Background: Given the rapid expansion of antiretroviral therapy (ART) services in South Africa, there is growing recognition of the importance of fertility intentions, contraceptive use and childbearing among women living with HIV (WLHIV). With the integration of family planning services in the prevention of mother-to-child transmission of HIV (PMTCT) services, understanding fertility intentions and contraceptive use is crucial in evaluating such programs. We investigated the relationship between future fertility intentions, contraceptive use and repeat pregnancies among WLHIV in Cape Town, South Africa. Methodology: We analyzed data from the MCH-ART study conducted at the Gugulethu Midwife Obstetric Unit (MOU) in Cape Town, South Africa, which followed women initiating ART during pregnancy through 36-60 months postpartum. Self-report data were collected using standardized questionnaires at repeated study visits. Data on repeat pregnancies were abstracted from the Western Cape Provincial Data Centre. Associations between maternal characteristics and repeat pregnancies were examined using Cox proportional hazards models. Results: Overall, 109 incident repeat pregnancies were recorded among the 471 women included in this analysis. The median time at risk per individual was 4.27 years. The rate of repeat pregnancies was 5.72 per 100 person-years (PY). This rate was significantly lower among women aged 35-45 years (2.11/100PY) compared to women aged 18-24 years [7.56/100 PY; adjusted hazard ratio (aHR), 0.26: 95% confidence interval [CI], 0.09, 0.81). A total of 333 women contributed data on future fertility intentions and contraceptive use at 12 months postpartum, with 9% reporting that they wanted another child in the future, and 82% reporting current contraceptive use; 16% (n=54) reported not wanting another child but no contraceptive use. The rate of repeat pregnancies was 3 folds higher among women who reported wanting a child in the future (12.59/100 PY) compared to women who did not want 5 a child in the future (4.31/100 PY; aHR, 3.46: 95% CI, 1.83, 6.50). Contraceptive use at 12 months postpartum was not associated with repeat pregnancies. Women who did not want a child and used contraceptives had a 45% decreased hazard of repeat pregnancies compared to women who did not want a child and did not use contraceptives (aHR 0.55: 95% CI [0.32, 0.94]. Conclusion: Among women initiating ART during pregnancy, a repeat pregnancy incidence rate of 5.72/100 PY was observed through 36-60 months postpartum, with the incidence lower among older women. At 12 months postpartum, a notable proportion of women reported not wanting another child but no contraceptive use. Wanting a child in the future was associated with a higher rate of repeat pregnancy, but contraceptive use at 12 months postpartum was not associated with repeat pregnancies. These results highlight the importance of understanding factors associated with the dissonance between fertility intentions and contraceptive use and childbearing to ensure delivery of quality integrated reproductive health services in the PMTCT framework.

The purpose of the study was to explore perceptions of PLWHA towards using traditional medicines (TM) together with antiretroviral therapy (ART). The study was conducted in two ART health facilities in the Manzini Region in Swaziland. Audiotaped individual interviews were conducted to collect data. The study population was PLWHA using TM and ART and were aged 18-49 years. Voice recording was used to capture data during the in-depth interviews until saturation was reached. One grand tour question was asked and follow-up probing questions were asked dependent on participant responses and study objectives. Findings of the study revealed that PLWHA are still searching for a cure, and the preexistence of TM prior to ART is influencing them to combine TM and ART. Several reasons for combining the two treatment modalities were, to boost the immune system, enhancing appetite, to treat opportunistic infections and ART side effects. There was stigma associated with long-life ART and discrimination for using TM experienced by PLWHA. It could benefit the country to repeat the similar research at National level, to include all the four regions, in both rural and urban settings. / Health Studies

No description available.

