Inibidores da HIV-integrase: potencial abordagem farmacológica para tratamento da AIDS

AIDS has the HIV as its etiological agent. Researches has been done to find new pharmacological agents to be used in therapy, because of problems of resistance and side effects. The HIV-integrase inhibitors are some of those new agents that are being studied. This updating focusses on the fundamental information about HIV and HIV-integrase and the main methods being used to develop these new drugs, with examples for each case.

Origem do conhecimento sobre HIV/Aids: entre o pessoal e o acadêmico

Há um conhecimento acumulado sobre HIV/AIDS após duas décadas de epidemia, no entanto, estudos mostram a necessidade de mudanças na abordagem do ensino para transformação das posturas dos futuros profissionais. Neste contexto, objetivou-se identificar o conhecimento sobre HIV/AIDS entre alunos do 5º ano de um curso de medicina. Encontrou-se uma auto-avaliação positiva sobre o conhecimento em relação ao HIV/AIDS atrelado à formação durante a graduação, principalmente no que diz respeito à biossegurança para o exercício profissional. Já em relação ao comportamento sexual, a formação acadêmica não teve o mesmo impacto, pois os estudantes indicam como determinante no exercício da sexualidade o conhecimento prévio, adquirido através da mídia, ensino médio, relações familiares e sociais. Os resultados apresentados mostraram que a instituição formadora deve ser responsável pela consciência crítica capaz de desenvolver a prevenção como a melhor forma de controlar a doença. Mas, este tipo de ensinamento tem que fazer sentido para o aluno enquanto futuro profissional da saúde e principalmente enquanto cidadão exposto a riscos.

Prevalência e fatores correlatos de infecção pelo hiv e sífilis em prostitutas atendidas em centro de referência DST/AIDS

Um estudo retrospectivo foi conduzido com análise dos prontuários médicos de prostitutas atendidas no Centro de Referência para DST/AIDS em Vitória (ES) no período de janeiro de 1993 a dezembro de 1996. Durante este período, 180 mulheres receberam atendimento médico e psicológico nesta clínica. A média de idade foi de 25,9 anos (DP = 6,8). De um total de 180 mulheres, 140 concordaram em serem testadas para HIV, das quais 12 (8,6%) apresentaram resultado positivo. De 157 mulheres que concordaram em serem testadas para sífilis, 13 (8,3%) apresentaram o VDRL positivo. Quanto ao nível de educação, 6 mulheres (3,3%) eram analfabetas, 114 (63,3%) completaram o primeiro grau, 37 (20,6%) estudaram até o segundo grau, 7 (3,9%) estavam na universidade e 16 (8,9%) não quiseram informar. Quanto ao estado civil, 141 (78,3%) eram solteiras, 17 (9,4%) casadas, 10 (5,5%) divorciadas e 4 (2,2%) viúvas. Quanto à freqüência do uso de condom, 56 (31,3%) relataram que sempre usavam, 93 (52,0%) às vezes e 30 (16,8%) nunca usavam. Doenças sexualmente transmissíveis (DST) prévias foram relatadas por 89 mulheres (49,4%) e 46 (25,6%) apresentavam alguma DST na ocasião da consulta. Nove mulheres (5,0%) relataram uso de drogas injetáveis. Houve diferença estatisticamente significante entre o grupo com sorologia para HIV negativo e o positivo quando se comparou o uso de drogas injetáveis (p=0,031) e a infecção por sífilis (p=0,014). O presente estudo mostrou que as taxas de prevalência da infecção pelo HIV em trabalhadoras do sexo são mais altas que as encontradas na população em geral. Isto aponta para a necessidade de reforçar a assistência médica e campanhas educativas, especialmente direcionadas para esta população de mulheres, abordando a importância do uso regular do preservativo e dos riscos associados ao uso de drogas injetáveis.

