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Founder virus envelope glycoproteins as novel oligomeric HIV-1 vaccine immunogensKillick, Mark Andrew 21 April 2015 (has links)
A thesis submitted to Faculty of Health Sciences,
University of the Witwatersrand,
in fulfillment of the requirements for the degree of
Doctor of Philosophy
Johannesburg, March 2014 / The ability to induce a broadly neutralizing antibody (bNAb) response following vaccination is regarded as a crucial aspect in developing an effective vaccine targeting the human immunodeficiency virus type 1 (HIV-1). The bNAbs target the HIV-1 envelope glycoprotein (Env) which is exposed on the surface of the virion, thereby preventing cell entry. Previous work in our laboratory focused on the generation of a 2dCD4S60C molecule (a variant of the CD4 primary Env receptor) with higher affinity for HIV-1 Env through targeted disulphide exchange. This study reports on the design and construction of an HIV-1 subtype C founder virus consensus Env immunogen derived from newly transmitted/founder virus sequences, and the ability of the purified recombinant Env proteins (2dCD4S60C-liganded and unliganded) to induce a broadly neutralizing antibody response in small animals. A total of 1894 founder sequences from 80 HIV-1 subtype C infected patients were available and downloaded from the databases. A consensus sequence was generated for each of the patients, and this alignment was subsequently used to generate a founder virus consensus env sequence. The env sequence was used to create codon-optimized constructs encoding monomeric (gp120FVCm), dimeric (gp120FVCGCN4d) and trimeric (gp140FVCGCN4t(+) and gp140FVCGCN4t(-) founder virus conformations cloned into the pcDNA3.1(-) mammalian expression vector. All four Env constructs were successfully expressed in HEK293T mammalian cell culture. The 2dCD4S60C was expressed in E. coli BL21 (DE3) and purified by nickel affinity chromatography. Large scale expression and purification of the gp120, gp120GCN4 and gp140GCN4 +/- in the unliganded or 2dCD4S60C liganded state were purified by lectin affinity chromatography, followed by conformation and complex purification using size exclusion chromatography. Immunogens/immune complexes were evaluated by ELISA, SDS-PAGE, native PAGE and surface plasmon resonance, and confirmed they were functional and conformationally intact. Immunogenicity of each conformation alone or complexed to 2dCD4S60C was evaluated in rabbits. Breadth and potency of the rabbit sera was tested against 12 pseudoviruses (Tiers 1-3), derived from HIV-1 subtype B and C Env, using the PhenoSense Neutralizing antibody assay (Monogram Bioscience, Inc.). Minimal neutralizing breadth was obtained from animals immunized exclusively with Env conformations. However, animals that received the Env/2dCD4S60C complex showed extensive neutralizing capacity against all 12 viruses tested, including the tier 2 and 3 virus strains. End-point ELISA titer results revealed that the rabbits that were immunized with Env/2dCD4S60C produced both Env and 2dCD4S60C specific titers, but those directed towards 2dCD4 were on average 10x lower than the 2dCD4S60C control group. This implies a proportion of the NAb activity is directed towards conserved epitopes exposed on
the Env/2dCD4S60C immunogens. Overall, these results show that the use of founder Env/2dCD4S60C complexes as vaccine immunogens dramatically improves the antibody neutralization breadth and magnitude as compared to founder Env or 2dCD4S60C alone. This level of broad neutralization has not been previously reported in the literature, and these results provide encouraging data to inform us of the best envelope vaccine immunogen to include in a preventative vaccine.
