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In sub-Saharan Africa, resource-limitation results in scarce availability of HIV prognostic tools such as CD4+ T-Lymphocyte (CD4) count and HIV viral load. To facilitate counselling and clinical decisions in this setting, widely available and inexpensive markers of prognosis are required. Chapter one gives an overview of the epidemiology and pathophysiology of HIV infection (with particular reference to sub-Saharan Africa), and its clinical manifestations. Staging systems for HIV infection and aspects of management in resource-poor environments are briefly discussed. Chapter two describes the epidemiological, pathophysiological and clinical aspects of tuberculosis (TB) in HIV infected patients, the commonest opportunistic infection in sub-Saharan Africa. It further provides HIV and TB prevalence data from the Western Cape, South Africa. In chapter three a study is presented demonstrating the usefulness of the total lymphocyte count (TLC) in combination with the World Health Organisation (WHO) clinical staging system to predict outcome in 831 HIV positive patients. A TLC of 1250/μL was found to be the equivalent of a CD4 count of 200/μL. Patients with early HIV disease (WHO stage 1&2) had low annual rates of progression to AIDS : 3-4% if the TLC was above 1250/μL, 12-14% if the TLC was below 1250/μL. Annual progression to AIDS increased to 25% and 46% in patients with clinical stage 3 and a TLC above or below 1250/μL respectively. Patients with AIDS had 30-55% one-year mortality rates depending on the TLC. Chapter four illustrates that pulmonary tuberculosis (PTB) in HIV infected patients presents with a radiographic spectrum reflecting the degree of HIV induced immune suppression. Chest radiographs and pre-treatment total lymphocyte counts provide prognostic information. Upper zone cavitatory infiltrates typical of reactivation PTB were associated with a preserved CD4 count (mean 389/μL) and predicted a 100% two-year survival. Pleural effusions were associated with a mean CD4 count of 184/μL and predicted 65% two-year survival. Patients with atypical radiographic presentation, including lower and mid-zone infiltrates, hilar and mediastinal adenopathy or interstitial patterns, had low CD4 counts (mean 105/μL) and a 36% survival at two years. Rather than classifying every patient with pleura-pulmonary tuberculosis as WHO stage 3, incorporation of the prognostic value of the chest radiograph into the clinical staging system, such that typical reactivation PTB becomes stage 2, tuberculous pleural effusion stage 3 and atypical PTB stage 4, would enhance the prognostic accuracy of HIV related tuberculosis. Chapter five demonstrates that patients with AIDS could be categorized accord ing to one of three survival patterns, relating to the type of opportunistic illness. One-year survival rates were highest for extra-pulmonary tuberculosis and herpes simplex virus infection (70% ); intermediate for oesophageal candidiasis, cryptococcal meningitis, kaposi sarcoma and pneumocystis carinii pneumonia (45%) ; and poorest for the HIV wasting syndrome, AIDS-dementia complex and performance status 4 (20%). Despite the overall poor prognosis associated with the acquired immunodeficiency syndrome, a substantial proportion of patients survive, even in the absence of anti-retroviral therapy, for a number of years. Chapter six concludes by proposing how the data presented in this thesis could be used in the clinical management of patients with HIV infection in a resource limited environment.

