Human immuno deficiency virus (HIV) incorporates host cellular protein, beta-2-microglobulin (β2m), into its surface envelope during budding. β2m is a cellular protein that belongs to the major histocompatibility complex (MHC) Class I molecules. Studies have shown anti- β2m monoclonal antibodies (mAbs) has the ability of to neutralize the virus. An epitope consisting of seven amino acids of the β2m protein designated as R7V produces antibodies that protect HIV infected people from progressing to AIDS. These protective antibodies, called anti-R7V antibodies, were able to neutralize different HIV isolates, despite their genomic variations, various cellular targets and geographic origin. Anti-R7V antibodies in the format of single chain variable fragments (scFvs) were produced in our laboratory using the M13 phage display technology. These scFv antibody fragments were used during in vitro studies for the detection and neutralization of the R7V antigen by enzyme linked immune sorbent assay (ELISA). The scFv fragments produced against the R7V epitope showed interaction, however the antibody-antigen affinity was too weak for the virus neutralization assay. Hence, this project focused on the affinity maturation of the anti-R7V scFv fragments through random mutagenesis using the error prone (EP) PCR method. The EP PCR method generated two mutated anti-R7V scFvs. The mutated clones were subcloned into the pAK400 expression vector. The computer-based models, created using the Swiss PDB Deep Viewer 4.02 software, were used to predict the antigen-binding site and affinity analysis of both parent and mutated scFv’s. Mutated clone 1 failed to bind to the R7V epitope whereas mutated clone 2 had similar binding pattern as the parent scFv. Mutated clone 2 was predicted to have a higher binding affinity compared to the parent scFv. The results obtained demonstrate the efficacy of EP PCR to generate high affinity antibodies. Future experiments using high affinity anti-R7V scFv’s may lead to its potential use in diagnostics, therapeutics or vaccine development. Copyright / Dissertation (MSc)--University of Pretoria, 2012. / Biochemistry / unrestricted

Purpose of the study - Identify predictors of mortality and develop a related care plan for patients who are on antiretroviral therapy (ART) in Gondar, Ethiopia. Design - A quantitative, retrospective cohort study was conducted analysing medical records of HIV patients who presented to Gondar University Hospital (GUH), Gondar, and started ART between 1 January 2007 and 30 June 2010. Results - In defining the predictors of mortality, the findings in bivariate analysis revealed: female sex, CD4 cell count ≤ 50/μl, CD4 cell count 51-199/μl, a haemoglobin concentration ≤8g/dl, a history of oral candidiasis, tuberculosis and Cryptococcus meningitis were all statistically significant. A female sex, CD4 cell count ≤ 50/μl and CD4 cell count 51-199/μl maintain their significance level in the multivariate analysis. Conclusions - The study therefore recommends that clinicians and case managers be vigilant of these predictors of mortality while managing HIV patients who are on ART. Key Concepts- ART, AIDS, HIV, predictors of mortality / Health Studies / (M.A. (Public Health))

Indiana University-Purdue University Indianapolis (IUPUI) / While insomnia/sleep disturbance has been identified as an independent predictor of cardiovascular disease in the general population, no studies have examined whether insomnia contributes to the elevated cardiovascular disease (CVD) risk in people with human immunodeficiency virus (HIV). Thus, the current study examined whether insomnia symptoms predict incident atherosclerotic CVD in the Veterans Aging Cohort Study 9 (VACS9), a prospective cohort of HIV-infected (n = 3,138) and uninfected (n = 3,010) Veterans utilizing self-report measures and administrative data. In partial support of my hypotheses, I found that HIV-infected Veterans bothered a lot by difficulty falling or staying asleep have greater CVD risk than HIV-infected Veterans without these symptoms. This study failed to replicate previous findings that insomnia symptoms are predictive of incident CVD in uninfected adults, which may be due to issues related to the validity of the insomnia symptoms assessment. A number of methodological issues are identified and considered in the interpretation of the current study results. Given the novelty of examining insomnia as a predictor of incident CVD in HIV-infected adults and the limitations of the present study, future research is needed to better elucidate the association between insomnia and future CVD in this population.

