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[Neoplasms associated with human immunodeficiency virus infection. Study of the clinical course of 70 patients].

BACKGROUND: A different epidemiologic pattern of the neoplasms associated to the human immunodeficiency virus (HIV) has been described in the Mediterranean area. The aim of the present study was to analyze the epidemiologic, clinical and evolutive characteristics of these patients. METHODS: A retrospective study of 74 neoplasms in 70 patients (15% of AIDS cases) was carried out. The following variables were analyzed: risk group, state of the infection (HIV), stage and type of tumor, immunohematologic data, opportunistic infections (OI), response to treatment, evolution and prognostic factors. RESULTS: Thirty-four Kaposi's sarcomas (SK) were diagnosed, 32 non Hodgkin's lymphomas (NHL), 4 Hodgkin's disease (HD), 2 seminomas, 1 cutaneous carcinoma and one undifferentiated tumor. Sixty-eight patients were males with a mean age of 32 years. The risk group was: homosexual (52%), drug abuse (24%), hemophilia (14%), and heterosexual contact (10%). The neoplasm was the first manifestation of HIV infection in 60% of the patients. Sixteen patients with SK were treated with chemotherapy (CMT), radiotherapy (RT) or interferon and stabilization of the disease was achieved in 50% of the cases. Twenty-six patients with NHL received treatment: 26 with CMT, 9 with RT and 4 with surgery. Complete remission was achieved in 27% and partial in 61% of the cases. Overall mortality was 56% and median survival 13 months. Most of the patients died due to progression of the tumor or infection. The prognostic factors associated to shortened survival were: advanced stage of AIDS, OI at the time of diagnosis of the tumor and a decrease in hemoglobin, total lymphocytes and CD4. CONCLUSIONS: The lower incidence of neoplasms among patients with acquired immunodeficiency disease and the differences in the distribution of the histologic types may be related with the demographic features of the risk groups in Spain. Survival is determined more by opportunistic infections than by the tumor itself.

Acquired Immunodeficiency Syndrome↗

Molecular evolution of human immunodeficiency virus env in humans and monkeys: similar patterns occur during natural disease progression or rapid virus passage.

Neonatal rhesus macaque 95-3 was inoculated with nonpassaged simian-human immunodeficiency virus strain SHIV-vpu(+), which encodes env of the laboratory-adapted human immunodeficiency virus (HIV) strain IIIB and is considered nonpathogenic. CD4(+) T-cell counts dropped to <200 cells/microl within 4.6 years, and monkey 95-3 died with opportunistic infections 5.9 years postinoculation. Transfer of blood from 95-3 to two naive adult macaques resulted in high peak viral loads and rapid, persistent T-cell depletion. Progeny virus evolved in 95-3 despite high SHIV-vpu(+) neutralizing antibody titers and still used CXCR4 but, in contrast to parental SHIV-vpu(+), productively infected macrophages and resisted neutralization. Sequence analysis revealed three new potential glycosylation sites in gp120; another two were lost. Strikingly similar mutations were detected in a laboratory worker who progressed to AIDS after accidental HIV-IIIB infection (T. Beaumont et al., J. Virol. 75:2246-2252, 2001), thus supporting the SHIV-vpu(+)/rhesus macaque system as a relevant model. Similar mutations were also described after rapid passage of chimeric viruses encoding IIIB env in rhesus and pig-tailed macaques (M. Cayabyab et al., J. Virol. 73:976-984, 1999; Z. Q. Liu et al., Virology 260:295-307, 1999; S. V. Narayan et al., Virology 256:54-63, 1999; R. Raghavan et al., Brain Pathol. 7:851-861, 1997; E. B. Stephens et al., Virology 231:313-321, 1997). Thus, HIV-IIIB env evolved similarly in three different species; this selection occurred in chronically infected individuals during disease progression as well as after rapid virus passage. We postulate that evolutionary pressure led to the outgrowth of more aggressive viral variants in all three species.

Amino Acid Sequence↗

[Leishmaniasis and ENT].