Orientador: Lenice do Rosário Souza / Banca: André Pentean Trindade / Banca: Cilmery Suemi Kurokawa / Banca: Érika Ferrari Rafael da Silva / Banca: Mariangela Ribeiro Resende / Resumo: O uso da terapia antirretroviral (TARV) tem aumentado a sobrevida com melhora da qualidade de vida das pessoas vivendo com HIV/Aids (PVHA), o que também tem resultado em maior expectativa de vida. A infecção crônica pelo HIV e seu tratamento prolongado têm sido associados a diversas complicações ou eventos tardios, tais como, doenças metabólicas, cardiovasculares e renais, anormalidades na densidade mineral óssea (DMO) e osteoporose. Assim, o uso crônico da TARV tem demonstrado alta prevalência de deficiência de vitamina D, maior declínio da DMO e aumento do risco de fraturas de quadril, coluna vertebral e punhos, que têm sido relacionados principalmente ao uso de efavirenz, tenofovir e/ou inibidores de protease. Objetivos: estimar a prevalência e os fatores de risco das alterações ósseas e de fraturas, pela ferramenta FRAX, verificando a interferência da TARV sobre o nível sérico da vitamina D e na DMO em portadores do HIV. Casuística e métodos: foram estudadas 160 PVHA, com idades acima de 20 anos, de ambos os sexos, que atenderam aos critérios de inclusão para o estudo. Tratouse de estudo observacional realizado no Serviço de Ambulatórios Especializados de Infectologia "Domingos Alves Meira", Botucatu/SP. Foram incluídos pacientes adultos, com idade de 20 anos ou mais, em uso ou não de TARV e excluídos gestantes e mulheres menopausadas, além de indivíduos com diagnóstico de hipogonadismo. Prontuários médicos além de questionário específico foram utilizados para... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The use of antiretroviral therapy (ART) has increased survival and improved quality of life for people living with HIV/Aids (PLWH), this therapy has also resulted in longer life expectancy. Chronic HIV infection and its prolonged treatment have been associated with various complications or late events, such as metabolic, cardiovascular and renal diseases, abnormalities in bone mineral density (BMD), and osteoporosis. Thus, chronic usage of ART, has caused high prevalence of vitamin D deficiency, greater decline in BMD, and increased risk of hip, spine and fist fractures, that has been mainly related to use of efavirenz, tenofovir and/or protease inhibitors. Objectives: To estimate the prevalence and risk factors of bone alterations and fractures using the fracture risk assessment tool (FRAX), to verify the interference of ART on the serum level of vitamin D and in BMD among HIV patients. Casuistry and methods: 160 PLWH were studied, of both sexes, with ages over 20 years, who meet inclusion criteria for the study. This observational study was performed at the Domingos Alves Meira Department of Specialized Ambulatory Infectology (SAEI-DAM) - Botucatu/SP/Brazil. The study included adult patients, aged 20 years or older, in regular use of ART or not; pregnant, menopausal women and individuals who had been diagnosed with hypogonadism were excluded. Medical records and a specific questionnaire were used to obtain demographic data, information on life habits, family and individual histories of bone fractures and antiretroviral uses. Serum dosages were measured, with chemiluminescence for vitamin D and parathyroid hormone and dry chemistry for calcium, phosphorus and alkaline phosphatase, CD4+ T lymphocyte counts were made using flow cytometry, HIV viral load determinations were taken using real-time PCR and sandwich enzyme linked immunosorbent assay (ELISA Kit Elabscience) was used for a ... (Complete abstract click electronic access below) / Doutor

Nous avons évalué l’accessibilité, l’acceptabilité et l’efficacité à 12 mois du traitement antirétroviral précoce (TAP) initié avant 2 ans chez l’enfant infecté par le VIH en Côte d’Ivoire et au Burkina Faso. Nous avons mené deux enquêtes de base, puis analysé le recrutement et la réponse dans la cohorte thérapeutique recrutée en amont de l’essai MONOD ANRS 12206. En dépit d’une couverture prénatale du dépistage VIH élevée de 88%, seulement 29% [IC à 95% : 27-32] des enfants exposés avaient eu accès au diagnostic virologique précoce en 2011 à Ouagadougou. En termes de connaissances, 97% des parents/tuteurs d’enfants connaissaient la principale voie de transmission du VIH chez les nourrissons. Tous les parents pensaient que le TAP de l’enfant était nécessaire, sans savoir en quoi il consistait. Parmi les 217 enfants référés pour inclusion, 161 (74%) ont initié un TAP à un âge médian de 13,5 mois ; 70% avaient atteint le stade 3/4 de l'OMS, et 57% un déficit immunitaire sévère. Les raisons de non-inclusion étaient : peur ou refus du père (48%), mortalité (24%), faux-positifs (16%), autres (12%). Avoir déjà partagé le statut VIH de l'enfant ou de la mère avec le père et avoir un âge ≥12 mois étaient les deux facteurs associés à l’initiation du TAP. Parmi les 156 enfants ayant reçu un TAP à base de LPV/r, 11 enfants sont décédés (7%), 5 perdus de vue (3%), 140 ont été suivis à 12 mois (90%), avec 70% de succès virologique (charge virale<500 cp/mL). En 2011-2013, les défis pour améliorer l’accès au TAP chez les enfants infectés par le VIH en Afrique de l'Ouest demeurent. L’accès tardif est associé à une forte mortalité précoce. Néanmoins, le taux de succès au TAP est élevé. / We assessed the accessibility, acceptability and efficacy at 12 months of early antiretroviraltherapy (EAT) initiated before two years of age in children HIV-infected in Côte d'Ivoire andBurkina Faso.We conducted two baseline surveys and analyzed the enrolment and therapeutic response inthe cohort recruited ahead of the MONOD ANRS 12206 trial.Despite a high prenatal HIV screening coverage of 88%, only 29% [95% CI: 27-32] exposedchildren had access to early HIV diagnosis in 2011 in Ouagadougou.In terms of knowledge, 97% of parents/caregivers of children were aware of the main route ofHIV transmission in infants. All the parents thought the child EAT was necessary, withoutreally know in what it consists.Among the 217 children referred for inclusion, 161 (74%) have initiated EAT with a medianage of 13.5 months; 70% had reached the 3/4 WHO stage, and 57% had a severe immunedeficiency. The reasons for non-inclusion were: fear or the father's refusal (48%), mortality(24%), false positives (16%), others (12%). Having already shared the child or the motherHIV status with the father and having an age ≥ 12 months were the factors associated with theinitiation of EAT.Among the 156 children who received an EAT-based lopinavir/ritonavir, 11 children died(7%), 5 were lost to follow-up (3%), 140 were followed for 12 months (90%), with 70%virological success (viral load <500 cp / mL).In 2011-2013, the challenges for improving access to EAT in HIV-infected children in WestAfrica remain. Late access is associated with a high early mortality. Nevertheless, the successrate of EAT is high.

