic of China
    Sexually transmitted infections, 2008
    Co-Authors: Joseph D Tucker, X. Ren
    Abstract:

    Tens of thousands of commercial Sex Workers in China are administratively detained each year in female re-education through labor (RTL) centres for moral education and vocational training. Recent increases in syphilis and heteroSexual HIV make tailored HIV prevention efforts for Sex Workers increasingly important in many regions of China. However, RTL centres focused on detaining commercial Sex Workers have not traditionally been linked to Sexually transmitted infections (STI)/HIV programmes. The stigma of being incarcerated and selling Sex complicates STI/HIV prevention for these women. Incarcerated Sex Workers represent a particularly marginalised HIV risk group that has been excluded from domestic and international HIV programmes to date. Although several laws and administrative decrees provide a legal mandate for Sex Worker STI/HIV testing, treatment and rights, there is still substantial variation in how laws are implemented. Creating devoted medical services and legal aid for incarcerated Sex Workers is important in curbing the spread of heteroSexual HIV and other STIs in China. Recent legal and social developments suggest that China’s RTL system will be transformed in the near future, gaining momentum for reform that could improve the Sexual and human rights of incarcerated Sex Workers.

B Yang - One of the best experts on this subject based on the ideXlab platform.

  • female Sex Worker social networks and sti hiv prevention in south china
    PLOS ONE, 2011
    Co-Authors: Joseph D Tucker, H Peng, K Wang, H Chang, L G Yang, Sen Miao Zhang, B Yang
    Abstract:

    Background: Reducing harm associated with selling and purchasing Sex is an important public health priority in China yet there are few examples of sustainable successful programs to promote Sexual health among female Sex Workers. The limited civil society and scope of nongovernmental organizations circumscribe the local capacity of female Sex Workers to collectively organize advocate for their rights and implement STI/HIV prevention programs. The purpose of this study was to examine social networks among low-income female Sex Workers in South China to determine their potential for Sexual health promotion. Methods/Principal Findings: Semi-structured interviews with 34 low-income female Sex Workers and 28 health outreach members were used to examine how social relationships affected condom use and negotiation STI/HIV testing and health-seeking behaviors and dealing with violent clients. These data suggested that Sex Workers laoxiang (hometown social connections) were more powerful than relationships between women selling Sex at the same venue in establishing the terms and risk of commercial Sex. Female Sex Workers from the same hometown often migrated to the city with their laoxiang and these social connections fulfilled many of the functions of nongovernmental organizations including collective mobilization condom promotion violence mitigation and promotion of health-seeking behaviors. Outreach members observed that Sex Workers accompanied by their laoxiang were often more willing to accept STI/HIV testing and trust local Sexual health services. Conclusions/Significance: Organizing STI/HIV prevention services around an explicitly defined laoxiang social network may provide a strong foundation for Sex Worker health programs. Further research on dyadic interpersonal relationships between female Sex Workers group dynamics and norm establishment and the social network characteristics are needed.

  • p2 s2 10 Sex Worker collective organization in the absence of ngos a qualitative analysis of female Sex Worker hometown social networks in south china
    Sexually Transmitted Infections, 2011
    Co-Authors: Joseph D Tucker, H Peng, K Wang, H Chang, L G Yang, S Zhang, B Yang
    Abstract:

    Background Reducing harm associated with selling and purchasing Sex is an important public health priority in China, yet there are few examples of sustainable, successful programs to promote Sexual health among female Sex Workers. Programs focusing on empowering Sex Workers using a rights-based framework have been effective in India and other regions, but have been challenging to replicate in China. The limited civil society and scope of nongovernmental organizations circumscribe the local capacity of female Sex Workers to collectively organise, advocate for their rights, and implement STI/HIV prevention programs. The purpose of this study was to examine social networks among low-income female Sex Workers in South China to determine their potential for Sexual health promotion. Methods Semi-structured interviews with 34 low-income female Sex Workers and 28 outreach members were used to examine how social relationships affected condom use and negotiation, STI/HIV testing and health-seeking behaviours, and dealing with violent clients. Results These data showed that Sex Worker9s hometown social connections were more powerful than relationships between women selling Sex at the same venue in establishing the terms and risk of commercial Sex. Female Sex Workers from the same hometown often migrated to the city with their hometown sisters and these social connections fulfilled many of the functions of non-governmental organizations, including collective mobilisation, condom promotion, violence mitigation, and promotion of health-seeking behaviours. Outreach members observed that Sex Workers accompanied by their hometown sisters were often more willing to accept STI/HIV testing and trust local Sexual health services. Conclusions Organising STI/HIV prevention services around an explicitly defined hometown social network may provide a strong foundation for Sex Worker health programs. Further research on dyadic interpersonal relationships between low-income female Sex Workers, group dynamics and norm establishment, and the social network characteristics are needed. Hometown social networks may represent a powerful force for organising STI/HIV prevention among low-income Sex Workers in China and other regions with limited civil society.