Includes bibliographical references / Introduction: Tuberculosis (TB) notification in South Africa has increased six fold over the last two decades mainly because of the Human Immunodeficiency Virus (HIV) epidemic. Globally, it was estimated that 73% of the TB cases were co-infected with HIV with more than 25% of this global co-infection burden being in South Africa alone. In 2012, globally 1.3 million deaths occurred due to TB; moreover 0.3 million were HIV-associated TB death. In 2010 TB was the leading cause of natural deaths in the population aged 15 to 24 years accounting for 14% of the total deaths in South Africa. In 2013 the proportion of patients with TB who were co-infected with HIV was extremely high at 62%.The outcome of co-infected patients was poorer than the outcome of HIV negative TB patients. However, there is little information available on the risk factors associated with TB treatment outcomes and the influence of co-infection. Method: A cross sectional study analysed Electronic TB Register (ETR.net) data from the Metro East Geographic Service Area (GSA) of the Cape Town Metro district. The dataset included adult patients aged 15 years or more, who initiated TB treatment between 1st July 2011 and 30th June 2012. In the descriptive analysis we analysed death separately but for the regression we merged death with unfavourable treatment outcome. Relative risks were used for measures of association. Univariate and multivariate analyses were performed using a generalized linear regression model. Statistically significant variables in the univariate analysis were included in the multivariate analysis. Findings: TB case notification in Eastern GSA was 922 per 100 000 population. Of the 12672 TB patients registered, 50% were co-infected with HIV. The incidence of death in co-infected was 5% versus 3% in uninfected, treatment success 67% versus 73% and unfavourable treatment outcome 28% versus 24%. The Khayelitsha sub-district had the highest proportion of the TB burden (37%) and of co-infection (65%). Fourteen percent of patients had extra-pulmonary TB (EPTB), 66% of whom were co-infected with HIV. In the multivariate analysis HIV (RR 1.2), retreatment (RR 1.4) and sputum smear microscopy not done (RR 1.4) were significantly associated with unfavourable treatment outcome. The sub districts Eastern (RR 0.9) and Northern (RR 0.7) were less likely to develop unfavourable outcome compared to Khayelitsha. In the stratified analysis, retreatment (RR 1.3) and smear not done (RR 1.3) were significant risk factors for an unfavourable treatment outcome in co-infected patients. Amongst HIV negative patients retreatment (RR 1.6) and smear not done (RR 1.6) were significant risk factors for an unfavourable treatment outcome. Conclusions: The incidence of TB is extremely high in the Eastern GSA of Cape Town however the prevalence of co-infection varies across the sub-districts. Although treatment outcomes have been improving, co-infection, retreatment and smear microscopy not done pre-treatment were factors significantly associated with an unfavourable treatment outcome. Eastern and Northern sub-districts were significantly more likely to have favourable treatment outcomes compared to Khayelitsha, where both TB incidence and HIV co-infection were greatest.

No / In this study, we assessed if the superimposition of incident sexually transmitted infections (STIs) on HIV phylogenetic analyses could reveal possible sexual behaviour misclassifications in our HIV-infected population. HIV-1 sequences collected between 1997 and 2014 from 1169 individuals attending a HIV clinic in Antwerp, Belgium were analysed to infer a partial HIV transmission network. Individual demographic, clinical and laboratory data collected during routine HIV follow-up were used to compare clustered and non-clustered individuals using logistic regression analyses. In total, 438 (37.5%) individuals were identified in 136 clusters, including 76 transmission pairs and 60 clusters consisting of three or more individuals. Individuals in a cluster were more likely to have a history of syphilis, Chlamydia and/or gonorrhoea (P < 0.05); however, when analyses were stratified by HIV transmission risk groups (heterosexual and men who have sex with men [MSM]), this association only remained significant for heterosexuals with syphilis (P = 0.001). Under closer scrutiny, this association was driven by six heterosexual men who were located in six almost exclusively MSM clusters. A parsimonious conclusion is that these six individuals were potentially misclassified as heterosexual. Improving the accuracy of sexual behaviour reporting could improve care.

