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PubMed2005

Protective correlates against HIVs may have evolved in human populations in the areas of historic occurrence of primate-to-man transmissions of SIVs ancestral to HIVs: studies in these populations may provide crucial insights for treatment and prevention of HIV infection.

Recent findings suggest that Human Immunodeficiency Viruses, HIV-1 and 2, might have been transmitted to humans from particular primate species. It is thought that some Simian Immunodeficiency Viruses (SIVs), from which HIVs presumably originated, existed in their primate hosts for ages. Behavioral characteristics increasing the probability of contact between these primates and humans (such as keeping monkeys for pets, hunting monkeys for food, improper handling of the monkey meat, etc.) documented in some African countries could have facilitated cross-species transmissions (CSTs) of HIVs. As it has been shown, multiple CSTs took place for both HIVs (1 and 2) and then, in a globalizing world, these local events led to the pandemic. Here, it is brought forward that in the regions of epizooty of SIVs closely related to HIVs, some human populations might have had exposure history to these viruses dating back hundreds years. Lacking the important framework for further spread provided by nowadays globalization, these CSTs could have led to isolated local HIV outbreaks limited to particular tribes or groups. The infections could have extinguished some populations while on the other hand provided evolutionary pressure to select for mechanisms protective for HIV infection and/or disease. Thus, here it is hypothesized that in the areas of the habitat of primates infected with SIVs, from which HIVs are thought to be originated, there could be historically exposed populations which might possess biological correlates of protection from HIVs. Current knowledge on the distribution of primates hosting HIV-related SIVs suggests that epidemiological, primatological, anthropological and molecular biological studies in the areas of Cameroon, Gabon, both Congos and Equatorial Guinea (for HIV-1) and Guinea-Bissau, Senegal, Guinea, Ivory Cost, Sierra Leone and Liberia (for HIV-2) could lead to the discoveries of correlates of protection against HIVs. It is also hypothesized that virology studies in the same areas might reveal less virulent and/or infective viruses which could provide insights in the HIV pathogenesis and vaccinology.

Acquired Immunodeficiency Syndrome↗
PubMed2004

Plasma RNA viral load is not associated with intrapatient quasispecies heterogeneity in HIV-1 infection.

The human immunodeficiency virus type 1 (HIV-1) viral set point has been associated with the rate of, disease progression and with the level of HIV-specific immune response. The analysis of the possible association between viral set point and quasispecies heterogeneity has important consequences in the understanding of HIV-1 in vivo evolution. In this study, we analyzed the association between intrapatient viral diversity and RNA viral load in 16 antiretroviral therapy-naive HIV-1-infected patients at a single time point, during the disease free period. Patients were separated into low and high viral load groups according to plasma RNA values. HIV-1 quasispecies complexity was assessed in the C2-V5 env region. The average intrapatient quasispecies heterogeneity in both groups was not significantly different (t-test, P > 0.05). However, while within the low viral load group both synonymous and non-synonymous mutations contribute to the variation observed, in the heterogeneity observed in the high viral load group there was an increase in the contribution of the non-synonymous mutations. Thus, this study show that although intrapatient quasispecies heterogeneity is not associated with viral set point in HIV-1 infection, some differences exist between the two groups in the pattern of mutation accumulation.

Amino Acid Substitution↗
PubMed2001

Increased ability for selection of zidovudine resistance in a distinct class of wild-type HIV-1 from drug-naive persons.

Transmission of HIV-1 with reduced susceptibility to antiretroviral drugs raises public health concerns. Through surveillance of drug-resistant HIV-1 in 603 treatment-naive, recently diagnosed HIV-1-infected persons, we identified a distinct group of viruses that have mutations at codon 215 of the reverse transcriptase (RT) gene that are different from either the wild-type (WT) T or the zidovudine (AZT)-selected T215Y/F. These mutations included 215D/C/S and were found in 20 patients (3.3%). The 215D, 215C, and 215S mutations differ from 215Y by a 1-nt change compared with 2 nt for the WT T215 and likely represent revertants of 215Y. These viruses all were found to have WT susceptibility to AZT, and all replicated efficiently as WT HIV-1(T215). However, differences in fitness among HIV-1(215D), HIV-1(215C), and HIV-1(215S) were seen when RT backgrounds were changed, demonstrating a role of the RT background in the selection of these revertants. In vitro selection with AZT showed that HIV-1(215D) and HIV-1(215C) acquired 215Y more rapidly than did WT HIV-1(T215), likely reflecting the need for only 1-nt change to evolve to 215Y. Our study demonstrates that HIV-1 with unusual mutations at codon 215 replicate efficiently, have WT susceptibility, and are commonly found in treatment-naive persons. The increased ability for selecting resistance mutations defines this class of WT HIV-1 and highlights the higher potential of these viruses to compromise the efficacy of antiretroviral therapy.