Gestantes vivendo com HIV/AIDS: características antropométricas e peso ao nascer dos seus recém-nascidos

OBJETIVO:Descrever características antropométricas e da gestação de mulheres com HIV/AIDS, usuárias do Sistema Único de Saúde (SUS) e o peso de seus recém-nascidos. MÉTODOS: Participaram do estudo gestantes atendidas nos serviços de assistência à DST/AIDS da Secretaria Municipal de Saúde do município de São Paulo. A avaliação antropométrica foi realizada por nutricionistas treinadas e as demais informações foram obtidas em prontuários. Para a comparação entre os dados do estudo e os da população geral, foram utilizados dados secundários da mãe e da gestação oriundos das Declarações de Nascidos Vivos, disponíveis no Sistema de Informações sobre Nascidos Vivos. As variáveis contínuas foram resumidas por meio da média e desvio padrão ou pelos percentis 25, 50 e 75, valores mínimo e máximo. As demais variáveis são apresentadas em porcentagens. As médias foram comparadas por meio dos testes t Student ou Kruskall-Wallis, a depender do cumprimento das pressuposições, com decisão baseada no valor de p. RESULTADOS: Observaram-se presença de inadequação nutricional materna se considerada a prega cutânea do tríceps (60,9%), baixo peso (18,5%) e sobrepeso ou obesidade (40%), segundo o índice de massa corporal (IMC) gestacional; ausência de associação entre diagnóstico (HIV ou AIS) e peso, estatura, massa magra e gorda. Para filhos de mães com HIV/AIDS, observou-se peso médio ao nascer menor ao da população sem esta condição. CONCLUSÕES: Os resultados do presente estudo indicam a necessidade de desenvolvimento de curvas adaptadas que permitam a avaliação nutricional mais acurada deste grupo populacional.

DNA fingerprinting of Mycobacterium tuberculosis from patients with and without AIDS in Rio de Janeiro

Isolates of Mycobacterium tuberculosis derived from patients with AIDS from a single hospital in Rio de Janeiro were typed using a standardized RFLP technique detecting IS6110 polymorphism. Nineteen isolates were obtained from 15 different patients. Eleven distinct IS6110 patterns were found, with 4 banding patterns shared by 2 patients. The clustering value of 53% was much higher in comparison with clustering of M. tuberculosis strains from TB patients without clinical signs for HIV infection from randomly selected health centers. We present these results as preliminary data on M. tuberculosis strain polymorphism in Brazil and on the higher risk for recent transmission amongst patients with AIDS

HHV-8 infection in patients with AIDS-related Kaposi's sarcoma in Brazil

The aims of the present study were to determine the prevalence of human herpesvirus type 8 (HHV-8) in HIV-positive Brazilian patients with (HIV+/KS+) and without Kaposi's sarcoma (HIV+/KS-) using PCR and immunofluorescence assays, to assess its association with KS disease, to evaluate the performance of these tests in detecting HHV-8 infection, and to investigate the association between anti-HHV-8 antibody titers, CD4 counts and staging of KS disease. Blood samples from 66 patients, 39 HIV+/KS+ and 27 HIV+/KS-, were analyzed for HHV-8 viremia in peripheral blood mononuclear cells by PCR and HHV-8 antigenemia for latent and lytic infection by immunofluorescence assay. Positive samples for latent nuclear HHV-8 antigen (LNA) antibodies were titrated out from 1/100 to 1/409,600 dilution. Clinical information was collected from medical records and risk behavior was assessed through an interview. HHV-8 DNA sequences were detected by PCR in 74.3% of KS+ patients and in 3.7% of KS- patients. Serological assays were similar in detecting anti-LNA antibodies and anti-lytic antigens in sera from KS+ patients (79.5%) and KS- patients (18.5%). HHV-8 was associated with KS whatever the method used, i.e., PCR (odds ratio (OR) = 7.4, 95% confidence interval (CI) = 2.16-25.61) or anti-LNA and anti-lytic antibodies (OR = 17.0, 95%CI = 4.91-59.14). Among KS+ patients, HHV-8 titration levels correlated positively with CD4 counts (rho 0.48, P = 0.02), but not with KS staging. HHV-8 is involved in the development of KS in different geographic areas worldwide, as it is in Brazil, where HHV-8 is more frequent among HIV+ patients. KS severity was associated with immunodeficiency, but no correlation was found between HHV-8 antibody titers and KS staging.

