Human immunodeficiency virus (HIV) infection has reached epidemic proportions in South Africa. The availability of highly active anti-retroviral therapy (HAART) prolongs life in HIV-infected persons, who may subsequently present with chronic manifestations of HIV-infection. The respiratory morbidity attendant to HIV-infection, even in the presence of HAART is high, the aftermath of which is lung tissue destruction and bronchiectasis. As a consequence of the political decision not to offer HAART to HIV-infected children, a number of children in South Africa have been left with severe consequences of uncontrolled HIV-infection. Bronchiectasis is one of those and because children with this devastating condition were numerous in the Pretoria region, the author and her colleagues began a Chronic Lung Disease Clinic in that region. This prompted the idea of investigating both the epidemiological profiles of these children and an attempt to intervene with both standard bronchiectasis guideline care and the use of a form of therapy commonly employed in other forms of bronchiectasis. This thesis explores those ideas. Important new and novel findings that were consequent were; that bronchiectasis is diagnosed late in HIV-infected children at a mean age of 6.9 years. The predominant organisms cultured from the airways are Haemophilus influenzae and parainfluenzae in 49% of samples. Pseudomonas aeruginosa (PA), common in cystic fibrosis (CF)-bronchiectasis is an uncommon pathogen in HIV-related bronchiectasis; isolated in only 2% of specimens. Tuberculosis (TB), at least as reported, is a significant antecedent of bronchiectasis, reported in 48.5%of children. A further 21.2% of the patients had received more than two courses of anti-TB treatment. However, proof of TB infection has been lacking. Respiratory morbidity is significant with the mean forced expiratory flow in one second (FEV1) of 53%, in this cohort at the time of presentation. Thirty-six percent of all children were exposed to environmental tobacco smoke, although this was not correlated with disease severity or HIVdisease progression. There is elevation of immunoglobulins in HIV-related bronchiectasis, with a mean IgE of 79 kU/l. This was not, though, associated with HIV disease progression as previously described in adult studies, nor with the presence of allergic bronchopulmonary aspergillosis (ABPA). The elevation in IgE was also not associated with an elevation of T helper-2 mediated cytokines, confirming the lack of association with atopy. The predominant cytokine, identified is interleukin (IL)-8, both systemically and locally (in airway secretions). There was elevation of other T helper-1 driven cytokines, reflecting an ability to mediate adequate inflammatory responses, which was independent of the level of immunosuppression. With the presence of HAART, there was a decline in the pro-inflammatory cytokines over time, which may be attributed to the ongoing effect of HAART that ties in to, or goes beyond the restoration of T cell numbers. Soluble triggering receptor expressed on myeloid cells (sTREM), an innate immune marker, is elevated in children with HIV-related bronchiectasis when compared to a control group of children with cystic fibrosis-related bronchiectasis. sTREM is not associated with the presence of exacerbations and the level of immunosuppression. The use of an anti-inflammatory drug erythromycin also did not impact the sTREM values. There was also no relationship between sTREM and pro and antiinflammatory cytokines and chemokines. Fluorine-18-fluorodeoxyglucose positron emission tomography (18F-FDG PET) could not reliably predict the presence of pulmonary exacerbations. Its diagnostic value was limited to identifying disease activity in acute pneumonia. 18F-FDG PET also had no significant correlation with CRP, inflammatory cytokines or markers of HIV disease activity. In a randomised controlled trial of erythromycin, a cost-effective immunomodulatory drug, compared to placebo, erythromycin was ineffective in reducing the number of pulmonary exacerbations. Erythromycin also failed to demonstrate any effect on systemic and local pro- and anti-inflammatory cytokines/chemokines. With access to anti-retroviral therapy, airway clearance, nutritional rehabilitation and vigilant follow up there was an improvement in pulmonary function parameters and stability of the degree of bronchiectasis that we propose is probably in keeping with an organ system disease modifying effect that may be, an as yet, undefined and undescribed byproduct of HAART. / Thesis (PhD)--University of Pretoria, 2012. / Paediatrics and Child Health / unrestricted

