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PubMed2004

Drug resistance, virus fitness and HIV-1 mutagenesis.

The evolution of antiretroviral drug resistance is a major problem in the treatment of human immunodeficiency virus type 1 (HIV-1) infection. Drug therapy failure is associated with accumulation of drug resistance mutations and results in the development of drug resistance. Drugs targeted against reverse transcriptase (RT) as well as drug-resistant RT have been shown to increase HIV-1 mutation frequencies. Furthermore, combinations of drug and drug-resistant RT can increase virus mutation frequencies in a multiplicative manner. The evolution of drug resistance also alters virus fitness. The correlation of increased HIV-1 mutation rates with the evolution of antiretroviral drug resistance indicates that drug failure could increase the likelihood of further resistance evolving from subsequent drug regimens. These observations parallel studies from microbial systems that provide evidence for a correlation between drug resistance development and increased pathogen mutation rates. Although increased mutant frequencies may be detrimental to effective therapy, the lethal mutagenesis of the HIV-1 genome may provide a new means for antiretroviral therapy.

Animals↗
PubMed2004

Fuzzy modeling in symptomatic HIV virus infected population.

This paper introduces a model for the evolution of positive HIV population and manifestation of AIDS (acquired immunideficiency syndrome). The focus is on the nature of the transference rate of HIV to AIDS. Expert knowledge indicates that the transference rate is uncertain and depends strongly on the viral load and the CD4+ level of the infected individuals. Here, we suggest to view the transference rate as a fuzzy set of the viral load and CD4+ level values. In this case the dynamic model results in a fuzzy model that preserves the biological meaning and nature of the transference rate lambda. Its behavior fits the natural history of HIV infection reported in the medical science domain. The paper also includes a comparison between the fuzzy model and a classic Anderson's model using data reported in the literature.

Acquired Immunodeficiency Syndrome↗
PubMed1993

[Infection by Borrelia burgdorferi in patients with the human immunodeficiency virus. A diagnostic problem].

BACKGROUND: Given that Lyme's disease and HIV infection may present with similar clinical symptoms and that the serologic tests for the determination of antibodies against Borrelia burgdorferi present frequent false positives, the presence of antibodies against B. burgdorferi in patients with HIV in different evolutive stages was studied. METHODS: Antibodies against B. burgdorferi were determined by IFI and ELISA in a serum sample of 72 individuals with HIV. Western blot (WB) against B. burgdorferi was performed in the sera which were positive by one method or the other. The presence of antiphospholipid antibodies was also studied. RESULTS: A total of 24 sera (33%) were positive by IFI and/or ELISA. Twenty-one (29%) by IFI and 7 (10%) by ELISA (chi 2; p = 0.006). Four (5.5%) were positive by both methods. Only one of the sera was positive by IFI, ELISA and WB. No statistical relation was found upon comparison of the positive results against B. burgdorferi with the different evolutive stages of HIV infection or with the presence of antiphospholipid antibodies. CONCLUSIONS: The high prevalence of false positive serology to B. burgdorferi in the collective of patients with the human immunodeficiency virus infection together with the possibility of presenting similar clinical manifestations has led to extreme prudence in the diagnosis of infection by B. burgdorferi in patients with HIV infection.

Antibodies, Antiphospholipid↗
PubMed2004

Expansion of quasispecies diversity but no evidence for adaptive evolution of SHIV during rapid serial transfers among seronegative macaques.

