Purpose: The aim of this study is to model the impact of needle exchange interventions on human immunodeficiency virus (HIV) and hepatitis C virus (HCV). Methods: In order to model the impact of needle exchange interventions, behavioural effects (sexual and drug use) were translated into estimates of the number of HIV and HCV cases averted by the programs through a mathematical model. Behavioural effects data on 63 clients had been collected previously by two Health Units in Ontario. The secondary data were analyzed to estimate the number of HIV and HCV cases averted while accounting for co-infection. A Bernoulli process model was used to estimate the number of averted cases for the condom distribution and counselling aspects of the needle exchange intervention. A modification of the Bernoulli process model was used for needle exchange interventions to account for drug use behaviours. Furthermore, this model estimated the number of cases averted while also accounting for the clients’ partner’s co-infection status. Once the number of HIV and HCV cases averted was determined, a cost analysis was conducted to estimate the net medical savings of the interventions. Costs were converted to 2011 Canadian dollars. Results: Of the 63 clients, 21.40 HIV and 5.18 HCV cases were directly averted by the needle exchange intervention when HIV/HCV co-infection status of the partner was not taken into account. When the clients’ partners’ co-infection status was taken into account, lesser numbers were directly averted by the needle exchange intervention. The discounted medical savings averted were $6,950,028 and $6,741,331 when co-infection was and was not accounted for, respectively, for the 63 individuals. Conclusion: The study demonstrated a different modeling method to account for HIV and HCV cases averted in the context of needle exchange. This study provides a foundation for future large scale cost-effectiveness studies. / Thesis (Master, Community Health & Epidemiology) -- Queen's University, 2014-04-29 13:45:07.698

The Human Immunodeficiency Virus 1 (HIV-1) epidemic continues to claim millions of lives, despite intense research and public health programs. A natural model of resistance is crucial for the development of an effective vaccine. We have identified a group of sex workers in Nairobi, Kenya, who appear to be resistant to infection with HIV. Research on this cohort has identified numerous immunological and genetic correlates to HIV resistance, but has failed to completely explain the phenomenon. Genetic studies have shown that HIV resistance occurs in families, with both sex worker and non-sex worker relatives of HIV resistant women less likely to be HIV infected. In addition, HIV resistance has been associated with altered innate immune responses, as measured by cytokine production to toll-like receptor stimuli. To test the hypothesis that there is a genetic component to HIV resistance, we will address two specific objectives within this thesis: 1) identify known polymorphisms associated with HIV resistance in the kindred of these women; more specifically interferon regulatory factor 1 (IRF-1) polymorphisms, and 2) identify polymorphisms within toll-like receptors (TLRs) that may be responsible for the altered and apparently successful immune responses in HIV resistant women. Our findings show an association between HIV resistant kindred and an IRF-1 microsatellite, as well as, with an IRF-1 single nucleotide polymorphism. No associations were found between HIV resistance and the investigated TLR2 and TLR4 polymorphisms. These results also suggest a genetic component to HIV resistance, but do not fully explain the altered immune responses observed within these women.

HIV/AIDS, discovered in the early 1980s, has now become a world-wide epidemic. The most affected area is Africa, in particular sub-Saharan Africa. This exploratory research project examined the challenges facing grandmothers and focused on Zambia because with 1,291,079 orphans, Zambia has the highest proportions of orphans in the world. Evidence demonstrates that grandmothers care for approximately 43% of the 845,546 AIDS orphans. Young men and women aged between 15 and 49, despite good health and higher education, have continued to die from AIDS, leaving behind children who are cared for by their grandparents and in particular their grandmothers. The experiences of these grandmothers are not known due to a paucity of studies on the subject. This study is a scoping review of literature on HIV/AIDS in Zambia and its impact on the family. A number of journals, books, and reports were investigated. The major themes arising from the literature were identified and discussed; they include HIV/AIDS in sub-Saharan Africa and HIV/AIDS in Zambia, impact of HIV/AIDS on households and Zambia’s response to the epidemic. This research uses three perspectives: conflict theory, social capital and role conflict to guide the exploration of the social impact of HIV/AIDS on families and society. The study provided an opportunity to identify and examine the challenges facing grandmothers who care for their AIDS orphans and consequently to offer potential solutions. It also contributed to a broader understanding of the social significance of HIV/AIDS.

