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[Trends in human immunodeficiency virus infection prevalence in homosexual/bisexual men in Madrid (1986-1995)].

BACKGROUND: We analysed the trend in seroprevalence for human immunodeficiency virus (HIV) in homosexual or bisexual men who voluntary requested the test in a sexually transmitted disease/HIV clinic in Madrid. PATIENTS AND METHODS: We studied 5,424 homo/bisexual non-injecting drug user (non-IDU) men, who came for the first time since 1986 to 1995. We analysed the HIV seroprevalence taken into account the year, age and exchange of sex by money. A hundred and thirty-six IDU homo/bisexual men were also attended during the same period and they were compared with non-IDU. RESULTS: HIV seroprevalence among the 5,424 non-IDU homo/bisexual men were 20.2%, rising from 19.6% in 1986 to 29.6% in 1990. After then, the trend decreased to 15.3% in 1995 (chi 2 for trend, 66.8; p < 0.0001). Average age was three years higher among seropositives (p < 0.0001), and showed an upward trend from 29.9 in 1986 to 34.6 in 1995 (p = 0.0059). Seroprevalence among homosexuals younger than 25 fell in the last years. One percent of individuals had ever practiced the prostitution. They were younger (average age, 27.6), and their HIV seroprevalence were 25.9%. A hundred and thirty-six IDU homo/bisexual men were also attended for the first time, being 2.4% of overall homo/bisexual men. They had a higher seroprevalence (48.5%) than non-IDU (p < 0.0001), and did not show any significative time-trend. CONCLUSIONS: A favourable evolution can be observed in HIV seroprevalence among homo/bisexual from Madrid, Spain, men who came to be tested, especially among the youngest. Prevention programs should make an effort to maintain this trend.

Adult↗

The nature of human immunodeficiency virus type 1 strand transfers.

The diploid nature of human immunodeficiency virus type 1 (HIV-1) suggests that recombination serves a central function in virus replication and evolution. A system was developed to examine HIV-1 strand transfers, including the obligatory DNA primer strand transfers as well as recombinational crossovers during reverse transcription. Sequence heterogeneity between different strains of HIV-1 was exploited for examining primer transfer events. Both intra- and intermolecular primer transfers were observed at similar frequencies during minus-strand DNA synthesis, whereas primer transfers during plus-strand DNA synthesis were primarily intramolecular. Sequence analysis of long terminal repeats from progeny proviruses also revealed a high rate of homologous recombination during minus-strand synthesis, corresponding to an overall rate of approximately three crossovers per HIV-1 genome per cycle of replication. These results imply that both viral genomic RNAs serve as templates during HIV-1 reverse transcription and that primer strand transfers and recombination may contribute substantially to the rapid genetic variation of HIV-1.

Base Sequence↗

Divergence of HIV-1 quasispecies in an epidemiologic cluster.

BACKGROUND: During treatment with blood components prepared from an HIV-infected donation, two recipients became infected in 1985. One recipient infected her sexual partner. OBJECTIVE: To evaluate the evolution of the originally-shared HIV-1 quasispecies in different human hosts over time, sequence data were obtained from serum from the actual donation sample of blood, and from plasma samples collected from the four members of the epidemiologic cluster over a period extending from 1986 to 1993. METHODS: The V3 hypervariable region of env and the gag p17 gene were analysed. CD4 and CD8 counts, as well as HIV RNA burden data, were collected. RESULTS: One patient died from AIDS during the study. This patient showed a greater degree of diversity in the V3 region, with a higher positive charge over time, than the other individuals. Phylogenetic analysis revealed that the V3 sequences from each of the four individuals occupied separate branches of a phylogenetic reconstruction (tree). Two distinct subgroups evolved in the donor, one with GPGR and the other with GSGR/GSGK at the tip of the V3 loop. This latter group was not detected in the other individuals. The sequences in the sexual partner were no more related to those in the infecting transfusion recipient than to sequences from the other members of the cluster, consistent with sexual transmission having occurred at a time shortly after the recipient was infected. CONCLUSION: The shared HIV-1 quasispecies in this epidemiologic cluster diverged in an individual-specific manner.

Amino Acid Sequence↗

Hepatitis C virus co-infection is a negative prognostic factor for clinical evolution in human immunodeficiency virus-positive patients.

