The association between CD4+ lymphocyte count and measures of body composition in HIV-infected men

Purpose. This project was designed to describe the association between wasting and CD4 cell counts in HIV-infected men in order to better understand the role of wasting in progression of HIV infection.^ Methods. Baseline and prevalence data were collected from a cross-sectional survey of 278 HIV-infected men seen at the Houston Veterans Affairs Medical Center Special Medicine Clinic, from June 1, 1991 to January 1, 1994. A follow-up study was conducted among those at risk, to investigate the incidence of wasting and the association between wasting and low CD4 cell counts. Wasting was described by four methods. Z-scores for age-, sex-, and height-adjusted weight; sex-, and age-adjusted mid-arm muscle circumference (MAMC); and fat-free mass; and the ratio of extra-cellular mass (ECM) to body-cell mass (BCM) $>$ 1.20. FFM, ECM, and BCM were estimated from bioelectrical impedance analysis. MAMC was calculated from triceps skinfold and mid-arm circumference. The relationship between wasting and covariates was examined with logistic regression in the cross-sectional study, and with Poisson regression in the follow-up study. The association between death and wasting was examined with Cox's regression.^ Results. The prevalence of wasting ranged from 5% (weight and ECM:BCM) to almost 14% (MAMC and FFM) among the 278 men examined. The odds of wasting, associated with baseline CD4 cell count $<$200, was significant for each method but weight, and ranged from 4.6 to 12.7. Use of antiviral therapy was significantly protective of MAMC, FFM and ECM:BCM (OR $\approx$ 0.2), whereas the need for antibacterial therapy was a risk (OR 3.1, 95% CI 1.1-8.7). The average incidence of wasting ranged from 4 to 16 per 100 person-years among the approximately 145 men followed for 160 person-years. Low CD4 cell count seemed to increase the risk of wasting, but statistical significance was not reached. The effect of the small sample size on the power to detect a significant association should be considered. Wasting, by MAMC and FFM, was significantly associated with death, after adjusting for baseline serum albumin concentration and CD4 cell count.^ Conclusions. Wasting by MAMC and FFM were strongly associated with baseline CD4 cell counts in both the prevalence and incidence study and strong predictors of death. Of the two methods, MAMC is convenient, has available reference population data, may be the most appropriate for assessing the nutritional status of HIV-infected men. ^

HIV-1 tropism and CD4 T lymphocyte recovery in a prospective cohort of patients initiating HAART in Ribeirao Preto, Brazil

While human immunodeficiency virus (HIV)-1 chemokine co-receptors 5 tropism and the GWGR motif in the envelope third variable region (V3 loop) have been associated with a slower disease progression, their influence on antiretroviral response remains unclear. The impact of baseline V3 characteristics on treatment response was evaluated in a randomised, double blind, prospective cohort study with patients initiating highly active antiretroviral therapy with lopinavir or efavirenz plus azithothymidine/3TC (1:1) over 48 weeks. Similar virological and immunological responses were observed for both treatment regimens. The 43 individuals had a mean baseline CD4 T cell count of 119 cells/mm(3) [standard deviation (SD) = 99] and a mean viral load of 5.09 log(10) copies/mL (SD = 0.49). The GWGR motif was not associated with a CD4 T cell response, but predicted R5 tropism by the geno2pheno([clinical20%]) algorithm correlated with higher CD4 T cell levels at all monitoring points (p &lt; 0.05). Moreover, higher false-positive rates (FPR) values from this analysis revealed a strong correlation with CD4 T cell recovery (p &lt; 0.0001). Transmitted drug resistance mutations, documented in 3/41 (7.3%) cases, were unrelated to the assigned antiretroviral regimen and had no impact on patient outcomes. In conclusion, naive HIV-1 R5 infected patients exhibited higher CD4 T cell counts at baseline; this difference was sustained throughout therapy. The geno2pheno[clinical] option FPR positively correlated with CD4 T cell gain and may be useful in predicting CD4 T cell recovery.

