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Genetic Evolution Between HIV-1 Groups M and O: HIV-1/MO Recombinant Forms.

HIV exhibits significant genetic diversity, with genetic recombination being a major evolutionary process. The co-circulation of HIV-1/M and HIV-1/O variants has led to the description of 20 HIV-1/M+O dual infections since 1998. Despite the genetic divergence between these variants, HIV-1/M+O dual infections have resulted in the emergence of HIV-1/MO intergroup recombinant forms, with 20 unique HIV-1/MO recombinant forms (URF_MO) currently described, raising the question of a possible benefit of the recombination and the modalities of their emergence. This review summarized the current knowledge of HIV-1/MO recombinant forms, including their virological and genetic characteristics, phylogenetic analysis, genome profiles, and breakpoints number and location. This study also identified the potential impacts of HIV-1/MO recombination on diagnosis, monitoring, and treatment, as well as the replicative capacity of such recombinants. This review highlighted the greater diversity and complexity of HIV-1/MO recombinants than originally thought, offering new research perspectives on their emergence and virological properties.

HIV-1

Distinct modes of evolution drive HIV escape from two broadly neutralizing antibodies.

Broadly neutralizing antibodies (bNAbs) show promise for HIV treatment and prevention, but are vulnerable to resistance evolution. Comprehensively understanding in vivo viral escape from individual bNAbs is necessary to design bNAb combinations that will provide durable responses. We characterize viral escape from two such bNAbs, 10-1074 and 3BNC117, using deep, longitudinal sequencing of full length HIV envelope (env) genes from study participants treated with bNAb monotherapy. Improved sequencing depth and computational evolutionary analyses permit us to identify in vivo routes and parallelism underlying HIV escape from each bNAb, providing new insights into this evolutionary process: 10-1074 escape is restricted to a small number of previously documented pathways, but these escape mutations 1) pre-exist in intra-host viral populations before therapy, 2) are not all equally preferred, and 3) emerge with a high degree of genetic parallelism within and across viral populations. In contrast, 3BNC117 escape follows background-specific patterns in which specific escape mutations present in one population rarely emerge or spread in other populations, but often still exhibit parallel evolutionary responses within their host. That bNAbs elicit starkly different in vivo escape profiles depending on their Env target exposes the limitations of generalizing escape patterns across therapies and highlights the substantial challenges in predicting a viral population's bNAb susceptibility from genetic diversity alone.

Journal Article

Prolonged clinically asymptomatic evolution after HIV-1 infection is marked by the absence of complement C4 null alleles at the MHC.

The length of time after which persons infected with HIV-1 progress to AIDS is variable. Certain alleles at the MHC have been shown to influence negatively the clinical outcome of HIV-1-infected persons and to be associated with special clinical manifestations. We investigated the MHC class I, class II and class III antigens in 54 Caucasian HIV-1-infected persons. The MHC profile of individuals with a prolonged period before AIDS is marked by a lower frequency of C4 null alleles.

Acquired Immunodeficiency Syndrome

[The evolutionary profile of HIV infection in children].

The evolution of HIV infection in children is bimodal, not depending on the vertical or horizontal route of transmission and with no assemblence with AIDS evolution in adults. The contaminated children with fast evolution to death in maximum two years, develop a severe neurological and infectious symptomatology. The others even symptomatic show slowly evolution with not so frequent and not so serious acute infectious. The natural history of the HIV infection in children of our country will be better defined in the future for now it is observed only for three years.

Child, Preschool

[Immunologic profile of HIV-2 seropositive African individuals (follow-up)].

In the geographic distribution of HIV-2, it is known that this infection is most prevalent in West Africa. Since 1986 we have studied seropositive and seronegative clusters, in Guinea-Bissau with follow-ups in 1988, 1989, 1990 and 1991. Analysis of the results show the high incidence of this infection. 8.51% of the 4,372 people of the general population studied were seropositive, showing the high predominance of HIV-2 infection. Only 4 cases were exclusively reactive to HIV-1 and a slow evolution of HIV-1 infections. In the seroconversions of HIV-2 infections the antibodies appeared first to the core components and secondly to the surface glycoproteins. Some of the laboratory parameters affected in the evolution of the infection include a gradual increase in immunoglobulins and a decrease in CD4 lymphocytes and in the CD4/CD8 ratio. A comparison of these variations in HIV-2 infected people, with or without cross-reactivity to HIV-1, reveals that they are much more evident in exclusively HIV-2 positive people. This fact can indicate that the variants responsible for the cross-reactions are less pathogenic and phylogenetically less developed.