Introduction: Improvements in early detection of human immunodeficiency virus (HIV), linkage to treatment, and availability of antiretroviral therapy (ART) have contributed to increasing life expectancy for people living with HIV (PLHIV) in South Africa. These improvements have resulted in the decline of HIV cause-specific mortalities. In addition to existing tuberculosis burden in PLHIV, cases of chronic non-communicable diseases (NCDs) are increasing in the general population. Considering the ageing population of PLHIV in South Africa, it is important to understand their health needs, as well as identify potential drivers of comorbidities that may provide avenues for future interventions. This study aimed at exploring HIV and comorbidity profiles in a virtual cohort of a population of healthcare clients accessing care in public facilities in Khayelitsha, Cape Town. Methods: Routinely collected data for healthcare clients accessing care in public facilities in 2016/17 were obtained from the Western Cape Provincial Health Data Centre, and analysed to describe ascertained comorbidities, comparing the profiles of PLHIV and HIV-negative individuals. The risks of comorbidity occurrence in PLHIV, in the context of other comorbidities and HIV metrics such as ART duration, viral load and CD4 cell counts, including the contribution of comorbidities to unsuppressed viral load levels in PLHIV were explored. Findings: The findings show that accessing HIV care may lead to earlier ascertainment of common chronic NCDs – hypertension, diabetes, chronic kidney disease (CKD), cervical cancer in PLHIV, compared to HIV-negative clients. Analysis of routine health data suggests that ascertainment of comorbidities differs for healthcare clients due to sub-population differences including age, sex, HIV status and reasons for accessing care. Routine laboratory testing results for renal function reflect distinct healthcare experiences by age for healthcare clients with and without HIV. Analysis of routine data shows that presence of an existing comorbidity may contribute to the incidence of other comorbidities and unsuppressed viral load levels in PLHIV. Conclusion: From real life routine health data, this study has explored comorbidities profiles of PLHIV and HIV-negative clients and observed that routine health data could provide a better understanding of disease profiles, healthcare access and requirements for both PLHIV and HIV-negative clients.

No description available.

Thesis (Ph.D.)--University of Alabama at Birmingham, 2007. / Title from PDF title page (viewed on Sept. 16, 2009). Includes bibliographical references.

No description available.

Thesis advisor: Welkin Johnson / HIV-associated comorbidities including neurological disorders (HAND) and cardiovascular diseases (CVD) persist in people living with HIV (PLWH) regardless of adherence to antiretroviral therapies (ART). The development of these comorbidities correlates with increased monocyte/macrophages activation and accumulation. Studies report that the development of CVD and HAND are connected in PLWH, but few studies have examined the roles that monocyte/macrophages activation have in their co-development. We first asked how frequently CD8+ T lymphocyte depleted, SIV-infected rhesus macaques with AIDS co-developed cardiac pathology and SIV encephalitis (SIVE) compared to animals that developed CVD or SIVE alone, and animals with no significant cardiac pathology (NSF) and SIV with no encephalitis (SIVnoE) (Chapter 2). We sought to determine whether animals with concomitant CVD and SIVE had more monocyte activation, cardiac macrophages accumulation, and productively infected SIV-RNA+ and SIV- gp41+ cells in the heart and brain compared to animals with CVD or SIVE alone, and animals with NSF and SIVnoE. We found that animals with AIDS co-developed CVD and SIVE more frequently than animals developed CVD or SIVE alone, and NSF and SIVnoE. Animals with CVD and SIVE had increased biomarkers of monocyte activation, cardiac macrophages inflammation, and productively infected macrophages in the brain. We found that the quantity of SIV-RNA+ cells in the heart was sparse compared to the brain. When detected, cardiac SIV-RNA+ cells are CD68+ and CD206+ cardiac macrophages. Levels of plasma soluble CD163 (sCD163) correlated with plasma galectin-3 (Gal-3), galectin-9, and interleukin-18 (IL-18), more so than plasma viral load. We then assessed cardiac tissues from PWLH with HIV encephalitis (HIVE) and HIV no encephalitis (HIVnoE). We found that PLWH with HIVE had more cardiac inflammation and fibrosis than PLWH with HIVnoE. These findings indicate that CVD and HAND pathogenesis are connected, and that the level of myeloid cell activation correlates with the development and severity of concomitant CVD and HAND. The findings from this study emphasize the importance that macrophages accumulation has in developing AIDS-related comorbidities. Our findings highlight the importance of targeting monocyte/macrophages activation and accumulation in future HIV therapies. The persistence of CVD in the post-ART era suggests that ART successfully inhibits AIDS pathogenesis and HIV replication, but fails to block monocyte activation and macrophages accumulation correlated with CVD pathogenesis. We hypothesize that the optimal therapeutic approach for HIV-infection includes blocking AIDS pathogenesis and viral replication, and inhibiting monocyte/macrophages activation. Methylglyoxal-bis-guanylhydrazone (MGBG) is a polyamine biosynthesis inhibitor selectively taken up by monocytes and macrophages. MGBG treatment blocks monocyte/ macrophages activation in vitro, AIDS pathogenesis, and decreases inflammation in cardiac and brain tissues of SIV- infected rhesus macaques. We asked whether animals treated with ART and adjunct MGBG (ART+MGBG) had an additive decrease in monocyte activation and turnover, cardiac macrophages inflammation and collagen deposition compared to animals on ART, and untreated animals (Chapter 3). We found that animals on ART+MGBG had lower percentages of cardiac collagen deposition than animals on ART. Animals on ART, and ART+MGBG did not develop AIDS, and had decreased cardiac inflammation and collagen, and monocyte activation and turnover compared to untreated animals. Finally, we identified two populations of Gal-3 expressing (Gal-3+) cells in the heart, CD163+ Gal-3+ cardiac macrophages and CD163- Gal-3+ cells. Animals on ART, and ART+MGBG had decreased numbers of CD163+ Gal-3+ cardiac macrophages compared to untreated animals. All animals had similar numbers of CD163- Gal-3+ cells, and low frequencies of SIV-RNA+ cardiac macrophages regardless of treatment. These data suggests that blocking AIDS pathogenesis with ART, and ART+MGBG correlates with decreased monocyte activation and cardiac inflammation and collagen deposition. Overall, we did not find an additive effect in animals on ART+MGBG compared to animals on ART. Our findings show how targeting monocyte/macrophages activation with ART+MGBG blocks AIDS pathogenesis and decreases cardiac macrophages inflammation. This study demonstrates the advantages of therapeutic strategies blocking myeloid cell activation in conjunction with ART. / Thesis (MS) — Boston College, 2024. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Biology.