HIV-1 tropism and CD4 T lymphocyte recovery in a prospective cohort of patients initiating HAART in Ribeir��o Preto, Brazil

While human immunodeficiency virus (HIV)-1 chemokine co-receptors 5 tropism and the GWGR motif in the envelope third variable region (V3 loop) have been associated with a slower disease progression, their influence on antiretroviral response remains unclear. The impact of baseline V3 characteristics on treatment response was evaluated in a randomised, double blind, prospective cohort study with patients initiating highly active antiretroviral therapy with lopinavir or efavirenz plus azithothymidine/3TC (1:1) over 48 weeks. Similar virological and immunological responses were observed for both treatment regimens. The 43 individuals had a mean baseline CD4 T cell count of 119 cells/mm�� [standard deviation (SD) = 99] and a mean viral load of 5.09 log10 copies/mL (SD = 0.49). The GWGR motif was not associated with a CD4 T cell response, but predicted R5 tropism by the geno2pheno[clinical20%] algorithm correlated with higher CD4 T cell levels at all monitoring points (p < 0.05). Moreover, higher false-positive rates (FPR) values from this analysis revealed a strong correlation with CD4 T cell recovery (p < 0.0001). Transmitted drug resistance mutations, documented in 3/41 (7.3%) cases, were unrelated to the assigned antiretroviral regimen and had no impact on patient outcomes. In conclusion, na��ve HIV-1 R5 infected patients exhibited higher CD4 T cell counts at baseline; this difference was sustained throughout therapy. The geno2pheno[clinical] option FPR positively correlated with CD4 T cell gain and may be useful in predicting CD4 T cell recovery.

Quantitative Trait Loci for CD4:CD8 Lymphocyte Ratio Are Associated with Risk of Type 1 Diabetes and HIV-1 Immune Control

Abnormal expansion or depletion of particular lymphocyte subsets is associated with clinical manifestations such as HIV progression to AIDS and autoimmune disease. We sought to identify genetic predictors of lymphocyte levels and reasoned that these may play a role in immune-related diseases. We tested 2.3 million variants for association with five lymphocyte subsets, measured in 2538 individuals from the general population, including CD4+ T cells, CD8+ T cells, CD56+ natural killer (NK) cells, and the derived measure CD4:CD8 ratio. We identified two regions of strong association. The first was located in the major histocompatibility complex (MHC), with multiple SNPs strongly associated with CD4:CD8 ratio (rs2524054, p = 2.1 �� 10���28). The second region was centered within a cluster of genes from the Schlafen family and was associated with NK cell levels (rs1838149, p = 6.1 �� 10���14). The MHC association with CD4:CD8 replicated convincingly (p = 1.4 �� 10���9) in an independent panel of 988 individuals. Conditional analyses indicate that there are two major independent quantitative trait loci (QTL) in the MHC region that regulate CD4:CD8 ratio: one is located in the class I cluster and influences CD8 levels, whereas the second is located in the class II cluster and regulates CD4 levels. Jointly, both QTL explained 8% of the variance in CD4:CD8 ratio. The class I variants are also strongly associated with durable host control of HIV, and class II variants are associated with type-1 diabetes, suggesting that genetic variation at the MHC may predispose one to immune-related diseases partly through disregulation of T cell homeostasis.