Four successive, rapid serial passages of the nonpathogenic, CCR5-tropic simian-human immunodeficiency virus SHIV(SF162) in rhesus macaques resulted in an increase in acute plasma viremia with each passage and the emergence of a pathogenic isolate SHIV(SF162P3) in one of the passage three transfer animals (macaque T353). To explore the mechanism(s) underlying increased virulence of SHIV(SF162) upon in vivo passage, the evolution of the HIV-1 envelope gene was characterized in plasma and PBMC samples obtained from animals before (week 1) and after (week 3) the time of virus transfer. We found no evidence in support of adaptive evolution of the HIV gp120 during rapid serial passage; however, the animals which later received passage virus had more diverse quasispecies. SHIV(SF162P3)-like gp120 sequences were first detected in macaque T353 at week 6, after seroconversion. These sequence changes increased in frequency and number at later time points. The first sequence change conferred neutralization escape but not an increase in viral infectivity that could account for the apparent increase in replicative capacity of the later passage viruses. Collectively, our data argue against any host-specific adaptation of the HIV-1 envelope gp120 as the basis for the generation of more aggressive SHIV variants during rapid serial transfers in seronegative macaques, and support the model of quasispecies diversity as a predictor of pathogenesis. Envelope sequence changes accumulate principally in response to immune pressure exerted by the host, generating viral variants that can persist in the presence of a strong host immune response.

Amino Acid Sequence↗
PubMed1991

[Routes of HIV infection in a pregnant population in metropolitan France: evolution over a three year period].

Routes of HIV transmission among seropositive pregnant women were studied over a three year period in a nationwide multicenter study in France. A total of 2,346 cases were included: 666 in 1987, 809 in 1988 and 871 in 1989. The principal route of transmission was intravenous drug use (IVDU), however an increase in heterosexual transmission was observed. From 1987 to 1989, the proportion of cases related to IVDU decreased from 66.4 percent to 48.2 percent while sexually transmitted cases increased from 24.9 percent to 41.8 percent. The trend towards heterosexual transmission among pregnant women was more marked in the Paris region than in the rest of France. This tendency may be overestimated because of changes in population, such as an increase in women from sub Saharan Africa, the extension of serodiagnosis among IVDU and the extension of systematic testing of pregnant women over the study period. Heterosexual transmission of HIV does appear to be increasing in Europe as can be observed among female AIDS cases.

Adult↗
PubMed1992

Phlegmonous gastritis associated with HIV-1 seroconversion. Endoscopic and microscopic evolution.

A 40-year-old man presented with peritonitis. Diagnosis of phlegmonous gastritis was made by laparotomy. Conservative treatment combined with antibiotics was successful. Multiple endoscopies with biopsies illustrate the natural history of this disease. The patient developed HIV-1 seroconversion during hospital stay. Prompt diagnosis and treatment may improve the prognosis of this often lethal disease.

Abscess↗
PubMed2004

Differential virus evolution in blood and genital tract of HIV-infected females: evidence for the involvement of drug and non-drug resistance-associated mutations.

There is increasing evidence that male or female genital tract represent a distinct replication compartment for human immunodeficiency virus type 1 (HIV-1) and that such compartments may serve as a virus reservoir. Forty-four paired plasma and vaginal samples from HIV-infected females undergoing HAART were collected to examine the viral responses to antiretroviral therapy and to assess the possible role of the vaginal tract as a reservoir for drug-resistant variants. Twenty-one females had detectable viral RNA both in plasma and vaginal fluid, whereas 14 females had detectable virus only in plasma. Twelve paired samples were used to analyze HIV-1 pol sequences for the presence of drug resistance-associated mutations. Nine of the twelve paired samples exhibited discordant drug resistance mutation patterns. The other three females showed identical drug resistance-associated mutations. However, further examination of protease and RT showed numerous non-drug-associated mutations that corresponded to predefined CTL epitopes. These non-drug-associated mutations were different between plasma and vaginal viruses, suggesting that evolution of HIV-1 was independent in these two compartments.

Adult↗
PubMed1996

[Cerebral malaria and AIDS: case report].