Anti-HIV Agents↗
PubMed2001

Dynamics of HIV infection: a cellular automata approach.

We use a cellular automata model to study the evolution of human immunodeficiency virus (HIV) infection and the onset of acquired immunodeficiency syndrome (AIDS). The model takes into account the global features of the immune response to any pathogen, the fast mutation rate of the HIV, and a fair amount of spatial localization, which may occur in the lymph nodes. Our results reproduce the three-phase pattern observed in T cell and virus counts of infected patients, namely, the primary response, the clinical latency period, and the onset of AIDS. The dynamics of real experimental data is related to the transient behavior of our model and not to its steady state. We have also found that the infected cells organize themselves into spatial structures, which are responsible for the decrease on the concentration of uninfected cells, leading to AIDS.

Cell Death↗
PubMed1997

[Course and prognosis of levels of CD4 molecules in HIV-infected patients].

OBJECTIVE: To measure CD4 molecule concentration on lymphocyte surface. And observe its evolution during one year, in HIV infected patients. To assess the importance of this measure as a prognostic marker for disease progression, compared with the total number of CD4 lymphocytes. METHODS: Clinical and analytical data from 107 patients were collected; 64 fulfilled a one-year follow-up. 45 were initially asymptomatic (ASN), 13 had AIDS-related complex (CRS) and 6 had AIDS. CD4 cell count was higher than 500 in 16, between 500 and 200 in 20, and lower than 200 in 28. CD4 molecule concentration in lymphocytes was measured with immunoassay capcellia CD4/CD8 (Pasteur Institute, Paris). During one year 12 patients progressed cunically. RESULTS: There was significant decrease of T4 lymphocytes in the following groups whole population, CRS, more than 500 (initially). There were significant decreases of CD4 molecules in the following groups: whole population, ASN, CRS, more than 500 (initially), between 500 and 200 (initially), the mean number of T4 lymphocytes was 140/mm3 in progressors versus 358 in non-progressors (p < 0.05). Initial CD4 molecule concentration was 3.87 pmol/l in progressors versus 11.50 pmol/l in non-progressors (p < 0.05). CONCLUSIONS: Both total number of T4 lymphocytes and CD4 molecule concentration decrease with time. However, in asymptomatic patients only CD4 molecule decrease reaches statistical signification. Both T4 lymphocyte number and CD4 molecule concentration were lower in progressors. Measurement of CD4 molecule concentration is a parameter of similar value with respect to T4 lymphocyte count, and with similar value as progression marker.

Adult↗
PubMed1994

Evolution of a disrupted TAR RNA hairpin structure in the HIV-1 virus.

Human immunodeficiency virus type 1 (HIV-1) RNA contains an extended hairpin structure at the 5' end (the TAR element) that is essential for viral replication. The upper part of the stem-loop structure binds the virally encoded transcriptional activator protein Tat and cellular co-factors, but no clear function for the lower stem region has been established. Here, we report that mutant HIV-1 viruses with base substitutions in the lower stem region are dead, most likely at the level of transcription from an integrated provirus. By using large amounts of these mutant DNA constructs for transfections, revertant viruses with a great variety of genetic changes (point mutations, short deletions) could be isolated in prolonged culture experiments that lasted over 6 months. The pattern and evolution of these changes supported the notion that base-pairing of the lower stem region is essential for optimal HIV-1 replication. The functional and genetic plasticities of this RNA domain and the HIV-1 long terminal repeat promoter are discussed.

Base Composition↗
PubMed1997

Lymphocyte subset changes between 3 and 15 months of age in infants born to HIV-seropositive women in South Africa.

The evolution of T-lymphocyte subsets during infancy in perinatally HIV-infected African babies has not been previously described. In a hospital-based cohort study, T-lymphocyte subset changes were investigated in 72 South African black children born to HIV seropositive mothers. Sixteen (22.2%; children were classified as infected and 56 (77.8%) as uninfected by 18 months of age. Four (25%) of the infected infants died before the age of 9 months from HIV-related disease. The CD4 and CD8 T-lymphocyte subsets, expressed in absolute numbers, as percentages, percentiles or as ratios, were clear indicators of HIV infection at all ages between 3 and 15 months. The most marked changes were a decreased percentage of CD4 cells and an increase in percentage of CD8 cells in the infected group. In the 4 infected infants who died, CD8 count and CD4:CD8 ratio clearly predicted poor clinical outcome at 3 months. Taken together, both CD4:CD8 ratio and CD4 percentage are reliable markers of HIV infection in an African paediatric population; however, a raised CD8 lymphocyte count rather than a CD4 count is a more specific prognostic marker of disease progression in HIV infected children.

