Thesis (M Med(Family Medicine)) -- University of Limpopo, 2010. / Objectives This study sought to detennine the knowledge, attitude and practices of Goma University students about condom use for the purpose of reducing HIV infection. Design A descriptive cross-sectional quantitative study using a self-administered questionnaire. Setting Goma UniversitylNorth Kivu Province, Democratic Republic of Congo (DRC). Subjects 138 students from Goma University selected randomly completed the self- administered questionnaires. Results Their ages varied between 18 and 33 years. Most of them were males 111 (80 %), (93 %) were single; Most participants were protestant and Roman Catholic. The most important results were the following, The majority (99 %) of participants knew about condoms,132 (96 %) knew that condoms are available and sold in Pharmacy,72 (52 %) knew that condom can prevent at the same time HIV, Pregnancy and ST!, 94 (68 %) said they know how to use a condom, 111 (80 %) stated that the price of condoms is not a barrier for condom use, 102 (74 %) suggested that the university should supply students with condoms, 91 (66 %) were engaging in sexually activity, 98 (71 %) of respondents reported that they had unprotected sex. Conclusions The main conciusions ofthis study can be summarized as follows: Condom awareness was high with varying sources of information, Condom use was generally accepted as a means of preventing HIV / AIDS, sexual transmitted diseases and pregnancy, and Condoms in DRC are cheap and affordable for university students. In some ethnic groups, religions and cultures were not in favour of condom use. Consistent use of the condom was low among Goma University students. The results of statistics test (Fisher test) have shown that there is no difference in condom knowledge, attitudes and practices among Goma University students depending on several socio- demographic factors (sex, marital status, field of studies, class of study, tribe, etc)

Thesis ( MPH ) -- University of Limpopo (Medunsa Campus), 2013. / Background and introduction Disclosure of HIV sero-status is critical in the control of the spread of HIV and research. To better understand the factors influencing disclosure will enhance the development of prevention interventions and ultimately lead to better control of the spread of the disease. However literature shows that the rates of disclosure are generally low and vary substantially in different populations. Study purpose To determine the prevalence, reasons for disclosure, partner reaction to disclosure, and intentions of disclosure to sexual partners among HIV positive adults receiving antiretroviral treatment. Study design Cross sectional survey was conducted with 400 adult patients aged 18 years and above, who receive ART, and have known their HIV status for six more than six months. Structured close ended self-administered questionnaire was used to collect data. The study participants were recruited from a wellness clinic of an academic hospital in the City of Johannesburg, Gauteng province between October and November 2012. Descriptive and inferential statistics were performed using STATA 10 for analysis. Pearson X2 tests were used to determine variables associated with disclosure. Results A total of 400 HIV positive adults participated in the survey. There were slightly more female (n=229, 57%) than male (n=171, 43%), the mean age of participants was 39.9 years, (range 18-80 years). Almost half (n=176, 46%) had known of their HIV diagnosis for more than 5 years. High proportion (n=293, 73%) were sexually active three months prior to the survey, (n=250, 63%) knew their partner’s HIV status, more than a third (n=145, 36.3%) had more than one sexual partner, (n=263, 73.5%) reported condom use, (n=261, 75%) disclosed to their partners. Gender, discussing HIV testing with sexual partner, knowing partner’s HIV status, and living with partner were significantly associated with disclosure. iv The most common cited reasons for disclosure were that they needed to protect their partner from being infected with HIV, and needed support from their partner. Partner reactions to disclosure included support, shock, and denial of the test results, blame, abandonment, violence, anger, and divorce. The most cited reasons for nondisclosure were concerns that the partner might leave, partner might be afraid of catching HIV, partner might think they were unfaithful, partner might get angry, partner might hurt them physically and that partner might stop financial support. Conclusion The study concludes that the prevalence of disclosure to sexual partners among sexually active adults was high and that most respondents disclosed immediately after they were diagnosed with HIV. However, disclosure to multiple sexual partners was lower as compared to disclosure to the steady partner. Respondents disclosed to protect the partner from HIV infection and to receive support. Nondisclosure was mainly used to protect self from negative reactions from the partner. Recommendations Researchers and health care providers needs to take cognisant of the risk sexual behaviour an low condom use among HIV positive adults receiving ART. Secondary prevention efforts targeting risky sexual behaviour among HIV-positive persons need to receive greater attention.

