Characteristics and comprehensiveness of adult HIV care and treatment programmes in Asia-Pacific, sub-Saharan Africa and the Americas: results of a site assessment conducted by the International epidemiologic Databases to Evaluate AIDS (IeDEA) Collaboration

INTRODUCTION HIV care and treatment programmes worldwide are transforming as they push to deliver universal access to essential prevention, care and treatment services to persons living with HIV and their communities. The characteristics and capacity of these HIV programmes affect patient outcomes and quality of care. Despite the importance of ensuring optimal outcomes, few studies have addressed the capacity of HIV programmes to deliver comprehensive care. We sought to describe such capacity in HIV programmes in seven regions worldwide. METHODS Staff from 128 sites in 41 countries participating in the International epidemiologic Databases to Evaluate AIDS completed a site survey from 2009 to 2010, including sites in the Asia-Pacific region (n=20), Latin America and the Caribbean (n=7), North America (n=7), Central Africa (n=12), East Africa (n=51), Southern Africa (n=16) and West Africa (n=15). We computed a measure of the comprehensiveness of care based on seven World Health Organization-recommended essential HIV services. RESULTS Most sites reported serving urban (61%; region range (rr): 33-100%) and both adult and paediatric populations (77%; rr: 29-96%). Only 45% of HIV clinics that reported treating children had paediatricians on staff. As for the seven essential services, survey respondents reported that CD4+ cell count testing was available to all but one site, while tuberculosis (TB) screening and community outreach services were available in 80 and 72%, respectively. The remaining four essential services - nutritional support (82%), combination antiretroviral therapy adherence support (88%), prevention of mother-to-child transmission (PMTCT) (94%) and other prevention and clinical management services (97%) - were uniformly available. Approximately half (46%) of sites reported offering all seven services. Newer sites and sites in settings with low rankings on the UN Human Development Index (HDI), especially those in the President's Emergency Plan for AIDS Relief focus countries, tended to offer a more comprehensive array of essential services. HIV care programme characteristics and comprehensiveness varied according to the number of years the site had been in operation and the HDI of the site setting, with more recently established clinics in low-HDI settings reporting a more comprehensive array of available services. Survey respondents frequently identified contact tracing of patients, patient outreach, nutritional counselling, onsite viral load testing, universal TB screening and the provision of isoniazid preventive therapy as unavailable services. CONCLUSIONS This study serves as a baseline for on-going monitoring of the evolution of care delivery over time and lays the groundwork for evaluating HIV treatment outcomes in relation to site capacity for comprehensive care.

Essentials from the 2015 European AIDS Clinical Society (EACS) guidelines for the treatment of adult HIV-positive persons.

BACKGROUND The European AIDS Clinical Society (EACS) guidelines are intended for all clinicians involved in the care of HIV-positive persons, and are available in print, online, and as a free App for download for iPhone and Android. GUIDELINE HIGHLIGHTS The 2015 version of the EACS guidelines contains major revisions in all sections; antiretroviral treatment (ART), comorbidities, coinfections and opportunistic diseases. Among the key revisions is the recommendation of ART for all HIV-positive persons, irrespectively of CD4 count, based on the Strategic Timing of AntiRetroviral Treatment (START) study results. The recommendations for the preferred and the alternative ART options have also been revised, and a new section on the use of pre-exposure prophylaxis (PrEP) has been added. A number of new antiretroviral drugs/drug combinations have been added to the updated tables on drug-drug interactions, adverse drug effects, dose adjustment for renal/liver insufficiency and for ART administration in persons with swallowing difficulties. The revisions of the coinfection section reflect the major advances in anti-hepatitis C virus (HCV) treatment with direct-acting antivirals with earlier start of treatment in individuals at increased risk of liver disease progression, and a phasing out of interferon-containing treatment regimens. The section on opportunistic diseases has been restructured according to individual pathogens/diseases and a new overview table has been added on CD4 count thresholds for different primary prophylaxes. CONCLUSIONS The diagnosis and management of HIV infection and related coinfections, opportunistic diseases and comorbidities continue to require a multidisciplinary effort for which the 2015 version of the EACS guidelines provides an easily accessable and updated overview.

