Objetivo: Evaluar si existe asociación entre el abandono con la falla terapéutica en inmigrantes venezolanos con infección por el virus de inmunodeficiencia humana (VIH) que reinicien tratamiento antirretroviral de gran actividad (TARGA). Métodos: Llevamos a cabo una cohorte retrospectiva en el Hospital Nacional Arzobispo Loayza. Incluimos pacientes que reiniciaron tratamiento TARGA. La variable de resultado fue la falla terapéutica (FT), compuesta por falla inmunológica (FI), virológica (FV) y clínica (FC). La variable de exposición fue el abandono terapéutico, aquellos que no recibieron tratamiento por 30 días, de 30 días a seis meses y de seis meses a más. Las variables control fueron el sexo, la orientación sexual, el nivel de instrucción, la edad y comorbilidades. Utilizamos modelos lineales generalizados de Poisson con errores estándar robustos para calcular riesgo relativo a nivel crudo (RR) y ajustado por criterio estadístico (RRa1) y epidemiológico (RRa2). Resultados: Incluimos 294 pacientes, 47,7% de ellos abandonaron TARGA, 32,7% abandono menos de seis meses, 15% abandonó mas de seis meses y el 27,9% tenían FT. Comparado con aquellos que no abandonaron, un abandono menor a 6 meses [RRa1: 1,98 (IC95%: 1,27 a 3,09);] y de seis meses a más [RRa1: 3,17 (IC95%: 2,02 a 4,95);] incrementó el riesgo de FT. El abandono de hasta seis meses [RRa1: 2,32 (IC95%: 1,40 a 3,84)] y de seis meses a más [RRa1: 3,93 (IC95%: 2,39 a 6,45)]; aumentó el riesgo de FV. En el caso de la FC [RRa1: 1,96 (IC95%: 0,67 a 5,79)] y la FI [RRa1: 2,99 (IC95%: 0,87 a 10,30)] no encontramos evidencia estadística de asociación con el abandono terapéutico. Conclusiones: El abandono del TARGA incrementa el riesgo de FT y FV en pacientes inmigrantes venezolanos. Dentro de la valoración integral que los pacientes con VIH debe explorarse el abandono como una variable de alta a importancia. / Objective: To evaluate the association between antiretroviral treatment interruption with the treatment failure in adults with human immunodeficiency virus (HIV) infection that reinitiates (HAART). Methods: We carried out a retrospective cohort study at the Hospital Nacional Arzobispo Loayza. We included immigrant patients who reinitiate HAART. The outcome was treatment failure (TF) may be immunological (IF), virological (VF), and clinical (CF) failure. The exposure variable was antiretroviral treatment interruption. The control variables measured were sex, sexual orientation, educational level, age, and comorbidities. We performed linear Poisson models with robust standard errors to calculate relative risk at the crude level (RR) and adjusted by statistical and epidemiological criteria. Results: We included 294 in the analysis. 47.7% of them defaulted treatment, 32.7% abandoned less than six months, 15% abandoned more than six months and 27.9% did TF; 24.6% VF; 6.8% IF, and 6.4% CF. A treatment interruption less than 6 months [aRR: 1.98 (95% CI: 1.27 to 3.09);] and from six months to more [aRR: 3.17 (95% CI: 2.02 to 4.95)] increased the risk of TF. Likewise, treatment interruption of up to six months [aRR: 2.85 2.32 (95% CI: 1.40 to 3.84)] and from six months to more [aRR: 3.93 (95% CI: 2.39 to 6,45)]; increased the risk of VF concerning patients who did not abandon treatment. In the CF [aRR: 1,96 (IC95%: 0,67 a 5,79)] and IF [aRR: 2,99 (IC95%: 0,87 a 10,30)] case, we did not find statistical evidence of an association with the abandonment time. Conclusions: The HAART treatment interruption is associated with the development of therapeutic and virologic failure. Treatment interruption should be explored as a variable of high importance in the assessment of patients with HIV. / Tesis

