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PubMed2001

[Primary pulmonary hypertension in human immunodeficiency virus infection. Study of 9 cases amd review of the literature].

PURPOSE: In medical literature, primary pulmonary hypertension occurs in 0.5% of human immunodeficiency virus (HIV)-infected patients, irrespective of the stage of the HIV disease, and is more frequent in drug users. Plexogenic arteriopathy is the most frequent histological lesion. METHODS: We retrospectively report on nine cases of primary pulmonary hypertension during HIV infection. RESULTS: The subjects were four women and five men, mean age 38 years old. Four of them had been sexually contaminated and five had contracted the disease through intravenous drug use. At the time primary pulmonary hypertension was diagnosed, mean CD4 cell count was 234 +/- 217/mm3 and the viral load was low or undetectable. Primary pulmonary hypertension has been diagnosed an average of 7 months after the first cardiovascular clinical signs had started. Despite anti-coagulant (7/9 cases), vasodilatator (4/9 cases) and/or diuretic (7/9 cases) therapy, the progression of the disease quickly turned out to be negative (seven deaths). CONCLUSION: Diagnosis of primary pulmonary hypertension should be considered when unexplained dyspnea occurs in an HIV-positive patient. At initial evaluation, alterations of hemodynamic parameters are usually less severe than during idiopathic primary pulmonary hypertension, but their progression is quicker and more severe, independent of the patient's immune status. Current data do not allow the determination of whether antiretroviral therapy is active in primary pulmonary hypertension evolution. Therapeutic evaluation with prostacyclin is currently being carried out. While the life expectancy of HIV-infected patients extends, primary pulmonary hypertension occurrence could increase and call for early diagnosis, thus allowing for specific care.

Adult↗

PubMed1994

[Extensive Kaposi's disease with fatal outcome in a young togolese with negative HIV serology].

This is a rare case of extensive multifocal type of Kaposi's disease which developed in a young child. The patient's age, the major and progressive weight loss, the appearance of adenopathies and of a suspected tuberculous pleuritis, the evolution of cutaneous lesions extension, followed by death in short time (5 years) led us to suspect an eventual association with HIV infection. Serologic tests performed three times which remained negative and the absence of other important AIDS signs excluded this diagnostic.

Adult↗

PubMed2006

Immunodomination in the evolution of dominant epitope-specific CD8+ T lymphocyte responses in simian immunodeficiency virus-infected rhesus monkeys.

Because the control of HIV-1 replication is largely dependent on CD8+ T lymphocyte responses specific for immunodominant viral epitopes, vaccine strategies that increase the breadth of dominant epitope-specific responses should contribute to containing HIV-1 spread. Developing strategies to elicit such broad immune responses will require an understanding of the mechanisms responsible for focusing CD8+ T lymphocyte recognition on a limited number of epitopes. To explore this biology, we identified cohorts of rhesus monkeys that expressed the MHC class I molecules Mamu-A*01, Mamu-A*02, or both, and assessed the evolution of their dominant epitope-specific CD8+ T lymphocyte responses (Gag p11C- and Tat TL8-specific in the Mamu-A*01+ and Nef p199RY-specific in the Mamu-A*02+ monkeys) following acute SIV infection. The Mamu-A*02+ monkeys that also expressed Mamu-A*01 exhibited a significant delay in the evolution of the CD8+ T lymphocyte responses specific for the dominant Mamu-A*02-restricted SIV epitope, Nef p199RY. This delay in kinetics was not due to differences in viral load kinetics or magnitude or in viral escape mutations, but was associated with the evolution of the Mamu-A*01-restricted CD8+ T lymphocyte responses to the highly dominant SIV epitopes Gag p11C and Tat TL8. Thus, the evolution of dominant epitope-specific CD8+ T lymphocyte responses can be suppressed by other dominant epitope-specific responses, and this immunodomination is important in determining the kinetics of dominant epitope-specific responses.

Amino Acid Sequence↗

PubMed2006

Neutralizing antibody responses against autologous and heterologous viruses in acute versus chronic human immunodeficiency virus (HIV) infection: evidence for a constraint on the ability of HIV to completely evade neutralizing antibody responses.