Although it has not been definitely proven that the severity of malaria is associated to human immunodeficiency virus (HIV) we know that infection through Plasmodium falciparum can favor a rapid evolution of the HIV infection. Besides, association of malaria with HIV/AIDS from a clinical point of view can be clinically severe in the face of the occurrence of other microorganisms or neoplasias, which worsens the evolution and prognosis of the affected patients. The concurrence of HIV with Plasmodium in malaria endemic zones is a possibility which should always be taken into consideration, since transmission is related to risk factors caused by people's behavior which are not always promptly revealed and/or identified. The authors report one case of brain malaria infection by Plasmodium vivax and Plasmodium falciparum in a patient with AIDS. They describe the clinical evolution and therapy.

Acquired Immunodeficiency Syndrome↗
PubMed1990

[Preoperative HIV infection in cardiovascular surgery].

PURPOSE: To evaluate patients in the preoperative period of cardiovascular surgery for HIV antibody in the serum. MATERIAL AND METHODS: 1200 patients older than 15 years tested for HIV antibody before cardiovascular surgery with an enzyme immunoassay test (ELISA). When the results were ELISA positive ou inconclusive, another sample was collected for confirmatory test (Western Blot). We also analysed risk factors, clinical status of HIV infection and postoperative evolution. RESULTS: ELISA test for HIV antibody were negative in 1180 (98.3%) patients, inconclusive in 14 and positive in 6. One ELISA inconclusive and six ELISA positive patients resulted Western Blot positive. All of the seven patients were asymptomatic (group II) in relation to HIV infection, including four bisexual men, two transfusion recipients men and a woman with an undetermined source of infection. Only the two transfusion recipients had their risk factor identified before testing. All of them were submitted to surgery with no immediate postoperative complication. CONCLUSION: Seven (0.58%) patients had HIV antibody (Western Blot assay) but in only two risk factors were identified by routine preoperative anamnesis.

AIDS Serodiagnosis↗
PubMedDate not supplied

[Effect of treatment with methadone on utilization of medical care by addicts seropositive for the AIDS virus. Results of a descriptive study, Bayonne, 1996].

Since two years, 80 patients received methadone maintenance treatment in Bayonne Médecins du Monde Center. In this population, 48% are HIV positive... The aim of this study is to determine the impact of methadone maintenance treatment on the medical status of a group of HIV positive subjects. In addition to the Addiction Severity Index collected data and quality of life evaluation by the TEAQV, the following data are collected: compliance to appointments HIV clinic, CD4 status, evolution of weight, observance of HIV medicine. Preliminary results are presented, showing precisely and confirming the good influence of methadone maintenance treatment on medical care of patients with HIV and AIDS. This kind of study, before and during the maintenance treatment (base line, third month and every six months) appears as a very important stake: for this patients with HIV and AIDS, in term of personal and medical status, for us, in term of methadone treatment impact, and health public care.

Adult↗
PubMed2006

Genetic analysis of HIV-1 strains in rural eastern Cameroon indicates the evolution of second-generation recombinants to circulating recombinant forms.

The HIV-1 genetic diversity in most parts of Cameroon is well described and shown to be very broad. However, little is known about the composition of the HIV-1 epidemic in the rural parts of eastern Cameroon. Therefore, we investigated 25 specimens from this region for their subtypes in gag, pol, and env gene fragments. Along with genetic material of subtypes A1, C, G, CRF01_AE, CRF02_AG, and CRF11_cpx, we also identified a large number (24%, 6/25) of distinct env sequences within the subtype A radiation. CRF02_AG was the predominant genetic form in all genes studied. Half of the specimens studied were considered "pure" based on concordant subtypes in the genes studied, whereas the other half were unique recombinant forms (URFs). Except for 1 URF, all were second-generation recombinants (SGRs), 90% of which contained genetic material of CRF02_AG in at least 1 gene. Notably, we identified individuals from 3 different villages infected with CRF01_AE(gag)CRF02_AG(pol)A(env) strains, which is indicative of the evolution of this URF to a circulating recombinant form (CRF). In addition, we identified a CRF02_AG(pol)C(env) recombinant infecting a man and a woman living in the same village, suggesting horizontal transmission of this recombinant. The current study emphasizes the power of HIV-1 recombination through the generation of SGRs and the evolution of URFs into CRFs. These findings suggest that, in a region where a predominant HIV-1 strain cocirculates among several subtypes, recombination could eventually decrease the proportion of this strain over time, such as CRF02_AG in Cameroon.