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Sensitivity of HIV-1 subtype C viruses to Griffithsin, cyanovirin-N and scytovirin: potential HIV-1 microbicidesAlexandre, Kabamba Bankoledi 07 May 2013 (has links)
Thesis (Ph.D. (Virology))--University of the Witwatersrand, Faculty of Health Sciences, 2012 / The majority of HIV-1 infections around the world occur via sexual intercourse and
women, especially in developing countries, are disproportionately affected. Recently a
number of strategies have been proposed to control the spread of HIV, among these the
use of microbicides to prevent the sexual transmission of the virus. A clinical trial of 1%
tenofovir gel that conferred up to 39% protection provided a proof-of-concept that an
anti-HIV microbicide is feasible. Various other compounds, acting at different stages of
HIV-1 life cycle, are also being investigated as potential microbicides. These include the
lectins Griffithsin (GRFT), cyanovirin-N (CV-N) and scytovirin (SVN). GRFT was
isolated from the red algae griffithsia sp. while CV-N and SVN were isolated from the
blue green alga Nostoc ellipsosporum and the cyanobacterium Scytonema varium,
respectively. These lectins bind mannose-rich glycans found on the surface of HIV-1
envelope and act as entry inhibitors. Although HIV-1 subtype C is the main cause of
infections around the world, almost all studies conducted with GRFT, CV-N and SVN
are based on subtype B viruses. The Chapter Two sought to establish the neutralization
sensitivity of HIV-1 subtype C viruses to the three lectins, using both a cell line and
primary cells, and compared this sensitivity to subtype B. This Chapter also examined
mannose-rich glycans on HIV-1 that are involved in GRFT, CV-N and SVN binding. The
conclusion from this study was that the neutralization of subtype C viruses by these
lectins is similar to subtype B and that the 234 and 295 mannose-rich glycans were
involved in their interaction with the virus. In general these data supported further studies
on the use of GRFT, CV-N and SVN for prevention of HIV-1 subtype C sexual
transmission. In Chapter Three, the ability of GRFT to expose the CD4 binding site
(CD4bs) on HIV-1 gp120 is explored. I found that this exposure resulted in the
enhancement of HIV-1 binding to plates coated with anti-CD4bs antibodies b12 and b6
or the CD4 receptor mimetic CD4-IgG2. This lectin also synergized with b12 and HIVpositive
plasma containing antibodies to the CD4bs to neutralize the virus. Furthermore,
the glycan at position 386, which shields the CD4bs, was shown to be involved in both
GRFT enhancement of HIV-1 binding to b12 and b6 and in the synergistic interaction
between the lectin and these antibodies. The importance of this study is that it
investigated in details the effect of GRFT binding on HIV-1 envelope and also suggests
this lectin can be used in combination with anti-HIV-1 antibodies to synergistically
enhance the anti-viral activity. In Chapter Four I investigated GRFT, CV-N and SVN
inhibition of the virus binding to the DC-SIGN receptor and their inhibition of the DCSIGN
transfer of HIV-1 to target cells. These lectins only moderately inhibited the virus
binding to the receptor while they potently inhibited its transfer to target cells. However,
the inhibition of transfer was stronger when the virus bound the lectins after binding the
DC-SIGN receptor compared to when it bound the lectins prior to binding the receptor.
These three lectins can, therefore, inhibit the sexual transmission of HIV-1 since the DCSIGN-
mediated transfer of the virus to susceptible cells is pivotal to this mode of
transmission. Chapter Five is an investigation of the ability of HIV-1 subtype C to escape
GRFT, CV-N and SVN, which involved growing the virus under escalating
concentrations of these compounds. This was to know how this virus behaves under
conditions of continuous exposure to the lectins. I found that HIV-1 subtype C became
increasingly resistant to the lectins and viral envelope sequence analysis showed that this
was associated with the deletion of mannose-rich glycans on gp120. Furthermore, of the
11 potential mannose-rich glycosylation sites on gp120 seven (230, 234, 241, 289, 339,
392 and 448) were involved in GRFT, CV-N and SVN resistance. Thus, the conclusion
was that although these three lectins are potent inhibitors of HIV-1 infection, the virus is
also able to escape their neutralization by deleting mannose-rich glycans on its envelope.