Acute human immunodeficiency virus (HIV) infection is associated with the rapid development of neutralization escape mutations. The degree to which viral evolution persists in chronic infection has not been well characterized, nor is it clear if all patients develop high-level neutralization antibody escape. We therefore measured neutralizing antibody responses against autologous and heterologous viruses in a cohort of acutely and chronically infected subjects (n = 65). Neutralizing antibody responses against both autologous virus and heterologous viruses were lower among individuals with acute infection than among those with chronic infection. Among chronically infected individuals, there was a negative correlation between the level of neutralizing antibodies against autologous virus and the level of viremia. In contrast, there was a positive correlation between the level of neutralizing antibodies against a panel of heterologous viruses and the level of viremia. Viral evolution, as defined by the presence of higher neutralizing titers directed against earlier viruses than against contemporaneous viruses, was evident for subjects with recent infection but absent for those with chronic infection. In summary, neutralizing antibody responses against contemporaneous autologous viruses are absent in early HIV infection but can be detected at low levels in chronic infection, particularly among those controlling HIV in the absence of therapy. HIV replication either directly or indirectly drives the production of increasing levels of antibodies that cross-neutralize heterologous primary isolates. Collectively, these observations indicate that although HIV continuously drives the production of neutralizing antibodies, there may be limits to the capacity of the virus to evolve continuously in response to these antibodies. These observations also suggest that the neutralizing antibody response may contribute to the long-term control of HIV in some patients while protecting against HIV superinfection in most patients.

Acute Disease↗

PubMed1994

Serum immunoglobulin profiles in asymptomatic HIV-1 seropositive adults and in patients with AIDS in Dar es Salaam, Tanzania.

Serum levels of immunoglobulin classes and IgG subclasses were determined in healthy seronegative (n = 50) and in HIV-1 seropositive adults (n = 50) from Tanzania, a region with heterosexual HIV-1 transmission pattern. The mean levels of total IgG, IgG1, IgG3, IgA, IgM, and IgD obtained were found to be significantly higher in HIV-1 seropositive sera than in control sera. The mean IgA, IgM, IgD and IgG3 levels showed an increasing trend with progression from asymptomatic phase to AIDS phase. The mean levels for total IgG, IgG1 and IgG2 remained constant while that for IgG4 decreased with progression to AIDS phase. From the findings, it is concluded that polyisotypic hypergammaglobulinaemia and serum IgG subclass changes occur in HIV-1 seropositive individuals in Tanzania. The characteristic changes observed for IgD, IgG3 and IgG4 levels with evolution from asymptomatic to AIDS phases could be of value in monitoring disease progression.

Acquired Immunodeficiency Syndrome↗

PubMed2007

Evaluating liver fibrosis progression and the impact of antiretroviral therapy in HIV and hepatitis C coinfection using a noninvasive marker.

The effects of highly active antiretroviral therapy (HAART) on progression of hepatic fibrosis in hepatitis C virus (HCV) coinfection with HIV are not well understood and are difficult to measure because of the need for repeated liver biopsy. We evaluated the evolution of a noninvasive measure of liver fibrosis, the alanine aspartyl transferase (AST)-to-platelet ratio index (APRI), longitudinally and determined its predictive value for hepatic outcomes in HIV-positive patients with and without HCV coinfection. A total of 673 HIV-positive patients without liver complications at baseline (540 with HIV only, 133 with HIV-HCV coinfection) were followed between 1991 and 2004 for a median of 4.6 years (3524 person-years). At baseline, HIV-HCV coinfection had a higher median APRI compared with HIV infection alone (0.59 vs. 0.33; P < 0.0001). The natural logarithm of the APRI [ln(APRI)] changed significantly over time, particularly among patients with HIV-HCV coinfection. The baseline ln(APRI) was predictive of liver complications (hazard ratio [HR] = 4.0, 95% confidence interval [CI]: 2.5 to 6.4 per log), as was HCV (HR = 4.5, 95% CI: 1.5 to 14). Cumulative HAART did not protect against liver complications, although it was significantly associated with progression of APRI scores in HIV-HCV coinfection and in HIV alone. In conclusion, the APRI may be a useful marker for longitudinal evaluation of the progression of liver disease in HIV-HCV coinfection.

