Monocyte-derived macrophages (MDMs) from HIV-infected patients and MDMs infected in vitro with HIV manifest inhibition of various cytokines including IL 12. Recently, IL-27 was shown to inhibit HIV replication in macrophages. Whether HIV infection or HIV regulatory proteins such as tat, impact IL-23 or IL-27 production in macrophages remains unknown. I have demonstrated that intracellular HIV-tat expression as well as HIV-tat basic domain peptides inhibited LPS-induced IL-23 and IL-27 proteins and their subunits in MDMs. First I investigated the signalling pathways involved in the regulation of LPS-induced IL-23 and IL-27 production in MDMs infected with control pLXIN retrovirus-infected MDMs. The p38 MAPK, SHP-1 and PI3K signalling molecules positively regulated LPS-induced IL-23 expression. In contrast, Src kinases and JNK MAPK negatively regulated LPS-induced IL-23 production. On the other hand, LPS-induced IL-27 production was positively regulated by the PI3K, p38 MAPKs and SHP-1 and Src kinases. Src kinases positively regulated LPS-induced IL-27 production whereas Src kinases and JNK negatively regulated LPS-induced IL-23 production. HIV-Tat significantly inhibited p38 MAPK and PI3K which were implicated in HIV-Tat-mediated inhibition of LPS-induced IL-23 and IL-27 production. Even though HIV-Tat inhibited ERK and JNK MAPK activation, these kinases were not involved in HIV-Tat-mediated inhibition of LPS-induced IL-23 and IL-27 production. While SHP-1 regulated LPS-induced IL-23 and IL-27 production, HIV-Tat did not inhibit SHP-1 and therefore were not involved in HIV-Tat-mediated inhibition of LPS-induced IL-23 and IL-27 production. HIV-Tat did not inhibit Src kinases and hence were not involved in HIV-Tat-mediated inhibition of LPS-induced IL-27 production. Furthermore, HIV-Tat did not inhibit the expression of upstream TLR4-activated signaling molecules including TRAF3, TRIF, MyD88, IRAK1, IRAK3, IRAK4, TRAF-1, TRAF-2, cIAP-1, cIAP-2 and, xIAP. These results suggest association of IL-23 and IL-27 inhibition by HIV with decreased HIV-specific immune responses, and increased viral replication. These results further suggest novel strategies to improve cellular immune responses and inhibition of HIV replication.

In a BBC radio report last year, one speaker reported that Africa South of the Sahara is the worst affected by the HIV and AIDS pandemic. Is it that African Christians are more promiscuous than say their European and American counterparts? After living in U.S.A. myself and after having traveled in Europe, I felt that the truth of the matter may be the direct opposite. It may be that apart from sex there must be other ways through which HIV and AIDS is spreading in Southern Africa. Things like rites of passage and other African cultural practices may be what have made HIV and AIDS to find a fertile soil in Southern Africa. There have been a number of women who are infected with the HIV and AIDS virus in Zambia and Africa as a whole (UNICEF reports on Zambia 2003). Women are more vulnerable to AIDS than men in Zambia for a number of reasons, some of which are the collapse of the support systems leading to poverty, the dying of African moral values, etc. Therefore there is a need to intensify our efforts to find out the relationship between cultural practices in rites of passage and the spread of HIV and AIDS in patrilineal and matrilineal Zambian cultures? To promote effective joint involvement into finding the solution to this problem the following objectives will be achieved: To explore the salient cultural practices of rites of passage which promotes and hinders the spread of HIV and AIDS in Zambian women and the people of Zambia, to explore through a narrative approach, cultural practices and gender, to collect stories of women who have been the victims of these cultural practices, to look at rites of passage, a theological reflection. Since culture plays a major role in people’s lives in Zambia and Africa as a whole, there is need to take Zambian or African culture seriously so that we can look at the salient cultural practices in rites of passage which influence the spread of HIV and AIDS. / Thesis (PhD)--University of Pretoria, 2010. / Practical Theology / unrestricted