Frances M Cowan - One of the best experts on this subject based on the ideXlab platform.

  • mobility and Sex work why where when a typology of female Sex Worker mobility in zimbabwe
    Social Science & Medicine, 2019
    Co-Authors: Calum Davey, Jeffrey Dirawo, Phillis Mushati, Sitholubuhle Magutshwa, James R Hargreaves, Frances M Cowan
    Abstract:

    Sex-Worker mobility may have implications for health and access to care but has not been described in sub-Saharan Africa. We described Sex-Worker mobility in Zimbabwe and a mobility typology using data from 2591 and 2839 female Sex Workers in 14 sites from 2013 and 2016. We used latent class analysis to identify a typology of mobile Sex Workers. More women travelled for work in 2016 (59%) than in 2013 (27%), usually to find clients with more money (57% of the journeys), spending a median of 21 (2013) and 24 (2016) days away. A five-class mixture model best fitted the data, with 39% women in an infrequent work-mobility class, 21% in a domestic-high-mobility class, 16% in an international-high-mobility class, 16% in an infrequent opportunistic-non-work-mobility class, and 7% who travel with clients. More-mobile classes were better educated; risk behaviours differed by class. Mobility is increasing among Sex Worker in Zimbabwe, multi-faceted, and not explained by other vulnerabilities.

  • author s responsefemale Sex Worker typology too complicated to be used pragmatically
    International Journal of Epidemiology, 2011
    Co-Authors: Raluca Buzdugan, James F Blanchard, Stephen Moses, Andrew Copas, Shajy Isac, B M Ramesh, Reynold Washington, Shiva S Halli, Frances M Cowan
    Abstract:

    Centre for Sexual Health & HIV Research, Department of Infection and Population Health, University College London, London, UK, Department of Community Health Sciences, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada, Department of Medical Microbiology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada, Karnataka Health Promotion Trust, Bangalore, Karnataka, India and St John’s Research Institute, Bangalore, Karnataka, India

  • p89 becoming a Sex Worker the nexus between violence gender disadvantage and poverty
    Sexually Transmitted Infections, 2011
    Co-Authors: Maryam Shahmanesh, Sonali Wayal, Frances M Cowan
    Abstract:

    Background Female Sex Workers (FSWs) in India remain most vulnerable to contracting HIV immediately after initiation into Sex work. We explored the process of initiation to inform interventions. Methods In-depth interviews were conducted with sixteen purposively selected FSWs in Goa (December 2004–December 2005). The life narratives were interrogated using grounded theory. Results The narratives showed a dynamic interplay between underlying vulnerabilities, precipitating factors, and how women entered Sex work: The ubiquitous mitigating theme that emerged was violence: dysfunctional and violent family life; Sexual violence; and violence from intimate male partners. Other underlying vulnerabilities were also manifestations of gender disadvantage: being unwanted; Sexual naivete; early Sexual debut; entrapment in loveless marriages; and lack of life skills. Loss of social support through bereavement and abandonment or financial need, were the commonest events that precipitated entry into Sex work. The clearest division in the route into Sex work was between traditional caste-based Sex Workers (devadassi) and those who were either introduced by peers, or sold through a broker; however the underlying and precipitating factors for both routes were remarkably similar. Conclusion The interplay between caste, economy, gender, and violence drives entry into Sex work. HIV prevention interventions must work upstream on the context within which women enter Sex work and downstream to strengthen their agency. The peers who introduce women into Sex work are potential vehicles to “deliver” HIV prevention services. Ultimately, the challenge is to ensure that the structural vulnerabilities that prevent effective HIV prevention early after entry into Sex work do not also become barriers preventing FSWs from accessing HIV treatment.

Joshua Kimani - One of the best experts on this subject based on the ideXlab platform.