Adolescent↗

PubMed2006

T cell receptor excision circles (TRECs), CD4+, CD8+, and their CD45RO+, and CD45RA+, subpopulations in hepatitis C virus (HCV)-HIV-co-infected patients during treatment with interferon alpha plus ribavirin: analysis in a population on effective antiretroviral therapy.

Interferon (IFN)-alpha induced CD4(+) T lymphopenia is a toxic effect of the treatment of chronic hepatitis C virus (HCV) in human immunodeficiency virus (HIV)-co-infected patients. To increase the knowledge about this secondary effect, we performed an analysis of the evolution of the T cell receptor excision circles (TRECs), CD4(+) and CD8(+) T cells and of their CD45RO(+) and CD45RA(+) subpopulations during the treatment of chronic hepatitis HCV with peginterferon alpha (pegIFN-alpha) + ribavirin. Twenty HCV/HIV-co-infected patients, with undetectable HIV load after highly active antiretroviral therapy (HAART), were treated with pegIFN-alpha + ribavirin. TRECs were determined using real-time polymerase chain reaction. CD4(+) and CD8(+) T cells and their CD45RO(+) and CD45RA(+) subpopulations were analysed by two-colour flow cytometry. Median baseline CD4(+) and CD8(+) T cells were 592 mm(3) and 874 mm(3), respectively. Median baseline CD45RO(+) subpopulation was 48% for CD4(+) T and 57% for CD8(+) T lymphocytes. A progressive decrease in both T cell populations, as well as of their CD45RO(+) and CD45RA(+) subpopulations, was detected, with a difference between the baseline and nadir levels approaching 50%. The evolution of T cell populations and TRECs was independent of the response to the treatment. T lymphocytes and their subpopulations returned to baseline levels at 24 weeks after the end of treatment, with the exception of the T CD4(+) CD45RA(+) subpopulation. The ratio of CD4(+) CD45RO(+)/CD4(+) CD45RA(+) increased from 0.89 (baseline) to 1.44 (24 weeks after the end of the therapy). TRECs/ml did not return to the basal values. In conclusion, a significant reduction of CD4(+) and CD8(+) T cells, and of their CD45RA(+) and CD45RO(+) subpopulations, in HIV/HCV co-infected patients treated with pegIFN-alpha was observed. Both subpopulations increased after the suppression of treatment, but the CD4(+) CD45RA subpopulation did not reach the basal levels as a consequence, at least in part, of a decrease in thymic production.

Adult↗

PubMed1998

Dual effect of interleukin 4 on HIV-1 expression: implications for viral phenotypic switch and disease progression.

We report that interleukin 4 (IL-4) inhibits the propagation of non-syncytia-inducing and increases the propagation of syncytia-inducing HIV-1 isolates by two mechanisms. It differentially regulates the two major HIV-1 coreceptors, CCR5 and CXCR4, in human peripheral blood mononuclear cells, increasing CXCR4 and decreasing CCR5 expression in primary CD4(+) T-lymphocytes. In addition, IL-4 stimulates the expression of all HIV-1 isolates via a transcriptional activation mechanism. The combination of these effects results in increased propagation of CXCR4-using and inhibition of CCR5-using HIV-1 strains. IL-4 also activates HIV-1 expression in primary monocytes/macrophages but does not affect CCR5 expression. These results identify IL-4 as an important regulator of HIV-1 and suggest a critical role for this cytokine in the control of viral evolution and in the phenotypic switch from non-syncytia-inducing to syncytia-inducing, which leads to accelerated disease progression.

CD4-Positive T-Lymphocytes↗

PubMed2006

Evolution of the uniquely adaptable lentiviral envelope in a natural reservoir host.