MPH / Department of Public Health

MPH / Department of Public Health / Background: South Africa presently has a very high HIV burden. It has adopted the UNAIDS “90-90-90 targets” to curb its HIV burden. This target aims to attain sustained viral suppression in 90% of all persons receiving antiretroviral therapy. This is supported by several studies. Studies to observe if patients are achieving and sustaining viral suppression in Limpopo, South Africa, are few. Objective: To investigate the viral and immunologic responses of patients in Vhembe District to highly active antiretroviral therapy (HAART) between the 1st of January 2004 and 31st of July 2016. Methodology: This was a retrospective medical record review conducted in Vhembe District in rural Limpopo. It included the medical records of 1247 individuals from Thohoyandou Community Health Centre. Analysis was done using SPSS 24.0. To model the factors associated with virologic and immunologic responses, each independent variable was tested for association with the dependent variable (viral suppression and CD4 count increase of ≥ 50 cells/μL from baseline to 6 months). The independent variables included age, year of initiation, gender, marital status, baseline BMI, haemoglobin, clinical stage and estimated creatinine clearance. The Pearson Chi square (X2) was used for all categorical independent variables and the t-test, for all continuous independent variables, to test for association. The estimate used was a 95% confidence interval, and a p-value of < 0.05 was considered significant. Results: The study showed that 52.6% of individuals were in clinical stage I at baseline. Viral suppression (viral load < 50 copies/ml) at 6 months was 64% (n = 648), 72% (n =193) at 60 months and 94% (n = 16) at 132 months. Fifty-nine percent had consistent viral suppression for a period of at least 6 months. Consistent viral suppression (viral load < 50 copies/ml on at least one consecutive occasion without any intervening viral load > 50 copies/ml) for at least 54 months was only 14%, while 2.3% had a delay in switching from a failing regimen. The mean CD4 count at baseline was 227 cells/μL, and 538 cells/μL at 60 months. The mean CD4 cell count increase from baseline to 6 months was 190 cells/μL. The immuno-virologic discordance was 27%. Patients with higher baseline CD4 count and females were significantly (p = 0.001 and 0.031 respectively) more likely to achieve viral suppression at 6 months. Those below 45 years and females were v significantly (p = 0.011 and 0.043 respectively) more likely to achieve adequate CD4 count increase at 6 months. Conclusions: The proportion of individuals with viral suppression in the District increased from 6 months onwards, and is fairly adequate. However, sustainability of viral suppression, once attained, is low. Adequate immunologic response, however, seems high. Males and age group above 45 years appear to have poorer responses to HAART.