Cameroon↗
PubMed2003

Gradual adaptation of HIV to human host populations: good or bad news?

The continuous evolution and adaptation of HIV to its host has produced extensive global viral diversity. Understanding the kinetics and directions of this continuing adaptation and its impact on viral fitness, immunogenicity and pathogenicity will be crucial to the successful design of effective HIV vaccines. Here we discuss some potential scenarios of viral and host coevolution.

Adaptation, Biological↗
PubMed1999

[Papillomavirus-induced anogenital lesions in 121 HIV seropositive men. Clinical, histological, viral study, and evolution].

OBJECTIVE: To determine the prevalence of the Human Papillomavirus (HPV) in Human Immunodeficiency Virus (HIV) infected men, using clinical examination and molecular hybridization in situ. PATIENTS AND METHODS: From May 1995 to May 1997 we studied the prevalence, clinical and histological characteristics, the types and the evolution of the HPV lesions among 121 HIV-infected men. The HPV DNA was determined by molecular hybridization in situ, using biotinylated probes which recognized HPV types 6/11, 16/18 and 31/33/35 in 79 p. 100 (5/19) of the patients (17 biopsies). RESULTS: Sixteen per cent (19/121) of the patients are HPV infected: genital warts in 37 p. 100 (7/19), anal warts in 37 p. 100 (7/19), and ano-genital warts in 26 p. 100 (5/19) of the patients. In every case of anal codyloma, intracanalar lesions were found. In 47 p. 100 (9/19) of the cases, histological exam showed an intra-epithelial neoplasia. The HPV types 6/11, 16/18 and 31/33/51 were positive in 53 p. 100 (9/17), 35 p. 100 (6/17) and 35 p. 100 (6/17) biopsies respectively. High-risk types of HPV have been noted in 71 p. 100 (12/17) of the biopsies. The evolution of the clinical lesions was: recovering in 47 p. 100 (9/19) of the patients (after 3 months of treatment), recurrence in 16 p. 100 (3/19) of the anal warts (after 1 to 3 months of treatment), stabilization in 16 p. 100 (3/19) of the genital warts (after 6 months of treatment) and extension in 11 p. 100 (2/19) of the anogenital warts (after 3 months of treatment). CONCLUSION: The high prevalence of condyloma and dysplasia emphasizes the importance of the anogenital exam in HIV-positive patients. In case of anal lesions, anuscopy and biopsy are required. We insist on the need to closely follow these patients with HPV lesions in order to adapt treatment. Anal cytology and HPV-DNA detection by Hybrid Capture Assay, should be developed for screening and prevention of the malignant transformation of HPV lesions in this population.

AIDS-Related Opportunistic Infections↗
PubMed2005

HIV-1 genotype resistance pattern and evolution in patients failing nelfinavir-containing regimens.

Clinical and in vitro studies have suggested that nelfinavir (NFV)-containing regimens may not preclude the use of other protease inhibitors (PIs) in treatment sequencing. We have studied the prevalence of 30N mutation in a human immunodeficiency virus-1 (HIV-1)-infected cohort and the virological response to a PI-containing regimen in patients who had previously failed NFV. A total of 335 patients were included in the study; 32 of them were antiretroviral-naive and 303 were antiretroviral-experienced (251 were PI-experienced). Mutations 30N and/or 90M were not detected in sequences obtained either from the antiretroviral naive or non-PI-experienced patients. The 30N mutation was detected in 21/251 (8.3%) of PI-experienced patients and 90M in 103/251 (41%). Moreover, we have observed that the 88D and 77I mutations were present in more than 75% of patients harbouring the 30N HIV-1 variant and the 71T mutation was present in almost 50% of them. Finally, mutations 30N+90M were never detected together in the same HIV-1 strain. The 30N and 90M mutations were not observed together. The presence of mutations at positions 36, 46, 71, 77, and/or 88 in a 30N background, increases the risk of the cross-resistance to other PIs. The use of NFV as a first-line PI, as an application of drug sequencing strategies, may help preserve future PI options.