Background Depression has been found in the literature to be a major problem in people living with HIV/AIDS. Not only does this impact on their daily functioning but has been shown to have negative HIV related outcomes, and result in poorer adherence to antiretroviral medication. The population under study was pregnant at the time of diagnosis. It would seem likely that their risk for depression would be greater than even a general HIV infected population, because of the pregnancy and the fact that they might have concerns around the health and future of the unborn infant. There are a limited number of studies looking at levels of depression over time and possible determinants of this depression even in a general HIV infected population. It was thus felt necessary to establish levels of depression and to establish if there were any factors associated with changes over time in this pregnant population. Method Two hundred and ninety three women were recruited at antenatal clinics in Tshwane from June 2003 and December 2004. They were interviewed at approximately 28 weeks gestational age and were followed for 18 months after the birth. Data included socio demographic variables, a “self efficacy score”, past history of violence, disclosure, CD4 count and knowledge score. Psychological variables included measures of stigma, social support, self esteem and coping. Depression was measured using a modified CES-D (Center for Epidemiological Studies Depression Score) Repeated measures mixed linear analysis was used to assess if there were changes in depression scores over time and if there were factors associated with these changes. Results Two hundred and twenty four women were included in the mixed linear analysis. The mean age of the women was 26.5 years (standard deviation -5.1). Seventy six percent (152) were single with a partner. Seventy six percent (171) had some form of secondary education and 14% (32) had some form of tertiary education. Sixty percent (135) lived in a brick house and 35% (79) had running water in the house. Twenty nine percent (64) had a per capita income below the poverty line. The prevalence of borderline depression (CES-D scores above 12) for this group of women at baseline was 45%. There were significant changes in depression scores over time. This was not a linear relationship (significant quadratic time to interview term p=0.008). This was evidenced by the fall off in scores at 3-9 months followed by a subsequent rise. The factors associated with higher depression scores overall were lower active coping (p=0.004), higher avoidant coping (p=0.003), higher internalised stigma (p=0.001), higher housing scores (0.026), lower self–esteem (0.002), a history of violence (p<0.0001) and having no partner (p=0.005). No factors were associated with changes over time. Conclusion There are significant changes in depression scores over time in this cohort of women Depression scores while falling after the birth of the child as in other cohorts, start to rise again. Although there are no specific factors associated with these changes, overall women who have a history of violence, who have no partner, who live in better housing circumstances, who have poor self esteem, who have high levels of internalized stigma and make use of negative coping strategies are more likely to be depressed. Women who make use of active coping strategies are less likely to be depressed. There are a large number of women at baseline who have scores considered to be diagnostic of borderline depression and because of the potential negative consequences to the woman and child, an intervention aimed at addressing the above issues should be devised. This should start in the antenatal period and carry on beyond this time. Copyright / Dissertation (MSc)--University of Pretoria, 2010. / Clinical Epidemiology / unrestricted

Orientadores: Pablo Agustin Vargas, Luiz Paulo Kowalski / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba / Made available in DSpace on 2018-08-22T08:56:49Z (GMT). No. of bitstreams: 1 Gondak_RogeriodeOliveira_D.pdf: 3115921 bytes, checksum: 6a0ba84f4ad5ecaa9e8dbd843e421cf0 (MD5) Previous issue date: 2013 / Resumo: Na infecção pelo HIV, as células dendríticas (CDs) podem desempenhar vários papéis, incluindo a provável captação inicial do HIV, transporte para os linfonodos, e posterior transferência para células T, desempenhando um importante papel no sistema imune. As manifestações orais observadas em pacientes infectados pelo HIV, incluindo aquelas associadas ao HSV-1 podem estar diretamente relacionadas à injúria das CDs. A proposta deste estudo foi identificar e quantificar as CDs intersticiais na língua de pacientes autopsiados com AIDS e portadores de infecção herpética lingual (n=10), pacientes com AIDS e sem lesões linguais (n=10) e pacientes sem AIDS e sem lesões linguais (n=10) por meio de reações imunoistoquímicas. Além disso, investigamos a população de CDs nos linfonodos e tonsilas palatinas de pacientes com AIDS (n=32) e sem AIDS (n=21). Nos tecidos linguais, foram