The questionnaire text in English, Afrikaans and Native language / The aim of the study was to minimise non-adherence to antiretroviral (ARV) treatment amongst HIV/AIDS adult patients at a hospital in Namibia thereby promoting successful outcomes in patients on ARV treatment. A quantitative cross-sectional descriptive study was conducted on a sample of 112 non-adherent adults. Data collection was through structured interviews and patients’ records review. Data analysis was by descriptive statistics. Rate of non-adherence was 36.7%. Characteristics common in the sample were, being a woman, age of 31-45 years, being unmarried, low educational status, lack of HIV status disclosure, feeling that taking ARVs reminded one of HIV and experience of ARV side effects. Reasons for missed doses included forgetting, alcohol use, access to care, work commitments, lack of food, stress and travelling. Of the respondents, 86.6% had unsupressed viral loads. Recommendations include use of reminders, automated SMS, establishing treatment supporters and collaborative efforts in reducing active substance use to improve adherence. / Health Studies / M.A. (Nursing Science)

Magister Public Health - MPH / Antiretroviral regimens have side effects that can threaten adherence by patients resulting in evolution of viral resistance due to suboptimal drug levels. Studies have shown that drug adherence of at least 80% can result in viral load suppression. There is no literature on the association between the level of adherence to antiretroviral therapy and the degree of virological suppression in Namibia. The aim of the present study was to determine the therapeutic and virological outcomes in HIV/AIDS patients at 6 and 12 months after initiation of highly-active antiretroviral therapy (HAART) in an urban population in Namibia. The distribution of viral load results showed a low uptake (35%) of virological monitoring at 6 month time point and even lower (12%) at 12 months. A conservative viral load threshold for virological response is required in the Namibian setting. The current adherence level of >80% encourage increased ARV therapy rollout. Poor virological outcome was associated with self-reported adherence. / South Africa

Magister Curationis - MCur / Depression is defined as a psychiatric condition, wherein a person experiences extreme sadness, social withdrawal, and expresses self-deprecating thoughts. Across the world, millions of people with Human Infectious Virus (HIV) suffer from depression each year. Depression is regarded as the most common disabling medical condition that affects both HIV-positive and HIV-negative individuals, globally. It is further reported that depression is the most common neuropsychiatric disturbance observed in HIV infected individuals. In South Africa, the prevalence of depression symptoms among Antiretroviral Therapy (ART) clients is reported to be 25.4%. However, depression among this group is often underdiagnosed and untreated in Primary Health Care settings. The need for routine screening is encouraged by studies confirming that depression and anxiety disorders accelerate the progression of HIV disease. Methods A quantitative descriptive research design was used. The study population included 1 440 males and females, aged eighteen years and over, who were HIV positive and received ART at the Clinic. A randomly selected sample of 372 respondents were recruited, but 110 had to be excluded because of eligibility issues; therefore, 262 respondents completed the Beck Depression Inventory (BDI) questionnaire. Mann-Whitney U test, Fisher’s exact test and the Spearman Rank test were used to analyse the data, using GraphPad Prism software. Depression symptoms were evaluated, using BDI, and a score of -> 10 indicated depression. Results Of the 262 respondents, 52% had club membership, compared to 48%, who were only on ART. There were significantly more female respondents (44%) involved in Adherence Clubs, as opposed to their male counterparts (8%), a difference of 36% overall (p=0.016). In summary, the number of individuals, who were suffering from some form of depression, enrolled in ART Adherence Clubs was 8.4% of the total sample, compared to 10% of those who were not in ART adherence clubs. The overall prevalence of depression in this current study was 18.4 %, which was in line with other studies conducted in a South African context, and a similar setting. Clinical depression status represents the main outcome of interest in this research project. The model category was 0-10, which indicated that a significant majority, 69.5%, n= 182, of the enrolled respondents were classified as healthy, in terms of clinical depression status. Beck depression scores were consistent across gender. Depression seemed to be more severe in the 35-44 age category. Fisher’s exact test confirmed the absence of any statistical difference between ART club membership and their depression status. Spearman rank correlation coefficient of -0.02 indicates a very low association between length of HIV seropositivity and Beck Depression score. Conclusion This is the first study reporting on the prevalence of depression, in relation to HIV infection, as well as ART treatment, and the associated adherence programme in Cape Town. Further research on a similar topic is recommended, using other instruments in the same geographic area.