Incidence of AIDS-Defining and Other Cancers in HIV-Positive Children in South Africa: Record Linkage Study.

BACKGROUND Little is known on the risk of cancer in HIV-positive children in sub-Saharan Africa. We examined incidence and risk factors of AIDS-defining and other cancers in pediatric antiretroviral therapy (ART) programs in South Africa. METHODS We linked the records of five ART programs in Johannesburg and Cape Town to those of pediatric oncology units, based on name and surname, date of birth, folder and civil identification numbers. We calculated incidence rates and obtained hazard ratios (HR) with 95% confidence intervals (CI) from Cox regression models including ART, sex, age, and degree of immunodeficiency. Missing CD4 counts and CD4% were multiply imputed. Immunodeficiency was defined according to World Health Organization 2005 criteria. RESULTS Data of 11,707 HIV-positive children were included in the analysis. During 29,348 person-years of follow-up 24 cancers were diagnosed, for an incidence rate of 82 per 100,000 person-years (95% CI 55-122). The most frequent cancers were Kaposi Sarcoma (34 per 100,000 person-years) and Non Hodgkin Lymphoma (31 per 100,000 person-years). The incidence of non AIDS-defining malignancies was 17 per 100,000. The risk of developing cancer was lower on ART (HR 0.29, 95%CI 0.09-0.86), and increased with age at enrolment (>10 versus <3 years: HR 7.3, 95% CI 2.2-24.6) and immunodeficiency at enrolment (advanced/severe versus no/mild: HR 3.5, 95%CI 1.1-12.0). The HR for the effect of ART from complete case analysis was similar but ceased to be statistically significant (p=0.078). CONCLUSIONS Early HIV diagnosis and linkage to care, with start of ART before advanced immunodeficiency develops, may substantially reduce the burden of cancer in HIV-positive children in South Africa and elsewhere.

When to Monitor CD4 Cell Count and HIV RNA to Reduce Mortality and AIDS-Defining Illness in Virologically Suppressed HIV-Positive Persons on Antiretroviral Therapy in High-Income Countries: A Prospective Observational Study.

OBJECTIVE To illustrate an approach to compare CD4 cell count and HIV-RNA monitoring strategies in HIV-positive individuals on antiretroviral therapy (ART). DESIGN Prospective studies of HIV-positive individuals in Europe and the USA in the HIV-CAUSAL Collaboration and The Center for AIDS Research Network of Integrated Clinical Systems. METHODS Antiretroviral-naive individuals who initiated ART and became virologically suppressed within 12 months were followed from the date of suppression. We compared 3 CD4 cell count and HIV-RNA monitoring strategies: once every (1) 3 ± 1 months, (2) 6 ± 1 months, and (3) 9-12 ± 1 months. We used inverse-probability weighted models to compare these strategies with respect to clinical, immunologic, and virologic outcomes. RESULTS In 39,029 eligible individuals, there were 265 deaths and 690 AIDS-defining illnesses or deaths. Compared with the 3-month strategy, the mortality hazard ratios (95% CIs) were 0.86 (0.42 to 1.78) for the 6 months and 0.82 (0.46 to 1.47) for the 9-12 month strategy. The respective 18-month risk ratios (95% CIs) of virologic failure (RNA >200) were 0.74 (0.46 to 1.19) and 2.35 (1.56 to 3.54) and 18-month mean CD4 differences (95% CIs) were -5.3 (-18.6 to 7.9) and -31.7 (-52.0 to -11.3). The estimates for the 2-year risk of AIDS-defining illness or death were similar across strategies. CONCLUSIONS Our findings suggest that monitoring frequency of virologically suppressed individuals can be decreased from every 3 months to every 6, 9, or 12 months with respect to clinical outcomes. Because effects of different monitoring strategies could take years to materialize, longer follow-up is needed to fully evaluate this question.