Introducción: El Síndrome Inflamatorio de Reconstitución Inmune ocurre por una recuperación rápida desregulada del sistema inmune tras el inicio de terapia antirretroviral en algunos pacientes, cuya causa más común es por tuberculosis. Este puede ser de tipo paradójico (empeoramiento de una enfermedad preexistente en tratamiento) o desenmascarado (luego del inicio de tratamiento). Pocos estudios han evaluado los factores de riesgo para el desarrollo de este síndrome en su forma desenmascarada. Objetivo: Determinar si el recuento de CD4 células/microL y otras covariables están asociadas al desarrollo de IRIS TB desenmascarada en pacientes que inician terapia antirretroviral en un hospital peruano. Materiales y métodos: Estudio caso control anidado en una cohorte retrospectiva, en base a registros clínicos de pacientes atendidos en el servicio de infectología del Hospital Nacional Arzobispo Loayza durante los años 2007-2018. Se evaluó la asociación mediante análisis bivariado y modelo de regresión logística. Resultados: En el análisis bivariado se encontró asociación entre IRIS TB desenmascarada y el valor de hemoglobina (p=0.015), recuento de CD4 ≤100 células/microL (p=0.002) y carga viral expresada en logaritmo de copias/ml (p=0.033). En el modelo ajustado se encontró asociación con el recuento de CD4 ≤100 células/microL (OR:4.16, IC: 1.09-15.98, p=0.038). Discusión: Es importante hacer un intensivo tamizaje de tuberculosis antes de iniciar terapia antirretroviral, especialmente en países donde hay elevada incidencia de esta enfermedad y estar alerta a los síntomas que presenten posterior al inicio de tratamiento, especialmente en los que presentan un recuento de CD4 ≤100 células/microL. / Introduction: Immune Reconstitution Inflammatory Syndrome occurs due to a rapid dysregulated recovery of the immune system after the start of antiretroviral therapy in some patients, which is most associated with tuberculosis. This can be paradoxical (worsening of a pre-existing disease under treatment) or unmasking (after the start of antiretroviral therapy). Few studies have evaluated the risk factors for the development of this syndrome in its unmasking form. Objective: To determine if the CD4 cells/microL count and other covariates are associated with the development of unmasking tuberculosis-associated IRIS in patients starting antiretroviral therapy in a Peruvian hospital. Materials and methods: Nested case control study, based on clinical records of patients treated in the infectious diseases service of a public hospital in Lima, Perú during the years 2007-2018. Association was evaluated using bivariate analysis and logistic regression model. Results: In the bivariate analysis, an association was found between unmasking tuberculosis-associated IRIS and the hemoglobin value (p = 0.015), CD4 count ≤100 cells/microL (p = 0.002) and viral load expressed in logarithm of copies/ml (p = 0.033). In the adjusted model, an association was found with the CD4 count ≤100 cells/microL (OR: 4.16, CI: 1.09-15.98, p = 0.038). Discussion: It is important to do an intensive screening for Tuberculosis before starting antiretroviral therapy, especially in countries where there is a high incidence of this disease and be alert to the symptoms they present after starting treatment, especially in those with a CD4 count of ≤100 cells/microL . / Tesis

Master of Public Health - MPH / Background: According to the Joint United Nations Programme on HIV/AIDS (UNAIDS) 340 000 children between 0-14years of age are living with HIV in South Africa as of 2019. Decentralization of HIV services was included in South Africa’s paediatric guidelines since 2010 in a bid to improve access to care. The current study sought to address the paucity of Eastern Cape (EC) data on the outcomes of down-referred paediatric antiretroviral therapy (ART) patients. These outcomes included retention in care (RIC) and virological suppression after 12 months Methodology: This retrospective analysis was conducted in the Buffalo City Municipality (BCM) district of the EC. The study population included HIV positive males and females, 0-14 years of age at transfer, who were initiated on ART at a tertiary or a regional hospital and subsequently down-referred, between June 2013 and June 