<p>The use of high active antiretroviral therapy in people living with HIV/AIDS is increasing worldwide. In Rwanda, above 70 % of people in need of antiretroviral therapies is getting them. This drug therapy is associated with abnormal fat redistribution and metabolic complications which increase the risks of cardiovascular and diabetes diseases among these patients. The best recommended preventive and treating modality for these complications is physical activity participation. Despite this recommendation, there is lack of information about physical activity in HIV individuals under high active antiretroviral therapy. The current study aims to determine physical activity levels among people living with HIV treated with high active antiretroviral therapy in Kigali, Rwanda. A cross-sectional design using quantitative method was used. The participant&rsquo / s levels of physical activity participation and their association with anthropometric profiles were measured, using a structured self-administered questionnaire adapted from the Sub-Saharan Africa Activity Questionnaire. Based on a scientific calculation, 407 clients passing through the clinics were included in the study. A convenient sample of people attending the clinics approached to participate voluntarily in the study. The statistical package for social sciences version 19.0 and descriptive statistics were used to analyze the data. Inferential statistics like Chi-square test was used to determine the associations between physical activity levels and anthropometric profiles (p&lt / 0.05). Of the participants, 77% were female with a mean age of 38.82 years (SD=8.9. According to body mass index and weight hip ration, approximately 40% and 43% were obese and overweight respectively. Obesity was more common amongst the females (45%). The study found a high prevalence of inactivity in the following activities, of leisure-time (82.6%), household (71%), walking to/from work (61.7%) and work related physical activities (75%). Obesity was found to be strongly associated with inactivity in all types of activity. The findings of the current study highlighted the lack of motivation, lack of time and fear of worsening the disease amongst the strong barriers to physical activity participation. The current study recommends education about the benefits of physical activity participation and encouragement of patient treated with high active antiretroviral therapy in Rwanda to be emphasized on to improve their lives.</p>

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. / February 2007

A Thesis submitted to The University of Arizona College of Medicine - Phoenix in partial fulfillment of the requirements for the Degree of Doctor of Medicine. / The purpose of this study was to examine health care providers’ experiences regarding the processes of disclosure and assent in pediatric HIV/AIDS patients. The study population included providers who were involved with the care of pediatric HIV/AIDS. A survey was distributed through email and asked questions to explore provider demographics, the average age of assent to treatment and research, the average age of disclosure of HIV, what factors determine the age of disclosure, barriers to disclosure, provider opinions, and provider perceptions of conflict within the disclosure process. While results showed that there are wide variations among individual patients and providers, most providers agree that disclosure should occur in older school age children (between ages 6-10 years), which is also the time that they typically are able to assent to treatment and clinical trials. Providers often agreed that there is a conflict between the ages of disclosure and assent. Parental concerns (fear of stigma, inappropriate disclosure, and personal guilt) were most often the reason for delays in the disclosure process. The disclosure process was felt to be most effective when done in a step-wise manner that includes multiple practitioners and counseling with families.

Human immunodeficiency virus type 1 (HIV-1) genome consists of two identical RNAs that appear noncovalently linked near their 5' ends. The 5' untranslated region is called leader region. The 3' part of leader, i.e. nucleotides U200 to G335 in HIV-1 genomic RNA, between the primer binding site and the gag gene, can fold into 3 stem-loops: the kissing-loop domain (KLD) or stem-loop 1 (SL1), the 5' splicing junction hairpin (SD) or SL2 and SL3. The KLD, from nucleotide (nt) 243 to 277, forms a stem-loop (kissing loop hairpin) seated on top of a small stem bulge (stem B and loop B). The kissing-loop hairpin, or dimerization initiation site (DIS) hairpin consists of stem C and loop C. Loop C contains the autocomplementary sequence (ACS) GCGCGC262 or GUGCAC262, also called DIS. / In the kissing-loop model of HIV-1 genome dimerization, HIV-1 RNA dimerization is initiated by base pairing between the ACS of one RNA monomer and that of an adjacent monomer. / To understand the role of the ACS in HIV-1 replication and HIV-1 genomic RNA dimerization, we replaced the central CGCG261 (or tetramer) of the HIV-1 Lai ACS by other tetramers. Genomic RNAs containing the UUAA tetramer (non-HIV-1 tetramer) were half dimeric, but UUAA genome packaging was unaffected. This was the first evidence that genomic RNA dimerization and packaging can be dissociated (Chapter 2). Destroying stem-loop C reduced genomic RNA dimerzation by ~50%, proviral DNA synthesis by ~85%, and reduced viral infectivity by ~3 logarithmic units. Destroying stem-loop B had similar effects on genome dimerization, reverse transcription, and viral infectivity. We also observed that mutations in stem-loop B and in the DIS hairpin were "non additive" (Chapter 2). / The existence of stem-loop C is supported by phylogenetic evidence, while that of stem-loop B is not, namely, its sequence is completely conserved. We investigated the role of stem B and loop B nucleotides in viral replication, and genomic RNA dimerization. The putative CUCG246/CGAG277 duplex was replaced by 9 alternative complementary sequences, 4 likely to base pair in long (~500 nts) RNAs, as assessed by the algorithm mfold. Among the 4 sequences, 3 preserved genome dimerzation, 1 did not significantly inhibit it, and 2 preserved viral replication. We also asked if 9 deletions or nucleotide substitutions within nucleotide 200 to 242 and/or 282 to 335 could influence genome dimerization. Delta200--226 and Delta236--242 genomic RNAs dimerized relatively poorly despite having neutral or positive influences on stem B, loop B and klh folding (Chapter 3). / Mutations within the Matrix, Capsid, p2 and nucleocapsid genes suppress several functional defects caused by KLD destruction. We tested the effect of these suppressor mutations on genome dimerization and infectiousness of viruses bearing moderate to crippling KLD mutations. Our conclusion is that these suppressor mutations can restore genomic RNA dimerization when DIS is weakened, but not when DIS is denatured or the KLD is destroyed (Chapter 4).