This non-experimental, retrospective, descriptive and correlational study investigated adherence to antiretroviral drugs among HIV positive patients at Mpilo Central Hospital in Bulawayo Zimbabwe. Data among 118 patients was extracted from clinic registers and patient facility held medical records to determine level of adherence to ART using pharmacy refills (a non-immunological adherence parameter) and compared to CD4 cell count ( an immunological adherence parameter). Adherence levels obtained in this study using pharmacy refills was low (62.7%) and a relatively high non-adherence level of 37.3%. The pharmacy refill adherence level obtained was comparable to CD4 cell count adherence level of 64.6% (as indicated by a 50% CD4 cell count gain). These findings would seem to indicate the need for more education on the importance of adherence and further the need for better adherence monitoring systems / Health Studies / M.A. (Public Health)

This non-experimental, retrospective, descriptive and correlational study investigated adherence to antiretroviral drugs among HIV positive patients at Mpilo Central Hospital in Bulawayo Zimbabwe. Data among 118 patients was extracted from clinic registers and patient facility held medical records to determine level of adherence to ART using pharmacy refills (a non-immunological adherence parameter) and compared to CD4 cell count ( an immunological adherence parameter). Adherence levels obtained in this study using pharmacy refills was low (62.7%) and a relatively high non-adherence level of 37.3%. The pharmacy refill adherence level obtained was comparable to CD4 cell count adherence level of 64.6% (as indicated by a 50% CD4 cell count gain). These findings would seem to indicate the need for more education on the importance of adherence and further the need for better adherence monitoring systems / Health Studies / M.A. (Public Health)

Des progrès importants ont été réalisés dans la thérapie des personnes vivant avec le VIH (PVVIH) avec le développement d’antirétroviraux (ARV) de plus en plus efficaces, sûrs avec une bonne innocuité et tolérance. Cependant, des défis thérapeutiques demeurent chez les PVVIH dont le VIH pourrait être porteur de mutations génétiques conférant de la résistance aux traitements soit en raison d’une histoire d’échec thérapeutique antérieur soit en raison d’une exposition antérieure à une mono/bithérapie aux inhibiteurs nucléosidiques de la transcriptase inverse (INTI) (thérapie sous-optimale qui se faisait avant l’ère des trithérapies). Chez ces patients, les cliniciens peuvent tenter des combinaisons peu étudiées dans l’espoir de mieux contrôler la charge virale ou de réduire les effets secondaires. Ainsi, cette thèse par articles avait trois objectifs qui visaient à étudier des thérapies utilisées chez ces patients mais pour lesquelles il y a peu ou pas de données. Le premier objectif (article 1) consistait à déterminer si l'efficacité du régime ARV avec dolutégravir chez les patients stables (dont la charge virale est supprimée) variait en présence d'une histoire d’échec virologique ou d’exposition antérieure à la thérapie sous-optimale. Le deuxième objectif (article 2) visait à comparer l’issue virologique des PVVIH stables ayant un échec virologique documenté ou une exposition antérieure à la thérapie sous-optimale et qui ont maintenu leur régime inhibiteur de la protéase/ritonavir (IP/r) par rapport à ceux qui sont passés au dolutégravir. Finalement, le troisième objectif (article 3) était de comparer le risque d’échec virologique chez les PVVIH avec une histoire d’échec virologique ou de thérapie sous-optimale prenant un traitement non standard d’ARV composé d’abacavir/ténofovir disoproxil (ABC/TDF) avec un 3e ARV d’une classe différente par rapport à un régime composé d’un traitement de fond standard. Nous avons utilisé les données de la cohorte VIH du Québec qui regroupe 10 219 PVVIH suivies au niveau de quatre centres à Montréal incluant la Clinique de médecine urbaine du Quartier Latin (CMUQL), la Clinique