  • hiv 1 subtypes and 5 ltr leader sequence variants correlate with seroconversion status in pumwani Sex Worker cohort
    Viruses, 2017
    Co-Authors: Joshua Kimani, Francis A Plummer, Raghavan Sampathkumar, Joel Scottherridge, Binhua Liang, Ma Luo
    Abstract:

    Within the Pumwani Sex Worker cohort, a subgroup remains seronegative, despite frequent exposure to HIV-1; some of them seroconverted several years later. This study attempts to identify viral variations in 5’LTR-leader sequences (5’LTR-LS) that might contribute to the late seroconversion. The 5’LTR-LS contains sites essential for replication and genome packaging, viz, primer binding site (PBS), major splice donor (SD), and major packaging signal (PS). The 5’LTR-LS of 20 late seroconverters (LSC) and 122 early seroconverters (EC) were amplified, cloned, and sequenced. HelixTree 6.4.3 was employed to classify HIV subtypes and sequence variants based on seroconversion status. We find that HIV-1 subtypes A1.UG and D.UG were overrepresented in the viruses infecting the LSC (P < 0.0001). Specific variants of PBS (Pc < 0.0001), SD1 (Pc < 0.0001), and PS (Pc < 0.0001) were present only in the viral population from EC or LSC. Combinations of PBS [PBS-2 (Pc < 0.0001) and PBS-3 (Pc < 0.0001)] variants with specific SD sequences were only seen in LSC or EC. Combinations of A1.KE or D with specific PBS and SD variants were only present in LSC or EC (Pc < 0.0001). Furthermore, PBS variants only present in LSC co-clustered with PBS references utilizing tRNAArg; whereas, the PBS variants identified only in EC co-clustered with PBS references using tRNALys3 and its variants. This is the first report that specific PBS, SD1, and PS sequence variants within 5’LTR-LS are associated with HIV-1 seroconversion, and it could aid designing effective anti-HIV strategies.

  • kir3dl1 alleles and their epistatic interactions with human leukocyte antigen class i influence resistance and susceptibility to hiv 1 acquisition in the pumwani Sex Worker cohort
    AIDS, 2017
    Co-Authors: Ma Luo, Joshua Kimani, Chris Czarnecki, Michelle Nebroski, Nicole Bernard, Francis A Plummer
    Abstract:

    OBJECTIVE To determine the associations of KIR3DL1/S1(3DL1/S1) and its epistatic interactions with human leukocyte antigen class I (HLA-I) alleles with resistance and susceptibility to HIV-1. DESIGN Despite repeated exposure to HIV-1, a subset of women enrolled in the Pumwani Sex Worker cohort remain HIV uninfected. Previous studies have shown that specific HLA class I and II alleles were associated with this natural immunity. In this study, we investigated the association of 3DL1/S1 and its epistatic interactions with HLA-I, with resistance or susceptibility to HIV-1 acquisition. METHODS We used a sequence-based typing method to genotype 3DL1/S1 of 641 women in this cohort. The association of 3DL1/S1 and its epistatic interactions with HLA-I were analyzed using SPSS statistics software. RESULTS 3DL1041 is enriched in the HIV-1-resistant women [P = 0.009, Pc = 0.0468, odds ratio (OR): 3.359, 95% confidence interval (CI): 1.39-8.32], whereas, 3DL1020 was associated with susceptibility to HIV-1 infection before correction for multiple comparisons (P = 0.029, Pc = 0.0858, OR: 0.316, 95%CI: 0.10-1.04). Epistatic interactions between several 3DL1 alleles and specific HLA-I alleles were observed. Among them the cocarriage of 3DL1041 with Bw4 (P = 1E - 05, Pc = 0.0015, OR: 13.33, 95%CI: 3.43-51.9), or Bw6 (P = 0.008, Pc = 0.272, OR: 3.92, 95%CI: 1.51-10.17), increased the odds of remaining HIV-1 uninfected. Further, 3DL1041+/Bw4+ women who entered the cohort HIV negative remained uninfected (P = 0.032, Pc = 0.0858). Cocarriage of 3DL101501 with C02 : 10 (P = 2.73E - 07, Pc = 7.0954E - 06), B15 : 03 (P = 3.21E - 04, Pc = 0.0042), A24 supertype (P = 8.89E - 04, Pc = 0.0077), or A23 : 01 (P = 0.0036, Pc = 0.0236) was associated with increased susceptibility to seroconversion. CONCLUSION The effects of interactions between 3DL1 and HLA-I alleles on resistance/susceptibility to HIV-1 infection suggest that innate immunity plays an important role in HIV-1 acquisition and should be studied and explored for HIV prevention.