Acquired Immunodeficiency Syndrome↗
PubMed1999

A theoretical model of the evolution of virulence in sexually transmitted HIV/AIDS.

INTRODUCTION: The evolution of virulence in host-parasite relationships has been the subject of several publications. In the case of HIV virulence, some authors suggest that the evolution of HIV virulence correlates with the rate of acquisition of new sexual partners. In contrast some other authors argue that the level of HIV virulence is independent of the sexual activity of the host population. METHODS: Provide a mathematical model for the study of the potential influence of human sexual behaviour on the evolution of virulence of HIV is provided. RESULTS: The results indicated that, when the probability of acquisition of infection is a function both of the sexual activity and of the virulence level of HIV strains, the evolution of HIV virulence correlates positively with the rate of acquisition of new sexual partners. CONCLUSION: It is concluded that in the case of a host population with a low (high) rate of exchange of sexual partners the evolution of HIV virulence is such that the less (more) virulent strain prevails.

Acquired Immunodeficiency Syndrome↗
PubMed2003

HIV biological variability unveiled: frequent isolations and chimeric receptors reveal unprecedented variation of coreceptor use.

OBJECTIVE: To follow the evolution of coreceptor use in HIV-1-infected individuals with varying rates of disease progression. METHODS: The coreceptor use of 278 sequential HIV-1 isolates from 23 individuals was tested by infection of two human cell lines, U87.CD4 and GHOST(3), expressing CD4 and CCR1, CCR2b, CCR3, CCR5, CXCR4, CXCR6 or BOB. Differences in coreceptor use were further dissected by testing chimeric coreceptors constructed by exchanging successively larger parts of CCR5 for corresponding regions of CXCR4. RESULTS: Three patterns of coreceptor use were distinguished: no evolution, evolution to CXCR4 use, and fluctuation. No evolution with stable CCR5 use (R5 phenotype) was linked to slow progression over 8-10 years in four patients. CXCR4-using virus was present from the onset (five patients) or appeared during clinical progression in all other patients, while taking zidovudine or didanosine monotherapy. The fluctuating pattern of coreceptor use, defined as reappearance of virus with R5 phenotype, was observed in five patients and, interestingly, followed initiation of highly active antiretroviral therapy in three of these. Monotropic R5 or X4 viruses were more selective in chimeric receptor use than R5X4 or multitropic viruses. Most importantly, the efficiency of chimeric receptor use increased over time. CONCLUSION: The increase in efficiency of chimeric receptor use allows a new interpretation of evolution of HIV-1 coreceptor use. Evolution could be a continuous process that may lead to changes in the way a coreceptor is used, with the potential of profound alteration in signalling at that receptor.

Adult↗
PubMed1992

Protozoan infections and HIV-1 infection: a review.

Reactivation of latent infection is the principal mechanism relating Toxoplasma gondii and Pneumocystis carinii to HIV. Less common is reactivation in Leishmania donovani, Trypanosoma cruzi, and microsporidian infections. An impaired primary immune response occurs in all these infections, and also with Cryptosporidium and Isospora belli. Association of HIV infection with gut parasites including Giardia lamblia and Entamoeba histolytica, and also with Trichomonas vaginalis infection is likely to be related to sexual modes of contact that favour both HIV and the parasite. The severity of malaria is not definitely associated with HIV, but Plasmodium falciparum infection may favour more rapid evolution of the HIV infection. Both malaria and trichomoniasis favour HIV transmission; the former by necessitating blood transfusion, and the latter by enhancing viral transmission during sexual contact.

AIDS-Related Opportunistic Infections↗