Seule une minorité des individus infectés par le virus de l’immunodéficience humaine (VIH) développe une réponse immunitaire capable de contrôler le virus. Chez la plupart des individus, on observe un échappement virologique et un épuisement des lymphocytes T CD8+ spécifiques du VIH. L’infection chronique non-traitée altère également les lymphocytes T CD4+ spécifiques du VIH caractérisé par l’expression accrue des récepteurs co-inhibiteurs et une signature des cellules auxiliaires T folliculaires (Tfh). La thérapie antirétrovirale (TAR) est très efficace pour supprimer durablement la charge virale dans le plasma. Néanmoins, elle ne permet pas une éradication complète du VIH car le virus persiste, intégré dans le génome des cellules réservoirs, desquelles le virus réapparaît lors de l’interruption de la thérapie. Cela démontre que l'immunité adaptive spécifiques du VIH n'est pas restaurée. Les anticorps neutralisants à large spectre (bNAbs) représentent une alternative potentielle à la TAR. En plus de la neutralisation du virus – et contrairement à la TAR – les bNAbs ne limitent pas la disponibilité de l'antigène et peuvent engager le système immunitaire. L'administration de bNAbs à des macaques rhésus induit des réponses immunitaires adaptatives associées à un contrôle prolongé de la virémie, mais cela n’a pas été établi chez l’Homme. Dans cette thèse, nous avons donc exploré la modulation des réponses des lymphocytes T spécifiques du VIH lors d'une TAR standard et d’une immunothérapie utilisant des bNAbs. Dans un premier objectif nous avons analysé la modulation persistante des réponses des lymphocytes T CD4+ spécifiques du VIH chez les individus sous TAR. Nous avons pu démontrer l'expansion persistante des Tfh spécifiques au VIH avec des caractéristiques phénotypiques et fonctionnelles les distinguant des Tfh spécifiques d’antigènes viraux comparatifs (cytomégalovirus, virus de l’hépatite B). Ces caractéristiques ont été induites au cours de l’infection chronique non-traitée, persistaient pendant la TAR et étaient associées au réservoir du VIH compétent pour la traduction. Ces données suggèrent qu’une stimulation antigénique persistante, malgré une TAR efficace, maintient des modifications immunologiques notamment au niveau des Tfh. Dans un second objectif, nous avons caractérisé les réponses T spécifiques du VIH à la suite d’un traitement utilisant des bNAbs et une interruption structurée de la TAR (IST). Des individus inclus dans une étude clinique de phase Ib ont reçu une perfusion d’une combinaison des bNAbs 10-1074 et 3BNC117 et ont démontré une suppression virale prolongée après l’IST. Chez ces participants, nous avons observé une augmentation des réponses immunitaires des lymphocytes T CD8+ et CD4+ spécifiques du VIH due à l'expansion des réponses immunitaires préexistantes et au développement de réponses ciblant de nouveaux épitopes. Cela suggère que la combinaison d’un traitement par bNAbs avec l’IST est associée au maintien de la charge virale plasmatique indétectable et à une intensification de la réponse immunitaire des lymphocytes T spécifiques du VIH. Nos travaux permettent une meilleure compréhension des réponses des lymphocytes T spécifiques du VIH au cours de la TAR et lors d’une immunothérapie. Ils peuvent contribuer au développement de stratégies thérapeutiques plus efficaces visant à contrôler la réplication virale sans la TAR. / Only a small fraction of individuals infected with the human immunodeficiency virus (HIV) develops effective immune responses able to control the virus. In most individuals, the virus escapes the antiviral immune response and HIV-specific CD8+ T cell responses become exhausted. Untreated progressive HIV infection also leads to alterations in HIV-specific CD4+ T cells. This includes increased expression of co-inhibitory receptors and skewing towards a T follicular helper cell (Tfh) signature. Antiretroviral therapy (ART) is highly effective in controlling the HIV viral load at undetectable levels in the plasma. However, ART does not represent a cure as the virus integrates into the genome of infected cells from where the virus rebounds once ART is stopped. This demonstrates that the HIV-specific T cell immunity is not restored. However, the changes that are introduced during progressive infection and that are maintained after viral suppression with ART are poorly known. Broadly neutralizing antibodies (bNAbs) represent a potential alternative to ART. In addition to virus neutralization and unlike ART, bNAbs to do not limit HIV antigen availability and can engage the immune system. bNAb administration elicited adaptive immune responses that were associated with long-lasting viral control in a simian animal model but this has not been established in HIV-infected individuals. In this thesis, we therefore proceeded to study the modulation of HIV-specific T cell responses during standard ART and after an immunotherapeutic intervention using bNAbs. The first objective was to better understand persistent modulation of HIV-specific CD4+ T cell responses in ART-treated individuals. Our results demonstrated the persistent expansion of HIV-specific Tfh cell responses with multiple phenotypic and functional features that differed from Tfh cells specific for comparative viral antigens (cytomegalovirus, hepatitis B virus). These features were induced during chronic untreated HIV infection, persisted during ART and correlated with the translation-competent HIV reservoir. This suggests that persistent HIV antigen expression, despite effective ART, maintains these altered immunological features specifically for Tfh responses. For the second objective, we characterized changes in the HIV-specific CD8+ and CD4+ T cell immunity after bNAb treatment and analytical treatment interruption (ATI). For this, we used samples obtained from participants enrolled in a clinical phase Ib study that received combined infusion of bNAbs 10-1074 and 3BNC117 and demonstrated prolonged viral suppression after ATI. In these individuals, we detected an increase of HIV-specific CD8+ and CD4+ T cell responses during ART interruption when compared to baseline. Increased T cell responses were due to both expansion of pre-existing responses and the emergence of responses to new epitopes. In contrast, HIV-specific T cell responses remained unchanged in ART-treated individuals who did not receive bNAb infusions. This suggests that bNAb treatment and ATI is associated with increased HIV-specific T cell immunity while viral suppression is maintained. Together our results contribute to a better understanding of HIV-specific T cell responses during ART and immunotherapy treatment. Our findings may help to develop more effective HIV treatment strategies to improve the host’s immune system so that HIV can be controlled without the need for ART.