Three cases of the infrequent mucocutaneous Leishmaniasis, with nasal involvement in two of them and affection of the hypophrarynx and larynx in the other one are presented. We remark, in the case with laryngeal disease, that it was the onset of an AIDS in a patient unknown to be HIV+. Leishmaniasis of the larynx has not been described before as the onset of an AIDS. Symptomatology, evolution and treatment of this disease are revised, pointing out the increasing association, in our country, between leishmaniasis and AIDS, and considering the possibility of including the leishmania infection as an AIDS criteria in HIV+ patients, and to rule out an IVH infection in a patient with an atypical leishmaniasis either for the site involved or the evolutive course of the disease.

Acquired Immunodeficiency Syndrome↗

Human immunodeficiency virus type 1 primary isolate neutralization resistance is associated with the syncytium-inducing phenotype and lower CD4 cell counts in subtype CRF01_AE-infected patients.

A number of human immunodeficiency virus type 1 (HIV-1) non-B-subtype products have been developed for present or future vaccine trials; in Thailand, several studies using subtype B and/or CRF01_AE vaccines have been conducted. To better characterize the biologic properties of these subtypes, 70 HIV-1 subtype B and E isolates were phenotyped as syncytium-inducing (SI) or non-syncytium-inducing (NSI) isolates and assessed for sensitivity to neutralizing antibody (NAb). A significantly higher number of NSI subtype E viruses were neutralization sensitive than SI subtype E viruses (P = 0.009), while no association between viral phenotype and sensitivity to NAb was observed for subtype B (P = 0.856), suggesting a difference in the neutralization patterns of subtypes B and E. Strikingly, concurrent CD4 T-cell numbers were significantly lower for subtype E-infected patients whose isolates were more resistant to NAb, both for the overall study group (P < 0.001) as well as for the 22 patients with NSI isolates (P = 0.013). Characterization of the evolution of biologic properties of both B and non-B HIV-1 subtypes will provide a clearer understanding of the repertoire of antibodies that must be elicited for a vaccine to be effective against all phenotypes and subtypes.

Antibodies, Viral↗

Simultaneous occurrence of kaposi's sarcoma and chronic myelogenous leukemia.

We report here a 75-year-old man from South France who developed Kaposi's Sarcoma (KS) 5 months after diagnosis of Philadelphia-chromosome positive chronic myelogenous leukemia (CML). He was found positive for HHV-8 by PCR, negative for both HIV 1 and HIV 2 by serology, and had a normal CD4/CD8 ratio. Favourable evolution of both CML and KS has been obtained with vinblastine and interferon alpha treatment. The patient is currently alive in complete remission of SK and major cytogenetic remission of CML with a 48 month follow-up. Since no immune deficiency could be documented in the patient, this rare observation suggests that CML may have triggered the onset of SK through cytokine release.

Aged↗

[Tuberculosis profile in HIV+ patient before and after the use of high activity antiretroviral treatment].

The high activity antiretroviral treatment (HAART) induces the restoration of the number and function of CD4+ T lymphocytes and is changing the landscape of tuberculosis in patients HIV-infected. The objective of this study is to evaluate the clinical, radiographic features and evolution of these patients and compare to the results obtained in a previous study with patients with no HAART use. A retrospective transversal study (with HAART) was done with patients HIV-infected that began the tuberculosis treatment in the Gaffrée e Guinle University Hospital, from 1997 to 2001 and compared to a previous study (no HAART) that was done from 1989 to 1990. The population studied was: 107 patients (with HAART) and 152 patients (no HAART) and in both studies there were a higher frequency in young white males. The relevant results included: (a) an increase in bacteriology and histopathology diagnosis confirmation; (b) a decrease number of associated diseases during tuberculosis treatment; (c) a higher end-treatment and the death rate decreased from 55% (no HAART) to 8% (with HAART); (d) pulmonary tuberculosis was more frequent in both studies although extra-pulmonary forms were more common than in general population. We concluded that the use of HAART turned the history of tuberculosis in HIV patients getting similar to that non-immunosupressed.