utilizados os anticorpos contra CD1a e CD83 para identificação das CDs e o anticorpo contra HSV-1 para detecção do vírus da herpes simples tipo 1. Nos linfonodos e tonsilas palatinas foi utilizados além dos anticorpos contra CD1a e CD83, o anticorpo contra fator XIIIa. Para a quantificação das CDs nos tecidos linguais foi utilizado análise histomorfométrica convencional e nos tecidos linfóides foi aplicado o método analítico Positive Pixel Count (software Image Scope). Os resultados mostraram uma intensa depleção na população de CDs em tecidos linguais e linfóides de pacientes com AIDS e a infecção lingual pelo HSV-1 não potencializou a redução de CDs / Abstract: During HIV infection, dendritic cells (DCs) may play several roles, including the probable initial uptake of HIV, transport to the lymph nodes, and subsequent transfer to T cells. Oral opportunistic infections observed in HIV-infected patients, including those associated with HSV-1 may be directly related to injury of DCs. The purpose of this study was to identify and quantify the interstitial DCs in the tongue of autopsied patients with AIDS and lingual herpes (n = 10), AIDS patients with normal tongues (n = 10) and non-AIDS patients with normal tongues (n = 10) by immunohistochemistry. Furthermore, we investigated the DCs population in lymph nodes and palatine tonsils of AIDS patients (n = 32) and non-AIDS patients (n = 21). CD1a and CD83 antibodies were carried out to identify DCs in lingual tissues and HSV-1 antibody for detection of herpes simplex virus type 1. In lymphoid tissues, CD1a, CD83 and factor XIIIa antibodies were carried out to identify DCs. Interstitial DCs were measured by conventional histomorphometry whereas the lymphoid DCs were measured by Positive Pixel Count Algorithm method using ImageScope software. The results showed a decreased population of DCs in lingual and lymphoid tissues of AIDS patients independently of the presence of concomitant infection by HSV-1 / Doutorado / Patologia / Doutor em Estomatopatologia

Orientadores: Maria Marluce dos Santos Vilela, Taís Nitsch Mazzola / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-26T10:36:44Z (GMT). No. of bitstreams: 1 Bernachi_JessicaSantana_M.pdf: 2518686 bytes, checksum: 58cf0214c9aa6fb37c051da8088bd63a (MD5) Previous issue date: 2014 / Resumo: A vacinação terapêutica com células dendríticas derivadas de monócitos (MDDC) têm sido associada com o controle da carga viral em adultos infectados pelo HIV, mas os seus efeitos em crianças não foram explanados. Nesse sentido, o objetivo deste trabalho foi avaliar a função das MDDC isoladas de crianças e adolescentes verticalmente infectados pelo HIV sob terapia antiretroviral combinada. Os pacientes foram recrutados no Ambulatório de Imunodeficiência Secundária Pediátrica do Hospital de Clínicas da Universidade Estadual de Campinas, sendo 25 com carga viral indetectável e 14 com carga viral ?1000 cópias de RNA/mL. Além disso, 20 crianças e adolescentes saudáveis participaram como controles. Monócitos obtidos do sangue periférico foram cultivados durante seis dias com GM-CSF e IL-4 para a obtenção das MDDC, as quais foram avaliadas por citometria de fluxo quanto à expressão de CD40, CD80, CD83, CD86, DC-SIGN e HLA-DR. As MDDC foram pulsadas com HIV-1 inativado por aldritiol-2 e cocultivadas com linfócitos autólogos para avaliação da expressão gênica e proteica de citocinas e da linfoproliferação HIV específica. Foram avaliados também hemogramas, subpopulações de células dendríticas mielóides e plasmocitóides e de linfócitos CD3, CD4 e CD8. As MDDC dos pacientes infectados pelo HIV apresentaram um fenótipo semelhante aos controles saudáveis e foram capazes de induzir a produção de citocinas do tipo Th1; no entanto, crianças com carga viral ?1000 cópias de RNA/mL apresentaram menor linfoproliferação HIV-específica. Em geral, as MDDC de crianças verticalmente infectadas pelo HIV geradas in vitro foram capazes de induzir resposta imune celular HIV específica, mostrando-se potenciais candidatos para imunização terapêutica usando MDDC / Abstract: Therapeutic vaccination with monocyte-derived dendritic cells (MDDC) has been associated with viral load control in immunized HIV-infected adults, but its effects in children were not explored yet. We aimed to evaluate the function of MDDC isolated from vertically HIV-infected children and adolescents under combined antiretroviral therapy. Patients were recruited at the Out-Patients Unit at the University of Campinas, which 25 patients had undetectable viral load and 14 patients had viral load ?1000 RNA copies/mL. In addition, 20 healthy children and adolescents