Few studies have assessed the optimum second line highly active anti-retroviral therapy (HAART) regimen in patients who had failed on the first-line HAART in resource-limited settings. This study aimed to compare the Protease inhibitor (PI)-based second line HAART regimens used in one clinic in Trinidad by comparing immunological, virological and clinical outcomes of patients on the different second line HAART regimens. The records of 35 treatment-experienced patients, over 21years of age and on PI-based regimens for at least six months, were analysed using SPSS version 20. The regimen containing TDF/FTC/AZT/LPV/r proved to produce superior outcomes compared to the other second line regimens. Due the small number of usable patients’ records, the findings cannot be generalised but indicate directions for future studies attempting to compare the treatment outcomes of different second line HAART regimens / Health Studies / M. A. (Public Health)

No description available.

Thesis (MPhil)--Stellenbosch University, 2013. / ENGLISH ABSTRACT: STUDY AIM The aim of the study is to explore the psychosocial characteristics of HIV positive clients who are yet to achieve viral load suppression after six months of commencing ARV at Sundumbili CHC in order to plan positive intervention strategies. RESEARCH DESIGN Non-experimental quantitative design was used in carrying out the study. The data was collected through retrieval of information from clinic records and completion of questionnaires to clients on ARV who met the inclusion criteria and consented to participating in the study. A total of 51 adults aged more than 18 years that were initiated in 2010/2011 and still access their treatment at Sundumbili CHC were enrolled into the study. They were selected through convenience sampling. FINDINGS Psychosocial challenges still exist among research participants whose viral load results were not suppressed after six months on ARV. This affected the adherence of some of them to their antiretroviral treatment. CONCLUSION Given the rural nature of Sundumbili and surroundings where the bulk of the patients reside, there are several psychosocial challenges affecting the patients. No known previous study has been undertaken to ascertain the psychosocial characteristics of this group of patients and the impact they may have on viral load suppression after six months of treatment. The study is therefore significant as the findings have provided more insight into the plight of the patients. It is envisaged that the recommendations from the study will assist the relevant management staff in the department in planning and subsequently implementing more positive intervention strategies. The strategies should be targeted at improving the quality of care of the HIV positive clients and attending to their psychosocial needs. / AFRIKAANSE OPSOMMING: STUDIEDOELWIT Die doel van die studie was om ondersoek in te stel na die psigososiale kenmerke van MIV-positiewe kliënte wie se virustellings ná ses maande van antiretrovirale (ARV) behandeling by die gemeenskapsgesondheidsentrum op Sundumbili steeds nie onder beheer was nie, ten einde positiewe intervensiestrategieë te beplan. NAVORSINGSONTWERP ’n Nie-eksperimentele kwantitatiewe ontwerp is gebruik om die studie te onderneem. Die data is ingesamel deur die herwinning van inligting uit klinieklêers sowel as die afneem van vraelyste onder kliënte op ARV’s wat aan die insluitingsmaatstawwe voldoen en tot deelname aan die studie toegestem het. Altesaam 51 volwassenes bo die ouderdom van 18 wat in 2010/2011 met ARV behandeling begin het en dit steeds by Sundumbili-gemeenskapsgesondheidsentrum ontvang, is in die studie opgeneem. Dié groep is deur middel van geriefsteekproefneming gekies. BEVINDINGE Psigososiale uitdagings was steeds te bespeur by navorsingsdeelnemers wie se virustellings nog nie ná ses maande op ARV’s onder beheer was nie. Dit het sommige se behandelingsgetrouheid beïnvloed. GEVOLGTREKKING In die lig van die landelike aard van Sundumbili en omgewing, waar die meeste van die pasiënte woon, kom pasiënte voor verskeie psigososiale uitdagings te staan. Daar is klaarblyklik nog nooit vantevore ’n studie onderneem om die psigososiale kenmerke van hierdie groep pasiënte, en die moontlike impak daarvan op die onderdrukking van virustellings ná ses maande van behandeling, te bepaal nie. Hierdie studie is dus waardevol, aangesien die bevindinge groter insig in die lot van die pasiënte bied. Daar word beoog dat die aanbevelings uit die studie tersaaklike bestuurspersoneel in die Departement van Gesondheid sal help om meer positiewe intervensiestrategieë te beplan en gevolglik in werking te stel. Die strategieë behoort daarop afgestem te wees om die gehalte van sorglewering aan MIV-positiewe kliënte te verbeter en in hul psigososiale behoeftes te voorsien.