However, the fact that escape to these lectins involved multiple deglycosylation and was
only partial suggests that HIV-1 subtype C escape from GRFT, CV-N and SVN in a
microbicide formulation may not be an easy process. We discuss the implications of these
findings in Chapter Six and suggest future studies that could complement data presented
in this thesis. Overall our data show that GRFT, CV-N and SVN can prevent the sexual
transmission of both free and DC-SIGN associated HIV-1 particles and supports further
development of these lectins as microbicides against HIV-1.
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Nurses’ counseling to mothers to prevent mother to child transmission of HIV through breastfeeding : A qualitative studyStaflin, Emma, Lundkvist, Jennie January 2011 (has links)
Introduction: HIV is a serious problem in Namibia, 13.1% of the adult population is HIV-positive or is a carrier of AIDS. This is one of the highest numbers in the world. HIV is passed from mother to child during pregnancy, during labour or through breast milk. 18.8 % of the pregnant mothers in Namibia who is in contact with the maternity welfare have HIV. Aim: The aim of the study was to describe nurses’ counseling to mothers to prevent mother to child transmission of HIV through breastfeeding. Method: Eight nurses working with PMTCT of HIV were interviewed in Namibia. The interviews were transcribed and a content analysis was made. 18 sub-categories and seven categories were found. Findings: It is important that nurses provide individual counseling, are supportive and motivate the mothers. Poverty is an obstacle for the mothers, stigmatization occurs and cultural differences can have influence on the mothers. It is also important that nurses are updated in counseling and PMTCT. Conclusion: Nurses should provide mothers with the correct information in a pedagogical way. Nurses need to be aware of obstacles for the mothers and their families to be able to meet their different demands. Men are not involved in PMTCT-counseling and nurses think that partner involvement would benefit PMTCT of HIV.
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Narratives around sexual behaviour and decisions regarding treatment-seeking of adolescent females who contracted a sexually transmitted infection: Birth to Twenty cohortQuan, Vanessa Cecilia January 2012 (has links)
Degree of Masters in Public Health by coursework and research report
Maternal and Child
Johannesburg, March 2012 / Adolescent sexual behaviour related to low condom-use and early sexual debut has
been a concern in the transmission of sexually transmitted infections (STIs) and HIV.
Treatment-seeking behaviour is a problem in adolescents due to embarrassment and
unfriendly health care services. The Birth to Twenty study group (Bt20) is a cohort of
singletons born in 1990 with approximately 10% having tested positive for STIs at an
early age. Their sexually activity and unprotected sex practices have increased their risk
for HIV infection. The objectives of this study were to explore the perceptions, sexual
behaviour and treatment-seeking behaviour of a sample of girls who had a previous STI,
through their narratives.
One-on-one narrative interviews were done on 19 girls with the aid of an interview
schedule. A life history of their sexual encounters was documented. The interviews were
taped and transcribed. Thematic analysis was performed.
The majority of the girls had no knowledge of STIs before they were counselled by the
Bt20 nurses yet 50% of the girls used condoms in their first sexual experiences. Once
counselled, almost all the girls went on to seek treatment for their STI. A third of the girls
reported poor service at the clinic and would prefer to be treated either privately or at
Bt20 if possible. Information regarding the role of STIs in the transmission of HIV seems
to be unclear. Improving the life orientation programme at schools with a focus on STIs
and pregnancy would positively impact on HIV transmission. One-on-one counselling is
effective but may not be feasible in under-resourced communities and the continued
education of nurses in clinics, whilst increasing the number of adolescent friendly clinics,
must be prioritised.