2017. Data were collected from electronic databases at the facilities (Tier.net), patient files and patient registers. A descriptive analysis was performed using SPSS Statistics software version 26. Results: In total, 80.1% of patients successfully down-referred to a primary healthcare (PHC) facility, in a median of 42 days. Of those, 95.4% of patients were retained in care at 6 months and 93.1% at 12 months after arrival, with a median of 4 scheduled monthly visits missed. For those with results, virological suppression was maintained in 96.7% of patients at 6 months, 92.2% at 12 months and 96.2% for the entire post-transfer period of 2-14 months. In the 2-14 months post down-referral only 76.9% of patients had at least one viral load (VL) result and 50.3% had one CD4 result. For those with results, immune response (IR) to ART was maintained in 100% of patients at 6 months, 94.3% at 12 months and 97.7% in the 2-14 month period post successful down-referral. Conclusions: This study confirmed that loss to follow-up (LTFU) and treatment interruption at the point of transfer are significant risk factors for paediatric ART patients. This study also demonstrated high levels of RIC once patients had successfully down-referred. However, missed clinic visits suggest possible treatment interruptions for many patients post down-referral. While good virological and immunological responses to ART were maintained at the PHC facilities, suboptimal VL and CD4 monitoring was highlighted by the low proportion of available results. Therefore, while there are a number of issues to address, this study confirms that down-referral is a feasible option for up-scaling paediatric HIV care in the EC.

AIM The objective of this study is to determine factors that may contribute to hospital admissions in a cohort of medically insured South African patients in the era of HAART. METHODS This was a retrospective cohort of all HIV-positive adult and paediatric patients enrolled on a medical aid disease management programme in South Africa over a period of three years. Patient-specific demographic and clinical information were obtained from the medical aid records. Survival analysis was used to analyse time to first admission looking at admissions occurring after enrolment to the programme, during the study period of between 01 January 2006 and 31 December 2008. Only the right censored cases were included in the analyses. Descriptive analyses were conducted on the key prognostic factors. Variables that were significant in the univariate were considered in the multivariate Cox proportional hazards model. RESULTS A total of 8440 patients were included in the analysis. Half of these patients had at least one admission during the observation periods with 43.28% having had 2 or more admissions. The average admission rate was 2 admissions per patient over the 36 month observation period. Young children, adolescents and the very old (> 60 years) were significantly more likely to be admitted than the middle age groups, HR = 1.30 [95%CI 1.21 -1.40] p<0.01, 1.24 [95%CI 1.10 – 1.41] and 1.13 [95% CI 1.10 – 1.27] p<0.01 respectively. Low CD4 cell counts of < 200 cells/ µL were significantly associated with a higher likelihood of hospitalizations with hazard ratios even greater for CD4 cell counts of less than 100 cells/ µL, HR= 1.34 [95%CI 1.29 – 1.39], p<0.01. Cases were more likely to be admitted by a clinical haematologist or gynaecologist than by other specialist categories.HR =1.58 [95%CI 1.29 –1.94] and 1.17[95%CI 1.08 – 1.27] respectively with p<0.01. CONCLUSION Factors that are associated with hospital admissions in this private sector, medically insured population are a younger and older age, low CD4 cell counts and admission by a clinical haematologist and gynaecologist. These results suggest that disease management strategies should be intensified for the younger and older age groups. All HIV-positive patients should be closely monitored for CD4 deterioration so that treatment is initiated timeously. Routine haematological investigations should be recommended for all HIV-positive patients in order to pick up and treat haematological conditions before they result in a hospital admission. Evidence based guidelines, outlining the place of caesarian section deliveries in the HIV population, should be developed for use by gynaecologists specifically in the private sector. Copyright / Dissertation (MSc)--University of Pretoria, 2011. / Clinical Epidemiology / unrestricted