A longitudinal study of human immunodeficiency virus (HIV)-infected individuals followed-up in 13 centres was performed to assess the influence of hepatitis C virus (HCV) on the clinical and immunological evolution of HIV-infected patients. Eight-hundred and twelve HIV-infected patients with known HIV acquisition date, 89 co-infected with HCV, were included in the cohort. Clinical progression was defined as: 30% decrease of Karnofsky's index; and/or 20% body weight loss; and/or acquired immune deficiency syndrome (AIDS)-defining illness; and/or death (except by accident, suicide, or overdose). Immunological progression was defined as a decrease of initial CD4 count to below 200 mm(-3). If immunological progression was not statistically different between groups (P=0.25), clinical progression was significantly faster in HCV-HIV co-infected patients in univariate (P=0.02) and multivariable survival analysis (hazard ratio=1.63, P=0.03). This argues for active management of hepatitis C chronic infection among HCV-HIV co-infected patients.

Adult↗

[Health care resources utilization in HIV-infected patients: creation of a data base and cost results].

OBJECTIVES: To make and validate a data base that allows to collect information about clinical characteristics and use of health care services by HIV-infected patients. An additional purpose is to obtain some data about costs of health care services utilization. METHODS: We have designed an informatic data base that includes: demographic data, clinical data and health care services utilization during the follow up. One hundred and nine patients were selected from 5 different hospitals in Spain and they were followed for 6 months (from January to June 1997). Analytic accounting of one hospital and official tariffs were used to calculate costs of the health care services. RESULTS: The informatic data base designed is useful and appropriate to collect the information of these patients. The annual average cost is 2.5 millions dollars, ranging from 1 million dollars for asymptomatic patients to 3.8 millions for AIDS patients. The comparison of our results with previous studies shows an increased cost of asymptomatic patients. CONCLUSIONS: These results give a preliminary information about health care services utilization by HIV-infected patients and confirm the possibility of using the designed instrument in the future. Since HIV-infection presents an uncertain evolution and a variable prognosis, to implant a tracking system is a necessary requirement in order to obtain a fast and accurate information system about the evolution of clinical variables and their economic repercussions.

Acquired Immunodeficiency Syndrome↗

Effect of increase of dietary micronutrient intake on oxidative stress indicators in HIV/AIDS patients.

Several recent studies in human immunodeficiency virus (HIV) patients have identified micronutrient deficiencies as affecting progression to acquired immunodeficiency syndrome (AIDS) and death. Although the mechanisms are not known, micronutrient deficiencies may exacerbate the oxidative stress induced by HIV. In addition, infection and its evolution likely lead to an increased requirement for nutritional micronutrients, especially antioxidants. To evaluate this, 40 relatively healthy, institutionalized HIV-infected individuals were recruited for assessment before or three months after fresh fruit and vegetable supply were increased due to seasonal supply. Seven-day dietary records were recorded at the beginning (December) and end of the three-month study period (March). Oxidative stress indices and CD4+, CD38+/CD8+, and CD95+ T-lymphocyte subsets were also measured at these times. No significant differences were found in calorie or protein intake across the study period, but vitamin A, C, and E intakes all increased. A number of redox indicators were modified (increase: total antioxidant status, glutathione peroxidase, and glutathione; and decrease: superoxide dismutase) during the study period. However, no change in malondialdehyde, hydroperoxides, or DNA damage was noted but a significant reduction in CD38+/CD8+ relative count was seen. Within the context and limitations of this study, the increase of dietary fruits and vegetables intake for three months had some beneficial effects on nutrition, systemic redox balance, and immune parameters in HIV-infected persons.

Adult↗

Prospective evaluation and follow-up of European patients with visceral leishmaniasis and HIV-1 coinfection in the era of highly active antiretroviral therapy.

A prospective descriptive study was designed to determine the impact of highly active antiretroviral therapy (HAART) in the evolution of visceral leishmaniasis (VL) in HIV-1 infected patients. Thirty-two patients were treated with meglumine antimoniate or amphotericin B in lipid formulations. Patients who had undergone previous HAART at study entry (n=17) continued with therapy while receiving treatment for VL. Patients who had never undergone HAART started it after VL treatment finished (n=15). Ten patients were lost to follow-up. All of the remaining patients (n=20) continued to receive HAART and were followed for an average of 441 days. Relapses were observed in 5 of 20 patients. These results indicate that HAART neither prevents the incidence of VL relapse nor modifies the clinical picture described in the pre-HAART era.