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Male circumcision as a bio-medical HIV intervention targeting male heterosexual sexually transmitted disease (STD) patients in China: an acceptability study and a single-arm test-of-concept trial. / 應用包皮環切手術作為預防中國男性性病患者HIV感染的生物醫學干預手段: 一項可接受性研究及一項測試概念的臨床實驗 / CUHK electronic theses & dissertations collection / Ying yong bao pi huan qie shou shu zuo wei yu fang Zhongguo nan xing xing bing huan zhe HIV gan ran de sheng wu yi xue gan yu shou duan: yi xiang ke jie shou xing yan jiu ji yi xiang ce shi gai nian de lin chuang shi yanJanuary 2013 (has links)
Wang, Zixin. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2013. / Includes bibliographical references (leaves 215-223). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract and appendixes also in Chinese.
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Developing country health systems and the governance of international HIV/AIDS fundingPoku, Nana K., Whitman, Jim R. January 2012 (has links)
Donor country initiatives for the prevention and mitigation of HIV/AIDS are not a matter of simple burden sharing. Instead, they have brought in their wake many of the complexities and unforeseen effects that have long been associated with more general overseas development assistance. In the case of funding directed toward HIV/AIDS, these effects are by no means either secondary or easily calculable. It is widely acknowledged that there is no consensus framework on how these impacts may be defined, no framework/toolkit for the evaluation of impacts and no longitudinally significant data that could provide the substance for those evaluations. The subject of this study focuses not on the health outcomes of funding but on how donor-recipient relations could be better deliberated, negotiated and coordinated. We argue that effective leadership and governance of developing country health systems for HIV/AIDS work requires a reconfiguration of how donor-recipient relations are conceived and contracted, and for this purpose, we propose an adaptation of the Organisation for Economic Co-operation and Development Paris Declaration principles of aid effectiveness.
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Risk perceptions, cognitive behavioral models and HIV-related risk behaviors among non-institutionalized male injecting drug users in China. / 中國社區男性靜脈注射吸毒者之風險認知、行為認知理論模型及愛滋病相關高危行為研究 / CUHK electronic theses & dissertations collection / Zhongguo she qu nan xing jing mai zhu she xi du zhe zhi feng xian ren zhi, xing wei ren zhi li lun mo xing ji ai zi bing xiang guan gao wei xing wei yan jiuJanuary 2010 (has links)
Conclusion. The significance of risk perception in predicting behavioral intention, hence actual future behaviors, is therefore evident. Conditional measures need to be used. HIV prevention can employ conditional risk perception approaches. Health behavioral theories can be strengthened by using such conditional measures on risk perceptions. The results add to this new and growing area of risk behavior research. / Introduction. Risk perception, a core element of key health behavioral theories and health interventions, is assumed to motivate people to avoid risk behaviors. Mixed findings however prevail in the literature due to methodological issues. Many of such studies are cross-sectional, using global risk perception measures that do not condition on type of risk behavior or partnership which may affect the level of risk. / Male injecting drug users (IDU) are driving the HIV epidemic in China and bridge HIV transmission to non-IDU female populations; they may be at risk of both unprotected sex and syringe sharing. HIV prevention targeting male IDU is greatly warranted and would benefit from understanding of the relationships between risk perceptions and behaviors, in the context of health behavioral theories such as the Health Action Process Approach (HAPA) model, which had not been applied to studies targeting IDU. / Objectives. This study refined the concepts and measures of HIV-related risk perception, conditioning on different types of behaviors and partners, and extended it to include others-directed risk perceptions. The relationship between such conditional risk perception measures and both prior risk behaviors and behavioral intention to avoid sex-related and drug-related risk behaviors in the future were investigated and were compared to those involving global unconditional risk perception measures. The nature of the aforementioned relationships, being motivational or reflective was investigated. A longitudinal component validated the predictive power of behavioral intention over actual future behaviors. / Results. Almost 90% of the respondents had had unprotected sex though <20% shared syringes with others in the last 6 months. Prior syringe sharing but not unprotected sex in the last 6 months was significantly associated with global unconditional risk perception measures. The picture is totally different when risk perception measures conditioned on type of sex partner and unprotected sex or syringe sharing were used instead of the global measures---higher levels of the conditional risk perception measures were significantly associated with higher levels of behavioral intention for consistent condom use and avoidance of syringe sharing, thus supporting the motivational hypothesis. Conditional others-directed risk perceptions (perceived risk of transmitting HIV to others via unprotected sex and syringe sharing) were also associated with the aforementioned behavioral intentions to avoid risk behaviors. A pilot longitudinal study showed that behavioral intentions strongly predict actual future behaviors. Other HAPA-based variables such as self-efficacy and outcome expectancies had predictive effects on behavioral intentions, independent from those of risk perceptions. / Subjects and methods. A total of 456 sexually active male IDU were recruited from Dazhou, Sichuan and Hengyang, Hunan, via snowball sampling. With informed consent, anonymous face-to-face interviews were conducted by trained and experienced staff of the local CDC in privacy settings. / Tsui, Hi Yi. / Adviser: Joseph Lau. / Source: Dissertation Abstracts International, Volume: 72-04, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves 118-130). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. Ann Arbor, MI : ProQuest Information and Learning Company, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese; appendix in Chinese.