Adolescent↗

[Three cases of early neurosyphilis in HIV patients].

In spite of the relative control of the disease in the late 20th century, syphilis, like other sexually transmitted diseases, has undergone a strong resurgence in recent years in the large urban centers of Europe and the US. Many patients with syphilis are also HIV+. The association between the two diseases may modify the clinical evolution of syphilis and increase the incidence of neurological disorders. We discuss the cases of three patients diagnosed with both diseases last year, with neurological presentation of syphilis occurring early and ophthalmic or cochlear vestibular involvement. This recent outbreak of syphilis seems to lead to an increase in the number of atypical cases presenting in our daily practice, where we must be prepared for early diagnosis and treatment.

Adult↗

Position paper on therapeutic drug monitoring of antiretroviral agents.

Monitoring drug concentrations in humans to optimize efficacy and reduce toxicity is not a new concept in clinical pharmacology. It has been successfully applied to many different classes of drugs. As a result of considerable concentration and response data, the concept of therapeutic drug monitoring (TDM) has been expanded to certain antiretroviral compounds. In particular, protease inhibitors and nonnucleoside reverse transcriptase inhibitors may be viable candidates for TDM, and limited clinical trial data suggest monitoring plasma concentrations of these agents may indeed clinically benefit patients with HIV infection. A primary distinction between TDM of antiretroviral drugs compared with other drugs is that multiple agents are concomitantly used to treat HIV infection. As with all illnesses that require self-administered drug therapy, poor adherence is a major impediment to success. However, in the treatment of HIV infection, inadequate drug concentrations will result in the appearance or evolution of drug resistance mutations that can endanger present and future drug treatment options. Procedures for sample collection, cross-validation of analytical procedures, and interpretation of assay results should be standardized. More clinical data are needed to confirm this approach and methods of implementing TDM should be further explored. This position paper offers guidelines to aid clinicians who choose to incorporate TDM into the routine care of their patients.

Anti-HIV Agents↗

Increase of HIV-1 subtype A in Central African Republic.

The concomitant presence of five distinct HIV-1 subtypes and of unclassified HIV-1 was reported in Bangui, Central African Republic (C.A.R.) between 1990 and 1991. This previous study was conducted in individuals belonging to the C.A.R. Armed Forces (FACA) Cohort and in patients from the University Hospital of Baugui. To follow the HIV-1 subtype distribution in Bangui over time, we conducted a cross-sectional surveillance of HIV-1 subtypes between 1987 and 1997 in three groups of individuals in Bangui: 47 men belonging to the FACA Cohort, 38 patients from the CNHUB hospital, and 51 individuals consulting the sexually transmitted diseases (STD) clinic. One hundred and ten HIV-1 were subtyped by heteroduplex mobility assay (HMA) and/or sequencing of env regions encompassing the V3 domain. By comparing the HIV-1 distribution in two time periods (1987-1991 and 1991-1996) in the FACA cohort, we observed a significant increase of subtype A from 43.7% to 83.9%. This subtype distribution does not seem specific to the FACA cohort, in that subtype A accounted for 46.7% of the HIV-1 infections in CNHUB patients in the first time period studied and for 69.6% in the second time period. In STD patients, subtype A infections were predominant in 1995 (72.7%) and 1997 (89.7%). Subtype E viruses could be identified in the second time period, but represented only between 6.5% and 21.8% of the infections in the three groups of individuals studied. Other subtypes (B, C, H) and non-classified HIV-1 in C2-V3 were detected with only a 3.2% to 9.1% frequency for each in the second time period. Phylogenetic analysis excluded infection by a single source for the individuals included in the study. Our data demonstrate an increase in the proportion of HIV-1 subtype A infections in Bangui that raises the question of a preferential transmissibility of specific HIV-1 variants.

Adult↗

Clinical manifestations and management of pediatric HIV infection.