CD4+ T-cell count increase in HIV-1-infected patients with suppressed viral load within 1 year after start of antiretroviral therapy

BACKGROUND: CD4+ T-cell recovery in patients with continuous suppression of plasma HIV-1 viral load (VL) is highly variable. This study aimed to identify predictive factors for long-term CD4+ T-cell increase in treatment-naive patients starting combination antiretroviral therapy (cART). METHODS: Treatment-naive patients in the Swiss HIV Cohort Study reaching two VL measurements <50 copies/ml >3 months apart during the 1st year of cART were included (n=1816 patients). We studied CD4+ T-cell dynamics until the end of suppression or up to 5 years, subdivided into three periods: 1st year, years 2-3 and years 4-5 of suppression. Multiple median regression adjusted for repeated CD4+ T-cell measurements was used to study the dependence of CD4+ T-cell slopes on clinical covariates and drug classes. RESULTS: Median CD4+ T-cell increases following VL suppression were 87, 52 and 19 cells/microl per year in the three periods. In the multiple regression model, median CD4+ T-cell increases over all three periods were significantly higher for female gender, lower age, higher VL at cART start, CD4+ T-cell <650 cells/microl at start of the period and low CD4+ T-cell increase in the previous period. Patients on tenofovir showed significantly lower CD4+ T-cell increases compared with stavudine. CONCLUSIONS: In our observational study, long-term CD4+ T-cell increase in drug-naive patients with suppressed VL was higher in regimens without tenofovir. The clinical relevance of these findings must be confirmed in, ideally, clinical trials or large, collaborative cohort projects but could influence treatment of older patients and those starting cART at low CD4+ T-cell levels.

CD4+ T cell count recovery in HIV type 1-infected patients is independent of class of antiretroviral therapy

BACKGROUND: In recent years, treatment options for human immunodeficiency virus type 1 (HIV-1) infection have changed from nonboosted protease inhibitors (PIs) to nonnucleoside reverse-transcriptase inhibitors (NNRTIs) and boosted PI-based antiretroviral drug regimens, but the impact on immunological recovery remains uncertain. METHODS: During January 1996 through December 2004 [corrected] all patients in the Swiss HIV Cohort were included if they received the first combination antiretroviral therapy (cART) and had known baseline CD4(+) T cell counts and HIV-1 RNA values (n = 3293). For follow-up, we used the Swiss HIV Cohort Study database update of May 2007 [corrected] The mean (+/-SD) duration of follow-up was 26.8 +/- 20.5 months. The follow-up time was limited to the duration of the first cART. CD4(+) T cell recovery was analyzed in 3 different treatment groups: nonboosted PI, NNRTI, or boosted PI. The end point was the absolute increase of CD4(+) T cell count in the 3 treatment groups after the initiation of cART. RESULTS: Two thousand five hundred ninety individuals (78.7%) initiated a nonboosted-PI regimen, 452 (13.7%) initiated an NNRTI regimen, and 251 (7.6%) initiated a boosted-PI regimen. Absolute CD4(+) T cell count increases at 48 months were as follows: in the nonboosted-PI group, from 210 to 520 cells/muL; in the NNRTI group, from 220 to 475 cells/muL; and in the boosted-PI group, from 168 to 511 cells/muL. In a multivariate analysis, the treatment group did not affect the response of CD4(+) T cells; however, increased age, pretreatment with nucleoside reverse-transcriptase inhibitors, serological tests positive for hepatitis C virus, Centers for Disease Control and Prevention stage C infection, lower baseline CD4(+) T cell count, and lower baseline HIV-1 RNA level were risk factors for smaller increases in CD4(+) T cell count. CONCLUSION: CD4(+) T cell recovery was similar in patients receiving nonboosted PI-, NNRTI-, and boosted PI-based cART.

CD4(+) T cell count decreases by ethnicity among untreated patients with HIV infection in South Africa and Switzerland