Introdução: O Tratamento Preventivo com Isoniazida (TPI) é indicado para os pacientes com HIV/aids e infecção latente por Micobacterium tuberculosis (ILMTb) para os quais não haja contraindicação à Isoniazida. Entretanto, barreiras de acesso podem impedir que os pacientes realizem este tratamento. Objetivos: O presente estudo avaliou a taxa de acesso à prescrição médica do TPI em sujeitos com HIV/aids e ILMTb em seguimento em um serviço especializado de HIV/aids no período de fevereiro de 2005 a dezembro de 2009. Para os sujeitos que não tiveram acesso à prescrição do TPI, buscou-se, em prontuário, justificativas para esta conduta. Também foi identificado o perfil epidemiológico, clínico e demográfico dos sujeitos com HIV/aids e ILMTb e foi descrita a característica do médico que solicitou o teste tuberculínico (TT) e do que prescreveu o TPI. Métodos: No período de 02 de fevereiro de 2005 a 31 de dezembro de 2009 que estavam em seguimento no SEAP HIV/Aids foram incluídos sujeitos com HIV/Aids e ILMTB, diagnosticada através do Teste Tuberculínico (TT). Informações referentes às variáveis analisadas foram coletadas nos prontuários médicos e através de consulta ao Sistema de Informação e Gestão Hospitalar (SIGH) - Módulo Farmácia. Resultados: Foram incluídos 238 sujeitos dentre os 310 que tiveram TT > 5 mm no período do estudo. Destes, 70,6% (168) eram do sexo masculino; a média de idade foi de 42,6 anos; 88,2% (210) dos sujeitos tiveram acesso à prescrição do TPI. O acesso à prescrição do TPI foi associado à idade, ao tamanho da resposta ao TT, ao nadir de Linfócitos TCD4+ dos sujeitos em TARV e à presença de cicatriz de BCG. Sujeitos mais jovens, com resposta ao TT igual ou maior do que 10 mm e com cicatriz de BCG tiveram maior acesso à prescrição do TPI. Uma das questões a ser explorada em futuros estudos se refere aos fatores que influenciam, ou não, a decisão do profissional de introduzir este tratamento na situação em que o mesmo está recomendado tecnicamente. Conclusão: Os sujeitos mais jovens, com melhor situação imunológica de base, maior valor de resposta ao TT e com presença da cicatriz de BCG, tiveram maior acesso ao TPI. Neste estudo foi evidenciada a necessidade de que as instituições de saúde invistam em educação continuada de seus profissionais para elevarem a cobertura de ações programáticas, como é o tratamento da ILMTB, previsto nos programas nacionais de tuberculose e de HIV/aids. Além disso, é necessário que as equipes interdisciplinares atuem de forma integrada e harmônica, para garantir o acesso às ações de saúde. É possível identificar, porém muitas barreiras que restam para a serem rompidas de modo que os cidadãos que vivem com HIV/aids tenham acesso a este e aos demais tratamentos de que tenham necessidade / Background: Isoniazid Preventive Treatment (IPT) is recommended for patients with HIV/AIDS and Latent Infection by Mycobacterium tuberculosis (ILMTb) and no contraindication to isoniazid. However, access barriers may prevent patients to undergo to this treatment. Objectives: This study evaluated the rate of access to the prescription of IPT in subjects with HIV/aids and ILMTb followed up in a specialized HIV/aids from February 2005 to December 2009. For subjects who did not have access to the prescription of IPT, we sought, on records, justification for this conduct. Also, the epidemiological, clinical and demographic profile of individuals with HIV/AIDS and ILMTb and the characteristic of the doctor who requested the tuberculin skin test (TST) and prescribed IPT were identified. Methods: from 02 February 2005 to 31 December 2009 subjects followed up at SEAP HIV/aids with HIV/aids and ILMTB, diagnosed by Tuberculin Test (TST) were included. Information was collected from the medical records and from the Hospital Information and Management System (SIGH) - Pharmacy Module. Results: 238 subjects were included, among the 310 who had TST > 5 mm during the study period. Of these, 70.6 % (168) were male and the average age was 42.6 years, 88.2 % (210) had access to the prescription of IPT. Access to IPT prescription was associated with age , size of response to TST, nadir of lymphocytes CD4 + in subjects on ART and presence of BCG scar: younger subjects with response to TST equal to or greater than 10 mm and BCG scar had higher access rate to IPT prescription. An issue to be explored in the future refers to variables that influence the professional\'s decision to prescribe this treatment when it is technically recommended. Conclusion: younger subjects with better immune status at baseline, greater response to TST and presence of BCG scar, had more access to IPT. This study highlighted the need of educational programs for health professionals, in order to improve the coverage of activities devoted to reduce morbidity and mortality in HIV/aids patients, as is the treatment of ILMTB, recommended in national tuberculosis and HIV/AIDS programs. Furthermore, it is crucial, for interdisciplinary health teams, to operate in an integrated and harmonious way, to ensure, for HIV/aids patients, a healthy and longer life