Comparison of the quantitative competitive and semiquantitative RT-PCR methods for the determination of interferon-gamma mRNA levels in AIDS-free HIV-infected individuals

IFN-gamma mRNA expression was evaluated in nonstimulated peripheral blood mononuclear cells (PBMC) of HIV-infected and seronegative individuals using quantitative competitive and semiquantitative RT-PCR and the sensitivity of these methods was compared. A significant correlation was found between quantitative competitive and semiquantitative RT-PCR in samples of both HIV-seronegative (P = 0.004) and HIV-infected individuals (P = 0.0004). PBMC from HIV-infected individuals presented a remarkable increase of IFN-gamma mRNA expression, as determined by both types of RT-PCR methods. Semiquantitative RT-PCR even without an internal standard is also acceptable for measuring cytokine mRNA expression, but less reliable if small amounts are quantified. Moreover, we found that increased IFN-gammamRNA expression is independent of CD4+ cell count in AIDS-free HIV-infected patients.

Factors associated with adherence to antiretroviral therapy in HIV/AIDS patients: a cross-sectional study in Southern Brazil

A cross-sectional study was conducted on HIV-infected adults being treated with antiretroviral drugs at a reference service in Southern Brazil. Participants answered a sociodemographic questionnaire and were tested by scales assessing sociocognitive variables. Adherence to treatment was assessed by a self-report inventory developed for the study. Clinical information was obtained from the patients' records. Significance tests were conducted using univariate logistic regressions followed by multivariate logistic regression analysis. A total of 195 patients participated in the study and 56.9% of them reported > or = 95% adherence on the previous two days. In univariate analysis, the odds of adherence increased with self-efficacy (a person's conviction that he/she can successfully execute the behavior required to produce a certain desired outcome) in taking medications as prescribed (OR = 3.50, 95% CI 1.90-6.55), and decreased with perception of negative affect and physical concerns (OR = 0.71, 95% CI 0.53-0.95). The odds were lower for taking antiretroviral medications >4 times a day (OR = 0.44, 95% CI 0.20-0.94) and higher for patients with 8 years of schooling (OR = 2.28, 95% CI 1.12-4.66). In the multivariate analysis, self-efficacy (OR = 3.33, 95% CI 1.69-6.56) and taking medication >4 times a day (OR = 0.34, 95% CI 0.14-0.80) were independently associated with adherence. Self-efficacy was the most important predictor of adherence, followed by number of times antiretroviral medication was taken per day. Among sociodemographic and clinical variables, only the number of years of schooling was associated with adherence. Motivational interventions based on self-efficacy may be useful for increasing treatment adherence.

Evaluation of genotype resistance testing for salvage antiretroviral therapy at AIDS care centers from Ribeirão Preto, São Paulo, Brazil

The availability of HIV-1 genotype resistance testing (GRT) to clinicians has been insufficiently studied outside randomized clinical trials. The present study evaluated the outcome of salvage antiretroviral therapy (ART) recommended by an expert physician based on GRT in a non-clinical trial setting in Ribeirão Preto, Brazil. A prospective, open, nonrandomized study evaluating easy access to GRT at six Brazilian AIDS Clinics was carried out. This cooperative study analyzed the efficacy of treatment recommended to patients whose salvage ART was guided by GRT with that of treatment with ART based only on previous ART history. A total of 112 patients with ART failure were included in the study, and 77 of them were submitted to GRT. The median CD4 cell count and viral load for these 77 patients at baseline were (mean ± SD) 252.1 ± 157.4 cells/µL and 4.60 ± 0.5 log10 HIV RNA copies/mL, respectively. The access time, i.e., the time elapsed between ordering the GRT and receiving the result was, on average, 71.9 ± 37.3 days. The study results demonstrated that access to GRT followed by expert recommendations did not improve the time to persistent treatment failure when compared to conventional salvage ART. Access to GRT in this Brazilian community health care setting did not improve the long-term virologic outcomes of HIV-infected patients experiencing treatment failure. This result is probably related to the long time required to implement ART guided by GRT.

