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[The clinico-epidemiological aspects of HIV infection in 167 children nonmaternally infected who have died with a diagnosis of AIDS].

The aim of this study was to evaluate the clinical and epidemiological particularity of pediatrics nosocomial HIV infection. Our study group consists of 167 HIV serum-positive nonmaternally infected children who died of AIDS in 1990-1997 (inclusive) in Colentina Hospital of Infections Diseases--Bucharest. Fifty per cent of institutionalized children and 28% of family children died in the first two years of life. About 80% of children were revealed too late as HIV infected. It has been observed a relatively high prevalence values for: multiple or recurrent pneumonia--74.8%, recurrent or chronic diarrhea--87.4%, encephalopathy--65.8%, weight-growth deficiency--100%, disseminated or extrapulmonary tuberculosis--13.8%, HBsAg carriage--59.8%; and low prevalence values for: lymphoid interstitial pneumonia--16.5%, Pneumocystis carinii pneumonia--11.4%, cytomegalovirus diseases--1.8%, cryptosporidiosis--1.8%. The evolution of HIV infection (weight-growth deficiency and encephalopathy) were aggravated in hospitalised children (especially, in the first two years of life). Nutrition and hygiene care factors positively influence the evolution of HIV infection. Multiple or recurrent pneumonia are out of an important prognostic value in the appreciation of SIDA evolution. The incidence and severity of tuberculosis increased at older children. The too late diagnostic of HIV infection had unfavourable influence upon the life expectancy of children.

Acquired Immunodeficiency Syndrome↗

[Clinical and laboratory evolution of children born to HIV positive mothers].

UNLABELLED: The vertical transmission of HIV (Human Immunodeficiency Virus) has become the main target of prophylactic Zidovudina (AZT) therapy during gestation, parturition as well as for the newborn. BACKGROUND: To characterize the clinical and laboratory evolution of HIV exposed children. METHODS: Prospective study of 64 HIV exposed children, classified into two groups. Group A, made up of 23 pairs of mothers and newborns, who did not receive AZT; Group B, made up of 41 pairs, who received AZT at some stage of prophylaxis. RESULTS: The average maternal age was 26.8 years, the use of illicit drugs occurred in 17.2% of the pregnant women, twenty (31.3%) of the women had diseases. Between the groups there were no significant differences related to prenatal frequency of maternal illnesses, birth body dimensions and growth sequence. Both study groups presented with similar lymphocyte and blood counts. On the average, seroreversion took place at 16 months. Vertical transmission occurred in 6 children (9.3%), none of the children in the subgroup who received prophylaxis during all phases were infected. CONCLUSIONS: The prophylactic therapy with AZT during all the periods recommended and the long term follow-up of the HIV exposed children constitute one of the best strategies for prevention of the acquired immunodeficiency syndrome (AIDS) in infants.

Adult↗

Genotypic analysis of HIV-1 drug resistance at the limit of detection: virus production without evolution in treated adults with undetectable HIV loads.

Human immunodeficiency virus (HIV) production continues in patients receiving highly active antiretroviral therapy (HAART) with undetectable (<50 copies/mL) virus loads. Our initial cross-sectional study showed that this viremia is composed of viruses that lack new resistance mutations to the HAART regimen. Here we describe a longitudinal, clonal genotypic analysis of plasma virus loads in treated adults who had undetectable virus loads. We document a continuous production of virus in 8 HIV-1-infected adults who maintained suppression of viremia for up to 15 months. Using analytical approaches for distinguishing selected resistance mutations from nonselected mutations and polymerase chain reaction errors, we detected no evolution of resistance in the reverse-transcriptase and protease genes. Sporadic resistance mutations were detected in some viral clones that were not selected for subsequently. Thus, in some patients, HAART suppresses replication to a level that does not allow the evolution of drug resistance over a time frame of years.

Adult↗

First case of mother-to-infant HIV type 1 group O transmission and evolution of C2V3 sequences in the infected child. French HIV Pediatric Cohort Study Group.

We report the first case of mother-to-infant transmission and follow-up for an HIV-1 group O virus from Cameroon. Isolates were obtained from the mother at delivery and from the child at birth and when 16 and 30 months old. We analyzed the viral evolution within mother and child by examining 51 sequences spanning C2V3 regions of the viral envelope gene. The mother carried two genotypes, v1 and v2. The genotype v1 was dominant in the child at birth, and persisted as a minor genotype at age 30 months. The genotype v2 was absent in the child sequences. The variability of the nucleotide sequences of the isolates from the child increased with age from 0.8 to 6%, and a novel genotype (v3) appeared at age 30 months. The nonsynonymous-to-synonymous mutation ratio increased with the age of the child, from 0.75 at birth to 1.86 at 30 months, indicating a high rate of fixation of amino acid changes in the child. The overall pattern was similar to that reported by Ganeshan et al. (J Virol 1997;71:663-677) for group M viruses infecting child with a slow-developing form of the disease.