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A cross-sectional survey and a randomized controlled trial to evaluate the efficacy of an enhanced HIV voluntary counseling and testing in reducing HIV-related behaviors targeting regular male sex partners among men who have sex with men in China: 中國有固定性伴的男男性接觸者高危性行為的橫斷面調查及隨機對照試驗研究 / 中國有固定性伴的男男性接觸者高危性行為的橫斷面調查及隨機對照試驗研究 / CUHK electronic theses & dissertations collection / cross-sectional survey and a randomized controlled trial to evaluate the efficacy of an enhanced HIV voluntary counseling and testing in reducing HIV-related behaviors targeting regular male sex partners among men who have sex with men in China: Zhongguo you gu ding xing ban de nan nan xing jie chu zhe gao wei xing xing wei de heng duan mian diao cha ji sui ji dui zhao shi yan yan jiu / Zhongguo you gu ding xing ban de nan nan xing jie chu zhe gao wei xing xing wei de heng duan mian diao cha ji sui ji dui zhao shi yan yan jiuJanuary 2015 (has links)
Introduction. The HIV prevalence among men who have sex with men (MSM) in China keeps increasing sharply. A high proportion of the MSM in China have male regular sex partner (RP) and prevalence of unprotected anal intercourse (UAI) involving such RP is higher than when non-RP is involved. Trust, intimacy and cognitive factors are the factors associated with UAI with RP. Several cross-sectional studies have been demonstrated the important factors associated with UAI with RP among MSM in China. However, no study about intervention for MSM-RP is found to be conducted. To reduce UAI with RP, an intervention tailored to RP is urgently developed and identified its efficacy. / Objectives. The study aimed to describe the prevalence of UAI, as well as of which associated factors among MSM-RP in Beijing and Chengdu, China, and to evaluate the efficacy of an enhanced HIV voluntary counseling and testing (VCT) in increasing condom use with RP among MSMRP in China by a randomized controlled trial (RCT). / Subjects and Methods. A cross-sectional survey and a randomized controlled trial have been conducted. For the cross-sectional survey, total 307 HIV negative MSM who have RP have been recruited by three ways. Face to face interview has been conducted to participants. Based on the associated factors found in the cross-sectional survey, interventions including video, education leaflets and enhanced counseling contents have been tailored to RP among MSMRP. For the randomized controlled trial, total 336 MSMRP have been recruited and randomly assigned 