Adult↗

Antiretroviral therapy: evaluating the new era in HIV treatment.

Tools for evaluating antiretroviral therapy are still evolving. Key components are available such as the laboratory assays themselves, but results from these assays are being analyzed and presented inconsistently, making interstudy comparisons difficult or impossible. In part, the problems in analysis and presentation reflect a lack of completed clinical trials in which new laboratory methods such as RNA copy numbers can be validated. Survival is the clearest valid end point in clinical trials of antiretroviral drugs. Beyond life and death, the next most important issue is quality of life. Because of the difficulty in agreeing what "quality of life" means, and the even greater problems measuring such an abstract concept, in most cases assessments are made of more quantifiable clinical elements: cognitive and motor function, growth, and the frequency of opportunistic infections. Laboratory markers of disease progression are very quantifiable but have meaning only when they predict clinical outcome. There is a consensus that CD4+ counts, CD4+ percentages, and HIV copy numbers measured by RNA PCR are important. There is not, however, a consensus approach to interpretation of data from any of these markers of HIV disease, particularly because the interpretation may vary based on the patient's level of clinical disease. With time and more clinical trials with which to clarify their use, these tools should become more uniformly applied, at which point cross-study comparisons might be possible. Progress is already being made in the development of new antiretroviral therapies, and with improved evaluation techniques the evolution of new anti-HIV treatments should become an even more efficient process.

Adolescent↗

Evidence for late stage compartmentalization of HIV-1 resistance mutations between lymph node and peripheral blood mononuclear cells.

OBJECTIVE: To determine the overall distribution of drug-resistance mutations to nucleoside reverse transcriptase inhibitors of HIV strains recovered from the lymph nodes (LN) and peripheral blood mononuclear cell (PBMC) compartments of four HIV-infected patients receiving zidovudine and didanosine and to compare them with antiretroviral-naive patients. DESIGN: Molecular comparison of major and minor HIV-1 env and pol region variants residing in LN and PBMC compartments. MATERIALS AND METHODS: Proviral DNA sequences were amplified by PCR from both PBMC and LN compartments, cloned into PGEM-T II Easy vector and sequenced. The clones were subjected to molecular and phylogenetic analysis. RESULTS: Comparison of PBMC and LN-derived HIV-1 variants in the env V3 region showed that nucleotide and amino acid variability was a characteristic feature of LN-derived variants. In contrast, a majority of resistance mutations to reverse transcriptase inhibitors were localized in the PBMC compartment rather than in LN, which is thought to be a reservoir of HIV. CONCLUSIONS: Distinct compartmentalization or independent evolution of pol and env gene variants between LN and PBMC could be due to the differential selection pressure imposed by the combination drug regimen, hence the bimodal distribution of resistance variants between LN and PBMC compartments.

Anti-HIV Agents↗

Study of some lymphocyte subset counts and cytokine levels in cryptococcosis associated with AIDS.

Approximately 100 new cases per year of cryptococcosis in HIV+ patients are observed in Muñiz Hospital, 35% of them suffer a fatal outcome within the first four weeks after diagnosis in spite of treatment. Apparently there is not a useful parameter that allows a clear prediction of this early fatal outcome of the disease. The aim of this study is to determine some cytokine levels and several lymphocyte subpopulations counts in order to correlate these results with the evolution of the disease. Forty HIV+ patients suffering culture confirmed cryptococcosis were enrolled in this study, 8 HIV+ patients without cryptococcosis and 8 healthy individuals with negative serology for HIV were included as controls. The following determinations were done in all cases: CD3+, CD4+, CD8+, CD16+CD3-, CD19+ cell counts, IL-1; IL-12, TNFalpha in serum and TNFalpha in CSF. Ten cases with cryptococcosis and AIDS were controlled three months after treatment. The average of CD4+ and NK cell counts in patients before treatment were 22/microl and 90/microl respectively; IL-1 levels were higher in the patients than in the healthy control group, conversely IL-12 levels did not show significant differences in the three studied groups. Serum concentrations of TNFalpha were higher in patients than in the control group and were not modified after treatment, conversely antifungal medication diminished IL-1 concentration and remarkably increased NK cell counts. At the same time antigen levels in serum and CSF decreased. The results obtained seem to show that the immunological alterations observed in these patients are those characteristically exhibited in severe HIV disease and that some parameters such as CD8+ cell counts lower than 200/microl, less than 50 CD4+/microl, more than 50 pg/ml of TNF-alpha and serum capsular antigen titer higher than 1:5000 seem to predict a rapidly fatal course of infection.

