Incomplete recovery of the CD4+/CD8+ ratio is associated with the late introduction of antiretroviral therapy among people living with HIV infection.

Despite being subject to lower AIDS-related mortality rates and having a higher life expectancy, patients with HIV are more prone to develop non-AIDS events. A low CD4+/CD8+ ratio during antiretroviral therapy identifies people with heightened immune senescence and increased risk of mortality. In clinical practice, finding determinants of a low CD4+/CD8+ ratio may be useful for identifying patients who require close monitoring due to an increased risk of comorbidities and death. We performed a prospective study on the evolution of the CD4+/CD8+ ratio in 60 patients infected with HIV (80% males), who were subjected to two different antiretroviral regimens: early and deferred therapy. The initial CD4+/CD8+ ratio was ≤1 for 70% of the patients in both groups. Older age, CD4+ cell count at inclusion, Nadir CD8+T-cell count, and Initial CD4+/CD8+ ratio ≤ 1 were risk factors for lack of ratio recovery. In the multivariate analysis, a CD4+/CD8+ ratio > 1 at the start of the treatment was found to be a determinant factor in maintaining a CD4+/CD8+ ratio > 1. The nadir CD4+T-cell count was lower in the deferred therapy group (p=0.004), and the last CD4+/CD8+ ratio ≤1 was not associated with comorbidities. Ratio recovery was not associated with the duration of HIV infection, time without therapy, or absence of AIDS incidence. A greater improvement was observed in patients treated early (p=0.003). In contrast, the slope of increase was slower in patients who deferred treatment. In conclusion, the increase in the CD4+/CD8+ ratio occurred mostly for patients undergoing early strategy treatment and its extension did not seem to be related to previous HIV-related factors.

Incomplete recovery of the CD4+/CD8+ ratio is associated with the late introduction of antiretroviral therapy among people living with HIV infection

ABSTRACT Despite being subject to lower AIDS-related mortality rates and having a higher life expectancy, patients with HIV are more prone to develop non-AIDS events. A low CD4+/CD8+ ratio during antiretroviral therapy identifies people with heightened immune senescence and increased risk of mortality. In clinical practice, finding determinants of a low CD4+/CD8+ ratio may be useful for identifying patients who require close monitoring due to an increased risk of comorbidities and death. We performed a prospective study on the evolution of the CD4+/CD8+ ratio in 60 patients infected with HIV (80% males), who were subjected to two different antiretroviral regimens: early and deferred therapy. The initial CD4+/CD8+ ratio was ≤1 for 70% of the patients in both groups. Older age, CD4+ cell count at inclusion, Nadir CD8+T-cell count, and Initial CD4+/CD8+ ratio ≤ 1 were risk factors for lack of ratio recovery. In the multivariate analysis, a CD4+/CD8+ ratio > 1 at the start of the treatment was found to be a determinant factor in maintaining a CD4+/CD8+ ratio > 1. The nadir CD4+T-cell count was lower in the deferred therapy group (p=0.004), and the last CD4+/CD8+ ratio ≤1 was not associated with comorbidities. Ratio recovery was not associated with the duration of HIV infection, time without therapy, or absence of AIDS incidence. A greater improvement was observed in patients treated early (p=0.003). In contrast, the slope of increase was slower in patients who deferred treatment. In conclusion, the increase in the CD4+/CD8+ ratio occurred mostly for patients undergoing early strategy treatment and its extension did not seem to be related to previous HIV-related factors.

Atypical presentation of histoplasmosis in an immunocompromised patient.

We present a case of disseminated cutaneous histoplasmosis in a male patient, rural worker, HIV positive for 20 years, with a history of irregular use of antiretroviral therapy, T cell counts below 50 cells/mm3 and with good response to treatment with Itraconazole. We highlight importance of skin lesions in clarifying early diagnosis, since this co-infection often leads patients to death.

HIV disease progression: is the Brazilian variant subtype B' (GWGR motif) less pathogenic than US/European subtype B (GPGR)?

BACKGROUND: The aim of this study was to investigate differences in HIV disease progression in patients infected with HIV subtype B with a GPGR motif in the V3 loop region (B-GPGR) versus the Brazilian subtype B variant with a GWGR motif (B'-GWGR). MATERIALS AND METHODS: Patients were enrolled in an ongoing cohort study at the University of São Paulo Dermatology Clinic in Sao Paulo, Brazil. V3 serology was performed by enzyme immunoassay with peptides representing two HIV subtype B strains, MN and SF2, and two Brazilian variant B'-GWGR strains. The incidence of AIDS-defining events was calculated, and Cox proportional hazards regression was used to estimate adjusted risk ratios. RESULTS: Of the samples from 114 patients studied, 23 (20%) were classified as B'-GWGR motif, and 91 (80%) as B-GPGR motif. Patients with T CD4+ cell counts less than 200 cells/mm3 or 200-400 cells/mm3 experienced an increased incidence of AIDS-defining events compared with patients who entered the cohort with T CD4+ cell counts greater than 400 cells/mm3. In a proportional hazard model including age, gender, T CD4+ cell count at entry into the cohort, and V3 serology, GWGR reactivity was associated with a decreased hazard rate for presenting an AIDS-defining condition during follow-up. Three patients in the group with GPGR serology died after experiencing an AIDS-defining event. None of the patients with GWGR serology died during follow-up. DISCUSSION: Survival analysis showed that patients infected with the Brazilian subtype B variant with a GWGR motif in the V3 loop had lower risk, adjusted for initial CD4+ cell count, of AIDS-defining events than patients infected with subtype B-GPGR strains.