Acquired Immunodeficiency Syndrome↗

Evidence for human immunodeficiency virus type 1 replication in vivo in CD14(+) monocytes and its potential role as a source of virus in patients on highly active antiretroviral therapy.

In vitro studies show that human immunodeficiency virus type 1 (HIV-1) does not replicate in freshly isolated monocytes unless monocytes differentiate to monocyte-derived macrophages. Similarly, HIV-1 may replicate in macrophages in vivo, whereas it is unclear whether blood monocytes are permissive to productive infection with HIV-1. We investigated HIV-1 replication in CD14(+) monocytes and resting and activated CD4(+) T cells by measuring the levels of cell-associated viral DNA and mRNA and the genetic evolution of HIV-1 in seven acutely infected patients whose plasma viremia had been <100 copies/ml for 803 to 1,544 days during highly active antiretroviral therapy (HAART). HIV-1 DNA was detected in CD14(+) monocytes as well as in activated and resting CD4(+) T cells throughout the course of study. While significant variation in the decay slopes of HIV-1 DNA was seen among individual patients, viral decay in CD14(+) monocytes was on average slower than that in activated and resting CD4(+) T cells. Measurements of HIV-1 sequence evolution and the concentrations of unspliced and multiply spliced mRNA provided evidence of ongoing HIV-1 replication, more pronounced in CD14(+) monocytes than in resting CD4(+) T cells. Phylogenetic analyses of HIV-1 sequences indicated that after prolonged HAART, viral populations related or identical to those found only in CD14(+) monocytes were seen in plasma from three of the seven patients. In the other four patients, HIV-1 sequences in plasma and the three cell populations were identical. CD14(+) monocytes appear to be one of the potential in vivo sources of HIV-1 in patients receiving HAART.

Amino Acid Sequence↗

Seroepidemiology of human immunodeficiency viruses in Africa.

The first generation of serological tests for anti-HIV-1 gave so many false positives with African sera that it was wrongly postulated that the virus was endemic in Africa. As there is no simian or other virus sufficiently closely related to HIV-1 as to suggest a recent common ancestor, the evolution of HIV-1 is obscure and there is no current evidence to support the hypothesis of an African origin. However, the similarity of HIV-2 to SIV and its geographical distribution do suggest an evolution of this virus in west Africa. The earliest anti-HIV-1 positive serum was from a subject in Kinshasa in 1959. Seroprevalence rose in pregnant women in Kinshasa from 0.25% in 1970, to 3.0% in 1980 and 5.7% in 1986. When two sexually promiscuous groups are compared, seropositivity rose sharply in female prostitutes in Nairobi from 4% in 1981, to 59% in 1984 and 64% in 1986, a curve which is approximately parallel to, but three years later than that of homosexual males in San Francisco. In central and east Africa, HIV-1 is now epidemic from Congo to Kenya and from Uganda to Zimbabwe. In west Africa, both HIV-2 and HIV-1 are epidemic: seroprevalence of HIV-2 is highest in southern Senegal, Guinea-Bissau and Côte d'Ivoire: HIV-1 has the highest frequency in Côte d'Ivoire and Ghana. HIV-2 has not been reported, and HIV-1 is pre-epidemic in Africa north of the Sahara, Nigeria, Angola, Mozambique and southern Africa, being found at significant frequency only in female prostitutes, patients with STD, or, in Morocco and South Africa only, in male homosexuals. Seroprevalence is greatest in female prostitutes and patients with STD: infection is more frequent in urban than in rural populations, except in Uganda. The peak frequency is at 30-34 yr in males and 20-24 yr in females. Other groups at risk are infants born to infected mothers, and those requiring blood transfusions, especially pre-school children, patients with sickle-cell disease and pregnant women. The doubling time for seropositivity is about one year in the sexually active age range in some populations. Even at existing seroprevalence, decimation or worse of the most productive age groups is inevitable during the next few years in certain countries.(ABSTRACT TRUNCATED AT 400 WORDS)

AIDS Serodiagnosis↗

Certain HLA-DR5 and -DR6 major histocompatibility complex class II alleles are associated with a CD8 lymphocytic host response to human immunodeficiency virus type 1 characterized by low lymphocyte viral strain heterogeneity and slow disease progression.