Journal Article↗

The intrinsic rate of increase of HIV/AIDS: epidemiological and evolutionary implications.

A method derived from demographic theory is presented for modeling the epidemiology of an infectious disease. For long-term infections, this method better accounts for host variation in survival and transmission rates than classical compartment models. Examples of the applications of this method focus on a single long-term infectious disease, HIV/AIDS. The method is employed to examine (1) how changes in transmission rates during different stages of infection affect the rate of spread of HIV/AIDS both in wholly susceptible populations and in populations where the number of potential hosts is limited, (2) the way the relative frequencies of the different stages of infection vary over time, (3) how the rate at which the epidemic is growing (or diminishing) affects the fraction of HIV-infected individuals who manifest the symptoms of AIDS, (4) the effect of treatment on the rate of spread of HIV, and (5) the potential effects of natural selection on the virulence of HIV.

Acquired Immunodeficiency Syndrome↗

Serological detection of attenuated HIV-1 variants with nef gene deletions.

OBJECTIVE: To investigate whether members of a transfusion-linked cohort (the Sydney Bloodbank Cohort) infected with a nef-deleted strain of HIV-1 could be differentiated from individuals infected with wild-type strains of HIV-1 by characterizing the Nef antibody response of cohort members. DESIGN: Retrospective and prospective analysis of the nef gene sequence and the antibody response to Nef peptides in HIV-infected subjects. METHODS: Plasma was obtained from all individuals of the Sydney cohort, and from a variety of HIV-1-infected and uninfected controls. Antibodies recognizing full-length recombinant HIV-1NL43 Nef protein and synthetic peptide analogues were assessed by enzyme-linked immunosorbent assay. RESULTS: All 34 individuals infected with wild-type HIV-1 had antibodies reacting with full-length Nef protein as well as with a series of synthetic peptides (6-23-mers) spanning most of the Nef protein of HIV-1NL43. Although the HIV-1 quasispecies infecting the Sydney cohort had a consensus deletion of the nef gene corresponding to amino-acids 165-206, HIV-1 strains from individual members of the cohort had additional deletions comprising up to 80% of the nef gene. Members of the cohort had antibodies to peptides homologous to all regions of the Nef protein tested, except for a single peptide (amino-acids 162-177) that lies within the consensus nef deletion for the cohort quasispecies. CONCLUSION: These data show that nef-deleted strains of HIV-1 can be detected serologically. In the Sydney cohort, detection of antibodies to all regions of Nef tested, except that corresponding to amino-acids 162-177, suggests that observed deletions outside this domain occurred after this virus had infected these subjects and stimulated an immune response. A Nef peptide serological assay may be useful for identifying further examples of individuals infected with nef-deleted, attenuated HIV-1 quasispecies and for assessing the evolution of those variants in vivo.

AIDS Serodiagnosis↗

The role of bronchoscopy in the diagnosis and treatment of pulmonary disease in HIV-infected patients.

BACKGROUND: Pulmonary disease is the most common reason for presentation and the major cause of death in HIV-infected patients. There has been an evolution in the optimal approach to the investigation of a pulmonary infiltrate in HIV-infected patients since the introduction of induced sputum for the diagnosis of Pneumocystis carinii pneumonia (PCP). AIMS: To evaluate the usefulness of flexible fibreoptic bronchoscopy (FFB), bronchoalveolar lavage (BAL), transbronchial biopsy (TBB) and bronchial brushings (BB) in the diagnosis of pulmonary disease in HIV-infected patients and to examine the effect of FFB on changes in therapy and survival. METHODS: The histories of all HIV-infected patients referred to Fairfield Hospital for FFB between January 1990 and June 1993 were examined retrospectively. RESULTS: Forty-two FFB were performed on 41 patients (40 male and one female). Definitive diagnoses made at FFB included Kaposi's sarcoma (KS) (n = 9), invasive aspergillosis (n = 5), PCP (n = 4), Mycobacterium avium complex (MAC) pneumonia (n = 2), cytomegalovirus (CMV) pneumonia (n = 1), Cryptococcus neoformans pneumonia (n = 1), microsporidium (n = 1) and Pseudomonas aeruginosa pneumonia (n = 1). TBB and BB did not provide a diagnosis for diseases not seen macroscopically at FFB or diagnosed by BAL. FFB findings altered diagnosis in 21/42 (50%) presentations and changed therapy in 26/42 (62%) cases. CONCLUSIONS: FFB together with BAL altered the working diagnosis and changed therapy in a significant number of patients. TBB and BB should not be routinely performed in all patients as these procedures are of limited value in this setting.