Introduction : Depuis 2015, l’OMS recommande la mise sous traitement antirétroviral systématique de tous les enfants infectés par le VIH pour réduire la mortalité précoce liée au VIH chez les nourrissons en l’absence de traitement. Cependant, malgré la disponibilité des tests de dépistage et des médicaments antirétroviraux, l’initiation précoce de ces traitements reste un défi majeur dans les pays à ressources limitées. L’étude ANRS 12140-PEDIACAM est mise en place pour évaluer la faisabilité, l’efficacité et la tolérance en routine du traitement précoce des enfants infectés par le VIH au Cameroun. Objectifs : Les objectifs de cette thèse visaient à étudier la mortalité et la réponse virologique à deux et quatre ans après l’initiation précoce d’un traitement antirétroviral chez les nourrissons infectés par le VIH, et à identifier les facteurs associés à l’obtention et au maintien d’un succès virologique.Méthodes : Les analyses ont porté sur les 190 enfants infectés par le VIH traités avant l’âge de 1 an (médiane=4 mois), inclus dans les trois sites cliniques du Cameroun participant à la cohorte prospective ANRS PEDIACAM initiée en 2007. La première étude a évalué les performances d’un critère basé sur le nombre de doses manquées de traitement rapporté dans un questionnaire d’observance pour dépister un échec virologique chez les nourrissons. La seconde étude portait sur l’estimation de la fréquence et des facteurs associés à l’obtention d’un succès virologique et à la mortalité à deux ans du traitement, utilisant un modèle de survie à risque compétitif. La troisième concernait l’évolution de la réponse virologique entre 2 et 4 ans du traitement selon le statut virologique obtenu à deux ans.Résultats : Les performances du questionnaire d’observance administré à l’accompagnant du nourrisson s’avèrent limitées, avec une valeur prédictive positive trop faible pour dépister un échec virologique en l’absence de charge virale disponible. La mortalité reste élevée à un an du traitement précoce (18,0% [IC95% : 13,0 - 24,0]). Elle est de 3,3% [IC95% : 0,4 - 6,2] entre 2 et 4 ans de traitement. La probabilité d’atteindre au moins un succès virologique avant 2 ans de traitement est de 80% environ, mais celle d’obtenir une suppression virologique maintenue sur au moins 6 mois n’est que de 67% au seuil de 1000 copies/mL, et de 60% au seuil de 400 copies/mL. A 4 ans du traitement initial, la proportion de charge virale contrôlée (<400 copies/mL) est de 75,2% [68,3-82,1]) chez les 144 enfants toujours vivants et suivis, mais pour 12% la charge virale n’a pas été mesurée. Le seul facteur associé significativement au succès virologique dans les 2 ans du traitement initial est la bonne observance rapportée par l’accompagnant. Et seuls un succès virologique obtenu à 2 ans et l’initiation plus récente du traitement antirétroviral sont associés à un charge virale contrôlée à 4 ans.Conclusion : Même si l’intérêt du traitement précoce des nourrissons infectés par le VIH est démontré, le succès virologique à moyen et long terme passe par des stratégies favorisant l’administration quotidienne soutenue des médicaments et une surveillance régulière de la réponse virologique. L’évaluation de l’observance par questionnaire présente une trop faible performance pour dépister précocement un échec virologique. Il est urgent de donner un accès large à la mesure de la charge virale en routine dans les pays à ressources limitées pour dépister rapidement les échecs virologiques chez les enfants recevant un traitement antirétroviral. / Introduction: Since 2015, the WHO recommends to start antiretroviral treatment promptly in all HIV-infected children in order to reduce HIV related mortality. Despite increasing availability of screening tests and antiretroviral drugs, early initiation of antiretroviral treatment (ART) remains challenging in resource-limited countries. The ANRS 12140-Pediacam study assesses feasibility, effectiveness and tolerability in routine practice of early treatment of HIV-infected children in Cameroon. Objectives: The objectives of this thesis are to study mortality and virologic response at 2 and 4 years of early initiation of ART in HIV-infected infants and identify factors associated with virologic success. Methods: The analysis concerned the 190 HIV-infected infants who have initiated ART no later than 1 year (median=4 months) and were enrolled in the 3 Cameroon clinical sites involved in the