HIV infects target cells via fusion events following surface envelope glycoprotein binding to the CD4 receptor and a chemokine co-receptor. Despite the high sequence variability of envelope across and within HIV-1 subtypes, this process requires conserved sequences and structures on gp120, which also represent good targets for HIV-1 neutralizing antibodies. Few examples of HIV-1 broadly neutralizing antibodies exist, but these antibodies may hold the key to a protective HIV-1 vaccine. One such antibody, IgG1 b12 (b12), binds the CD4 binding site on the HIV-1 envelope glycoprotein gp120. To date, no vaccine preparations have been able to elicit a b12-like response. A complete understanding of the mechanism of b12 binding to gp120 is essential to successful design of an b12-like immune response. Until now, strategies to map the b12 binding site on gp120 have utilized indirect techniques and/or core gp120 and have shown that b12 binds to a site on gp120 that overlaps the CD4 binding site. To more directly map the b12 epitope on intact gp120, epitope excision mass spectrometry mapping was carried out in the MALDI QqTOF platform. The putative epitope sequence was confirmed by tandem mass spectrometry sequencing. Epitope mapping revealed a novel binding site for IgG1 b12 at the gp120 amino terminus called Nterm. b12 bound a synthesized peptide of the epitope and the nature of the epitope was explored by ELISA. Although the Nterm epitope is involved in b12-gp120 interactions, ELISAs also show that the epitope does not make up the entire binding site on gp120. Rabbits immunized with a peptide version of the Nterm epitope do express antibodies that bind monomeric gp120, but these antibody responses do not neutralize HIV-1 in vitro. These data indicate that the b12 binding site on gp120 is much more complex than previously thought. The b12 binds the Nterm sequence of gp120, perhaps in conjunction with the CD4 binding site. It has been shown that another HIV-1-neutralizing antibody, 4E10, also binds this novel Nterm epitope, and this may indicate a similar mechanism of action utilized by these two different antibodies. Though not able to elicit neutralizing antibodies on its own, this epitope may be an important element of the neutralizing b12 epitope and an important component of HIV-1 neutralizing antibody responses.

The Human Immunodeficiency Virus 1 (HIV-1) epidemic continues to claim millions of lives, despite intense research and public health programs. A natural model of resistance is crucial for the development of an effective vaccine. We have identified a group of sex workers in Nairobi, Kenya, who appear to be resistant to infection with HIV. Research on this cohort has identified numerous immunological and genetic correlates to HIV resistance, but has failed to completely explain the phenomenon. Genetic studies have shown that HIV resistance occurs in families, with both sex worker and non-sex worker relatives of HIV resistant women less likely to be HIV infected. In addition, HIV resistance has been associated with altered innate immune responses, as measured by cytokine production to toll-like receptor stimuli. To test the hypothesis that there is a genetic component to HIV resistance, we will address two specific objectives within this thesis: 1) identify known polymorphisms associated with HIV resistance in the kindred of these women; more specifically interferon regulatory factor 1 (IRF-1) polymorphisms, and 2) identify polymorphisms within toll-like receptors (TLRs) that may be responsible for the altered and apparently successful immune responses in HIV resistant women. Our findings show an association between HIV resistant kindred and an IRF-1 microsatellite, as well as, with an IRF-1 single nucleotide polymorphism. No associations were found between HIV resistance and the investigated TLR2 and TLR4 polymorphisms. These results also suggest a genetic component to HIV resistance, but do not fully explain the altered immune responses observed within these women.

Proefschrift Universiteit van Amsterdam. / Met lit. opg. - Met samenvatting in het Nederlands.

Proefschrift Universiteit van Amsterdam. / Met bibliogr., lit. opg. - Met samenvatting in het Nederlands.

Proefschrift Universiteit van Amsterdam. / Met lit. opg. - Met samenvatting in het Nederlands.

Proefschrift Universiteit van Amsterdam. / Met bibliogr., lit. opg. - Met samenvatting in het Nederlands.

Proefschrift Universiteit van Amsterdam. / Met lit. opg. - Met een samenvatting in het Nederlands.