HIV infection has emerged as a colossal problem with epidemic proportions. According to an estimate from UNAIDS about 36.1 million people all over the world are infected at present. In India about 3.5 million people are infected. The infection has evolved into phase II process of disease evolution, spreading from high-risk population to the general population. The antenatal HIV seropositivity has shown a steady increase from 0.1% to 2% in some tertiary care hospitals in Mumbai. Pediatric HIV infection presents with diverse clinical manifestations. In developing countries like India, diagnosis of infection during first year of life in perinatally exposed infants poses a problem due to lack of easy accessibility and increased cost of diagnostic facilities like HIV-PCR, CD4/CD8 counts and viral cultures. Moreover, lack of adequate drugs and exorbitant cost of sustaining antiretroviral therapy complicates the management issues. An assortment of antiretovirals is available in USA and other developed countries. In India drugs like zidovudine, lamivudine, stavudine, nevirapine and indinavir are available and are used in symptomatic patients. CDC has defined definite treatment guidelines for pediatric population recently. These guidelines need to be modified in our set up. At the present juncture in India the emphasis remains on the prevention and treatment of opportunistic infections like tuberculosis and pneumocystis carinii and on prevention of perinatal transmission with zidovudine. This brief review deals with various clinical manifestations as relevant in a developing country like India and recent advances in antiretroviral therapy.

AIDS-Related Opportunistic Infections↗

Protection of macaques with a simian immunodeficiency virus envelope peptide vaccine based on conserved human immunodeficiency virus type 1 sequences.

This report describes the vaccination of rhesus macaques with peptides selected from regions of the simian immunodeficiency virus (SIV) envelope that are hydrophilic, immunoreactive, and highly homologous with corresponding conserved envelope sequences of the human immunodeficiency virus (HIV). The peptides, produced as beta-galactosidase fusion proteins, induced virus-neutralizing and peptide-specific antibodies. After challenge with virulent virus, controls became virus positive and developed gradually rising antibody titers to SIV over 63 weeks. Immunized macaques developed a postchallenge anamnestic response to SIVenv antigens within 3-6 weeks followed by a gradual, fluctuating decline in SIV antibody titers and partial or total suppression of detectable SIV. Virus suppression correlated with prechallenge neutralizing antibody titers. Although the average CD4+ cell count in the blood of immunized macaques remained constant, the control macaques exhibited a progressive decrease developing about week 55 after challenge. The conserved nature of the HIV and SIV peptides and the similar humoral immunoreactivity in the respective hosts suggest that homologous HIV peptides may be important components of a successful immunization strategy.

Amino Acid Sequence↗

An in vivo study on active cytomegalovirus infection in relation to active HIV replication in HIV-I infected drug addicts.

Human cytomegalovirus (CMV) is a major cause of severe disease in HIV-infected persons and some findings suggest that it may accelerate HIV disease. In this study, a total of 621 blood samples from patients with LAS-ARC and AIDS were analysed in parallel for CMV and HIV-I antigenaemias. Results indicate that the presence of CMV antigenaemia and the presence of HIV-I p24 in the blood are highly correlated statistically and encourage other studies on the role of CMV in the evolution of AIDS. In a smaller group of cases, CMV was also isolated from saliva and/or urine. The correlation with HIV replication was positive (although much lower) with CMV detected in saliva and completely negative with CMV isolated from urine.

Acquired Immunodeficiency Syndrome↗

Limited heterogeneity of HIV type 1 in infected mothers correlates with lack of vertical transmission.

The human immunodeficiency virus type 1 (HIV-1) envelope V3 region sequences of peripheral blood mononuclear cell DNA were analyzed from three nontransmitting mothers (infected mothers who failed to transmit HIV-1 to their infants in the absence of antiretroviral therapy), including one mother with two deliveries, and compared with the sequences of seven previously analyzed transmitting mothers. The coding potential of the envelope open reading frame, including several patient-specific amino acid motifs and previously described molecular features across the V3 region, were highly conserved. There was a low degree of heterogeneity within the sequences of each nontransmitting mother compared with the sequences of transmitting mothers. In addition, the estimates of genetic diversity of nontransmitting mother sequences were significantly lower compared with transmitting mother sequences. Phylogenetic analysis showed that the sequences of each nontransmitting mother formed distinct clusters that were well discriminated from each other and the sequences of seven transmitting mothers. In conclusion, a low degree of HIV-1 genetic heterogeneity in these infected mothers correlates with lack of vertical transmission; this finding may be useful in developing strategies for further prevention of maternal-fetal transmission.