Cross-culture perspectives on fear of HIV disease and AIDS in health care workers

Health care workers have been known to carry into the workplace a variety of judgmental and negative attitudes towards their patients. In no other area of patient care has this issue been more pronounced as in the management of patients with AIDS. Health care workers have refused to treat or manage patients with AIDS and have often treated them more harshly than identically described leukemia patients. Some health care institutions have simply refused to admit patients with AIDS and even recent applicants to medical colleges and schools of nursing have indicated a preference for schools in areas with low prevalence of HIV disease. Since the attitudes of health care workers do have significant consequences on patient management, this study was carried out to determine the differences in clinical practice in Nigeria and the United States of America as it relates to knowledge of a patient's HIV status, determine HIV prevalence and culture in each of the study sites and how they impact on infection control practices, determine the relationship between infection control practices and fear of AIDS, and also determine the predictors of safe infection control practices in each of the study sites.^ The study utilized the 38-item fear of AIDS scale and the measure of infection control questionnaire for its data. Questionnaires were administered to health care workers at the university teaching hospital sites of Houston, Texas and Calabar in Nigeria. Data was analyzed using a chi-square test, and where appropriate, a student t-tests to establish the demographic variables for each country. Factor analysis was done using principal components analysis followed by varimax rotation to simple structure. The subscale scores for each study site were compared using t-tests (separate variance estimates) and utilizing Bonferroni adjustments for number of tests. Finally, correlations were carried out between infection control procedures and fear of AIDS in each study site using Pearson-product moment correlation coefficients.^ The study revealed that there were five dimensions of the fear of AIDS in health care workers, namely fear of loss of control, fear of sex, fear of HIV infection through blood and illness, fear of death and medical interventions and fear of contact with out-groups. Fear of loss of control was the primary area of concern in the Nigerian health care workers whereas fear of HIV infection through blood and illness was the most important area of AIDS related feats in United States health care workers. The study also revealed that infection control precautions and practices in Nigeria were based more on normative and social pressures whereas it was based on knowledge of disease transmission, supervision and employee discipline in the United States, and thus stresses the need for focused educational programs in health care settings that emphasize universal precautions at all times and that are sensitive to the cultural nuances of that particular environment. ^

CONHECIMENTOS E PREVENÇÃO DE DST/AIDS EM ADOLESCENTES

A Psicologia da Saúde vem se desdobrando para atender a demanda da saúde pública, principalmente sobre prevenção de doenças e promoção da saúde. No que se refere a epidemia da AIDS e outras doenças sexualmente transmissíveis, o adolescente tem sido o público mais vulnerável. A adolescência é considerada uma fase perturbada e perturbadora. Nesse período da vida o adolescente está mais sujeito à contaminação das DST/AIDS em razão da instabilidade emocional e sua postura frente a valores e padrões de conduta. Este estudo tem por objetivo descrever conhecimentos e comportamentos de proteção e risco de práticas sexuais de adolescentes; descrever dados sócio-econômicos e demográficos desses adolescentes, descrever o conhecimento dos adolescentes em relação as DST/AIDS e descrever os comportamentos de proteção e riscos a respeito das DST/AIDS. A população deste estudo foi constituída por 95 adolescentes de ambos os gêneros, com um predomínio do gênero masculino, faixa etária entre 14 e 21 anos e com renda familiar média de 4 (quatro) salários mínimos. Trata-se de pesquisa descritiva, para o qual utilizou-se um questionário de autopreenchimento composto por questões norteadas ao tema. A coleta de dados ocorreu em sala de aula no período noturno, de uma escola estadual do município de Guarulhos. Após o término do preenchimento do questionário, os adolescentes assistiram uma palestra de prevenção e orientação sobre DST/AIDS, onde elucidaram dúvidas. Os resultados demonstram 67,4% dos adolescentes, tanto o gênero feminino quanto o gênero masculino, tem dificuldades de definir o conceito de sexualidade e 84,2% sabem corretamente a definição de doenças sexualmente transmissíveis. A maioria dos adolescentes (67,4%) respondeu conhecer algum tipo de doença sexualmente transmissível, destacando-se aqui a AIDS e a gonorréia. O gênero masculino teve início da vida sexual aos 10 anos e o gênero feminino aos 13 anos, representando 53,7% com vida sexual ativa. Neste estudo 58,9% informam saber quais são os comportamentos de proteção, porém entre estes, apenas 55,8% utilizam o preservativo masculino (camisinha). Não há diferenças significativas quanto à modalidade de relacionamento e o uso constante do preservativo masculino. Verificou-se que 63,1% dos adolescentes obtém informações e conhecimentos sobre as DST/AIDS através dos profissionais da educação e da saúde. Portanto, a sala de aula passa a ser um fator de proteção. Esse estudo confirma que parte dos adolescentes tem conhecimento e informações sobre conceitos relativos as DST/AIDS, porém quanto às práticas para um comportamento de proteção frente às mesmas apresentam conhecimentos frágeis, gerando assim comportamentos de risco. Estas situações comprometem a tomada de comportamentos de proteção. Portanto, um programa contínuo da área da saúde e da educação dentro da escola que desenvolva atividades interativas a fim de transformar o comportamento do adolescente sobre informações e conhecimentos em consciência de comportamentos de proteção efetivas poderá melhorar essa relação entre ter o conhecimento e utilizá-lo na prática.(AU)