169 subjects to the Intervention Group in which participants have been given enhanced VCT plus an audio-visual and four leaflets components and 167 subjects to the Control Group in which participants have been given only standard-of-care VCT at the baseline. Evaluation was conducted at Month 3 and 6. Statistical methods such as descriptive analyses, Chi-square test and logistic regression were used in this study. / Results. The results have been found were the prevalence of UAI with RP among MSMRP was 52.4%, and the Theory of Planned Behavior (TPB) related cognitions, trust, intimacy, depression and anxiety were associated with UAI with RP among MSMRP. In the RCT study, participants in the Intervention Group had less UAI (36.1% vs. 49.1%) than those of the Control Group at Month 3. / Conclusions. This study showed a high prevalence of UAI among MSMRP, whilst trust, intimacy and cognitive factors were associated with UAI with RP. The efficacy of Enhanced VCT tailored to RP has been identified. The acceptability and feasibility of the tailored intervention were demonstrated. In the future HIV prevention programs, the effective intervention should be considered to be incorporated into standard-of-care VCT procedures and be implemented in the specific population. / 介紹:中國男男性接觸者中的愛滋病發病率一直保持著上升的狀態。而在中國男男性接觸者中有很大比例存在著固定性伴侶。男男性接觸者同固定性伴發生無保護肛交行為的比例大於其同非固定性伴。信任,親密以及認知因素已經被證實是影響男男性接觸者同其固定性伴發生無保護肛交行為的因素。但是在中國還沒有發現專門針對有固定性伴的男男性接觸者的干預研究。為了降低男男性接觸者同其固定性伴的無保護肛交的發生率,針對有固定性伴的男男性接觸者的干預方法應該被發展同時證實其有效性。 / 目的:本研究目的在於調查北京及成都男男性接觸者的固定性伴的比例,及其影響因素,包括健康行為理論的影響因素以及人際關係因素。同時,本研究也驗證了以隨機對照實驗來評估針對有固定性伴男男性接觸者的提高型愛滋病自願檢測諮詢對減少其高危性行為的效果。 / 對象與方法:本研究由橫斷面研究以及隨機對照試驗組成。在橫斷面調查中,307名愛滋病陰性的有固定性伴的男男性接觸者被招募。基於在橫斷面調查中發現的對男男性接觸者與固定性伴間發生無保護性行為的影響因素,一項專門針對有固定性伴的男男性接觸者的提高型愛滋病自願檢測諮詢干預方法被發展應用了隨機對照試驗中已驗證其有效性。在隨機對照試驗中,169名和167名研究對象被招募並分別被隨機分配到干預組(接受提高型愛滋病自願檢測諮詢)和對照組(接受標準型愛滋病自願檢測諮詢)中。分別於干預後的3個月和6個月回訪進行干預結果的評估。在本次研究中,運用了卡方检验和logistic回歸等統計學方法。 / 結果:在橫斷面調查中發現,男男性接觸者同固定性伴的無保護肛交發生率為52.4%。影響與固定性伴無保護肛交的因素包括:健康行為理論(TPB)相關的認知,信任,親密以及抑鬱和焦慮。在隨機對照試驗中發現,在3個月隨訪中干預組的男男性接觸者與固定性伴發生無保護肛交的比例較對照組明顯降低(36.1% vs. 49.1%)。 / 結論:本研究結果顯示中國男男性接觸者的固定性伴的比例很高,同時幾乎一半的有固定性伴的的男男性接觸者同時有多個性伴,這就有增加感染愛滋病及其他性病的風險。一項針對有固定性伴的男男性接觸者設計的提高型愛滋病自願檢測諮詢方法在降低其危險性行為上的可接受性和有效性已經被證實。提示在今後的愛滋病干預項目中可以進一步的推廣應用。 / Li, Chunrong. / Thesis Ph.D. Chinese University of Hong Kong 2015. / Includes bibliographical references (leaves 149-178). / Abstracts and appendixes also in Chinese. / Title from PDF title page (viewed on 05, October, 2016). / Li, Chunrong. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only.