BACKGROUND: Estimates of the decrease in CD4(+) cell counts in untreated patients with human immunodeficiency virus (HIV) infection are important for patient care and public health. We analyzed CD4(+) cell count decreases in the Cape Town AIDS Cohort and the Swiss HIV Cohort Study. METHODS: We used mixed-effects models and joint models that allowed for the correlation between CD4(+) cell count decreases and survival and stratified analyses by the initial cell count (50-199, 200-349, 350-499, and 500-750 cells/microL). Results are presented as the mean decrease in CD4(+) cell count with 95% confidence intervals (CIs) during the first year after the initial CD4(+) cell count. RESULTS: A total of 784 South African (629 nonwhite) and 2030 Swiss (218 nonwhite) patients with HIV infection contributed 13,388 CD4(+) cell counts. Decreases in CD4(+) cell count were steeper in white patients, patients with higher initial CD4(+) cell counts, and older patients. Decreases ranged from a mean of 38 cells/microL (95% CI, 24-54 cells/microL) in nonwhite patients from the Swiss HIV Cohort Study 15-39 years of age with an initial CD4(+) cell count of 200-349 cells/microL to a mean of 210 cells/microL (95% CI, 143-268 cells/microL) in white patients in the Cape Town AIDS Cohort > or =40 years of age with an initial CD4(+) cell count of 500-750 cells/microL. CONCLUSIONS: Among both patients from Switzerland and patients from South Africa, CD4(+) cell count decreases were greater in white patients with HIV infection than they were in nonwhite patients with HIV infection.

Analysis of serious non-AIDS events among HIV-infected adults at Latin American sites

Acquired immune deficiency appears to be associated with serious non-AIDS (SNA)-defining conditions such as cardiovascular disease, liver and renal insufficiency and non-AIDS-related malignancies. We analysed the incidence of, and factors associated with, several SNA events in the LATINA retrospective cohort.

Lipodystrophy in HIV/AIDS patients with different levels of physical activity while on antiretroviral therapy

INTRODU����O: A lipodistrofia relacionada ao uso de terapia antirretroviral (TARV) pode causar estigma est��tico e elevar o risco de doen��as cardiovasculares. A atividade f��sica pode ser uma alternativa v��lida para o tratamento e preven����o da lipodistrofia. Entretanto, poucos estudos tratam dessa tem��tica. O objetivo deste estudo foi verificar a ocorr��ncia de lipodistrofia relacionada ao uso de TARV em portadores de HIV/AIDS, com diferentes h��bitos de atividades f��sicas. M��TODOS: A casu��stica foi formada por 42 portadores de HIV em uso de TARV, do Centro de Testagem e Aconselhamento de Presidente Prudente. Para obten����o do n��vel de atividade f��sica aplicou-se o Question��rio Internacional de Atividade F��sica (IPAQ); a lipodistrofia foi diagnosticada pelo autorrelato do paciente e a confirma����o m��dica. O percentual de gordura de tronco foi estimado pela absortometria por raio-X de dupla energia (DEXA). Foram coletados tamb��m dados referentes a sexo, idade, tempo de uso de TARV, valores de CD4 e carga viral. RESULTADOS: Verificou-se maior ocorr��ncia de lipodistrofia no grupo sedent��rio quando comparado ao ativo, al��m de fator protetor da pr��tica da atividade f��sica em rela����o �� ocorr��ncia da lipodistrofia. O grupo com valores mais elevados de CD4 tamb��m apresentou maior propor����o de sujeitos com lipodistrofia, al��m de maior propor����o de ativos e de indiv��duos com menor faixa et��ria. Os acometidos pela lipodistrofia apresentaram maiores valores de percentual de gordura de tronco, bem como, os sedent��rios em rela����o aos ativos. CONCLUS��ES: O estilo de vida fisicamente ativa resultou em efeito protetor para ocorr��ncia da lipodistrofia relacionada ao uso da TARV.

Cryptosporidium SP in HIV-infected individuals attending a Brazilian university hospital

The aim of the current work was to evaluate the occurrence of Cryptosporidium sp in AIDS patients in a region of S��o Paulo State, Brazil. Patients were divided into groups according to CD4+ T lymphocyte count and use of potent antiretroviral treatment. Two hundred and ten fecal samples from 105 patients were fixed in 10% formalin and subjected to centrifuge formol-ether sedimentation. Slides were stained with auramine and confirmed by modified Ziehl-Neelsen. Cryptosporidiosis occurrence was 10.5% with no relationship among gender, age or the presence of diarrhea. The number of oocysts in all samples was small, independent of CD4+ T lymphocyte count, HIV plasma viral load, and presence of diarrhea. These results may be due to the reduced prevalence of opportunistic infections in AIDS individuals after the advent of highly active antiretroviral therapy.