CONHECIMENTOS E PREVENÇÃO DE DST/AIDS EM ADOLESCENTES

A Psicologia da Saúde vem se desdobrando para atender a demanda da saúde pública, principalmente sobre prevenção de doenças e promoção da saúde. No que se refere a epidemia da AIDS e outras doenças sexualmente transmissíveis, o adolescente tem sido o público mais vulnerável. A adolescência é considerada uma fase perturbada e perturbadora. Nesse período da vida o adolescente está mais sujeito à contaminação das DST/AIDS em razão da instabilidade emocional e sua postura frente a valores e padrões de conduta. Este estudo tem por objetivo descrever conhecimentos e comportamentos de proteção e risco de práticas sexuais de adolescentes; descrever dados sócio-econômicos e demográficos desses adolescentes, descrever o conhecimento dos adolescentes em relação as DST/AIDS e descrever os comportamentos de proteção e riscos a respeito das DST/AIDS. A população deste estudo foi constituída por 95 adolescentes de ambos os gêneros, com um predomínio do gênero masculino, faixa etária entre 14 e 21 anos e com renda familiar média de 4 (quatro) salários mínimos. Trata-se de pesquisa descritiva, para o qual utilizou-se um questionário de autopreenchimento composto por questões norteadas ao tema. A coleta de dados ocorreu em sala de aula no período noturno, de uma escola estadual do município de Guarulhos. Após o término do preenchimento do questionário, os adolescentes assistiram uma palestra de prevenção e orientação sobre DST/AIDS, onde elucidaram dúvidas. Os resultados demonstram 67,4% dos adolescentes, tanto o gênero feminino quanto o gênero masculino, tem dificuldades de definir o conceito de sexualidade e 84,2% sabem corretamente a definição de doenças sexualmente transmissíveis. A maioria dos adolescentes (67,4%) respondeu conhecer algum tipo de doença sexualmente transmissível, destacando-se aqui a AIDS e a gonorréia. O gênero masculino teve início da vida sexual aos 10 anos e o gênero feminino aos 13 anos, representando 53,7% com vida sexual ativa. Neste estudo 58,9% informam saber quais são os comportamentos de proteção, porém entre estes, apenas 55,8% utilizam o preservativo masculino (camisinha). Não há diferenças significativas quanto à modalidade de relacionamento e o uso constante do preservativo masculino. Verificou-se que 63,1% dos adolescentes obtém informações e conhecimentos sobre as DST/AIDS através dos profissionais da educação e da saúde. Portanto, a sala de aula passa a ser um fator de proteção. Esse estudo confirma que parte dos adolescentes tem conhecimento e informações sobre conceitos relativos as DST/AIDS, porém quanto às práticas para um comportamento de proteção frente às mesmas apresentam conhecimentos frágeis, gerando assim comportamentos de risco. Estas situações comprometem a tomada de comportamentos de proteção. Portanto, um programa contínuo da área da saúde e da educação dentro da escola que desenvolva atividades interativas a fim de transformar o comportamento do adolescente sobre informações e conhecimentos em consciência de comportamentos de proteção efetivas poderá melhorar essa relação entre ter o conhecimento e utilizá-lo na prática.(AU)

Extracellular HIV-1 virus protein R causes a large inward current and cell death in cultured hippocampal neurons: Implications for AIDS pathology