  • influence of hla class i haplotypes on hiv 1 seroconversion and disease progression in pumwani Sex Worker cohort
    PLOS ONE, 2014
    Co-Authors: Raghavan Sampathkumar, Charles Wachihi, Joshua Kimani, Francis A Plummer, Thomas Bielawny, Lillian Mendoza, Elizabeth N Ngugi, Harold Peters, Ma Luo
    Abstract:

    We examined the effect of HLA class I haplotypes on HIV-1 seroconversion and disease progression in the Pumwani Sex Worker cohort. This study included 595 HIV-1 positive patients and 176 HIV negative individuals. HLA-A, -B, and -C were typed to 4-digit resolution using sequence-based typing method. HLA class I haplotype frequencies were estimated using PyPop 32-0.6.0. The influence of haplotypes on time to seroconversion and CD4+ T cell decline to <200 cells/mm3 were analyzed by Kaplan-Meier analysis using SPSS 13.0. Before corrections for multiple comparisons, three 2-loci haplotypes were significantly associated with faster seroconversion, including A*23∶01-C*02∶02 (p = 0.014, log rank(LR) = 6.06, false-discovery rate (FDR) = 0.056), B*42∶01-C*17∶01 (p = 0.01, LR = 6.60, FDR = 0.08) and B*07∶02-C*07∶02 (p = 0.013, LR = 6.14, FDR = 0.069). Two A*74∶01 containing haplotypes, A*74∶01-B*15∶03 (p = 0.047, LR = 3.942, FDR = 0.068) and A*74∶01-B*15∶03-C*02∶02 (p = 0.045, LR = 4.01, FDR = 0.072) and B*14∶02-C*08∶02 (p = 0.021, LR = 5.36, FDR = 0.056) were associated with slower disease progression. Five haplotypes, including A*30∶02-B*45∶01 (p = 0.0008, LR = 11.183, FDR = 0.013), A*30∶02-C*16∶01 (p = 0.015, LR = 5.97, FDR = 0.048), B*53∶01-C*04∶01 (p = 0.010, LR = 6.61, FDR = 0.08), B*15∶10-C*03∶04 (p = 0.031, LR = 4.65, FDR = 0.062), and B*58∶01-C*03∶02 (p = 0.037, LR = 4.35, FDR = 0.066) were associated with faster progression to AIDS. After FDR corrections, only the associations of A*30∶02-B*45∶01 and A*30∶02-C*16∶01 with faster disease progression remained significant. Cox regression and deconstructed Kaplan-Meier survival analysis showed that the associations of haplotypes of A*23∶01-C*02∶02, B*07∶02-C*07∶02, A*74∶01-B*15∶03, A*74∶01-B*15∶03-C*02∶02, B*14∶02-C*08∶02 and B*58∶01-C*03∶02 with differential seroconversion or disease progression are due to the dominant effect of a single allele within the haplotypes. The true haplotype effect was observed with A*30∶02-B*45∶01, A*30∶02-C*16∶02, B*53∶01-C*04∶01 B*15∶10-C*03∶04, and B*42∶01-C*17∶01. In these cases, the presence of both alleles accelerated the disease progression or seroconversion than any of the single allele within the haplotypes. Our study showed that the true effects of HLA class I haplotypes on HIV seroconversion and disease progression exist and the associations of HLA class I haplotype can also be due to the dominant effect of a single allele within the haplotype.

  • hla class i associations with rates of hiv 1 seroconversion and disease progression in the pumwani Sex Worker cohort
    Tissue Antigens, 2013
    Co-Authors: Trevor A Peterson, Charles Wachihi, Joshua Kimani, Thomas Bielawny, Lillian Mendoza, Subotheni Thavaneswaran, M J Narayansingh, T Kariri, Binhua Liangb Liang
    Abstract:

    Class I human leukocyte antigens (HLA) play an important role in the adaptive immune response by presenting antigens to CD8+ T cells. Studies have reported that several HLA class I alleles are associated with differential disease progression in human immunodeficiency virus (HIV)-infected individuals, however, few class I associations with resistance or susceptibility to HIV-1 infection have been reported. We typed HLA-A, -B and -C of >1000 women enrolled in the Pumwani Sex Worker Cohort using a sequence-based typing method. Kaplan-Meier analysis was used to identify alleles influencing seroconversion and disease progression to acquired immune deficiency syndrome (CD4 < 200/mm³). A*01 (P = 0.020), C*06:02 (P = 0.042) and C*07:01 (P = 0.050) are independently associated with protection from seroconversion. Women with any of these alleles are less likely to seroconvert [P = 0.00001, odds ratio (OR): 0.503, 95% confidence interval (CI): 0.320-0.790]. Conversely, A*23:01 (P = 0.004), B*07:02 (P = 0.003) and B*42:01 (P = 0.025) are independently associated with rapid seroconversion. Women with any of these alleles are twice as likely to seroconvert (P = 0.002, OR: 2.059, 95% CI: 1.290-3.285). The beneficial alleles confer threefold protection from seroconversion when compared with the susceptible alleles (P = 0.000001, OR: 0.268, 95% CI: 0.132-0.544). B*07:02 is the contributing allele, within the B7 supertype, to the rapid seroconversion. A*74:01 (P = 0.04/P = 0.006), B*14 (P = 0.003/P = 0.003) and B*57:03 (P = 0.012/P = 0.038) are independently associated with slower CD4+ decline and LTNP phenotype, while B*07:02 (P = 0.020), B*15:10 (P = 0.022) and B*53:01 (P = 0.007) are independently associated with rapid CD4+ T-cell decline. B7 supertype (P = 0.00006), B*35*-Py (P = 0.028) and B*35-Px (P = 0.001) were also significantly associated with rapid CD4+ T-cell decline. Understanding why these HLA class I alleles are associated with protection/susceptibility to HIV-1 acquisition and disease progression could contribute to the development of effective prophylactic and therapeutic vaccines for HIV-1.

  • a genetic polymorphism of frem1 is associated with resistance against hiv infection in the pumwani Sex Worker cohort
    Journal of Virology, 2012
    Co-Authors: Ma Luo, Philip Lacap, Jeff Tuff, Charles Wachihi, Joshua Kimani, J Sainsbury, Xin Y Yuan, Taha Hirbod, S Ramdahin
    Abstract:

    ABSTRACT A subgroup of women enrolled in the Pumwani Sex Worker cohort remain seronegative and PCR negative for human immunodeficiency virus type 1 despite repeated exposure through high-risk Sex work. Studies have shown that polymorphisms of genes involved in antigen presentation and viral restriction factors are associated with resistance to HIV infection. To discover other possible genetic factors underlying this HIV-resistant phenotype, we conducted an exploratory nonbiased, low-resolution, genome-wide single-nucleotide polymorphism (SNP) analysis comparing 60 HIV-resistant women to 48 HIV-infected controls. The SNP minor allele rs1552896, in an intron of FREM1 , was significantly associated with the resistant phenotype ( P = 1.68 × 10 −5 ; adjusted P = 2.37 × 10 −4 ; odds ratio [OR], 9.51; 95% confidence interval [CI], 2.82 to 32.05). We expanded the sample size by genotyping rs1552896 in the Pumwani cohort and comparing 114 HIV-resistant women to 609 HIV-infected controls and confirmed the association ( P = 1.7 × 10 −4 ; OR, 2.67; 95% CI, 1.47 to 4.84). To validate the association in a second cohort, we genotyped 783 women enrolled in a mother-child health study and observed the minor allele of rs1552896 enriched in HIV-uninfected women ( n = 488) compared to HIV-infected enrollees ( n = 295) ( P = 0.036; OR, 1.69; 95% CI, 0.98 to 2.93). Quantitative reverse transcription-PCR showed that FREM1 mRNA was highly expressed in tissues relevant for HIV-1 infection, and immunohistochemical analysis revealed that FREM1 protein is expressed in the ectocervical mucosa of HIV-resistant women. The significant association of rs1552896 with an HIV-resistant phenotype, together with the expression profile of FREM1 in tissues relevant to HIV infection, suggests that FREM1 is a potentially novel candidate gene for resistance to HIV infection.

Francis A Plummer - One of the best experts on this subject based on the ideXlab platform.