AIDS-Related Opportunistic Infections↗

Selective granulocyte/monocyte apheresis in the treatment of HIV-infected patients: short-term and long-term effects on immunological and virological parameters.

CD4 T cells constitute the major cellular target of HIV infection and, in the natural evolution of the disease, are gradually lost, leading to severe immunodeficiency. Highly active antiretroviral therapy (HAART) is generally effective in reducing HIV replication to undetectable levels and allows the recovery of CD4 T cells in the majority of patients treated. However, some sanctuaries of HIV replication persist even after years of effective HAART and are responsible for the rebound of viral replication when treatment is interrupted. Monocytes/macrophages are also infectable by HIV and are less susceptible to its cytopathic effects compared to CD4 T cells. Replication-competent HIV DNA is detectable in peripheral monocytes of patients under HAART. These cells may therefore contribute to the maintenance of HIV replication during treatment. In addition, both monocytes and granulocytes are abnormally activated during HIV infection and this results in overproduction of some pro-inflammatory cytokines, among them TNF-alpha. For these reasons we tested whether the renewal of the pool of circulating monocytes and granulocytes by selective apheresis (G1 apheresis) could influence some key immunological and virological parameters in HAART-treated patients. The results showed that treatment with G1 apheresis without discontinuation of HAART results in an accelerated immune reconstitution with sustained increases in CD4 T cell counts in those patients who respond virologically to HAART. G1 apheresis is also followed by a strong reduction of TNF-alpha and a reduction of cells bearing integrated HIV DNA. Taken together, the results indicate that G1 apheresis could be used to improve the immunological and virological response to HAART.

Antiretroviral Therapy, Highly Active↗

Endocarditis in the setting of HIV infection.

BACKGROUND: Cardiac complications are becoming more important in patients with HIV infection. The most common is infective endocarditis (IE) in patients who are intravenous drug addicts (IVDA). Other less common problems are pulmonary hypertension, cardiotoxicity, pericardial effusion, cardiac neoplasms, etc. PATIENTS AND METHODS: A literature review of published studies on IE was done and the personal experience of the authors is reflected. RESULTS: The clinical pattern of IE has remained unchanged. It is usually due to Staphylococcus aureus and is more commonly localized to the right side of the heart. It is not clearly defined if HIV infection is responsible for the worst evolution in these patients and the treatment is the same as that used in HIV- subjects. CONCLUSIONS: IE is responsible for 5-20% of hospital admissions and for 5-10% of total deaths in IVDA patients with HIV infection, but the clinical outcome of the patients depends on the affected valve and the culture germen rather than the HIV serostatus.

Anti-Bacterial Agents↗

[Immunodeficiency viruses].

In the first part of this article some structural and biological aspects of the HIV viruses are presented, in our opinion among the most interesting ones, connected with the AIDS viruses. Viral infection and its evolution, particularly related with infection by HIV-2, will be presented later, in the light of our experience, obtained over several years work with African people infected by the virus. The AIDS viruses are complex retroviruses, with their own identity, but also with marked structural and biological resemblances to other retroviruses, equally pathogenical for animals. The lentivirinae subfamily to which the AIDS viruses belong includes other agents, usually classified according to the host they infect. In this way, the lentiviruses of the primates contain in the same group, besides those of HIV-1 and HIV-2, viruses that infect monkeys such as SIVMAC, SIVAGM, SIVSMM, etc. The comparative study of molecular genetics and biology of human and animal retroviruses in recent years has permitted significant progress in the understanding of the possible mechanisms that lead to the Immunodepressive Acquired Syndrome that characterizes AIDS. The presence of a gene that deactivates the activated lymphocytes only present in the lentiviruses of the primates, as well as the known tropism of those viruses to CD4 lymphocytes, and not found in the other groups, are biological aspects that are pointed out. We also refer to other characteristics of HIVs such as the cytolytic and sincicial capacity of these viruses in lymphocyte culture. Finally we present an analysis of what we were able to observe in individuals infected by HIV-2 in their own and African habitat.

Acquired Immunodeficiency Syndrome↗