served as controls. Monocytes obtained from peripheral blood were cultured for six days with GM-CSF and IL-4 to get the MDDC, which were assessed by flow cytometry for CD40, CD80, CD83, CD86, DC-SIGN and HLA-DR expression. T cell proliferation and cytokine expression and production were evaluated in cocultures of MDDC pulsed with aldrithiol-2-inactivated HIV-1 and autologous lymphocytes. Hemogram, myeloid and plasmacytoid dendritic cells and CD3, CD4 and CD8 lymphocytes were evaluated in the peripheral blood. MDDC from HIV-infected children exhibited a similar phenotype to those in healthy individuals and were able to induce a Th1-type cytokine production; however, T lymphoproliferation was impaired in children with viral load ?1,000 RNA copies/mL. MDDC generated in vitro boosted HIV-specific cellular immune responses in vertically HIV-infected children and could be potential candidates for MDDC therapeutic immunization / Mestrado / Saude da Criança e do Adolescente / Mestra em Ciências

Orientadores: Lúcia Helena Simões da Costa Paiva, Ana Lúcia Ribeiro Valadares / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-26T11:55:03Z (GMT). No. of bitstreams: 1 Gomes_DeboraAlessandradeCastro_D.pdf: 2529493 bytes, checksum: f23f380cf45b3dbde66f595b53dd5ef9 (MD5) Previous issue date: 2014 / Resumo: Os avanços científicos com a utilização da terapia antiretroviral altamente potente (TARV), proporcionaram significativo aumento na expectativa de vida das mulheres HIV soropositivas. Por outro lado, elas estão vivenciando afecções próprias do envelhecimento, como a osteoporose de etiologia provavelmente multifatorial. Objetivo: Avaliar a densidade mineral óssea e fatores associados em mulheres climatéricas HIV soropositivas. Sujeitos e Métodos: Realizado estudo de corte transversal com 273 mulheres HIV soropositivas e 264 mulheres HIV soronegativas de 40 a 60 anos de idade, acompanhadas em atendimento ambulatorial especializado. Foram avaliadas características clínicas, laboratoriais e densidade mineral óssea. Análise estatística: Foram utilizados os testes de Yates, qui-quadrado de Pearson, Mann-Whitney e análises de regressão múltipla de Poisson e regressão linear. Resultados: A média etária das mulheres HIV soropositivas foi 47,7 anos e das soronegativas 49,8 anos. As mulheres HIV soropositivas apresentavam IMC menor que 25Kg/m² (51,6%) e 59,3% estavam na pré ou perimenopausa enquanto as HIV soronegativas 29,3% tinham IMC menor que 25 kg/m² e 42,1% estavam na pré ou peri menopausa. A prevalência de baixa massa óssea em L1-L4 foi de 33,5% no grupo soropositivo e 33,2 % no grupo soronegativo (p>0.999). No colo do fêmur foi de 33,1% no grupo HIV soropositivo e 27,6 % no grupo soronegativo (p=0,266). A análise de regressão linear múltipla mostrou associação inversa entre DMO da coluna lombar e estar na pós menopausa, ser HIV soropositiva, FSH > 40 mUI/ml e direta com IMC >25 Kg/m² . Em relação a DMO no colo do fêmur houve uma associação inversa com estar na pós menopausa, cor branca e associação direta com maior paridade e IMC >25 Kg/m². Dentre as mulheres HIV soropositivas o tempo médio da infecção era de 9.9 anos, 92% usavam TARV, tempo médio de TARV era de 9,4 anos, tempo decorrido desde o diagnóstico foi em média 9,9 anos. Os fatores associados à baixa massa óssea em L1-L4 foram maior idade (p<0,001), paridade > 2 (p=0,03), estar na pós menopausa (p<0,01) e FSH > 40 mUI/ml (p<0,001). No colo do fêmur a baixa massa óssea esteve associada à maior idade (p<0,001), não usar drogas ilícitas (p=0,03), estar na pós menopausa (p<0,01) e FSH >40 mUI/ml (p<0,001). Não houve associação de baixa massa óssea na coluna lombar (L1-L4) e colo do fêmur com variáveis associadas diretamente ao HIV. A análise de regressão múltipla de Poisson verificou associação entre baixa DMO em L1-L4 e colo do fêmur apenas com estar na pós menopausa. Conclusão: Não houve diferença significativa na DMO na coluna lombar L1-L4 e no colo do fêmur nas mulheres climatéricas HIV soropositivas e soronegativas. A prevalência de osteopenia/osteoporose em mulheres climatéricas HIV soropositivas recebendo TARV foi de 33,5% em L1-L4 e de 33,1% no colo do fêmur, enquanto nas soronegativas foram 33,2 % em L1-L4 e 27,6% no colo do fêmur. Os principais fatores associados à baixa DMO foram estar na pós menopausa e menor IMC em mulheres HIV soropositivas e negativas. Ser HIV soropositivo esteve associado a baixa DMO apenas em L1-L4 / Abstract: Scientific advances in the use of highly active antiretroviral therapy (HAART), have provided a significant increase in the life expectancy of HIV positive women. Moreover, they themselves are experiencing