Age Factors↗
PubMed2006

[Evolution of mortality and current status of an HIV-infected population cared for at a comprehensive HIV/AIDS center in Chile].

BACKGROUND: Chile, a middle-income country with an HIV epidemic of moderate proportions (global infection rate 0.2%) began a government sponsored, free, highly active antiretroviral therapy (HAART) for patients from the public health system in 2001 reaching in 2004 a 100% coverage. Arriaran Foundation (AF) is the largest public AIDS care center for adults in the country. AIM: To show the present status of the AF population and the evolution of mortality. MATERIAL AND METHODS: Review of AF database from 1991-2004 that at 12/31/2004 had a total cumulative population of 2,259 adult patients; an active census of 1,065 patients and admitting rate 160-190 patients per years. RESULTS: The global mortality registered was 33.4%, with decreasing annual mortality from 15.7% of its active population in 1995 to 1.9% in 2004. As of 12/31/2004, 817 patients (76.7%) were receiving antiretroviral therapy (ART); and 19.3% either did not require nor accept it. Thirty one percent received Combivir and nevirapine, with undetectable viral load (<400 copies per ml) in 78%. Thirty percent received Combivir and efavirenz with undetectable viral load in 80% at last count. Both regimens were used mainly as first therapy. Lopinavir/ritonavir was received by 6.3% of patients, mainly for post failure therapy and 58% had undetectable viral load. A baseline CD4 count <200 x mm(3) was present in 70% of patients, 45.3% had a count below 100 and 47.8% had clinical AIDS. At the last follow up assessment, CD4 count was <200 in 36.8%, <100 in 10.6% and 200-350 in 44.9%. CONCLUSION: The expanded access program to ART in a public, comprehensive AIDS care center in Chile has been highly successful in reaching high undetectability (75%), reducing mortality and improving immune status despite very advanced baseline disease.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Sequence of simian immunodeficiency virus from African green monkey, a new member of the HIV/SIV group.

Some wild African green monkeys are known to be naturally infected with a retrovirus related to human immunodeficiency virus (HIV) without having any apparent symptoms of an AIDS-like disease. This simian immunodeficiency virus, designated SIVAGM, may be helpful in clarifying the evolution and pathogenicity of HIV. Some virus strains that were previously reported to be isolated from African green monkeys were shown to be laboratory contaminations of SIVMAC (SIV from a rhesus macaque) Here we report the complete DNA sequence of authentic SIVAGM, which was isolated from a naturally infected African green monkey of Kenyan origin. Comparison of the genome of SIVAGM with those of known HIV/SIVs indicates that the virus is a new simian lentivirus that is approximately equally distantly related to HIV-1 and HIV-2 in contrast to SIVMAC, which is much closer to HIV-2 than to HIV-1 (refs 5, 9).

Amino Acid Sequence↗
PubMed1996

[Acute and chronic viral hepatitis in HIV positive patients].

In this study we evaluated the spreading of HBV, HCV, HDV and HIV among drug user patients. Spreading of hepatotropic viruses resulted high (HBV 84%, HCV 87%, HDV 7%), while spreading of HIV resulted relatively low (18%). During the period considered we did not observe any favourable effect of hepatotropic viruses on the progression of HIV infection, while the chronic evolution of acute viral hepatitis HBV related was high (90%) in HIV+ patients. HIV infection did not determine different histological findings in respect to HIV- patients with chronic hepatitis, HBV or HCV related

English Abstract↗
PubMedDate not supplied

[Evaluation of the prevalence of HIV infection in prison inmates at the time of their imprisonment during the period 1991-1995].