Objective: The objective of this retrospective cohort study is to assess whether demographic and anthropometric parameters, laboratory tests, co-morbidity, co-infection, treatment regimen, IRIS and adherence predict response to HAART as measured by CD4 count, weight gain and functional status in a cohort of patients in Roma, the Kingdom of Lesotho. Method: Data were collected from a computerised database of the Antiretroviral Centre of the hospital. A cohort of 300 subjects was identified from hospital records from January 2007. Each of these subjects was followed up over a period of 12 months with data obtained for at least two visits within the 12-month span. Data were obtained on weight and CD4 at baseline, three months and also at six and 12 months, and data for haemoglobin were obtained only at 12 months. Variables that may be potential confounders were identified and univariate and multivariate logistic regression analyses were carried out to establish differences independent of confounding factors for the combined endpoints, as well as for each endpoint separately. Results: Three-hundred patient records were analysed. Approximately 70% of the patients had a CD4 increase of at least 150 cells over baseline values at the end of the review period and in 52.3% of the patients an increase in weight of 10% over baseline measurements was seen. Seventy-nine patients (26.3%) had a haemoglobin level of at least 14g/dL at 12 months, regardless of baseline values or gender. The inclusion of Zidovudine (AZT) in treatment regimens was found in 73% of the patients and in multivariate analysis AZT was associated with not having anaemia at the end of the review period. However there was a slight reduction in haemoglobin level in the first two to three months of therapy in comparison with both Stavudine (d4T) and Tenofovir (TDF) but not significant enough to result in clinical anaemia. Baseline CD4 values were similar for all treatments options but dissimilar in other outcome variables and continued to vary significantly throughout the review period. The outcomes of multivariate analyses suggest that the male gender appears to have better response to HAART as seen in each of the multivariate models. The most important determinant of haemoglobin response was baseline haemoglobin values. In the haemoglobin-associated multivariate model, HAART is associated with an increase in haemoglobin over baseline values. A history of TB prior to HAART was a major factor in weight response and it is thought to be as a result of IRIS, which is the unmasking of latent infections as the immune system reconstitutes. CD4 values have no direct influence on weight however, but an increase in weight was observed in all therapy groups. Conclusion: Clinical and immunological parameters can be used to monitor response to HAART and predict treatment outcomes. These parameters can be organised into monitoring tools that will be useful in resource-limited areas. This study suggests that AZT-containing regimens appear not to result in anaemia and that symptomatic anaemia might need additional investigation. Treatment with TDF appeared to have shown the best possible response pattern more but patients on TDF therapy will have to be included in the study to justify this observation. / Dissertation (MSc)--University of Pretoria, 2012. / Clinical Epidemiology / unrestricted