The small HIV-1 accessory protein Vpr (virus protein R) is a multifunctional protein that is present in the serum and cerebrospinal fluid of AIDS patients. We previously showed that Vpr can form cation-selective ion channels across planar lipid bilayers, introducing the possibility that, if incorporated into the membranes of living cells, Vpr might form ion channels and consequently perturb the maintained ionic gradient. In this study, we demonstrate, by a variety of approaches, that Vpr added extracellularly to intact cells does indeed form ion channels. We use confocal laser scanning microscopy to examine the subcellular localization of fluorescently labeled Vpr. Plasmalemma depolarization and damage are examined using the anionic potential-sensitive dye bis(1,3-dibutylbarbituric acid) trimethine oxonol and propidium iodide (PI), respectively, and the effect of Vpr on whole-cell current is demonstrated directly by using the patch-clamp technique. We show that recombinant purified extracellular Vpr associates with the plasmalemma of hippocampal neurons to cause a large inward cation current and depolarization of the plasmalemma, eventually resulting in cell death. Thus, we demonstrate a physiological action of extracellular Vpr and present its mechanistic basis. These findings may have important implications for neuropathologies in AIDS patients who possess significant amounts of Vpr in the cerebrospinal fluid.

Identification of inflections in T-cell counts among HIV-1-infected individuals and relationship with progression to clinical AIDS

Studies of circulating T (CD3+) lymphocytes have shown that on a population basis T-cell numbers remain stable for many years after HIV-1 infection (blind T-cell homeostasis), but decline rapidly beginning approximately 1.5–2.5 years before the onset of clinical AIDS. We derived a general method for defining the loss of homeostasis on the individual level and for determining the prevalence of homeostasis loss according to HIV status and the occurrence of AIDS in more than 5,000 men enrolled in the Multicenter AIDS Cohort Study. We used a segmented regression model for log10 CD3+ cell counts that included separate T-cell trajectories before and after a time (the T-cell inflection point) where the loss of T-cell homeostasis was most likely to have occurred. The average slope of CD3+ lymphocyte counts before the inflection point was close to zero for HIV− and HIV+ men, consistent with blind T-cell homeostasis. After the inflection point, the HIV+ individuals who developed AIDS generally showed a dramatic decline in CD3+ cell counts relative to HIV− men and HIV+ men not developing AIDS. A CD3+ cell decline of greater than 10 percent per year was present in 77% of HIV+ men developing AIDS but in only 23% of HIV+ men with no onset of AIDS. Our findings at the individual level support the blind T-cell homeostasis hypothesis and provide strong evidence that the loss of homeostasis is an important mechanism in the pathogenesis of the severe immunodeficiency that characterizes the late stages of HIV infection.

Control of HIV-1 viremia and protection from AIDS are associated with HLA-Bw4 homozygosity

Certain HLA-B antigens have been associated with lack of progression to AIDS. HLA-B alleles can be divided into two mutually exclusive groups based on the expression of the molecular epitopes HLA-Bw4 and HLA-Bw6. Notably, in addition to its role in presenting viral peptides for immune recognition, the HLA-Bw4, but not HLA-Bw6, motif functions as a ligand for a natural killer cell inhibitory receptor (KIR). Here, we show that profound suppression of HIV-1 viremia is significantly associated with homozygosity for HLA-B alleles that share the HLA-Bw4 epitope. Furthermore, homozygosity for HLA-Bw4 alleles was also significantly associated with the ability to remain AIDS free and to maintain a normal CD4 T cell count in a second cohort of HIV-1-infected individuals with well defined dates of seroconversion. This association was independent of the presence of a mutation in CC chemokine receptor 5 (CCR5) associated with resistance to HIV-1 infection, and it was independent of the presence of HLA alleles that could potentially confound the results. We conclude that homozygosity for HLA-Bw4-bearing B alleles is associated with a significant advantage and that the HLA-Bw4 motif is important in AIDS pathogenesis.

Outreach risk reduction strategies for changing HIV-related risk behaviors among injection drug users : the National AIDS Demonstration Research (NADR) Project.

S/N 017-024-01531-8 (GPO)