BACKGROUND: The ability of emerging pathogens to infect new species is likely related to the diversity of pathogen variants present in existing reservoirs and their degree of genomic plasticity, which determines their ability to adapt to new environments. Certain simian immunodeficiency viruses (SIVcpz, SIVsm) have demonstrated tremendous success in infecting new species, including humans, resulting in the HIV-1 and HIV-2 epidemics. Although SIV diversification has been studied on a population level, the essential substrates for cross-species transmission, namely SIV sequence diversity and the types and extent of viral diversification present in individual reservoir animals have not been elucidated. To characterize this intra-host SIV diversity, we performed sequence analyses of clonal viral envelope (env) V1V2 and gag p27 variants present in individual SIVsm-infected sooty mangabeys over time. RESULTS: SIVsm demonstrated extensive intra-animal V1V2 length variation and amino acid diversity (le38%), and continual variation in V1V2 N-linked glycosylation consensus sequence frequency and location. Positive selection was the predominant evolutionary force. Temporal sequence shifts suggested continual selection, likely due to evolving antibody responses. In contrast, gag p27 was predominantly under purifying selection. SIVsm V1V2 sequence diversification is at least as great as that in HIV-1 infected humans, indicating that extensive viral diversification in and of itself does not inevitably lead to AIDS. CONCLUSION: Positive diversifying selection in this natural reservoir host is the engine that has driven the evolution of the uniquely adaptable SIV/HIV envelope protein. These studies emphasize the importance of retroviral diversification within individual host reservoir animals as a critical substrate in facilitating cross-species transmission.

Animals↗

PubMed1990

[Respiratory function abnormalities and pneumonia in HIV-positive patients. A prospective study of 112 patients].

Pulmonary function studies are often limited to the alone measurement of transfer lung factor for CO (TLCO) in screening for pneumonia in patients with Human Immunodeficiency Virus (HIV) infection. We prospectively measured pulmonary function tests (PFT) in 112 HIV seropositive patients. The population consisted of two groups: on one hand, a group free of clinical and radiological abnormalities, on the other hand, one with respiratory symptoms and/or abnormal chest X-Ray, with or without overt pneumonitis. For this latter group, a fiberoptic bronchoscopy with bronchoalveolar lavage was routinely performed in addition to PFT. In case of pneumonitis, PFT showed a restrictive disease and a reduced TLCO. The specificity of this functional pattern was however weaker in the subgroup of drug abusers than in the non-drug addicts. This difference was above all linked to a low TLCO value in the subgroup of drug addicts without pulmonary complications. Multivariate statistical analysis, including discriminant analysis, maintained the same sensibility and improved specificity of PFT in diagnosis of pneumonia, especially if the analysis takes the existence of drug abuse into account. Moreover, initial PFT, performed before any lung disease, improved the sensibility of the screening. The results are discussed in relation to new tests proposed for the screening of pneumonitis in HIV positive patients. At the present time, PFT seems to be useful and enables one to understand natural functional evolution.

Adult↗

PubMedDate not supplied

A highly divergent HIV-2-related isolate.

It has been suggested that the human immunodeficiency virus type 2 (HIV-2) and the simian immunodeficiency virus from rhesus macaques (SIVmac) evolved from the sooty mangabey virus SIVsm (ref. 1). We now describe an HIV-2-related isolate, HIV-2-D205, from a healthy Ghanaian woman that is genetically equidistant to the prototypic HIV-2 strains and to SIVsm and SIVmac. Supported by the observation that HIV-2D205 differs in a step of envelope glycoprotein processing, our data indicate that it could represent an alternative HIV-2 subtype and that viruses of the HIV-2/SIVsm/SIVmac group could have already infected humans before HIV-2 and SIVsm/SIVmac diverged.

Base Sequence↗

PubMed2004

[Treatment with interferon and ribavirin of chronic hepatitis C in HIV-infected patients].