>Magister Scientiae - MSc / Background and Aims Human Immunodeficiency Virus (HIV) type 1 group M subtype C (HIV-1C) accounts for nearly half of global HIV-1 infections, with South Africa (SA) being one of the countries with the highest infection burden. In recent years, SA has made great strides in tackling its HIV epidemic, resulting in the country being recognized globally as the one sub-Saharan country with the largest combination antiretroviral therapy (cART) programme. Regardless of the potency of cART, the efficacy of the treatment is limited and hampered by the emergence of drug resistance. The majority of research on HIV-1 infections, effect of antiretroviral (ARV) drugs and understanding resistance to ARV drugs has been extensively conducted, but mainly on HIV-1 subtype B (HIV-1B), with less information known about HIV-1C. HIV-1’s viral Integrase (IN) enzyme has become a viable target for highly specific cART, due to its importance in the infection and replication cycle of the virus. The lack of a complete HIV-1C IN protein structure has negatively impacted the progress on structural studies of nucleoprotein reaction intermediates. The mechanism of HIV-1 viral DNA’s integration has been studied extensively at biochemical and cellular levels, but not at a molecular level. This study aims to use in silico methods that involve molecular modeling and molecular dynamic (MD) simulations to prioritize mutations that could affect HIV-1C IN binding to DNA and the IN strand-transfer inhibitor (INSTI) dolutegravir (DTG). The purpose is to help tailor more effective personalized treatment options for patients living with HIV in SA. This study will in part use patient derived sequence data to identify mutations and model them into the protein structure to understand their impact on the HIV-1C IN protein structure folding and dynamics. Methods Our sample cohort consisted of 11 sample sequences derived from SA HIV-1 treatmentexperienced patients who were being treated with the INSTI raltegravir (RAL). The sequences were submitted to the Stanford HIV resistance database (HIVdb) to screen for any new/novel variants resulting from possible RAL failure. Some of these new variants were analyzed to analyse their effect, if any, on the binding of DTG to the HIV-1C IN protein. Additionally, an HIV-1C IN consensus sequence constructed from SA’s HIV-1 infected population was used to model a complete three-dimensional wild type (WT) HIV-1C IN homology model. All samples were sequenced by our collaborators at the Division of Medical Virology, Stellenbosch University together with the National Health Laboratory Services (NHLS), SA. The HIV-1CZA WT-IN protein enzyme was predicted using SWISS-MODEL, and the quality of the resulting model validated. Various analyses were conducted in order to study and assess the effect of the selected new variants on the protein structure and binding of DTG to the IN protein. The mutation Cutoff Scanning Matrix (mCSM) program was used to predict protein stability after mutation, while PyMol helped to study any changes in polar contact activity before and after mutation. PyMol was also used to generate four mutant HIV-1C IN complex structures and these structures together with the WT IN were subjected to production MD simulations for 150 nanoseconds (ns). Trajectory analyses of the MD simulations were also conducted and reported. Results A total of 21 new variants were detected in our sample cohort, from which only six were chosen for further analyses within the study. A homology model of HIV-1C IN was successfully constructed and validated. The structural quality assessment indicated high reliability of the HIV-1C IN tetrameric structure, with more than 90.0% confidence in modelled regions. Of the six selected variants, only one (S119P) was calculated to be slightly stabilizing to the protein structure, with the other five found to be destabilizing to the IN protein structure. Variant S119P showed a loss in polar contacts that could destabilize the protein structure, while variant Y143R, resulted in the gain of polar contacts which could reduce flexibility of the 140’s region affecting drug binding. Similarly, mutant systems P3 (S119P, Y143R) and P4 (V150A, M154I) showed reduced hydrogen bond formation and the weakest non-bonded pairwise interaction energy. These two systems, P3 and P4, also showed significantly reduced to none polar contacts between DTG, magnesium (MG) ions and the IN protein, compared to the WT IN and P2 mutant IN systems. Interestingly, the WT structure and systems P1 (I113V) and P2 (L63I, V75M, Y143R) showed the highest non-bonded interaction energy, compared to systems P3 and P4. This was further supported by the polar interaction analyses of simulation clusters from the WT IN and mutant IN system P2 (L63I, V75M, Y143R), which were the only protein structures that formed polar contacts with DTG, MG ions and DDE motif residues, while P1 only made contacts with DNA and IN residues. Conclusion Findings from this study leads to a conclusion that double mutants (S119P, Y143R) and (V150A, M154I) may result in a reduction in the efficacy of DTG, especially when in combination. Furthermore, variants identified in systems P1 and P2 may still allow for effective DTG binding to IN and outcompete viral DNA for host DNA to prevent strand transfer. To the best of our knowledge, this is the first study that uses the consensus WT HIV1C IN sequence to build an accurate 3D homology model to understand the effect of less frequently detected/reported variants on DTG binding in a South African context. https://etd.