Women face a number of physical, emotional and psychological challenges following an HIV positive diagnosis during pregnancy. Psychological challenges, such as maternal anxiety and low mood, have been associated with disruptions to mother-infant bonding in the general population. Despite significant numbers of women receiving an antenatal HIV diagnosis in the UK each year, there remains a limited understanding about the experiences of this group in bonding with their babies. This Grounded Theory study aimed to explore the experience of mothers in bonding with their baby following an HIV diagnosis during pregnancy. The study explored the perceived challenges to mother-infant bonding, and the factors mothers felt helped them to manage this process following diagnosis. Ten mothers diagnosed antenatally at a London sexual health service were interviewed about their experiences. Data analysis led to a theoretical model of mother-infant bonding following a maternal HIV positive maternal diagnosis. The model comprised four theoretical codes: facing barriers to bonding; feeling disconnected from the baby; developing a special bond; and strengthening and moving on. These codes were comprised of challenges to mother-infant bonding, as well as factors relating to maternal strength and resilience. The model used a chronological structure, with processes plotted from the point of antenatal diagnosis through to following the infant HIV testing process after birth. Challenges with bonding were experienced primarily during the early stages after birth, with maternal resilience and positivity about the future developing towards the end of infant testing. Circular relationships, in which positive and negative processes fed into and influenced each other, were highlighted throughout. The findings highlight important areas for development in clinical practice, including more targeted psychological support for women following an antenatal diagnosis, and the provision of timely information regarding mother-to-child transmission. Clinical implications from this study are discussed alongside suggestions for future research.

Student Number : 8403267 - PhD thesis - School of Pathology - Faculty of Health Sciences / Sub-Saharan Africa is the eye of the HIV epidemic. This study was conducted when treatment for the majority of HIV-infected patients in low resource settings was considered unattainable and the risks of diagnosing HIV often outweighed the benefits. Coupled with the complexities of HIV diagnosis in infancy, children typically were only diagnosed once already ill or not at all. Key strategies to address the paediatric epidemic focused on preventing mother to child transmission and reducing mortality and morbidity of infected children predominantly with co-trimoxazole prophylaxis. Both strategies required early diagnosis of HIV infection in infancy for monitoring prevention programs and identifying infected children respectively. The diagnostic algorithm for resource limited settings recommended the use of inexpensive, technically simpler HIV antibody detection assays that are unsuitable for use in HIV-exposed children under 12-months of age. Paradoxically this algorithm provided a barrier to HIV diagnosis in children because of high loss to follow-up rates and death in the first year of life. The objective of this study was to establish an accurate, affordable diagnostic algorithm for early diagnosis of HIV infection that could be rapidly implemented in South Africa and benefit other resource limited settings. The HIV infection status of 300 vertically exposed infants was determined according to first world criteria in a prospective, cohort study at Coronation Hospital, Johannesburg over 21 months. This status was used to assess the accuracy of clinical examinations and HIV assays in diagnosing HIV at 6-weeks, 3-, 7- and 12-months of age. The average cost of determining an infant’s HIV infection status was measured. A single HIV DNA PCR test at 6-weeks of age proved highly accurate in determining HIV status at a marginally increased cost to government and was incorporated by the South African Department of Health into national policy. The ultrasensitive p24 antigen assay and HIV antibody detection assays on serum and oral fluid were identified as valuable candidates where PCR testing is unavailable. Dried blood spot samples from heelpricks are critical for policy to be translated into practice since skills to perform venesection in 6-week old babies are limited. The next challenge lies in operationalising these findings at a clinical and laboratory level to the benefit of the 300 000 South African children annually exposed to HIV at birth. The urgency of early diagnosis has been increased by the availability of highly effective antiretroviral therapy.