médicale l’Actuel (CMA), le Centre hospitalier universitaire de Montréal (CHUM) et le Centre universitaire de santé McGill (CUSM). Une restriction à certains patients a été réalisée pour chacun des objectifs. Les patients avec une charge virale indétectable qui avaient reçu une thérapie avec dolutégravir + 2 INTI à partir de 2013 ont été retenus pour l’objectif 1. Le modèle de risque proportionnel de Cox avec score de propension a été utilisé afin de comparer l’issue virologique des patients sous dolutégravir en fonction de l’exposition étudiée. Pour l’objectif 2, les patients stables avec une histoire d’échec virologique documenté ou d’exposition à une thérapie sous-optimale qui étaient sous IP/r + 2 INTI à partir de 2014 ont été sélectionnés. Le modèle de Cox structurel marginal a permis de voir l’effet du changement de traitement vers le dolutégravir + 2 INTI en comparaison avec ceux qui sont restés sur IP/r + 2 INTI. Pour l’objectif 3, les patients avec une histoire d’échec virologique documenté ou d’exposition à une thérapie sous-optimale qui étaient sous traitements de fond standards (abacavir/lamivudine, ténofovir disoproxil/emtricitabine, ténofovir disoproxil/lamivudine) avec un agent autre qu’un INTI à partir du 1er janvier 2006 ont été retenus. Le modèle multivarié proportionnel de Cox a été utilisé afin de comparer l’issue virologique des patients passés à un régime de thérapie inhabituelle à base d’ABC/TDF par rapport à ceux qui sont restés sur traitement de fond standard. L’article 1 a montré une efficacité similaire du dolutégravir chez les patients stables avec ou sans histoire d’échec virologique documenté ou d’exposition à une thérapie sous-optimale (Hazard ratio ajusté (HRa)=0,84 (IC95% : 0,35 - 2,01)). Dans l’article 2, aucune preuve d'un risque accru d'échec virologique n’a été trouvée chez les patients stables ayant déjà eu un échec virologique antérieur ou une exposition à une thérapie sous-optimale qui ont eu un changement de régime vers le dolutégravir en comparaison avec ceux qui ont maintenu leur régime IP/r (HRa=0,57 (IC95% : 0,21 - 1,52)). Dans l’article 3, une réduction non significative du risque d’échec virologique avec le traitement de fond non standard à base d’ABC/TDF a été trouvée par rapport au traitement de fond standard (HRa=0,45 (IC95% : 0,06 - 3,36)). En conclusion, les résultats de cette thèse n’ont pas montré un effet de la présence d’échec virologique antérieur ou d’exposition à une thérapie sous-optimale sur l’efficacité du dolutégravir. Par ailleurs, les résultats ont permis de constater que le changement vers le dolutégravir + 2 INTI pour des patients stables sur un régime IP/r + 2 INTI peut être envisagé malgré la présence ou la suspicion de mutation de résistance aux INTI. Ces résultats sont importants puisqu’ils devraient permettre de faire changer les guides cliniques concernant le dolutégravir chez les patients stables. Par contre, nos résultats n’ont pas réussi à montrer un avantage significatif à utiliser le traitement de fond à base d’ABC/TDF en comparaison au traitement de fond standard chez des patients présentant une histoire d’échec virologique ou d’exposition à la thérapie sous-optimale. / Significant progress has been made in treatment for people living with HIV (PLHIV) with the development of increasingly effective antiretroviral (ARV) therapy, safe with good tolerability. However, clinicians can sometimes face treatment challenges related to the monitoring of PLHIV whose HIV could carry genetic mutations conferring resistance to treatments either because of a history of virologic failure or because of previous exposure to mono/bitherapy to nucleoside reverse transcriptase inhibitors (NRTIs) (suboptimal therapy that was provided before the era of triple therapy). In these patients, clinicians can sometimes try less studied combinations in the hopes to better control viral load or reduce side effects in these patients. Therefore, this thesis by articles had three objectives aiming to evaluate less studied therapies