AIM The purpose of this study was to explore and describe factors that contribute to the non-initiation of Antiretroviral Therapy (ART) amongst Pre-Antiretroviral Therapy eligible patients and to make recommendations for health care workers to enhance early initiation of pre-ART-eligible patients for primary health care facilities in Swaziland. METHOD A qualitative design was applied in rural primary health care (PHC) facilities in the Hhohho region of Swaziland. The target population for this study included nurses who have successfully completed the National Nurse Led Antiretroviral Therapy Initiation in Swaziland (NARTIS) training, and who actively initiated ART to eligible patients in rural PHC facilities. Data was collected through semi-structured interviews and field notes. Purposive, convenient sampling was applied. Eleven respondents were interviewed for the study, and data was collected until data saturation was reached. Data from transcripts and field notes was analysed and categorised with thematic analysis through Tesch’s open coding process. RESULTS The study identified the following three predominant themes: 1) systematic enablers of prompt ART initiation, 2) barriers to prompt ART initiation, 3) sources of support. Categories included public health care (PHC) factors, community level factors, the interdependence of the health care system, patient centred barriers, individual patient agency, and NARTIS nurse support. CONCLUSION The recommendations for health care workers that emerged from the study included continued HIV treatment scale-up and decentralisation to grass roots levels, aggressive treatment prioritisation among pre-ART patients, building the capacity of the local health care system and continued research initiatives. It is hoped that recommendations emerging from the findings of this study will have positive implications for programming and practice regarding the initiation of ART for eligible pre-ART patients in Swaziland. / Health Studies / M. PH.

The research objectives were to describe the age and gender of adult HIV positive clients on ART who received IPT; the incidence of tuberculosis among clients that received IPT and the defaulter rate among those that were commenced on IPT. Quantitative non-experimental descriptive retrospective cohort study was undertaken to ascertain the incidence of tuberculosis among adult HIV positive clients who received IPT. 104 clinic records of HIV positive adult clients accessing care at Isithebe Clinic, iLembe-South Africa who were commenced on IPT between 01 July 2010 and 30 November 2011 were analysed. The study found that 66 of 104 (63.5%) study respondents completed the course of IPT and the majority of those that defaulted were due to poor quality of care. Gender was statistically found to have played a role on whether a patient completes IPT. None of the study respondents that completed IPT was diagnosed with TB disease. / Health Studies / M.A. (Public Health)

The research objectives were to describe the age and gender of adult HIV positive clients on ART who received IPT; the incidence of tuberculosis among clients that received IPT and the defaulter rate among those that were commenced on IPT. Quantitative non-experimental descriptive retrospective cohort study was undertaken to ascertain the incidence of tuberculosis among adult HIV positive clients who received IPT. 104 clinic records of HIV positive adult clients accessing care at Isithebe Clinic, iLembe-South Africa who were commenced on IPT between 01 July 2010 and 30 November 2011 were analysed. The study found that 66 of 104 (63.5%) study respondents completed the course of IPT and the majority of those that defaulted were due to poor quality of care. Gender was statistically found to have played a role on whether a patient completes IPT. None of the study respondents that completed IPT was diagnosed with TB disease. / Health Studies / M.P.H.