AIDS incidence and mortality in a hospital-based cohort of HIV-1-seropositive patients receiving highly active antiretroviral therapy in São Paulo, Brazil.

Brazilian AIDS and HIV-1-seropositive patients have had free access to highly active antiretroviral therapy (HAART) since November 1996. Although secondary data based on official mortality statistics indicate a sharp decrease in AIDS mortality, few if any studies tried to estimate the prognosis for patients with HIV who have been followed from the beginning of the HAART era. An observational study, with retrospective and prospective components, was done in 233 adult HIV-1-infected subjects who were recruited in the last 10 years at the outpatient sector of the Secondary Immunodeficiencies Clinic of the Department of Dermatology, Hospital das Clinicas da FMUSP, Sao Paulo, Brazil. The definition of AIDS followed the guidelines issued by the Centers for Disease Control (CDC) in 1987. One hundred sixty patients were asymptomatic, 46 had AIDS, 24 had AIDS-related complex, and 3 presented with acute infection at study entry. Twenty-nine (18%) of the asymptomatic subjects developed AIDS during follow-up, with 5 (3%) deaths. Among the 46 AIDS cases at entry, 7 (17%) died during follow-up. Thus, a total of 12 people (5.2%) died of AIDS in this cohort over a mean follow-up of 5.2 years and 24 people were lost to follow-up (10.3%). Ninety percent of the survivors were on combined therapy (82% with 3 or more drugs, and 8% with 2 drugs), while 10% were not taking antiretrovirals. People with AIDS at entry were 5 times more likely to die during this period compared to patients who were asymptomatic at entry (p = 0.006). Women showed better outcomes than men, reflecting differences in CD4+ T-cell counts at study entry. All but 1 patient progressed to AIDS during the pre-HAART era (before 1996). In spite of its recent decline, mortality from AIDS-related conditions remains an important public health issue.

Tuberculosis among HIV-1-infected subjects in a tertiary out-patient service in São Paulo city, Brazil.

TB is currently considered to be the most important infectious disease among HIV-1-infected subjects in developing countries, such as Brazil. A retrospective analysis of TB cases was performed, occurring from January 1995 to December 2010 in our cohort of 599 HIV positive patients. The primary outcome was the occurrence of active TB. Forty-one TB cases were diagnosed over this period of 16 years, among 599 HIV positive patients in an open cohort setting in the city of Sao Paulo, Brazil. All-time lowest mean CD4 T cell count at the time of TB diagnosis was 146 and 186 cells/mm³, respectively. The mean HIV viral load was 5.19 log10 copies/mL, and 59% of the patients were on HAART. TB incidence was 1.47 per 100 person-years, for a total follow-up time of 2775 person-years. The probability of surviving up to 10 years after diagnosis was 75% for TB patients as opposed to 96% for patients with other, non-TB opportunistic diseases (p = 0.03). TB can be considered a public health problem among people living with HIV in Brazil despite of the widespread use of antiretrovirals for the treatment of HIV infection/AIDS.

Atypical presentation of histoplasmosis in an immunocompromised patient

We present a case of disseminated cutaneous histoplasmosis in a male patient, rural worker, HIV positive for 20 years, with a history of irregular use of antiretroviral therapy, T cell counts below 50 cells/mm3 and with good response to treatment with Itraconazole. We highlight importance of skin lesions in clarifying early diagnosis, since this co-infection often leads patients to death.

Tuberculosis among HIV-1-infected subjects in a tertiary out-patient service in São Paulo city, Brazil / Tuberculose entre pacientes infectados pelo HIV-1 em ambulatório terciário de São Paulo, Brasil

TB is currently considered to be the most important infectious disease among HIV-1-infected subjects in developing countries, such as Brazil. A retrospective analysis of TB cases was performed, occurring from January 1995 to December 2010 in our cohort of 599 HIV positive patients. The primary outcome was the occurrence of active TB. Forty-one TB cases were diagnosed over this period of 16 years, among 599 HIV positive patients in an open cohort setting in the city of Sao Paulo, Brazil. All-time lowest mean CD4 T cell count at the time of TB diagnosis was 146 and 186 cells/mm³, respectively. The mean HIV viral load was 5.19 log10 copies/mL, and 59% of the patients were on HAART. TB incidence was 1.47 per 100 person-years, for a total follow-up time of 2775 person-years. The probability of surviving up to 10 years after diagnosis was 75% for TB patients as opposed to 96% for patients with other, non-TB opportunistic diseases (p = 0.03). TB can be considered a public health problem among people living with HIV in Brazil despite of the widespread use of antiretrovirals for the treatment of HIV infection/AIDS.