disorders of aging, such as osteoporosis probably multifactorial etiology. Objective: To evaluate bone mineral density and associated factors in menopausal women HIV positive. Subjects and Methods: Conducted cross-sectional study of 273 HIV seropositive women and 264 HIV-seronegative women 40-60 years old, followed in a specialized outpatient care. Clinical and laboratory characteristics and bone mineral density were evaluated. Statistical analysis: tests Yates Mann-Whitney analysis of multiple Poisson regression and linear regression were used chi-square test, and. Results: The mean age of the HIV positive women was 47.7 years and 49.8 years for seronegative. HIV seropositive women had a BMI less than 25 kg / m² (51.6%) and 59.3% were pre- or perimenopausal HIV seronegative while 29.3% had a BMI less than 25 kg / m² and 42.1% were in pre- or peri-menopausal. The prevalence of low bone mass in L1-L4 was 33.5% in the HIV-positive group and 33.2% in the seronegative group (p> 0.999). Femoral neck was 33.1% in HIV-seropositive group and 27.6% in the seronegative group (p = 0.266). A stepwise multiple linear regression analysis showed an inverse association between lumbar spine BMD and being postmenopausal, be HIV seropositive, FSH> 40 mIU / ml and direct with BMI> 25 kg / m². In relation to BMD at the femoral neck there was an inverse association with being postmenopausal, white and direct association with higher parity, and BMI> 25 kg / m². Among the HIV-seropositive women the average time of infection was 9.9 years, 92% were using HAART, median time to ART was 9.4 years, time since diagnosis averaged 9.9 years. Factors associated with low bone mass in L1-L4 were older age (p <0.001), parity> 2 (p = 0.03), being postmenopausal (p <0.01) and FSH> 40 mIU / ml (p <0.001). Femoral neck low bone mass was associated with older age (p <0.001), not using illicit drugs (p = 0.03), being postmenopausal (p <0.01) and FSH> 40 mIU / ml (p <0.001). There was no association between low bone mass at the lumbar spine (L1-L4) and femoral neck variables associated directly with HIV. The analysis of multiple Poisson regression found an association between low BMD at L1-L4 and femoral neck only to be postmenopausal. Conclusion: There was no significant difference in BMD at the L1-L4 lumbar spine and femoral neck in women seropositive and seronegative climatic HIV. The prevalence of osteopenia / osteoporosis in menopausal women seropositive HIV receiving ART was 33.5% in L1-L4 and 33.1% at the femoral neck, while 33.2% were seronegative at L1-L4 and 27.6 % in the femoral neck. The main factor associated with low BMD were being menopausal and have lower BMI in HIV positive and negative women. HIV seropositive was associated with low BMD only in L1-L4 / Doutorado / Fisiopatologia Ginecológica / Doutora em Ciências da Saúde

Background: HIV/AIDS remains a major health concern worldwide and the number of people infected in Sub-Saharan Africa continues to increase. This despite increased awareness and availability of HIV drugs in most countries. The success of current HIV-1 drugs is overshadowed by the emergence of drug resistant viral strains and the adverse side-effects they may cause. It is these limitations and many more that drives the continuous search for better HIV treatments. Research into drug discovery and development using natural products is becoming better established. With natural products, there are endless opportunities for discovering novel compounds which either ends up as final drugs or as backbones of drug leads. Methods: In this thesis, sixteen Lamiaceae (mint) plants were investigated for inhibitory properties against HIV-1 as well as for beneficial immune enhancing effects. This family of plants is commonly used in traditional medicine preparations for the treatment of various ailments including those that are virus induced. Cytotoxicity of the plant material was determined using tetrazolium dyes and the results subsequently confirmed with flow cytometry and real-time cell analysis. Direct enzyme assays were used to determine the inhibitory properties of the extracts and isolated compounds against HIV-1 protease (PR), reverse transcriptase (RT) and integrase (IN). The effect of the plant materials was also evaluated in an in vitro model of chronic and latent infection by measuring HIV-1 p24 protein secretion of an infected cell line (U1) following treatment. Most HIV-infected individuals only seek treatment during the chronic stages of disease and latent reservoirs of the virus perpetuate treatment. The immune modulating properties were determined by quantitating the effects of plant