BACKGROUND: The rapid progression of chronic hepatitis C (CHC) in HIV-infected patients is now the most important cause of morbidity, mortality and hospital admissions. In order to avoid this evolution, the treatment of CHC is a major challenge in these patients. PATIENTS AND METHOD: The aim of this study is to evaluate the safety and efficacy of treatment of CHC in HIV-infected patients with subcutaneous IFN (3 MU 3 times a week) plus Ribavirin (RBV) administered per 200 mg dosage depending on their body weight, for 24 weeks for genotype 2 or 3 and 48 weeks for genotype 1 or 4. All the patients have a CD4 count over 150 cells/microl and HIV viral load < 50,000 copies/ml, with or without antiretroviral treatment. We defined sustained response as RNA-VHC below level of detection 24 weeks after the end of treatment. RESULTS: We included 28 patients in the study, with median age of 36.6 y.o. 82% of the patients were on antiretroviral treatment, with AZT in 60% of them. Genotype distribution was HCV-1 in 50%, HCV-3 in 35.7%, HCV-4 in 10.7% and HCV-2 in 3%. Liver biopsy was performed in all the patients. Adverse events leading to treatment discontinuation occurred in 5 patients (17.8%). The overall sustained response rate in the intent-to-treat analysis was 25.8% (50% for genotype 3 and 14% for genotype 1). CONCLUSION: This therapy provides cure in a rate significantly lower than that seen in HCV-monoinfected individuals, with a similar safety. The modern formulations of IFN (pegylated) will provide new expectatives in this group of patients.

AIDS-Related Opportunistic Infections↗

PubMed1992

[Pneumonia caused by non-opportunistic bacteria in patients infected with HIV. Incidence and evaluation of a non-invasive approach].

BACKGROUND: Pneumonia due to pathogenic bacteria is common in HIV infected patients. However, a global overview has not been yet performed and also the effectiveness of a non-invasive approach has not been tested. PATIENTS AND METHODS: An open study was conducted in 1989 including all HIV infected patients with a presumptive or definite diagnosis of bacterial pneumonia. Fiberoptic bronchoscopy procedures were used only in patients with a difficult diagnosis and/or problems in their clinical evolution. Clinical and biological data were compared among different etiologic groups, and their evolution was also recorded in relation with the use of non-invasive procedures. RESULTS: Among a total of 302 admissions of HIV infected patients, 113 developed a primary or secondary respiratory tract infection. Forty-three of those were bacterial pneumonia episodes. Etiologic diagnosis was achieved with non invasive methods in 18 cases (42%). Blood cultures were the most effective method used. Streptococcus pneumoniae was the most frequently identified microorganisms (9 cases, 21%). The identification of other bacteria was linked with more severe forms of disease regarding immunologic (leukopenia, p less than 0.001; T4 lymphopenia, p less than 0.05), and respiratory parameters (hypoxemia, p less than 0.05). Two deaths were directly related with pneumonia of known etiology. CONCLUSIONS: Bacterial pneumonia is the most frequent respiratory infection in HIV infected patients. An initial non-invasive approach yields a reasonable percentage of etiologic diagnosis and is not related with a poorer outcome.

Bacterial Infections↗

PubMed2004

Cyclophilin A retrotransposition into TRIM5 explains owl monkey resistance to HIV-1.

In Old World primates, TRIM5-alpha confers a potent block to human immunodeficiency virus type 1 (HIV-1) infection that acts after virus entry into cells. Cyclophilin A (CypA) binding to viral capsid protects HIV-1 from a similar activity in human cells. Among New World primates, only owl monkeys exhibit post-entry restriction of HIV-1 (ref. 1). Paradoxically, the barrier to HIV-1 in owl monkey cells is released by capsid mutants or drugs that disrupt capsid interaction with CypA. Here we show that knockdown of owl monkey CypA by RNA interference (RNAi) correlates with suppression of anti-HIV-1 activity. However, reintroduction of CypA protein to RNAi-treated cells did not restore antiviral activity. A search for additional RNAi targets unearthed TRIMCyp, an RNAi-responsive messenger RNA encoding a TRIM5-CypA fusion protein. TRIMCyp accounts for post-entry restriction of HIV-1 in owl monkeys and blocks HIV-1 infection when transferred to otherwise infectable human or rat cells. It seems that TRIMCyp arose after the divergence of New and Old World primates when a LINE-1 retrotransposon catalysed the insertion of a CypA complementary DNA into the TRIM5 locus. This is the first vertebrate example of a chimaeric gene generated by this mechanism of exon shuffling.

Amino Acid Sequence↗

PubMed2006

Genetic attributes of cerebrospinal fluid-derived HIV-1 env.