Atualmente, a tuberculose (TB) é considerada a doença infecciosa mais importante entre os pacientes infectados pelo HIV-1 nos países em desenvolvimento, como o Brasil. Análise retrospectiva dos casos de tuberculose ocorridos a partir de janeiro 1995 até dezembro de 2010 foi realizada em nossa coorte de 599 pacientes HIV positivos. O desfecho primário foi a ocorrência de TB ativa, e 41 casos da doença foram diagnosticados durante este período de 16 anos. As contagens médias do nadir de células T CD4 e ao momento do diagnóstico de TB foram de 146 e 217 células/mm³, respectivamente. A carga viral média de HIV foi de 5,19 log10 cópias/mL, e 59% dos pacientes estavam em tratamento com ART. A incidência de TB foi de 1,47 casos por 100 pessoas-ano, para um tempo total de seguimento da coorte de 2775 pessoas-ano. A probabilidade de sobreviver até 10 anos após o diagnóstico foi de 75% para pacientes com TB, em oposição a 96% para pacientes com outras doenças oportunistas não-TB (p = 0,03). A tuberculose pode ser considerada problema de saúde pública entre as pessoas que vivem com HIV no Brasil, apesar da ampla utilização de anti-retrovirais para o tratamento da infecção pelo HIV / AIDS.

Humoral response to hepatitis B vaccination and its relationship with T CD45RA+ (naïve) and CD45RO+ (memory) subsets in HIV-1-infected subjects.

HIV disease leads to defects in cell-mediated immunity, impairing the immune response to new and recall antigens. We studied 55 HIV 1-infected patients who received of recombinant DNA hepatitis B vaccine and 20 controls. The overall hepatitis B virus (HBV) seroconversion rate was 59%. The median CD4+ T cell count among responders was 452 cell/mm(3), higher than non-responders (359 cells/mm(3)). The HIV plasmaviral loads were higher in non-responders. We concluded that total T CD4 cell count, memory T CD4+ cells and lower plasma viral load among HIV-1-infected subjects treated with HAART could be used to predict the immune response to vaccination with hepatitis B vaccine. Thus, considering cost benefits, HVB vaccination should be preferentially provided to HIV-infected patients with T CD4 cells count over 450 cells/mm(3), preferentially whose under HIV replication controlled.

Hantavirus pulmonary syndrome: report of the first three cases in Sao Paulo, Brazil

A sindrome pulmonar por hantavirus foi reconhecido a partir dos casos ocorridos nos EUA em 1993. Esse alerta serviu tanto para os medicos americanos como para os de outros paises na identificacao de casos dessa doenca. Na cidade de Sao Paulo, Brasil, em 1993, foram registrados 3 casos com essa manifestacao de hantavirose; eram irmaos, do sexo masculino, jovens, residentes na regiao da Mata Atlantica, com desmatamento recente. Dois dos casos evoluiram para a morte causada por insuficiencia respiratoria aguda e o terceiro com recuperacao sem sequelas. No paciente sobrevivente o diagnostico foi estabelecido por criterio laboratorial pela pesquisa de anticorpos especificos das classes IgM e IgG pela tecnica de imunofluorescencia indireta...

Avaliação da restauração imune pela resposta vacinal anti-vírus da hepatite B e a quantificação de linfócitos T CD4+ virgens e de memória em pacientes infectados pelo HIV sob terapia anti-retroviral / Immunological recovery evaluation through the hepatitis B vaccine response and naïve and memory lymphocytes T CD4+ quantifying in HIV infected and under antiretroviral therapy patients

A infecção pelo HIV causa profundo defeito na imunidade mediada por células T e B, principalmente a antígenos novos.55 pacientes HIV+ e 20 controles HIV negativos, foram imunizados com vacina anti-hepatite B. Avaliado a subpopulação de linfócitos T CD4+, memória e virgem, carga viral do HIV e anti-HBs. A media no momento da imunização de células T CD4+ = 490 céls/mm3, sendo 25 por cento, 65 por cento e 81 por cento (Grupo: < 200, 200-500 e > 500 céls/mm3, respectivamente), taxa de soroconversão. A Mediana de células T CD4+ memória nos respondedores versus nos não respondedores (p=.03). Os principais fatores de soroconversão foram o número de células T CD4+ de memória, baixa carga viral e contagem de linfócitos T CD4+.HIV disease leads to defects in T and B cell-mediated immunity, principally to new antigens.55 patients HIV-1- infected and 20 controls negative HIV were immunized with hepatitis B vaccine. We studied T CD4+, memory and naïve subsets, HIV viral load and anti-HBs titers. At immunization moment, the mean T CD4+ cell count was 490 cells/mm3, The seroconversion rate 25 per cent, 65 per cent and 81 per cent (Group: < 200, 200-499 and > 500 cells/mm3, respectively). The median of memory T CD4+ cells in responders versus in non-responders (p=.03). The principal factors to seroconversion were memory T CD4+ cells, lower HIV viral load and the number T CD4+ cells...