extracts/compounds on Th1/2/17 cytokine production in human mononuclear cells using the cytometric bead array technology. Finally, anti-oxidant and anti-inflammatory properties were also assessed using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and nitric oxide colorimetric assays respectively. Results and discussion: The 50% cytotoxic concentration (CC50) of the extracts was between 4.2 and 100 μg/ml. Of the sixteen, extracts from six plants (Ocimum labiatum, Ocimum serratum, Plectranthus barbatus, Plectranthus neochilus, Salvia apiana and Stachys byzantina) were active against HIV-1. Four plants (P. neochilus, O. serratum, S. apiana and S. byzantina) demonstrated moderate inhibitory properties against HIV-1 PR, RT and IN (40-49%) and three of these plants (O. serratum, S. apiana and S. byzantina) significantly (p<0.05) suppressed HIV-1 replication in U1 cells. The most exciting data was obtained from extracts of P. barbatus and O. labiatum which demonstrated inhibition classified as good (>50%) against HIV-1 PR (IC50s 62 ±0.2 and 49.8 ±0.4 μg/ml), reduced the production of pro-inflammatory cytokines at non-cytotoxic concentrations and demonstrated strong antioxidant properties (IC50 values 13 ±0.8 and 15.8 ±0.3 μg/ml). O. labiatum extract also suppressed HIV-1 expression in U1 cells, significantly (p<0.05). In addition, one of the extracts (P. ciliatus) had anti-cancer potential with CC50 values <10 μg/ml. O. labiatum extract was purified to yield a chlorophyll derivative, pheophytin-a (phy-a); triterpene isomers (3-hydroxy-4,6a,6b,11,12,14b-hexamethyl- 1,2,3,4,6,6a,6b,7,8,8a,9,10,11,12,12a,14,14a,14b-octadecahydropicene-4,8adicarboxylic acid), amyrin and a labdane diterpenoid (labda-8(17),12E,14-triene-2R,18- diol). Phy-a inhibited HIV-1 PR with an IC50 value of 44.4 ±1.5 μg/ml. The triterpenes activated latent HIV-1 (a serious obstacle in the eradication of the virus) while the diterpenoid reduced the production of pro-inflammatory cytokines. These activities were observed at non-toxic concentrations of these compounds. There is an ongoing search for novel compounds that are able to activate latent HIV-1 to use in conjunction with HAART. If the triterpenes were to progress to clinical use, their use would be in activating latent virus for eradication by existing treatments. Conclusion: The findings presented in this thesis provide some scientific explanation for the anecdotal success of some Lamiaceae plants used traditionally to manage HIV/AIDS. The findings also conform to recommendations by the scientific community regarding the validation of the beneficial effects of plant products used traditionally. / Thesis (PhD)--University of Pretoria, 2013. / gm2014 / Biochemistry / unrestricted

Thesis (Ph. D. (Clinical Psychology)) -- Univesity of Limpopo, 2019 / The aim of the study was to determine the experience of ambiguous loss and grief reactions in adolescents affected by parental diagnosis of HIV/AIDS, and the identification of potential resilience factors that moderate the grieving symptoms. A convenient sample of 159 adolescents ninety-five (95) from families with a parental diagnosis of HIV/AIDS and a control group of sixty-four (64) adolescents whose parent(s) were diagnosed with cancer, participated in the study. The age of the participants from both families fell in the following ranges: 11-14 (n=45), 14-17 (n=65), 17-18 (n=45), 18 and above (n=2). Eighty-nine (89) were females whereas seventy (70) were males. A triangulation method of data collection was used wherein a biographical questionnaire designed by the researcher, a TRIG questionnaire to assess the level of grief in the participants and resilience scales were used in the quantitative phase. The family resilience scales included Family attachment and changeability Index 8 (FACI-8), Family Crisis Orientated Personal Evaluation Scale (F-COPES), Family Hardiness Index (FHI), and Relative and Friend Support Index (RFS). The Pearson correlation was used to identify the significance of potential resilience factors present in the affected families. Regression analysis was used to determine the predictability of variables to show moderating effect of resilience factors on the impact of experience of an ailing member of the family. Interviews were held with the adolescents in the qualitative phase using semistructured interview schedule. The questions elicited qualitative responses on the participants’ feelings towards the illness of the parents, the role they are playing and feelings towards the role, experience of feelings of loss, disclosure and the family qualities perceived to be helping them adapt to the