BACKGROUND: Inmates of Spanish prisons include a high number of intravenous drug users (IVDUs) and other people whose practices entail the risk of infection with the human immunodeficiency virus (HIV). The aim of this work is to find out the evolution of the prevalence of HIV infection at the time of admission to prison and the factors associated with it in this population group. This may enable us to form an idea of the effectiveness of risk reduction strategies and help to improve them. METHODS: All those people who were placed in a provincial penal institution in the northwest of Spain between 1991 and 1995. Socio-demographic, penal and HIV risk factor variables were gathered. The HIV infection test (ELISA and Western-blot) was carried out with the consent of the subjects. RESULTS: Of the 1,663 people studied, 19.4% were HIV-positive. The prevalence HIV infection was particularly marked statistically in: women (26.0%), the 25-34 age group (29.1%), whites (20.9%), single people (22.8%), those people with a tattoo (29.9%), those people with a background in self-inflicted injuries (42.2%), IVDUs (46.3%), those who admitted sharing syringes (61.5%) and those with a prison record of one or more years (37.3%). Logistical regression analysis showed the following as predictors of HIV infection: IVDUs, those who went to prison in 1992, women, the 25-34 and 35-44 age group, tattooed men, those with a background in self-inflicted injuries and those with a prison record, of more than one year. The gypsy ethnic group revealed a lower probability of HIV infection. The HIV infection time trend, stratified according to the prison record showed an almost significant drop (P = 0.064). The infection trend per IVDU did not show any modification (P = 0.16). CONCLUSIONS: A high prevalence of HIV infection was detected in a prison located in a region which has not been particularly affected by AIDS. IVDUs and some characteristics that may be related to this population group have an enormous influence on this phenomenon. The time trend for this infection in this population group has decreased through the lower number of IVDUs that are admitted to prison although very high levels of prevalence of the infection were maintained in this group over the five years of the study. It is recommended that risk-reduction programmes in prisons be fostered (methadone maintenance programmes, syringe exchange pilot programmes).

Acquired Immunodeficiency Syndrome↗
PubMed2005

The evolutionary history of the CCR5-Delta32 HIV-resistance mutation.

The CCR5 chemokine receptor is exploited by HIV-1 to gain entry into CD4+ T cells. A deletion mutation (Delta32) confers resistance against HIV by obliterating the expression of the receptor on the cell surface. Intriguingly, this allele is young in evolutionary time, yet it has reached relatively high frequencies in Europe. These properties indicate that the mutation has been under intense positive selection. HIV-1 has not exerted selection for long enough on the human population to drive the CCR5-Delta32 allele to current frequencies, fueling debate regarding the selective pressure responsible for rise of the allele. The allele exists at appreciable frequencies only in Europe, and within Europe, the frequency is higher in the north. Here we review the population genetics of the CCR5 locus, the debate over the historical selective pressure acting on CCR5-Delta32, the inferences that can potentially be drawn from the geographic distribution of CCR5-Delta32 and the role that other genetic polymorphisms play in conferring resistance against HIV. We also discuss parallel evolution that has occurred at the CCR5 locus of other primate species. Finally, we highlight the promise that therapies based on interfering with the CCR5 receptor could have in the treatment of HIV.

Evolution, Molecular↗
PubMed2003

Analysis of the evolutionary relationships of HIV-1 and SIVcpz sequences using bayesian inference: implications for the origin of HIV-1.

The most plausible origin of HIV-1 group M is an SIV lineage currently represented by SIVcpz isolated from the chimpanzee subspecies Pan troglodytes troglodytes. The origin of HIV-1 group O is less clear. Putative recombination between any of the HIV-1 and SIVcpz sequences was tested using bootscanning and Bayesian-scanning plots, as well as a new method using a Bayesian multiple change-point (BMCP) model to infer parental sequences and crossing-over points. We found that in the case of highly divergent sequences, such as HIV-1/SIVcpz, Bayesian scanning and BMCP methods are more appropriate than bootscanning analysis to investigate spatial phylogenetic variation, including estimating the boundaries of the regions with discordant evolutionary relationships and the levels of support of the phylogenetic clusters under study. According to the Bayesian scanning plots and BMCP method, there was strong evidence for discordant phylogenetic clustering throughout the genome: (1) HIV-1 group O clustered with SIVcpzANT/TAN in middle pol, and partial vif/env; (2) SIVcpzGab1 clustered with SIVcpzANT/TAN in 3'pol/vif, and middle env; (3) HIV-1 group O grouped with SIVcpzCamUS and SIVcpzGab1 in p17/p24; (4) HIV-1 group M was more closely related to SIVcpzCamUS in 3'gag/pol and in middle pol, whereas in partial gp120 group M clustered with group O. Conditionally independent phylogenetic analysis inferred by maximum likelihood (ML) and Bayesian methods further confirmed these findings. The discordant phylogenetic relationships between the HIV-1/SIVcpz sequences may have been caused by ancient recombination events, but they are also due, at least in part, to altered rates of evolution between parental SIVcpz lineages.