that are used in these patients. The first objective (Paper 1) was to determine whether the efficacy of ARV regimen with dolutegravir in stable patients (whose viral load is controlled) varied in the presence of a history of virologic failure or with a previous exposure to suboptimal therapy regimen. The second objective (Paper 2) was to study virologic outcome after switching to dolutegravir compared to remaining on a boosted protease inhibitor (PI/r) regimen in stables PLHIV with prior documented virologic failure or exposure to mono/dual NRTI. Finally, the third objective (Paper 3) was to compare the risk of virologic failure for PLHIV who have previous documented virologic failure or prior exposure to suboptimal therapy taking an ARV therapy composed of abacavir/tenofovor (ABC/TDF) with a third agent of a different class, versus an ARV regimen composed of a standard backbone also with a non-NRTI third agent. We used data from the Quebec HIV cohort which brings together clinical information from 10,219 PLHIV followed in four clinical care centers in Montreal including the “Clinique de médecine urbaine du Quartier Latin (CMUQL)”, “Clinique médicale l’Actuel (CMA)”, the “Centre hospitalier de l'Université de Montréal (CHUM)” and the “McGill University Health Center (MUHC)”. A restriction to some patients in the cohort was made with regards to each objective of this thesis. Patients with an undetectable viral load who had received therapy with dolutegravir +2 NRTI from 2013 were selected for the objective 1. A Cox proportional hazard model with propensity score was used to compare the virologic outcome of patients on dolutegravir according to the exposure. For objective 2, patients with an undetectable viral load with an history of documented virologic failure or exposure to suboptimal therapy who were on PI/r + 2 NRTI from 2014 were selected. A marginal structural Cox model was used to measure the effect of switching to dolutegravir +2 NRTI compared to those who remained on PI/r + 2 NRTI therapy. For objective 3, patients with a documented virologic failure or exposure to suboptimal therapy in standard backbone (abacavir/lamivudine, tenofovir disoproxil/emtricitabine, tenofovir disoproxil/lamivudine) with another agent from January 01, 2006 were selected. A Cox proportional multivariate model was used to compare the virologic outcome of patients who switched to a non-standard regimen including ABC/TDF therapy versus those who remained on standard backbone. The article 1 suggested similar virologic efficacy of dolutegravir in stables patients with or without an history of documented virologic failure or exposure to suboptimal therapy (adjusted Hazard Ratio (aHR)=0,84 (95%CI: 0,35 - 2,01)). In article 2, no evidence of an increased risk of virologic failure was found in stables patients who had a regimen switched to dolutegravir compared to those who maintained their regimen with PI/r in patients who have had previous virologic failure or exposure to suboptimal therapy (aHR=0,57 (95%CI: 0,21 - 1,52)). In article 3, a non-significant reduction in the risk of virologic failure with the non-standard backbone including ABC/TDF was found compared to standard backbone (aHR=0,45 (95%CI: 0,06 - 3,36)). In conclusion, the results of this thesis first suggested no effect of the presence of previous virologic failure or exposure to suboptimal therapy on the efficacy of dolutegravir in stables patients. In addition, the results showed that the switch to dolutegravir +2 NRTI for patients with an undetectable viral load on PI/r +2NRTI regimen can be considered despite the presence of proved or suspected NRTI resistance mutation. These results are of great importance as they should lead to changes the clinical guidelines for the use of dolutegravir in stable patients. On the other hand, our results failed to show a significant advantage to the use of the backbone ABC/TDF instead of standard backbones in patients with prior documented virologic failure or previous exposure to suboptimal therapy.