Evolu����o de pacientes com AIDS p��s cART: Evolu����o cl��nica e laboratorial de pacientes com AIDS ap��s 48 semanas de tratamento antirretroviral

Combination Antiretroviral Therapy (cART) aims to inhibit viral replication, delay immunodeficiency progression and improve survival in AIDS patients. The objective of this study was to compare two different schemes of cART, based on plasma viral load (VL) and CD4+ T lymphocyte count, during 48 weeks of treatment. For this purpose, 472 medical charts of a Specialized Outpatient Service were reviewed from 1998 to 2005. Out of these, 58 AIDS patients who had received a triple drug scheme as the initial treatment were included in the study and two groups were formed: Group 1 (G1): 47 individuals treated with two nucleoside reverse-transcriptase inhibitors (NRTI) and one non-nucleoside reverse-transcriptase inhibitor; Group 2 (G2): 11 patients treated with two NRTI and one protease inhibitor. In G1 and G2, 53.2% and 81.8% respectively were patients with an AIDS-defining disease. The T CD4+ lymphocyte count increased progressively up until the 24th week of treatment in all patients, while VL became undetectable in 68.1% of G1 and in 63.6% of G2. The study concluded that the evolutions of laboratory tests were similar in the two treatment groups and that both presented a favorable clinical evolution.

Characterization of mannose-binding lectin plasma levels and genetic polymorphisms in HIV-1-infected individuals

INTRODU����O: O presente estudo investigou a associa����o entre o polimorfismo no gene da lectina ligante de manose (MBL) e os n��veis s��ricos da prote��na com a infec����o pelo HIV-1. M��TODOS: As amostras de sangue (5mL) foram coletadas de 97 indiv��duos infectados pelo HIV-1 residentes em Bel��m, Estado do Par��, Brasil, que frequentavam a Unidade de Refer��ncia Especial para Doen��as Infecciosas e Parasit��rias Especiais (URE-DIPE). Os n��veis de linf��citos T CD4+ e da carga viral plasm��tica foram quantificados. Um fragmento de 349pb do exon 1 da MBL foi amplificado via PCR, utilizando DNA gen��mico extra��do das amostras controles e dos indiv��duos portadores do HIV-1, seguindo protocolos previamente estabelecidos. O n��vel plasm��tico de MBL nos pacientes foi quantificado usando kit de ensaio imunoenzim��tico. RESULTADOS: Dois alelos foram observados - MBL*O, com uma frequ��ncia de 26,3% em indiv��duos infectados e o alelo selvagem MBL*A (73,7%). Frequ��ncias similares foram observadas no grupo controle (p > 0,05). As frequ��ncias genot��picas estavam em equil��brio de Hardy-Weinberg em ambos os grupos. A m��dia dos n��veis plasm��ticos MBL variou por gen��tipo, com diferen��as significativas entre os gen��tipos AA e AO (p < 0,0001), e AA e OO (p < 0,001), mas n��o entre AO e OO (p=0,17). Al��m disso, os linf��citos T CD4+ e os n��veis plasm��ticos de carga viral n��o diferiram significativamente de acordo com o gen��tipo (p>0,05). CONCLUS��ES: Os resultados deste estudo n��o apoiam a hip��tese de que o polimorfismo no gene MBL ou baixa concentra����o plasm��tica de MBL poderia ter uma influ��ncia direta sobre a infec����o pelo HIV-1, embora um estudo com n��mero maior de pacientes seja necess��rio.

Altera����es mamogr��ficas em mulheres que vivem com HIV-aids

Funda����o de Amparo �� Pesquisa do Estado de S��o Paulo (FAPESP)