  • hiv 1 subtypes and 5 ltr leader sequence variants correlate with seroconversion status in pumwani Sex Worker cohort
    Viruses, 2017
    Co-Authors: Joshua Kimani, Francis A Plummer, Raghavan Sampathkumar, Joel Scottherridge, Binhua Liang, Ma Luo
    Abstract:

    Within the Pumwani Sex Worker cohort, a subgroup remains seronegative, despite frequent exposure to HIV-1; some of them seroconverted several years later. This study attempts to identify viral variations in 5’LTR-leader sequences (5’LTR-LS) that might contribute to the late seroconversion. The 5’LTR-LS contains sites essential for replication and genome packaging, viz, primer binding site (PBS), major splice donor (SD), and major packaging signal (PS). The 5’LTR-LS of 20 late seroconverters (LSC) and 122 early seroconverters (EC) were amplified, cloned, and sequenced. HelixTree 6.4.3 was employed to classify HIV subtypes and sequence variants based on seroconversion status. We find that HIV-1 subtypes A1.UG and D.UG were overrepresented in the viruses infecting the LSC (P < 0.0001). Specific variants of PBS (Pc < 0.0001), SD1 (Pc < 0.0001), and PS (Pc < 0.0001) were present only in the viral population from EC or LSC. Combinations of PBS [PBS-2 (Pc < 0.0001) and PBS-3 (Pc < 0.0001)] variants with specific SD sequences were only seen in LSC or EC. Combinations of A1.KE or D with specific PBS and SD variants were only present in LSC or EC (Pc < 0.0001). Furthermore, PBS variants only present in LSC co-clustered with PBS references utilizing tRNAArg; whereas, the PBS variants identified only in EC co-clustered with PBS references using tRNALys3 and its variants. This is the first report that specific PBS, SD1, and PS sequence variants within 5’LTR-LS are associated with HIV-1 seroconversion, and it could aid designing effective anti-HIV strategies.

  • kir3dl1 alleles and their epistatic interactions with human leukocyte antigen class i influence resistance and susceptibility to hiv 1 acquisition in the pumwani Sex Worker cohort
    AIDS, 2017
    Co-Authors: Ma Luo, Joshua Kimani, Chris Czarnecki, Michelle Nebroski, Nicole Bernard, Francis A Plummer
    Abstract:

    OBJECTIVE To determine the associations of KIR3DL1/S1(3DL1/S1) and its epistatic interactions with human leukocyte antigen class I (HLA-I) alleles with resistance and susceptibility to HIV-1. DESIGN Despite repeated exposure to HIV-1, a subset of women enrolled in the Pumwani Sex Worker cohort remain HIV uninfected. Previous studies have shown that specific HLA class I and II alleles were associated with this natural immunity. In this study, we investigated the association of 3DL1/S1 and its epistatic interactions with HLA-I, with resistance or susceptibility to HIV-1 acquisition. METHODS We used a sequence-based typing method to genotype 3DL1/S1 of 641 women in this cohort. The association of 3DL1/S1 and its epistatic interactions with HLA-I were analyzed using SPSS statistics software. RESULTS 3DL1041 is enriched in the HIV-1-resistant women [P = 0.009, Pc = 0.0468, odds ratio (OR): 3.359, 95% confidence interval (CI): 1.39-8.32], whereas, 3DL1020 was associated with susceptibility to HIV-1 infection before correction for multiple comparisons (P = 0.029, Pc = 0.0858, OR: 0.316, 95%CI: 0.10-1.04). Epistatic interactions between several 3DL1 alleles and specific HLA-I alleles were observed. Among them the cocarriage of 3DL1041 with Bw4 (P = 1E - 05, Pc = 0.0015, OR: 13.33, 95%CI: 3.43-51.9), or Bw6 (P = 0.008, Pc = 0.272, OR: 3.92, 95%CI: 1.51-10.17), increased the odds of remaining HIV-1 uninfected. Further, 3DL1041+/Bw4+ women who entered the cohort HIV negative remained uninfected (P = 0.032, Pc = 0.0858). Cocarriage of 3DL101501 with C02 : 10 (P = 2.73E - 07, Pc = 7.0954E - 06), B15 : 03 (P = 3.21E - 04, Pc = 0.0042), A24 supertype (P = 8.89E - 04, Pc = 0.0077), or A23 : 01 (P = 0.0036, Pc = 0.0236) was associated with increased susceptibility to seroconversion. CONCLUSION The effects of interactions between 3DL1 and HLA-I alleles on resistance/susceptibility to HIV-1 infection suggest that innate immunity plays an important role in HIV-1 acquisition and should be studied and explored for HIV prevention.