<p>The use of high active antiretroviral therapy in people living with HIV/AIDS is increasing worldwide. In Rwanda, above 70 % of people in need of antiretroviral therapies is getting them. This drug therapy is associated with abnormal fat redistribution and metabolic complications which increase the risks of cardiovascular and diabetes diseases among these patients. The best recommended preventive and treating modality for these complications is physical activity participation. Despite this recommendation, there is lack of information about physical activity in HIV individuals under high active antiretroviral therapy. The current study aims to determine physical activity levels among people living with HIV treated with high active antiretroviral therapy in Kigali, Rwanda. A cross-sectional design using quantitative method was used. The participant&rsquo / s levels of physical activity participation and their association with anthropometric profiles were measured, using a structured self-administered questionnaire adapted from the Sub-Saharan Africa Activity Questionnaire. Based on a scientific calculation, 407 clients passing through the clinics were included in the study. A convenient sample of people attending the clinics approached to participate voluntarily in the study. The statistical package for social sciences version 19.0 and descriptive statistics were used to analyze the data. Inferential statistics like Chi-square test was used to determine the associations between physical activity levels and anthropometric profiles (p&lt / 0.05). Of the participants, 77% were female with a mean age of 38.82 years (SD=8.9. According to body mass index and weight hip ration, approximately 40% and 43% were obese and overweight respectively. Obesity was more common amongst the females (45%). The study found a high prevalence of inactivity in the following activities, of leisure-time (82.6%), household (71%), walking to/from work (61.7%) and work related physical activities (75%). Obesity was found to be strongly associated with inactivity in all types of activity. The findings of the current study highlighted the lack of motivation, lack of time and fear of worsening the disease amongst the strong barriers to physical activity participation. The current study recommends education about the benefits of physical activity participation and encouragement of patient treated with high active antiretroviral therapy in Rwanda to be emphasized on to improve their lives.</p>

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.

Host genetics play an important role in regulating susceptibility to infectious diseases, including the human immunodeficiency virus (HIV). A polymorphism in a G protein signaling gene (GNB3) previously associated with rapid HIV disease progression is found at high frequencies among African populations, yet its impact on HIV acquisition and disease progression is unknown. The GNB3 gene is located on chromosome 12 near the CD4 gene, as well the gene encoding the regulatory protein lymphocyte activation gene 3 (LAG-3). The goal of this thesis was to characterize the impact of GNB3 genotype on risk of HIV acquisition and disease progression, as well as the relevance of LAG-3 expression to immune exhaustion during HIV infection. Because G proteins are involved in HIV entry and replication in T cells, polymorphisms affecting G protein signaling, such as GNB3 C825T, could dramatically alter susceptibility to HIV infection, viral replication and rates of disease progression. Similarly, the expression of the inhibitory protein LAG-3 could, like other exhaustion markers, mediate increasing immune dysfunction during chronic infection. Both GNB3 and LAG-3 could represent targets for therapeutic intervention to slow disease progression or restore lymphocyte function among HIV-infected individuals. Surprisingly, our studies showed that GNB3 genotype was not associated with the risk of HIV acquisition in either a female sex worker or perinatal transmission cohort. Disease progression and immune activation among healthy and HIV-infected women were also independent of GNB3 genotype. While the RNA splicing events typically associated with the presence of the GNB3 825T allele could not be detected among cohort participants, ii differences in LAG-3 expression were observed between women of differing GNB3 genotypes. In this cohort, LAG-3 expression on T cells, NK cells and iNKT cells in the peripheral blood was significantly increased among HIV+ women compared to healthy controls, and was not decreased by antiretroviral therapy. The increase in LAG-3 expression was greatest on NK and iNKT cells, an innate lymphocyte subset capable of rapid and robust cytokine production upon stimulation with CD1d-restricted lipid ligands. Lymphocytes derived from the female genital mucosa, the site of HIV acquisition in the female sex worker cohort, expressed significantly higher levels of LAG-3 compared to peripheral blood, suggesting a role for LAG-3 in regulating mucosal immunity, particularly on double negative (CD4-CD8-) T cells. Finally, we demonstrated that iNKT cells derived from HIV-infected women exhibited significantly lower IFN production compared to healthy controls upon lipid stimulation, which inversely correlated with iNKT LAG-3 expression. Lipid stimulation of PBMC from HIV+ and ARV-treated women also demonstrated perturbations in the secretion of multiple cytokines and chemokines, suggesting that iNKT function is not restored following ART. Together, these data imply that LAG-3 may play an important role in regulating iNKT function during chronic HIV infection. Blocking LAG-3 signaling could therefore restore components of innate immunity that are not improved by current ART, as well as alter HIV susceptibility at the female genital tract, making LAG-3 an attractive target for future therapeutics and viral eradication strategies.