Animals↗
PubMed2004

Between-host evolution of cytotoxic T-lymphocyte epitopes in human immunodeficiency virus type 1: an approach based on phylogenetically independent comparisons.

In human immunodeficiency virus type 1 (HIV-1), mutations that escape from cytotoxic T-lymphocyte (CTL) recognition have been documented, and sequence analyses have provided indirect support for the hypothesis that natural selection has favored CTL escape mutants within an infected host. In spite of such evidence for within-host selection by CTL, it has been more difficult to determine how natural selection by host CTL has influenced long-term evolution of HIV-1. We used statistical analysis of published HIV-1 genomic sequences to examine the role of natural selection in between-host evolution of CTL epitopes. Based on a phylogenetic analysis, we identified 21 pairs of closely related genomes isolated from different hosts and examined the pattern of nucleotide substitution in genomic regions encoding well-characterized CTL epitopes. The results revealed that certain CTL epitopes have been subject to repeated positive selection across the population, while others are generally conserved. Furthermore, evidence of positive selection was associated with divergence from the canonical epitope sequence and with an enhanced frequency of convergent amino acid sequence changes in CTL epitopes. The results support the hypothesis that CTL-driven selection has been a major factor in the long-term evolution of HIV-1.

Epitopes, T-Lymphocyte↗
PubMed2005

Limited sequence evolution within persistently targeted CD8 epitopes in chronic human immunodeficiency virus type 1 infection.

Studies in acute human immunodeficiency virus type 1 (HIV-1) infection indicate viral evolution under CD8 T-cell immune selection pressure, but the effects of ongoing immune pressure on epitope evolution during chronic infection are not well described. In this study, we performed a detailed longitudinal analysis of viral sequence variation within persistently targeted cytotoxic T-lymphocyte (CTL) epitopes in two HIV-1-infected persons during 6 years of persistent viremia. Responses were quantitated using freshly isolated peripheral blood lymphocytes in direct lytic assays as well as by gamma interferon (IFN-gamma) Elispot assays on cryopreserved cells. Seven targeted epitopes were identified in each person. In the majority of cases, the dominant epitope sequence did not change over time, even in the presence of responses of sufficient magnitude that they were detectable using fresh peripheral blood mononuclear cells in direct lytic assays. Only 4 of the 14 autologous epitopes tested represented potential CTL escape variants; however, in most cases strong responses to these epitopes persisted for the 6 years of study. Although persistent IFN-gamma responses were detected to all epitopes, direct lytic assays demonstrated declining responses to some epitopes despite the persistence of the targeted sequence in vivo. These data indicate limited viral evolution within persistently targeted CD8 T-cell epitopes during the chronic phase of infection and suggest that these regions of the virus are either refractory to sequence change or that persistently activated CD8 T-cell responses in chronic infection exert little functional selection pressure.

Acquired Immunodeficiency Syndrome↗
PubMed1998

[Evolution of the nutritional status of patients with HIV-AIDS. Effects of socioeconomic situation and dietetic counseling].

OBJECTIVES: To know HIV-AIDS patient's nutritional status in different infection's condition and their relation with the socioeconomic situation and, in that case, the nutritional condition improvement through the dietetic advice appropriated for each patient. METHODS: Prospective study of 79 patients with HIV-AIDS diagnostic in any illness's condition and recopilation of anthropometrics and biochemical variables. At the beginning of the study we got data about socioeconomic situation of patient with a scale of 1 to 5 points each variable and an score top of 35. In the survivors we checked, after dietetic advice, the variables at 6 and 12 months by sanitary personal (physician and nurse) who weren't implicated in direct assistance. The study was analyzed by Student "T" for matched data and the simple correlation test. RESULTS: We have objectivated a lost of initial weight over their habitual's with a progressive impairment in different stage of evolution that weren't modified by dietetic advice. We didn't observed significant variations in the biochemical variables included in advances states and in parameters which are usually affected in malnutrition. In the analysis of relation between nutritional condition and socioeconomic factors, it was estimated a lesser score, that was statistically significative, in patients who had a work, family situation and an affective upset positive. CONCLUSIONS: The results obtained induce to think that the nutritional advices appropriated for each patient are not related, in our series, with progressive deterioration of anthropometrics variables, neither biochemical parameters fluctuations at 6, 12 months of follow-up. The patient's socioeconomic situation is not influenced by nutritional condition except for the work, affectivity and family environment.

Acquired Immunodeficiency Syndrome↗