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Imunogenicidade da vacina meningocócica conjugada do grupo C em adolescentes e adultos jovens com aids / Immunogenicity of a meningococcal serogroup C conjugate vaccine in AIDS adolescents and young adultsBertolini, Daniela Vinhas 27 March 2014 (has links)
Pacientes infectados pelo HIV apresentam resposta de imunogenicidade menor àquela obtida pela população geral com a imunização de rotina. A vacina meningocócica C conjugada é indicada para essa população, não existindo pesquisas prévias que avaliassem a imunogenicidade desta, para esse grupo específico. O estudo realizou essa avaliação comparando a resposta vacinal entre os pacientes infectados e não infectados pelo HIV, as relações dessa resposta com parâmetros clínicos e laboratoriais da infecção pelo vírus e os eventos adversos à vacinação. Utilizou-se as técnicas ensaios de anticorpos bactericidas séricos ou ação bactericida no soro (SBA) e o enzyme-linked immunosorbent assay (ELISA). Tratou-se de um ensaio clínico, envolvendo 92 pacientes, com idades entre 10-20 anos, sendo 43 infectados e 49 não infectados pelo HIV. Após a vacinação, 72,1% do grupo HIV+ e 100% do grupo HIV- foram considerados protegidos. Os pacientes do grupo HIV+ não respondedores à vacinação foram revacinados, tendo sido respondedores a essa nova dose 40% destes. Portanto, 81,4% dos pacientes infectados pelo HIV adquiriram proteção com a vacina (após uma ou duas doses). Foi encontrada correlação da resposta vacinal com o número de esquemas antirretrovirais previamente utilizados e carga viral pré-vacinação, não havendo outras associações com os demais parâmetros clínicos e laboratoriais da infecção pelo HIV. Pacientes com adequada resposta vacinal tenderam a ser os de menor idade. Efeitos colaterais ocorreram em 16,3% no grupo HIV+ e em 44% no HIV-. Conclui-se que a vacina meningocócica C conjugada é segura e efetiva para uso em adolescentes e adultos jovens com aids, embora a resposta de anticorpos seja menor do que a observada em indivíduos saudáveis. Isso indica a necessidade de discussão de novos esquemas de imunização em infectados pelo HIV, objetivando uma proteção mais efetiva contra doença meningocócica / Children and adolescents infected with HIV typically have a weaker response to immunization in comparison with the healthy population. The meningococcal C conjugate vaccine is routinely recommended for those individuals. No studies, however, have evaluated the antibody response to this vaccine in HIV-infected patients yet. In this study, we compared the antibody response to the meningococcal C conjugate vaccine between HIV-infected and HIV-uninfected patients using the serum bactericidal antibody assay (SBA) and the enzyme-linked immunoabsorbent assay (ELISA). Additional objectives were to determine whether the acquired immunity correlated with clinical and laboratory features of HIV infection, and to evaluate the vaccine side effects in this population. This clinical trial included 92 patients aged 10 to 20 years old: 43 HIV-infected and 49 HIV-uninfected patients. After one single dose of the vaccine, 72.1% of the HIV-infected and 100% of the HIV-uninfected patients were considered protected. Of the HIV-infected patients (non-responders in first dose) who received a second dose of the vaccine, only 40% reached protective antibody levels. Overall, 81.4% of the HIV-infected patients reached protective antibody titres (after one or two doses of the vaccine). The antibody response in HIV-infected patients correlated with the number of prior antiretroviral therapy schedules and with the pre-vaccination viral load, but with no other clinical features or laboratory tests. Patients with adequate vaccinal response tended to be younger. Side effects occurred in 16.3% and 44% of the HIV-infected and HIV-uninfected groups, respectively. In conclusion, the meningococcal serogroup C conjugate vaccine proved to be safe and effective in HIV-infected adolescents and young adults, although their antibody response was weaker than that of HIV-uninfected patients. These results suggest that the immunization schedule for HIV-infected patients should be re-evaluated, in order to assure more effective protection against the meningococcal disease in this population