Amino Acid Sequence↗

Long-term CD4+ T-cell response to highly active antiretroviral therapy according to baseline CD4+ T-cell count.

Current treatment guidelines for HIV infection recommend a relatively late initiation of highly active antiretroviral therapy (HAART). Nevertheless, there is still a concern that immune recovery may not be as complete once CD4+ T cells have decreased below a certain threshold. This study addressed the long-term response of CD4+ T-cell counts in patients on HAART and analyzed the influence of baseline CD4+ T-cell counts, baseline viral load, and age. An observational analysis of evolution of CD4+ T cells in 861 antiretroviral therapy-naive chronic HIV-1-infected patients who started treatment consisting of at least 3 drugs in or after 1996 was performed. Patients were classified in 4 groups according to baseline CD4+ T cells: <200 cells/mm3, 200-349 cells/mm3, 350-499 cells/mm3, and >or=500 cells/mm3. The main outcome measures were proportion of patients with CD4+ T cells <200/mm3 and >500/mm3 at last determination and rate of CD4+ T-cell recovery. Patients were followed-up for a median of 173 weeks (interquartile range [IQR], 100-234). There were no differences in follow-up between the 4 groups. CD4+ T cells increased in the whole cohort from a median of 214 cells/mm3 (IQR, 90-355) to 499 cells/mm3 (IQR, 312-733) (P<0.001). Compared with the group with a baseline CD4+ T-cell count of >or=500/mm3, the relative risk of having a last determination of CD4+ T-cell counts >200 cells/mm3 was 0.79 (95% CI, 0.75-0.83), 0.92 (95% CI, 0.89-0.96) and 1 for baseline CD4+ T cells <200 cells/mm3, 200-349 cells/mm3, and 350-499 cells/mm3, respectively. The relative risk of having a last determination of CD4+ T-cell counts >500 cells/mm3 was 0.32 (95% CI, 0.27-0.39, P<0.001), 0.69 (95% CI, 0.60-0.79, P<0.001), and 0.94 (95% CI, 0.83-1.06, P=0.38) for baseline CD4+ T-cell counts <200 cells/mm3, 200-349 cells/mm3, and 350-0499 cells/mm3, respectively, compared with a baseline CD4+ T-cell count of >or=500 cells/mm3. The increase in CD4+ T cells from baseline was statistically significant and was maintained for up to 4 years of follow-up. This increase seemed to slow down after approximately 3 years and reached a plateau after 4-5 years of follow-up even in patients who achieved and maintained viral suppression in plasma. Long-term immune recovery is possible regardless of baseline CD4+ T-cell count. However, patients who start therapy with a CD4+ T-cell count <200 cells/mm3 have poorer immunologic outcome as measured by the proportion of patients with CD4+ T cells <200/mm3 or >500/mm3 at last determination. It seems that the immune recovery slows down after approximately 3 years of HAART and reaches a plateau after 4-5 years of HAART.

Acquired Immunodeficiency Syndrome↗

[Cutaneous and oral manifestations in HIV-infected children and adults--169 cases].

UNLABELLED: The aim of the study was to evaluate cutaneous and oral manifestations in infected HIV patients. MATERIALS AND METHODS: We retrospectively analyzed 169 cases admitted in Infectiouse Disease Department of Iaşi in 2001-2002 period. RESULTS: Cutaneous and oral manifestations were: candidiasis (99 cases), herpes virus infectious (36 cases), scabies and straphylococcal/streptococcal skin disease (26 cases), prurigo nodularis, psoriasis and verruca vulgaris (9 cases). Children of 0-13 year old group was 75.73 percent. Classification of HIV infection was related with CD4 count for 166 cases. Twelve cases with oral pharyngitis candidiasis, scabies and streptococcal skin diseases was 2-3 recurrent episodes of manifestations. Etiotrop treatment was associated with HAART therapy. CONCLUSIONS: Cutaneous and oral manifestations are occurred frequently in HIV infected patients, with a various etiology, but the severity, persistence and its evolution did not evaluate.