Hypomagnesemia is a risk factor for nonrecovery of renal function and mortality in AIDS patients with acute kidney injury

The objective of the present study was to determine the prevalence of electrolyte disturbances in AIDS patients developing acute kidney injury in the hospital setting, as well as to determine whether such disturbances constitute a risk factor for nephrotoxic and ischemic injury. A prospective, observational cohort study was carried out. Hospitalized AIDS patients were evaluated for age; gender; coinfection with hepatitis; diabetes mellitus; hypertension; time since HIV seroconversion; CD4 count; HIV viral load; proteinuria; serum levels of creatinine, urea, sodium, potassium and magnesium; antiretroviral use; nephrotoxic drug use; sepsis; intensive care unit (ICU) admission, and the need for dialysis. Each of these characteristics was correlated with the development of acute kidney injury, with recovery of renal function and with survival. Fifty-four patients developed acute kidney injury: 72% were males, 59% had been HIV-infected for >5 years, 72% had CD4 counts <200 cells/mm³, 87% developed electrolyte disturbances, 33% recovered renal function, and 56% survived. ICU admission, dialysis, sepsis and hypomagnesemia were all significantly associated with nonrecovery of renal function and with mortality. Nonrecovery of renal function was significantly associated with hypomagnesemia, as was mortality in the multivariate analysis. The risks for nonrecovery of renal function and for death were 6.94 and 6.92 times greater, respectively, for patients with hypomagnesemia. In hospitalized AIDS patients, hypomagnesemia is a risk factor for nonrecovery of renal function and for in-hospital mortality. To determine whether hypomagnesemia is a determinant or simply a marker of critical illness, further studies involving magnesium supplementation in AIDS patients are warranted.

Acute kidney injury in AIDS: frequency, RIFLE classification and outcome

The objective of the present study was to evaluate the characteristics of acute kidney injury (AKI) in AIDS patients and the value of RIFLE classification for predicting outcome. The study was conducted on AIDS patients admitted to an infectious diseases hospital inBrazil. The patients with AKI were classified according to the RIFLE classification: R (risk), I (injury), F (failure), L (loss), and E (end-stage renal disease). Univariate and multivariate analyses were used to evaluate the factors associated with AKI. A total of 532 patients with a mean age of 35 ± 8.5 years were included in this study. AKI was observed in 37% of the cases. Patients were classified as "R" (18%), "I" (7.7%) and "F" (11%). Independent risk factors for AKI were thrombocytopenia (OR = 2.9, 95%CI = 1.5-5.6, P < 0.001) and elevation of aspartate aminotransferase (AST) (OR = 3.5, 95%CI = 1.8-6.6, P < 0.001). General mortality was 25.7% and was higher among patients with AKI (40.2 vs17%, P < 0.001). AKI was associated with death and mortality increased according to RIFLE classification - "R" (OR 2.4), "I" (OR 3.0) and "F" (OR 5.1), P < 0.001. AKI is a frequent complication in AIDS patients, which is associated with increased mortality. RIFLE classification is an important indicator of poor outcome for AIDS patients.

'TINA', Aids, and the underdevelopment problem in Africa

The assumption that 'There Is No Alternative' (TINA) to capitalism as practiced in the United States of America and Western Europe has been the bane of aids effectiveness in assisting to solve the underdevelopment problem in Africa. This paper attempts to show that except there is a fundamental reorientation in the conceptualization of capitalism-free market and democracy-the underdevelopment problem would only be further complicated with aids.