PEDIACAM prospective cohort study since 2007. The first study evaluated adherence criterium based on the number of missed doses as reported through an adherence questionnaire in oerder to detect virologic failure in infants. The second study concerned the evaluation of the frequency and the factors associated with virologic success and mortality at 2 years of ART initiation, using competing risk regression. The third study concerned the evolution of virologic response between 2 and 4 years of QRT initiation depending on virologic status achieved at 2 years of ART initiation. Results: The performances of adherence questionnaire administered to the infant's caregiver are limited; the positive predictive value is low for detecting virologic failure in the absence of viral load exam. The mortality is high at 1 year after early ART initiation (18.0% [95% CI: 13.0 – 24.0]). The mortality is 3.3% [95%CI: 0.4 – 6.2] between 2 and 4 years of ART initiation. The probability of achieving at least once virologic success within the first 2 years of ART is around 80.0% but the probability of maintaining virologic success for at least 6 months was 67% for threshold=1000 copies/mL and 60% for threshold=400 copies/mL. At 4 years of ART initiation, the proportion of virologic success (viral load<400 copies/mL) is 75.2% [68.3-82.1]) in the 144 children still alive among whom viral load exam was not performed. The only factor associated with virologic success at 2 years of ART initiation is good adherence as reported by the caregiver. Et seuls un succès virologique obtenu à 2 ans et l’initiation plus récente du traitement antirétroviral sont associés à un charge virale contrôlée à 4 ans.Conclusion: Although the interest of early ART in HIV-infected infants is demonstrated, the mid and long term virologic success pass through strategies enhancing supporting steady and daily administration of drugs and regular monitoring of virologic response. The steady evaluation of adherence as reported by questionnaire has a very low performance for early detecting virologic failure. It is urgent to widely get access to routine viral load exam in resource-limited countries for quickly detecting virologic failures in children receiving antiretroviral treatment.

Thesis (M.Sc. (Physiology)) -- University of Limpopo, 2021 / The purpose of this study was to investigate the effect of cART on renal function and assess the association between renal function and cardiovascular risk factors in a black rural HIV-positive population in Limpopo Province, Mankweng district. We have conducted a cross-sectional study which included both male and female cART-treated patients (n=84), cART-naïve patients (n=27) and HIV-negative controls (n=44). We have measured biomarkers of renal function (plasma cystatin C, clusterin, retinol binding protein 4 [RBP4]) and determined the estimated glomerular filtration rate (eGFR) using the chronic kidney disease-epidemiology collaboration formula (CKD-EPI). We have also measured blood pressure (BP), body mass index (BMI) and fasting blood glucose (FBG). The prevalence of renal dysfunction was similar among the study groups. A significant difference in RBP4 was found among the groups after controlling for covariates (age, gender, alcohol consumption, BMI, systolic blood pressure and FBG) (F (2, 146) = [4.479], p=0.010). The significant difference in RBP4 was specifically observed between the cART-treated and cART-naïve groups (p=0.008). Cystatin C, clusterin and eGFR were not significantly different among the study groups after controlling for the covariates. The cardiovascular risk factors age (β=0.207; p=0.039), CD4+ T-cell count (β=-0.236; p=0.040), and duration of cART (β=0.232; p=0.043) were independently associated with cystatin C. The use of cART independently associated with RBP4 (β=0.282; p=0.004). Age (β=-0.363; p=0.001), CD4+ T-cell count (β=0.222; p=0.034) and duration of cART (β=-0.230; p=0.034) independently associated eGFR. Renal dysfunction is common in this HIV-positive population, with similar rates as the HIV-negative population. Plasma cystatin C as a promising alternative renal biomarker need to be re-evaluated in this HIV-positive population. RBP4 may be a more promising renal function biomarker in the HIV-positive population. Cardiovascular risk factors are associated with renal dysfunction in this rural HIV-positive population and CD4+ T-cell count may be an independent predictor for renal function.