stress of having a sick parent. The results showed that the two groups experienced ambiguous loss in the form of boundary ambiguity marked by enforced role changes following indisposed parent due to ill-health. Both groups of adolescents experienced forms of grief during the ailment of the parent(s). HIV/AIDS affected group experienced delayed grief whilst the control group of cancer affected individuals experienced acute and prolonged grief. Parental disclosure following diagnosis was higher among cancer affected families (75%) than those affected by HIV/AIDS (55%). There was, however, no significant difference between disclosure of disease status and the experience of grief, p=0.0120. Potential resilience factors in both families were F-COPES, FHI, and FACI-8. These factors were also found to have a moderating effect on the experience of grief in the HIV/AIDS affected families, but showed the opposite effect on the experience of grief in the cancer affected families. This shows the uniqueness of the study in the way the HIV/AIDs and Cancer affected families responded differently to the moderation of the resilience factors. The difference in the impact is in line with the shift in the status of HIV/AIDS from being a terminal condition to being manageable and considered chronic in contrast to cancer. The shift was seen occurring also in this study where previously high grief was associated with HIV/AIDS as its diagnosis was regarded as a death sentence. There was high stigma associated with HIV/AIDS diagnosis until recently when it was found to be controllable and also positively impacting on the life expectancy in South Africa that increased from 53 to 64 years post utilization of ARV’s.

Pathogenic mechanisms that account for the dramatic differences between the HIV-1 and HIV-2 epidemics remain unknown. Myeloid dendritic cells (DCs) are sentinels of the immune system, which sense invading pathogens and initiate immune responses. I hypothesize that failure of HIV-2 to overcome DC-intrinsic defense mechanisms results in diminished virus replication and reduced pathogenesis in vivo. Recent studies from our laboratory have identified capture of HIV-1 by CD169 (Siglec1), which results in preservation of virus infectivity in peripheral non-lysosomal compartments and transfer to CD4+ T cells, a mechanism of DC-mediated trans infection. HIV-1 interaction with CD169 was dependent on incorporation of a ganglioside, GM3, in the virus particle membrane. We hypothesized that reduced interaction of HIV-2 with CD169 is crucial for its attenuated pathogenic phenotype in vivo. Interestingly, HIV-2 virion assembly sites were divergent from HIV-1, which correlated with reduced incorporation of GM3 in HIV-2 virions, and a significant decrease in capture of HIV-2 compared to HIV-1 by mature DCs. Furthermore, reduced CD169-dependent HIV-2 capture by DCs attenuated access of HIV-2 to DC-mediated trans infection. In contrast to the trans infection pathway, HIV-2 could establish productive infection in DCs, though productive infection of DCs by HIV-2 resulted in innate immune activation, induction of IFN-α production and attenuated spread of virus in DC – CD4+ T cell co-cultures. As opposed to HIV-2, productive infection of DCs by HIV-1 was attenuated and failed to trigger type I IFN responses, thus allowing for efficient spread of HIV-1 in DC – CD4+ T cell co-cultures. These results suggest that immune sensing of HIV-2 in productively infected DCs limits viral spread. Finally, we investigated GM3-expressing nanoparticles (GM3-NPs) for delivery of therapeutics that trigger innate immune responses in CD169+ myeloid cells as a novel strategy to mimic myeloid cell-intrinsic virus control observed in HIV-2 infection. We tested the ability of GM3-coated nanoparticles that incorporated a TLR2 ligand, Pam3CSK4, to activate CD169+ cells. Interestingly, Pam3CSK4 containing GM3-NPs robustly activated CD169+ cells. These results suggest that induction of dendritic cell-intrinsic type I IFN responses might be a fruitful therapeutic strategy to restrict HIV-1 replication in vivo.

This purpose of this study was to investigate and examine the attitudes of therapists who treat HIV-positive (HIV+) clients. Specifically, therapists' perceptions of their own preparedness in dealing with specific issues and emotions of HIV+ clients were examined. Also, therapists' evaluation of their own efficacy of specific therapeutic approaches with HIV+ clients was examined. These therapists' perceptions and evaluations of all their clients in general were compared to their HIV+ clients. Comparisons were also made within the two groups.