  • influence of hla class i haplotypes on hiv 1 seroconversion and disease progression in pumwani Sex Worker cohort
    PLOS ONE, 2014
    Co-Authors: Raghavan Sampathkumar, Charles Wachihi, Joshua Kimani, Francis A Plummer, Thomas Bielawny, Lillian Mendoza, Elizabeth N Ngugi, Harold Peters, Ma Luo
    Abstract:

    We examined the effect of HLA class I haplotypes on HIV-1 seroconversion and disease progression in the Pumwani Sex Worker cohort. This study included 595 HIV-1 positive patients and 176 HIV negative individuals. HLA-A, -B, and -C were typed to 4-digit resolution using sequence-based typing method. HLA class I haplotype frequencies were estimated using PyPop 32-0.6.0. The influence of haplotypes on time to seroconversion and CD4+ T cell decline to <200 cells/mm3 were analyzed by Kaplan-Meier analysis using SPSS 13.0. Before corrections for multiple comparisons, three 2-loci haplotypes were significantly associated with faster seroconversion, including A*23∶01-C*02∶02 (p = 0.014, log rank(LR) = 6.06, false-discovery rate (FDR) = 0.056), B*42∶01-C*17∶01 (p = 0.01, LR = 6.60, FDR = 0.08) and B*07∶02-C*07∶02 (p = 0.013, LR = 6.14, FDR = 0.069). Two A*74∶01 containing haplotypes, A*74∶01-B*15∶03 (p = 0.047, LR = 3.942, FDR = 0.068) and A*74∶01-B*15∶03-C*02∶02 (p = 0.045, LR = 4.01, FDR = 0.072) and B*14∶02-C*08∶02 (p = 0.021, LR = 5.36, FDR = 0.056) were associated with slower disease progression. Five haplotypes, including A*30∶02-B*45∶01 (p = 0.0008, LR = 11.183, FDR = 0.013), A*30∶02-C*16∶01 (p = 0.015, LR = 5.97, FDR = 0.048), B*53∶01-C*04∶01 (p = 0.010, LR = 6.61, FDR = 0.08), B*15∶10-C*03∶04 (p = 0.031, LR = 4.65, FDR = 0.062), and B*58∶01-C*03∶02 (p = 0.037, LR = 4.35, FDR = 0.066) were associated with faster progression to AIDS. After FDR corrections, only the associations of A*30∶02-B*45∶01 and A*30∶02-C*16∶01 with faster disease progression remained significant. Cox regression and deconstructed Kaplan-Meier survival analysis showed that the associations of haplotypes of A*23∶01-C*02∶02, B*07∶02-C*07∶02, A*74∶01-B*15∶03, A*74∶01-B*15∶03-C*02∶02, B*14∶02-C*08∶02 and B*58∶01-C*03∶02 with differential seroconversion or disease progression are due to the dominant effect of a single allele within the haplotypes. The true haplotype effect was observed with A*30∶02-B*45∶01, A*30∶02-C*16∶02, B*53∶01-C*04∶01 B*15∶10-C*03∶04, and B*42∶01-C*17∶01. In these cases, the presence of both alleles accelerated the disease progression or seroconversion than any of the single allele within the haplotypes. Our study showed that the true effects of HLA class I haplotypes on HIV seroconversion and disease progression exist and the associations of HLA class I haplotype can also be due to the dominant effect of a single allele within the haplotype.

  • a trim5α exon 2 polymorphism is associated with protection from hiv 1 infection in the pumwani Sex Worker cohort
    AIDS, 2010
    Co-Authors: Heather Price, Philip Lacap, Jeff Tuff, Charles Wachihi, Joshua Kimani, T B Ball, Ma Luo, Francis A Plummer
    Abstract:

    OBJECTIVE The innate immune component TRIM5alpha has the ability to restrict retrovirus infection in a species-specific manner. TRIM5alpha of some primate species restricts infection by HIV-1, whereas human TRIM5alpha lacks this specificity. Previous studies have suggested that certain polymorphisms in human TRIM5alpha may enhance or impair the proteins affinity for HIV-1. This study investigates the role of TRIM5alpha polymorphisms in resistance/susceptibility to HIV-1 within the Pumwani Sex Worker cohort in Nairobi, Kenya. A group of women within this cohort remain HIV-1-seronegative and PCR-negative despite repeated exposure to HIV-1 through active Sex work. DESIGN A 1 kb fragment of the TRIM5alpha gene, including exon 2, from 1032 women enrolled in the Pumwani Sex Worker cohort was amplified and sequenced. Single-nucleotide polymorphisms (SNPs) and haplotypes were compared between HIV-1-positive and resistant women. METHODS The TRIM5alpha exon 2 genomic fragment was amplified, sequenced and genotyped. Pypop32-0.6.0 was used to determine SNP and haplotype frequencies and statistical analysis was carried out using SPSS-13.0 for Windows. RESULTS A TRIM5alpha SNP (rs10838525) resulting in the amino acid change from arginine to glutamine at codon 136, was enriched in HIV-1-resistant individuals [P = 1.104E-05; odds ratio (OR) 2.991; 95% confidence interval (CI) 1.806-4.953] and women with 136Q were less likely to seroconvert (P = 0.002; log-rank 12.799). Wild-type TRIM5alpha exon 2 was associated with susceptibility to HIV-1 (P = 0.006; OR 0.279; 95% CI 0.105-0.740) and rapid seroconversion (P = 0.001; log-rank 14.475). CONCLUSIONS Our findings suggest that a shift from arginine to glutamine at codon 136 in the coiled-coil region of TRIM5alpha confers protection against HIV-1 in the Pumwani Sex Worker cohort.

  • associations of human leukocyte antigen drb with resistance or susceptibility to hiv 1 infection in the pumwani Sex Worker cohort
    AIDS, 2008
    Co-Authors: Philip Lacap, Charles Wachihi, Joshua Kimani, Ma Luo, Thomas Bielawny, Janis Huntington, Nico J D Nagelkerke, Elizabeth N Ngugi, Francis A Plummer
    Abstract:

    A group of commercial Sex Workers in the Pumwani Sex Worker Cohort established in 1985 in Nairobi Kenya remain HIV-1 uninfected despite heavy exposure to HIV-1 through active Sex work. Previous studies showed that this resistance is associated with a strong CD4+ T-cell response which suggested that human leukocyte antigen class II antigens are important in resistance/susceptibility to HIV-1 infection. DRB1 is the most polymorphic locus among class II genes and forms haplotypes with DRB3 DRB4 and DRB5. The aim of this study is to investigate the role of DRB alleles/haplotypes on resistance/susceptibility to HIV-1 infection. In total 1090 women enrolled in the Pumwani cohort were genotyped for DRB1 DRB3 DRB4 and DRB5 using a high-resolution sequence-based method. Allele/ haplotype frequencies were compared between HIV-positive women and women who have remained HIV negative for more than 3 years despite frequent exposure. Human leukocyte antigen DRB genes were amplified sequenced and genotyped using a two-step sequence-based method. Allele/haplotype frequencies were determined using PyPop32-0.6.0. Statistical analysis was conducted using SPSS 11.0 for Windows. Three DRB1 alleles were associated with resistance: DRB1 010101 (P = 0.016; odd ratio (OR): 2.55; 95% confidence interval (CI): 1.16-5.61) DRB1 010201 (P = 0.019; OR: 1.86; 95% CI: 1.10-3.15) and DRB1 1102 (P = 0.025; OR: 1.72; 95% CI: 1.07-2.78). DRB1 030201 (P = 0.038; OR: 0.48; 95% CI: 0.23-0.98) DRB1 070101 (P = 0.035; OR: 0.54; 95% CI: 0.30-0.97) DRB1 1503 (P = 0.0004; OR: 0.34; 95% CI: 0.19-0.64) and DRB5 010101 (P = 0.001; OR: 0.37; 95% CI: 0.20-0.67) were associated with susceptibility. The haplotype DRB1 1102-DRB3 020201 was associated with HIV-1 resistance (P = 0.041; OR: 1.68; 95% CI: 1.02-2.78) whereas the haplotypes DRB1 070101-DRB4 01010101 (P = 0.041; OR: 0.52; 95% CI: 0.28-0.98) and DRB1 1503-DRB5 01010101 (P = 0.0002; OR: 0.30; 95% CI: 0.15-0.58) were associated with susceptibility. These associations with resistance/susceptibility to HIV-1 were independent of previously reported alleles HLA-DRB1 01 and HLA-A 2301. Our findings indicate that human leukocyte antigen DRB-specific CD4+ T-cell responses are an important factor in resistance/susceptibility to HIV-1 infection. (authors)