Either of two structurally related major histocompatibility complex class II alleles, DRB1*1102, which encodes a DR5 specificity, or DRB1*1301, which encodes a DR6 specificity, was found in 67% of individuals responding to human immunodeficiency virus type 1 (HIV-1) infection with a syndrome characterized by persistent circulating and diffusely infiltrative CD8 lymphocytosis (DILS), slow progression to opportunistic infections, and delayed CD4 T-cell depletion. These alleles were present in only 28% of ethnically matched HIV-positive controls (P = 0.001). The frequency of DRB1*1301 was increased in both Blacks and Caucasians with this syndrome, while that of DRBI*1102 was increased only in Blacks, where 80% had either of these alleles. To investigate whether the host response associated with these alleles influences the evolutionary divergence of the HIV-1 genome, sequencing of the envelope V3 loop was performed. This revealed a significantly diminished lymphocyte viral heterogeneity compared with random HIV+ controls matched for CD4 T-cell levels. These results suggest that the immunogenetics of the host influence the nature of the immune response to HIV-1, which may lead to constrained evolution of HIV-1 gene products. Of possible relevance, the alpha-helical third diversity region common to both the DRB1*1102 and DRB1*1301 allelic products was noted to have homology with the C-terminal region of the HIV-1 envelope V3 loop at six of nine consecutive residues. This suggests the possibility that these alleles may bias the anti-HIV T-cell receptor repertoire through a mimicry mechanism.

Alleles↗

[Prevalence of hepatitis C virus among HIV-infected patients in Area 2 of Madrid].

INTRODUCTION: The evolution of HIV infection, a rapid and fatal illness not long time ago, has become a chronic disease due to the implementation of new antiretroviral treatment. Therefore it is essential to focus on the management of concurrent illnesses such as chronic hepatitis C infection, specially as they share common routes of transmission. METHODS: A cross sectional survey was done to determine the prevalence of HIV and HCV coinfection, measuring different HIV and HCV variables among 651 HIV infected patients of a health area in Madrid. RESULTS: 500 patients (76.8%) were male and 151 female (23%). HCV serology was performed in all the patients and resulted positive in 45.7% (298) most of them drug users (84.8%). The CD4 cell count was lower in patients HIV-HCV coinfected compared to those HCV negative (p < 0.001). CONCLUSION: This study shows a high prevalence of HIV-HCV coinfection, mainly due to parenteral transmission. We emphasize the low percentage of coinfected patients treated with interferon and ribavirine which probably will increase in the future.

Adult↗

[Laryngeal tuberculosis: considerations on the most recent clinical and epidemiological data and presentation of a case report].

According to the "Global Tuberculosis Control" performed in 1999--the third complete, international, global report on tuberculosis infection--173 countries reported their infection data to the WHO; of these countries 102 met the criteria for "DOTS programs" at the end of 1997. The DOTS programs are the only control strategy able to produce a cure rate of 85%. Both at the national and international (Centers of Disease Control) levels, guidelines have been drawn up to improve and coordinate the fight against tuberculosis. New indicators and methods of analysis should be developed to quantify the full impact on the control of infection transmission, incidence, prevalence, mortality and prevention of drug resistance. In addition, two significant world-wide events have affected the increase morbidity rate seen in the last decade in the more highly industrial countries: immigration from countries outside the European Community and HIV infection. The tuberculosis infection worsens the evolution of HIV, facilitating viral replication. In the present work the authors discuss the most recent epidemiological data regarding tuberculosis infection and review the Literature on the primary laryngeal location of the disease. Then they present a clinical case which recently came under observation. This case is a typical example of the clinical picture of the laryngeal tuberculosis seen today. It must not be forgotten that in recent years there has been an increase in morbidity in Italy, in both the pulmonary and extrapulmonary forms of the disease, although in our country the problem of delayed or incomplete reporting is quite widespread. The data show that the age ranges with the highest incidence of both pulmonary and extrapulmonary forms are the 25-35 and 60-70 year groups. Distribution by sex, on the hand, shows that the pulmonary forms are most often seen in males while the extrapulmonary forms have practical the same frequency in both sexes. In recent years the clinical and morphological aspects of tubercular laryngitis have changed significantly from what they were before chemotherapy and the most common clinical form is pseudotumoral tuberculosis. This form requires a differential diagnosis to distinguish it from neoplasms because they present a similar objective picture and have no signs of simultaneous or previous pulmonary involvement.

Diagnosis, Differential↗

New HIV strains?

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Animals↗

Parallel evolution of drug resistance in HIV: failure of nonsynonymous/synonymous substitution rate ratio to detect selection.

Parallel or convergent evolution at the molecular level has been difficult to demonstrate especially when rigorous statistical criteria are applied. We present sequence data from the protease gene from eight patients infected with the human immunodeficiency virus (HIV-1). These patients have been on multiple drug therapies for at least 2 years. We present sequence data from two timepoints: time zero--the initiation of drug therapy--and a subsequent timepoint between 59 and 104 weeks after the initiation of drug therapy. In addition to the sequence data, we present viral load data from both initial and final timepoints. Our phylogenetic analyses indicate significant evolution of virus from initial to final time points, even in three of eight patients who show low viral loads. Of the five patients who escaped drug therapy, identical amino acid replacements were seen in all five patients at two different codon positions, an indication of parallel evolution. We also measured genetic diversity for these patients and found no correlation between genetic diversity and viral load. Finally, we calculated the nonsynonymous and synonymous substitution rates and showed that the ratio of nonsynonymous to synonymous substitution compared to the value of one may be a poor indicator of natural selection.