Introdução: O Tratamento Preventivo com Isoniazida (TPI) é indicado para os pacientes com HIV/aids e infecção latente por Micobacterium tuberculosis (ILMTb) para os quais não haja contraindicação à Isoniazida. Entretanto, barreiras de acesso podem impedir que os pacientes realizem este tratamento. Objetivos: O presente estudo avaliou a taxa de acesso à prescrição médica do TPI em sujeitos com HIV/aids e ILMTb em seguimento em um serviço especializado de HIV/aids no período de fevereiro de 2005 a dezembro de 2009. Para os sujeitos que não tiveram acesso à prescrição do TPI, buscou-se, em prontuário, justificativas para esta conduta. Também foi identificado o perfil epidemiológico, clínico e demográfico dos sujeitos com HIV/aids e ILMTb e foi descrita a característica do médico que solicitou o teste tuberculínico (TT) e do que prescreveu o TPI. Métodos: No período de 02 de fevereiro de 2005 a 31 de dezembro de 2009 que estavam em seguimento no SEAP HIV/Aids foram incluídos sujeitos com HIV/Aids e ILMTB, diagnosticada através do Teste Tuberculínico (TT). Informações referentes às variáveis analisadas foram coletadas nos prontuários médicos e através de consulta ao Sistema de Informação e Gestão Hospitalar (SIGH) - Módulo Farmácia. Resultados: Foram incluídos 238 sujeitos dentre os 310 que tiveram TT > 5 mm no período do estudo. Destes, 70,6% (168) eram do sexo masculino; a média de idade foi de 42,6 anos; 88,2% (210) dos sujeitos tiveram acesso à prescrição do TPI. O acesso à prescrição do TPI foi associado à idade, ao tamanho da resposta ao TT, ao nadir de Linfócitos TCD4+ dos sujeitos em TARV e à presença de cicatriz de BCG. Sujeitos mais jovens, com resposta ao TT igual ou maior do que 10 mm e com cicatriz de BCG tiveram maior acesso à prescrição do TPI. Uma das questões a ser explorada em futuros estudos se refere aos fatores que influenciam, ou não, a decisão do profissional de introduzir este tratamento na situação em que o mesmo está recomendado tecnicamente. Conclusão: Os sujeitos mais jovens, com melhor situação imunológica de base, maior valor de resposta ao TT e com presença da cicatriz de BCG, tiveram maior acesso ao TPI. Neste estudo foi evidenciada a necessidade de que as instituições de saúde invistam em educação continuada de seus profissionais para elevarem a cobertura de ações programáticas, como é o tratamento da ILMTB, previsto nos programas nacionais de tuberculose e de HIV/aids. Além disso, é necessário que as equipes interdisciplinares atuem de forma integrada e harmônica, para garantir o acesso às ações de saúde. É possível identificar, porém muitas barreiras que restam para a serem rompidas de modo que os cidadãos que vivem com HIV/aids tenham acesso a este e aos demais tratamentos de que tenham necessidade / Background: Isoniazid Preventive Treatment (IPT) is recommended for patients with HIV/AIDS and Latent Infection by Mycobacterium tuberculosis (ILMTb) and no contraindication to isoniazid. However, access barriers may prevent patients to undergo to this treatment. Objectives: This study evaluated the rate of access to the prescription of IPT in subjects with HIV/aids and ILMTb followed up in a specialized HIV/aids from February 2005 to December 2009. For subjects who did not have access to the prescription of IPT, we sought, on records, justification for this conduct. Also, the epidemiological, clinical and demographic profile of individuals with HIV/AIDS and ILMTb and the characteristic of the doctor who requested the tuberculin skin test (TST) and prescribed IPT were identified. Methods: from 02 February 2005 to 31 December 2009 subjects followed up at SEAP HIV/aids with HIV/aids and ILMTB, diagnosed by Tuberculin Test (TST) were included. Information was collected from the medical records and from the Hospital Information and Management System (SIGH) - Pharmacy Module. Results: 238 subjects were included, among the 310 who had TST > 5 mm during the study period. Of these, 70.6 % (168) were male and the average age was 42.6 years, 88.2 % (210) had access to the prescription of IPT. Access to IPT prescription was associated with age , size of response to TST, nadir of lymphocytes CD4 + in subjects on ART and presence of BCG scar: younger subjects with response to TST equal to or greater than 10 mm and BCG scar had higher access rate to IPT prescription. An issue to be explored in the future refers to variables that influence the professional\'s decision to prescribe this treatment when it is technically recommended. Conclusion: younger subjects with better immune status at baseline, greater response to TST and presence of BCG scar, had more access to IPT. This study highlighted the need of educational programs for health professionals, in order to improve the coverage of activities devoted to reduce morbidity and mortality in HIV/aids patients, as is the treatment of ILMTB, recommended in national tuberculosis and HIV/AIDS programs. Furthermore, it is crucial, for interdisciplinary health teams, to operate in an integrated and harmonious way, to ensure, for HIV/aids patients, a healthy and longer life