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Imunogenicidade da vacina meningocócica conjugada do grupo C em adolescentes e adultos jovens com aids / Immunogenicity of a meningococcal serogroup C conjugate vaccine in AIDS adolescents and young adultsDaniela Vinhas Bertolini 27 March 2014 (has links)
Pacientes infectados pelo HIV apresentam resposta de imunogenicidade menor àquela obtida pela população geral com a imunização de rotina. A vacina meningocócica C conjugada é indicada para essa população, não existindo pesquisas prévias que avaliassem a imunogenicidade desta, para esse grupo específico. O estudo realizou essa avaliação comparando a resposta vacinal entre os pacientes infectados e não infectados pelo HIV, as relações dessa resposta com parâmetros clínicos e laboratoriais da infecção pelo vírus e os eventos adversos à vacinação. Utilizou-se as técnicas ensaios de anticorpos bactericidas séricos ou ação bactericida no soro (SBA) e o enzyme-linked immunosorbent assay (ELISA). Tratou-se de um ensaio clínico, envolvendo 92 pacientes, com idades entre 10-20 anos, sendo 43 infectados e 49 não infectados pelo HIV. Após a vacinação, 72,1% do grupo HIV+ e 100% do grupo HIV- foram considerados protegidos. Os pacientes do grupo HIV+ não respondedores à vacinação foram revacinados, tendo sido respondedores a essa nova dose 40% destes. Portanto, 81,4% dos pacientes infectados pelo HIV adquiriram proteção com a vacina (após uma ou duas doses). Foi encontrada correlação da resposta vacinal com o número de esquemas antirretrovirais previamente utilizados e carga viral pré-vacinação, não havendo outras associações com os demais parâmetros clínicos e laboratoriais da infecção pelo HIV. Pacientes com adequada resposta vacinal tenderam a ser os de menor idade. Efeitos colaterais ocorreram em 16,3% no grupo HIV+ e em 44% no HIV-. Conclui-se que a vacina meningocócica C conjugada é segura e efetiva para uso em adolescentes e adultos jovens com aids, embora a resposta de anticorpos seja menor do que a observada em indivíduos saudáveis. Isso indica a necessidade de discussão de novos esquemas de imunização em infectados pelo HIV, objetivando uma proteção mais efetiva contra doença meningocócica / Children and adolescents infected with HIV typically have a weaker response to immunization in comparison with the healthy population. The meningococcal C conjugate vaccine is routinely recommended for those individuals. No studies, however, have evaluated the antibody response to this vaccine in HIV-infected patients yet. In this study, we compared the antibody response to the meningococcal C conjugate vaccine between HIV-infected and HIV-uninfected patients using the serum bactericidal antibody assay (SBA) and the enzyme-linked immunoabsorbent assay (ELISA). Additional objectives were to determine whether the acquired immunity correlated with clinical and laboratory features of HIV infection, and to evaluate the vaccine side effects in this population. This clinical trial included 92 patients aged 10 to 20 years old: 43 HIV-infected and 49 HIV-uninfected patients. After one single dose of the vaccine, 72.1% of the HIV-infected and 100% of the HIV-uninfected patients were considered protected. Of the HIV-infected patients (non-responders in first dose) who received a second dose of the vaccine, only 40% reached protective antibody levels. Overall, 81.4% of the HIV-infected patients reached protective antibody titres (after one or two doses of the vaccine). The antibody response in HIV-infected patients correlated with the number of prior antiretroviral therapy schedules and with the pre-vaccination viral load, but with no other clinical features or laboratory tests. Patients with adequate vaccinal response tended to be younger. Side effects occurred in 16.3% and 44% of the HIV-infected and HIV-uninfected groups, respectively. In conclusion, the meningococcal serogroup C conjugate vaccine proved to be safe and effective in HIV-infected adolescents and young adults, although their antibody response was weaker than that of HIV-uninfected patients. These results suggest that the immunization schedule for HIV-infected patients should be re-evaluated, in order to assure more effective protection against the meningococcal disease in this population
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