Anti-HIV Agents↗

Evolution of anti-HIV drug candidates. Part 1: From alpha-anilinophenylacetamide (alpha-APA) to imidoyl thiourea (ITU).

Stemming from work on a previous clinical candidate, loviride, and other alpha-APA derivatives, a new series of potent non-nucleoside reverse transcriptase inhibitors (NNRTIs) has been synthesized. The ITU analogues, which contain a unique diarylated imidoyl thiourea, are very active in inhibiting both wild-type and clinically important mutant strains of HIV-1.

Acetamides↗

Evolution of anti-HIV drug candidates. Part 2: Diaryltriazine (DATA) analogues.

A synthesis program directed toward improving the stability of imidoyl thiourea based non-nucleoside reverse transcriptase inhibitors (NNRTIs) led to the discovery of diaryltriazines (DATAs), a new class of potent NNRTIs. The synthesis and anti-HIV structure-activity relationship (SAR) studies of a series of DATA derivatives are described.

Anti-HIV Agents↗

Evolution of anti-HIV drug candidates. Part 3: Diarylpyrimidine (DAPY) analogues.

The synthesis and anti-HIV-1 activity of a series of diarylpyrimidines (DAPYs) are described. Several members of this novel class of non-nucleoside reverse transcriptase inhibitors (NNRTIs) are extremely potent against both wild-type and a panel of clinically significant single- and double-mutant strains of HIV-1.

Anti-HIV Agents↗

Molecular cloning and characterization of a German HIV-1 isolate.

The genetic diversity of HIV-1 is well documented. Except for the HIV-1 isolate LAV-1BRU, no nucleic acid sequence of a European isolate of HIV-1 has been published to date. To further investigate the extent of the genetic variability and the evolution of HIV-1, we have isolated, cloned, and subsequently sequenced HIV-1 from a German patient with AIDS-related complex. Comparative studies of the nucleic acid sequence revealed that this isolate, designated HAN2, is highly divergent from the North American and African subtypes of HIV-1 and may represent a European subtype of HIV-1. Furthermore, a full-length molecular clone was derived from this isolate which was infectious in human T-cell lines. Therefore this new isolate will be particularly useful for studies on the genetic evolution and biology of HIV-1 as well as for testing antiviral substances and for developing vaccines.

Amino Acid Sequence↗

Human immunodeficiency virus (HIV) infection in parenteral drug users: evolution of the epidemic over 10 years. Valencian Epidemiology and Prevention of HIV Disease Study Group.

BACKGROUND: Evaluation of acquired immunodeficiency syndrome (AIDS) prevention strategies requires an on-going follow up of the frequency of human immunodeficiency virus (HIV-1) infection. The aim of this study was to examine the trends in prevalence and incidence of HIV-1 infection among injecting drug users (IDU) during the period 1987-1996. METHODS: Transversal and cohort studies were designed which included a consecutive sample of 7132 IDU who attended three AIDS Prevention and Information Centres in the Region of Valencia (Spain) and voluntarily asked to be tested for HIV antibodies. The prevalence was estimated for each year based on the serological status of HIV-1 when the patient first visited the centre. The annual incidence rates were calculated based on the seronegative patients in which a new determination of HIV-1 was done. In order to control the possible effects on the estimations of age, sex and duration of addiction of the people studied, Poisson and logistic regression models were adjusted. RESULTS: Prevalence and incidence rates of HIV-1 infection showed parallel trends over time. The overall prevalence found was 43.6% (95% confidence intervals [CI]: 42.4-44.7%). Of the 4023 seronegative individuals, 1746 were followed up over the whole of the study period. The incidence rate observed was 6.85 x 100 persons/year (95% CI : 6.04-7.66). The prevalence figures show a decrease, which is most marked from 1990 onwards and then they tend to stabilize over the past few years. The incidence rates increase slightly up to 1991 (9.8 x 100 persons/year), and then begin to decrease. CONCLUSION: Trends of prevalence of HIV-1 infection approximate trends of subjacent incidence rate. Despite decrease in HIV-1 infection frequency observed over 10 years, both the prevalence and incidence figures continue to be high in absolute terms. It is necessary to intensify and adapt preventive measures to each subgroup at risk of infection and in the case of heterosexual transmission ensure that the failure observed in the case of IDU is not repeated.

Acquired Immunodeficiency Syndrome↗