Magister Public Health - MPH / Background: With the improvements in the effectiveness and availability of antiretroviral therapy (ART), perinatally infected children are surviving to adolescence and emerging as a significant sub-population living with HIV/AIDS in Zimbabwe. Adolescents, aged 10-19 years, face unique challenges related to adherence to chronic medication due to this period of vulnerability that is characterised by decreased parental support and supervision, decreased inhibition, increased risk-taking, and immature judgement. It is widely reported that poor adherence to ART leads to viral rebound, disease progression and drug resistance, in addition to increasing the risk of transmitting resistant strains of HIV to others. It is imperative to determine the factors that influence ART adherence among HIV positive adolescents so that effective interventions can be put in place. The current study described the factors that are associated with adherence to ART among HIV positive adolescents in Zimbabwe. Methodology: A cross-sectional survey of 136 randomly selected adolescents (10-19 years) who were receiving ART at two referral hospitals in Masvingo District in 2019 was undertaken. A questionnaire was administered to collect data on socio-demographic characteristics, adherence and factors related to adherence such as person/patient, health system, medication, disease characteristics and social factors. Clinical data were extracted from the Electronic Monitoring Patient System. SPSS v24 was used for descriptive and inferential analysis. Results: More than half of the participants (61%) had combined optimal adherence (dose adherence, schedule adherence and adhered to dietary instructions) in the previous three days. The most frequent reasons reported for missing HIV medications in the previous month was being away from home (50%); forgetfulness (25%); and having too many pills to take (25%). In bivariate analysis, only duration of time since HIV diagnosis was significantly associated with combined adherence to ART in the previous three days. Conclusion: Tailored interventions are recommended to address low adherence amongst adolescents. These interventions should include convenient clinic appointment schedules for adolescents to pick up medication, reminders to take medication, regimen change to a single dose, and peer education and adherence clubs to improve knowledge about HIV and treatment, and curb treatment fatigue.

Master of Public Health - MPH / Background: HIV/AIDS remains a major public health issue that is affecting all population groups and communities in Zambia. Among the most affected groups are key populations (KPs) such as female sex workers. KPs are considered at high risk of contracting HIV but have limited access to HIV services and retention in care due to internalized stigma, discrimination, criminalization, and negative attitudes towards HIV treatment. Under the USAID Open Doors project in Zambia, KPs access comprehensive HIV prevention, care and treatment services. The test and treat strategy is implemented by the project in support of the UNAIDS 90-90-90 targets by 2020 to diagnose 90% of people living with HIV, put 90% of them on treatment, and for 90% of them to have suppressed viral load. Aim: This study aimed to determine retention in care among female sex workers (FSWs) in the first six months after ART initiation using the HIV care cascade. Methodology: A retrospective cohort study was conducted of all new HIV positive female sex workers (FSWs) initiated on ART between October 2018 and June 2019 (9 months period) based on the electronic records. Data were extracted from SmartCare, an electronic health record system used by the ART clinic. Microsoft Excel and Epi-Info 7 software were used for data entry and analysis. Kaplan–Meier survival analysis was conducted to examine differences in retention rates. Results: A total of 205 FSWs were initiated on ART, out of which 180 were active on ART (36 youths and 144 adults) and 25 were lost to follow-up (four youths and 21 adults) during the 9 months study period. Of the 180 FSWs active on ART, 36 were FSWs aged 18 – 24 years (youths) representing 90% retained in care while 144 were FSWs aged 25 – 42 years (adults) with 87% being retained on ART treatment. Retention in ART care was not significantly different in the survival curves between the age groups of FSW youths and FSW adults during the study period (p-value = 0.637). Retention in ART care was not statistically significant for education (p-value = 0.481), marital status (p-value = 0.545), and occupation (p-value = 0.169). Conclusion: Retention in ART care among FSWs was 88%. However, there were no significant differences by age group identified in this study. While this study shows 88% retention rate among FSWs, it will be used as a baseline in meeting the UNAIDS 90-90-90 goals.

Patients with human immunodeficiency virus (HIV)/AIDS live a far different life today compared with those who were infected in the 1980s and 1990s. Antiretroviral therapy has evolved from a once poorly tolerated, heavy pill burden to the availability of many once-daily single-tablet regimens. The improvements in therapy have necessitated the need to be cognizant of comorbidities as well as drug-drug interactions. Despite the tremendous advances in therapy, newer therapies are in the pipeline and continue to emerge, making care for patients burdened by HIV perhaps easier than it has ever been.