AIDS-Related Opportunistic Infections↗

Fibrosis is worse in HIV-HCV patients with low-level immunodepression referred for HCV treatment than in HCV-matched patients.

Hepatitis C virus (HCV) infection is frequent in human immunodeficiency virus (HIV)-infected patients. It is known to have an aggressive course in significantly immunosuppressed patients, and cirrhosis C has become one of the main causes of mortality in HIV-HCV coinfected patients since the improvement of antiretroviral therapy. The reasons for this severe fibrotic evolution are unclear. This prospective study compared chronic HCV lesions, liver immunocompetent cells, fibrosis and liver HCV loads in 2 cohorts of naive patients referred for HCV treatment: 33 HIV-HCV coinfected patients with CD4 >250/microL and 33 HCV-infected patients matched for the main risk factors of fibrosis. Fibrosis, particularly perisinusoidal fibrosis, was more marked in the coinfected patients. This occurred in the absence of a significant difference in disease activity. The number of CD3+ cells in the liver was higher in the HIV-HCV patients than in the HCV patients. Conversely, the number of liver CD4+ cells was lower in HIV-HCV patients than in HCV patients. The numbers of CD8+ and CD68+ cells were similar in the 2 groups. Finally, liver HCV load, assessed by immunostaining and reverse-transcription polymerase chain reaction, was similar in the 2 groups. We conclude that in the population of HIV-HCV coinfected patients with low-level immunosuppression referred for HCV treatment, fibrosis is worse than in HCV patients and the proportion of CD4+ lymphocytes among CD3+ cells is markedly decreased in the liver, whereas intrahepatic viral load is similar. Our data confirm the need to treat such patients against HCV, and suggest that HIV infection could favor fibrosis via the modulation of the intrahepatic immune response.

Antigens, CD↗

HIV-1 genomic RNA diversification following sexual and parenteral virus transmission.

Human immunodeficiency virus type 1 (HIV-1) genomic RNA variation was studied in seven presumed donor-recipient pairs directly following sexual (6/7) or parenteral (1/7) transmission. The first RNA-positive serum sample of each recipient and the serum sample of the virus transmitter, identified by epidemiological history and taken within a time bracket of three months of the recipient seroconversion, were analyzed by polymerase chain reaction amplification followed by sequencing of eight cDNA clones of 276 bp, including the V3 coding region. The sequence populations of the recipients were without exception homogeneous, while the sequence populations of the transmitters showed varying degrees of heterogeneity. Nucleotide distance between consensus sequences of unrelated individuals from the Amsterdam population (interpatient variation) averaged 11% (range 7-15%). The largest distance between two clonal sequences of one individual (intrapatient variation) was also 11%. Consensus sequences of five recipients differed by only 0-1% from the consensus sequence of the presumed transmitter, including two pairs of which the transmission was either proven or highly probable. This contrasted with a difference of 10-12% in two pairs, casting doubt on the epidemiological relatedness. Antibody reactivity to a panel of V3 peptides with varying degrees of similarity to the V3 sequences obtained did not augment the discriminatory power of sequence analysis. Results of the sequential sequencing of samples of one transmitter suggest that this was due to an anamnestic antibody response of the transmitter to early variants. From the loss of sequence heterogeneity following transmission and the consensus sequence similarities observed within five transmitter-recipient pairs, we conclude that HIV-1 transmission results in the selection of a limited number of genomes carrying on the infection in the new host, but does not generally lead to a shift in the sequence population as defined by the consensus sequence.

Amino Acid Sequence↗