Factors influencing the normalization of CD4+ T-cell count, percentage and CD4+/CD8+ T-cell ratio in HIV-infected patients on long-term suppressive antiretroviral therapy

Torti, Carlo; Prosperi, Mattia; Motta, Davide; Digiambenedetto, Simona; Maggiolo, Franco; Paraninfo, Giuseppe; Ripamonti, Diego; Cologni, Giuliana; Fabbiani, Massimiliano; Caputo, Sergio Lo; Sighinolfi, Laura; Ladisa, Nicoletta; El-Hamad, Issa; Quiros-Roldan, Eugenia; Frank, Ian

doi:10.1111/j.1469-0691.2011.03650.x

Cited by 61 publications

(73 citation statements)

References 36 publications

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“…In this study, we first demonstrated that the HIV-positive subjects, after 6 months of HAART, experienced significant decreases in viral loads and 0.4-to 3-fold increases in CD4 ϩ /CD8 ϩ T cell ratios. These findings were expected and were consistent with previous studies that showed inverse correlation of CD4 ϩ /CD8 ϩ T cell ra- tios with antiretroviral therapy (51)(52)(53). As the particular focus of the present study, the microbial analysis data showed differences in oral microbial colonization among HIV-seronegative subjects, HIV-seropositive subjects before HAART, and HIV-seropositive subjects 6 months after HAART.…”

Section: Discussionsupporting

confidence: 93%

HIV Infection and Microbial Diversity in Saliva

et al. 2014

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f Limited information is available about the effects of HIV and subsequent antiretroviral treatment on host-microbe interactions. This study aimed to determine the salivary microbial composition for 10 HIV-seropositive subjects, before and 6 months after highly active antiretroviral therapy (HAART), compared with that for 10 HIV-seronegative subjects. A conventional culture and two culture-independent analyses were used and consistently demonstrated differences in microbial composition among the three sets of samples. HIV-positive subjects had higher levels of total cultivable microbes, including oral streptococci, lactobacilli, Streptococcus mutans, and Candida, in saliva than did HIV-negative subjects. The total cultivable microbial levels were significantly correlated with CD4 ؉ T cell counts. Denaturing gradient gel electrophoresis (DGGE), which compared the overall microbial profiles, showed distinct fingerprinting profiles for each group. The human oral microbe identification microarray (HOMIM) assay, which compared the 16S rRNA genes, showed clear separation among the three sample groups. Veillonella, Synergistetes, and Streptococcus were present in all 30 saliva samples. Only minor changes or no changes in the prevalence of Neisseria, Haemophilus, Gemella, Leptotrichia, Solobacterium, Parvimonas, and Rothia were observed. Seven genera, Capnocytophaga, Slackia, Porphyromonas, Kingella, Peptostreptococcaceae, Lactobacillus, and Atopobium, were detected only in HIVnegative samples. The prevalences of Fusobacterium, Campylobacter, Prevotella, Capnocytophaga, Selenomonas, Actinomyces, Granulicatella, and Atopobium were increased after HAART. In contrast, the prevalence of Aggregatibacter was significantly decreased after HAART. The findings of this study suggest that HIV infection and HAART can have significant effects on salivary microbial colonization and composition.

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Section: Discussionsupporting

confidence: 93%

HIV Infection and Microbial Diversity in Saliva

et al. 2014

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“…We also investigated the potential association of neutralization breadth with the CD4 ϩ /CD8 ϩ ratio. It has been suggested that the cutoff ratio of Ͻ1.0 is associated with immunosenescence and mortality (47)(48)(49). We therefore evaluated the levels of neutralization breadth (number of subtypes crossed) in patients with CD4 ϩ /CD8 ϩ ratios of Ͻ1 and Ն1.…”

Section: Demographic Characteristicsmentioning

confidence: 99%

“…A reduction greater than 30% is considered positive. response in patients with healthy CD4 ϩ /CD8 ϩ ratios (Ն1) (47)(48)(49), within the first year of HIV infection, and with patients with lower ratios. Neutralization breadth was significantly higher in patients with CD4 ϩ /CD8 ϩ ratios similar to those of healthy individuals.…”

Section: Figmentioning

confidence: 99%

Detection of Broadly Neutralizing Activity within the First Months of HIV-1 Infection

Sánchez-Merino

Fabra-García

Gonzàlez

et al. 2016

J Virol

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A fraction of HIV-1 patients are able to generate broadly neutralizing antibodies (bNAbs) after 2 to 4 years of infection. In rare occasions such antibodies are observed close to the first year of HIV-1 infection but never within the first 6 months. In this study, we analyzed the neutralization breadth of sera from 157 antiretroviral-naive individuals who were infected for less than 1 year. A range of neutralizing activities was observed with a previously described panel IMPORTANCEThere are very few individuals able to mount broadly neutralizing activity (bNA) close to the first year postinfection. It is not known how early in the infection cross-neutralizing responses can be induced. In the present study, we show that bNAbs, despite being rare, can be induced much earlier than previously thought. The identification of HIV-1-infected patients with these activities within the first months of infection and characterization of these responses will help in defining new immunogen designs and neutralization targets for vaccine-mediated induction of bNAbs. O ne of the main challenges for the development of a preventive human immunodeficiency virus type 1 (HIV-1) vaccine is the design of immunogens and immunization strategies that allow the induction of neutralizing antibody responses against multiple HIV-1 isolates. The main target of neutralizing antibodies is the trimeric envelope glycoprotein spike (Env). Unfortunately, when these recombinant proteins are used as immunogens, there is minimal induction of cross-reactive neutralizing antibody responses (1, 2). Despite these hurdles, high titers of broadly neutralizing antibodies (bNAbs) have been found in some chronically infected patients (3, 4). Data from many studies indicate that between 10 and 25% of patient sera displayed broadly neutralizing capacity against diverse HIV-1 strains (2-5), and one large study showed that 50% of sera from chronic infection can neutralize 50% of virus strains (6). Antibody responses have been studied extensively in these chronically infected patients, new bNAbs have been isolated, and the molecular determinants recognized by these antibodies have been characterized. Although these antibodies do not protect infected patients, they exert selective pressure on the virus (7-9). On the other hand, and more importantly, passive transfer of broadly neutralizing antibodies to monkeys and humanized mice effectively protects them against chimeric simianhuman immunodeficiency virus (SHIV) infection and HIV infection, respectively (10-18). Additionally, promising results have been obtained in recent years with approaches based on the production of broadly neutralizing antibodies against HIV and SHIV, or molecules resembling these antibodies, by adeno-associated vectors in animal models (19,20). In humans, passive transfer of bNAbs also has shown some efficacy in controlling viral replication in two recent studies, showing that passive transfer of mono-

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“…In the general population, a low CD4/ CD8 ratio is considered a surrogate marker of immunosenescence, and has been associated with persistent cytomegalovirus replication and with all-cause mortality. 19e22 In untreated HIV infection, the CD4/CD8 ratio has been investigated as a predictor of poor prognosis, 23e26 and has shown to independently predict immune restoration, 24 AIDS-related 25 and non-AIDS-related morbidities. 26 However, after several years of treatment, some patients still show an inverted ratio despite the normalization of CD4 counts, and the clinical and biological significance of this finding remains unknown.…”

Section: Introductionmentioning

confidence: 99%