>Magister Scientiae - MSc / Background: Despite the effort of scientific research on HIV therapies and to reduce the rate of HIV infection, AIDS still remains one of the major causes of death in the world and mostly in Sub-Saharan Africa. To date, neither a cure, nor an HIV vaccine had been found and the disease can only be managed by using High Active Antiretroviral Therapy (HAART) if detected early. The need for an effective early diagnostic and non-toxic therapeutic treatment has brought about the necessity for the discovery of additional HIV diagnostic methods and treatment regimens to lower mortality rates. Antimicrobial Peptides (AMPs) are components of the first line of defence of prokaryotes and eukaryotes and have been proven to be promising therapeutic agents against HIV. Methods: With the utility of computational biology, this work proposes the use of profile search methods combined with structural modelling to identify putative AMPs with diagnostic and anti-HIV activity. Firstly, experimentally validated anti-HIV AMPs were retrieved from various publicly available AMP databases, APD, CAMP, Bactibase and UniprotKB and classified according to super-families. Hidden Markov Model (HMMER) and Gap Local Alignment of Motifs (GLAM2) profiles were built for each super-family of anti- HIV AMPs. Putative anti-HIV AMPs were identified after scanning genome sequence databases using the trained models, retrieved AMPs and ranked based on their E-values. The 3-D structures of the 10 peptides that were ranked highest were predicted using 1-TASSER. These peptides were docked against various HIV proteins using PatchDock and putative AMPs showing highest affinity and having the correct orientation to the HIV -1 proteins gp 120 and p24 were selected for future work so as to establish their function in HIV therapy and diagnosis. Results: The results of the in silica analysis showed that the constructed models using the HMMER algorithm had better performances compare to that of the models built by the GLAM2 algorithm. Furthermore, the former tool has better statistical and probability explanation compared to the latter tool. Thus only the HMMER scanning results were considered for further study. Out of 1059 species scanned by the HMMER models, 30 putative anti-HIV AMPs were identified from genome scans with the family specific profile models after elimination of duplicate peptides. Docking analysis of putative AMPs against HIV proteins showed that from the 10 best performing anti-HIV AMPs with the highest Escores, molecules 1,3, 8 and 10 firmly binds the gp120 binding pocket at the VIN2 domain and at the point of interaction between gp120 and T cells, with the 1st and 3rd highest scoring anti-HIV AMPs having the highest binding affinities. However, all 10 putative anti-HIV AMPs bind to the N-terminal domain of p24 with large surface interaction, rather than the C-terminal. Conclusion: The in silica approach has made it possible to construct computational models having high performances, and which enabled the identification of putative anti-HIV peptides from genome sequence scans. The in silica validation of these putative peptides through docking studies has shown that some of these AMPs may be involved in HIV/AIDS therapeutics and diagnostics. The molecular validation of these findings will be the way forward for the development of an early diagnostic tool and as a consequence initiate early treatment. This will prevent the invasion of the immune system by blocking the VIN2 domain and thus designing of a successful vaccine with broad neutralizing activity against this domain.