HIV-1 often invades the CNS during primary infection, eventually resulting in neurological disorders in up to 50% of untreated patients. The CNS is a distinct viral reservoir, differing from peripheral tissues in immunological surveillance, target cell characteristics and antiretroviral penetration. Neurotropic HIV-1 likely develops distinct genotypic characteristics in response to this unique selective environment. We sought to catalogue the genetic features of CNS-derived HIV-1 by analysing 456 clonal RNA sequences of the C2-V3 env subregion generated from CSF and plasma of 18 chronically infected individuals. Neuropsychological performance of all subjects was evaluated and summarized as a global deficit score. A battery of phylogenetic, statistical and machine learning tools was applied to these data to identify genetic features associated with HIV-1 neurotropism and neurovirulence. Eleven of 18 individuals exhibited significant viral compartmentalization between blood and CSF (P < 0.01, Slatkin-Maddison test). A CSF-specific genetic signature was identified, comprising positions 9, 13 and 19 of the V3 loop. The residue at position 5 of the V3 loop was highly correlated with neurocognitive deficit (P < 0.0025, Fisher's exact test). Antibody-mediated HIV-1 neutralizing activity was significantly reduced in CSF with respect to autologous blood plasma (P < 0.042, Student's t-test). Accordingly, CSF-derived sequences exhibited constrained diversity and contained fewer glycosylated and positively selected sites. Our results suggest that there are several genetic features that distinguish CSF- and plasma-derived HIV-1 populations, probably reflecting altered cellular entry requirements and decreased immune pressure in the CNS. Furthermore, neurological impairment may be influenced by mutations within the viral V3 loop sequence.

Amino Acid Sequence↗

PubMed2004

A robust measure of HIV-1 population turnover within chronically infected individuals.

A simple nonparameteric test for population structure was applied to temporally spaced samples of HIV-1 sequences from the gag-pol region within two chronically infected individuals. The results show that temporal structure can be detected for samples separated by about 22 months or more. The performance of the method, which was originally proposed to detect geographic structure, was tested for temporally spaced samples using neutral coalescent simulations. Simulations showed that the method is robust to variation in samples sizes and mutation rates, to the presence/absence of recombination, and that the power to detect temporal structure is high. By comparing levels of temporal structure in simulations to the levels observed in real data, we estimate the effective intra-individual population size of HIV-1 to be between 10(3) and 10(4) viruses, which is in agreement with some previous estimates. Using this estimate and a simple measure of sequence diversity, we estimate an effective neutral mutation rate of about 5 x 10(-6) per site per generation in the gag-pol region. The definition and interpretation of estimates of such "effective" population parameters are discussed.

Evolution, Molecular↗

PubMedDate not supplied

[Clinical-echocardiography of 210 HIV-Ab positive patients: retrospective study].

Through the retrospective study of 210 HIV Ab+ patients in different disease's stages, recovered in the "D. Cotugno-Naples" hospital during the period February 1989-February 1991, the authors have valued the prevalence of cardiological alterations underlined by ecocardiograph. Pericardial pouring has been observed in four patients out of thirty, belonged to stages II, III and ARC. Ventricles' movement alterations have been observed in twenty patients out of thirty (66%), belonged prevalently to the fourth group. Kaposi's sarcoma has been observed in two patients out of thirty (6.6%), belonged to the fourth group. In the patients showing alterations, the authors have also noticed a correlation among the observed cardiological alterations and the immunital outline and the frequent homosexuality's presence. The follow up between the alterations' observation and the possible patient's death is on an average 4.3 months (range 1-12). They suggest that a wider and more precocious ecocardiographical research of HIV Ab+ patients is the only way, at the moment, to underline and follow the cardiac alterations' evolution, also in relation to a precocious antiretroviral therapy.

Adolescent↗

PubMed2002

[Cytomegalovirus retinitis in HIV positive patients].

UNLABELLED: First it is shown an up-date about cytomegalovirus retinitis, concerning pathogeny, diagnosis, evolution and treatment. Then is a study about incidence and evolution of cytomegalovirus retinitis in AIDS patients, which have the diagnosis among january 1994-september 2002. CONCLUSIONS: In Romania the incidence of cytomegalovirus retinitis in AIDS patients is lower than in western countries, because over 60% of patients are children.

AIDS-Related Opportunistic Infections↗