La thérapie antirétrovirale (TAR) réduit drastiquement la transmission verticale du VIH. Cependant, des études récentes démontrent une association entre l'utilisation de la TAR pendant la grossesse, particulièrement à base d’inhibiteurs de protéases (IP), et les issues adverses, notamment l’accouchement prématuré. Les objectifs principaux de mon mémoire étaient de caractériser le profil immunitaire/inflammatoire au niveau placentaire et systémique chez les personnes enceintes vivant avec le VIH (PEVVIH) et les comparer en fonction du statut VIH et de la classe de TAR. Au niveau placentaire, l'immunotypage des cellules Hofbauer a révélé que les placentas des PEVVIH contenaient un niveau significativement plus élevé de leucocytes CD45+ attribuable à une augmentation du nombre de cellules Hofbauer que le groupe contrôle. Les analyses multivariables ont révélé que cette augmentation des cellules immunitaires était associée à un profil prédominant CD163+ dans tous les sous-groupes de TAR par rapport au groupe de contrôle. Au niveau systémique, la quantification de 12 médiateurs inflammatoires dans le plasma périphérique a révélé que la TAR à base d'IP est associée à une libération de cytokines pro-inflammatoires et antivirales significativement plus élevée par rapport à la TAR à base d'InSTI aux deux trimestres étudiés, en plus d’être associée à l’accouchement prématuré et une charge virale plus élevée au deuxième trimestre. Ces résultats suggèrent que la classe de TAR n'affecte pas intrinsèquement la sélection des cellules Hofbauer CD163+ et CD68+ au niveau placentaire, mais que la TAR à base d'IP est associée à une réponse immunologique distincte qui augmente le risque d'accouchement prématuré. / Antiretroviral therapy (ART) drastically reduces vertical transmission of HIV. However, recent studies demonstrate an association between the use of ART during pregnancy, particularly protease inhibitor (PI)-based ART, and adverse outcomes, including preterm delivery. The main objectives of my dissertation were to characterize the inflammatory profile at the placental and systemic levels in pregnant people living with HIV (PPLWH) and compare them according to HIV status and ART class. At the placental level, Hofbauer cell immunotyping revealed that placentas of PPLWH contained a significantly higher number of CD45+ leukocytes due to an increase in Hofbauer cells compared to controls. Multivariate analyses revealed that this increase in immune cells was associated with a predominantly CD163+ profile in all ART subgroups compared with the control group. At the systemic level, the quantification of 12 inflammatory mediators in peripheral plasma revealed that PI-based ART was associated with significantly higher pro-inflammatory and antiviral cytokine release compared to InSTI-based ART in both trimesters studied, in addition to being associated with preterm delivery and higher viral load. These results suggest that the class of ART does not intrinsically affect the selection of CD163+ and CD68+ Hofbauer cells in the placenta, but that PI-based ART is associated with a distinct immunological response which may increase the risk of preterm delivery.

Human Immunodeficiency Virus (HIV) is a virus that is transmitted through certain bodily fluids and compromises the immune system of its host. Despite the emergence of antiretroviral therapy (ART) converting human immunodeficiency virus type 1 (HIV-1) infection from a fatal disease to a chronic condition, there is still no cure. ART frequently reestablishes peripheral CD4+ T cell counts, but persistent immune dysfunction and inflammation strongly correlate with increased risks of attaining non-AIDS morbidity and mortality. Elimination of this reservoir may occur by the proposed mechanism of combining latency-reversing agents (LRAs) with immune effectors, such as CD8+ T cells (Meås et al., 2020). Here, our study investigates Toll-like receptor 7/8 (TLR 7/8) superagonists that may act as potent, effective latency reversal agents (LRAs). Whether this will prove to be the case needs to be further studied, and potential adverse toxicities must be identified. Whether comparable results will be observed in peripheral blood mononuclear cells (PBMCs) infected with HIV-1 as in our study using PBMCs infected with simian immunodeficiency virus (SIV) remains to be tested. Our results provide further hope for a potential cure for HIV-infected individuals.

This study analysed data obtained from respondents and their medical records to determine the barriers and motivators for good adherence to ART. Respondents' records were also reviewed together with their pharmacy refill records to identify any correlation between .CD4 cell counts, viral load, VL and adherence to antiretroviral drugs at extension 15 ARV clinic in Gaborone, Botswana. The study investigated whether the combination of pharmacy refills and pill counts adherence measurement methodologies could predict immunological recovery and virologic response through increased CD4 cell counts and suppressed VL. . There was a positive relationship between adherence, CD4 cell counts and VL. Pharmacy refills and pill counts adherence measurement methodologies scored high on sensitivity, specificity, and positive predictive values but low on negative predictive values. / Health Studies / M.A. (Public Health)