Africa, Western

Evolutionary dynamics of HIV-1 recombinants: analysis of contemporary and historical viral populations in East Africa.

BACKGROUND: Understanding the genetic evolution of HIV-1 Transmitted/Founder (T/F) virus is crucial for developing effective treatment and prevention strategies due to its rapid mutation and recombination rates. METHODS: This study compared the genetic diversity of 24 contemporary T/F viruses collected between 2016 and 2021 in Uganda and Kenya with 29 historical T/F sequences sampled between 2006 and 2011. RESULTS: Subtype analysis based on near-full-length (NFL) HIV-1 T/F genomes revealed that 57.1% (12/21) of contemporary viruses were recombinants, predominantly involving Subtype A1, D, and increasing Subtype C, with 33.3% (7/21) being A1D recombinants (A1 > D) and 19% (4/21) classified as complex recombinants involving three or more subtypes. Historical viruses showed a similar overall proportion (69%) but were mainly A1D mosaics (D > A1) with recombination confined primarily to the envelope region. In contrast, contemporary viruses shifted towards more complex recombinant patterns affecting additional genomic regions, including pol and accessory genes. Phylogenetic analysis demonstrated that contemporary viruses clustered into distinct, well-supported (98% bootstrap) sub-branches, suggesting divergency attributed to an imbalance in their proportions of subtype A1 and D sequences as well as a different content of A1 and D segments in the A1/D mosaic recombinants. CONCLUSIONS: These findings underscore the dynamic and shifting nature of HIV-1 genetic diversity in East Africa, highlighting the need for continuous molecular surveillance and region-specific treatment guidelines.

HIV-1

[HIV-1 infection in patients with hemophilia. The Argentinian experience from 1983 to 1990].

We present studies on the evolution of HIV-1 infection in 638 hemophilic patients receiving commercial antihemophilic concentrates (CAH) at the Institute of Hematological Research and the Argentine Foundation of Hemophilia between 1983 and 1990. Positive serology for HIV-1 was detected in 30% of the patients studied. Prevalence of HIV-1 infection was higher (about 70%) in the group with severe hemophilia requiring more CAH, but there were no differences between patients with hemophilia A or B. Sexual transmission was demonstrated in 8/64 women (13%) with stable sexual relationship with HIV-1 + hemophilic patients. Three of them became pregnant, and HIV-1 infection was demonstrated in two of the three children. In general, the clinical evolution, as well as the hematologic and immunologic parameters of infected patients were similar to those described for the hemophilic population in other occidental countries. Opportunistic infections were also those observed elsewhere (with predominance of P. carinii pneumonia and disseminated Candida infections). However, the presence of fatal chagasic encephalitis in two of the patients with AIDS is unusual. Thus, central nervous system localization of T. cruzi (which can be observed during the acute period of T. cruzi infection or in immunosuppressed patients), must be considered as a possible severe complication of HIV-1 disease in T. cruzi infected patients.

AIDS-Related Opportunistic Infections

[Spanish Pediatric Association. Madrid. Human immunodeficiency virus infection. Spanish multicenter study].

The results of an epidemiological survey in Spain organized by the "Spanish Pediatric Association" of children born to HIV+ mothers from 1981-1989 are presented. The objectives were, a) to document in the different parts of Spain the number of HIV+ children born to HIV+ mothers, and b) to identify the risk factors involved in the HIV infection. Only in public hospitals, a total of 1938 HIV+ children born to HIV+ mothers were identified. A systematic yearly increase of HIV+ newborns was evident since 1985. Madrid, Catalonia, Valencia, Basq and Andalucia communities incorporated 85% of all cases. 93% of mothers were IVDU and 51% of them were married. Prematurity occurred in 27% of cases and low birth weight in 33% of NB's. The rate of transmission in children over 18 months of age was 25.6% Breast feeding could be a risk factor in the transmission of HIV infection observed in children over 18 months of age. No other maternal risk factors responsible for the HIV transmission were identified. 12% of children died with AIDS. Clinical classification and evolution of HIV infection did not significantly differ from similar studies in other parts of the world. In spite of only public hospitals being involved, Spain has more identified HIV+ children than Italy, Switzerland, Federal Republic of Germany, United Kingdom, Sweden and Belgium combined. The pediatric centres with large number of cases require interdisciplinary pediatric specialized units to cope with the increase demand of medical services, now inadequate and insufficient. To fight drug use and HIV infection in Spain, health education and family support, are indispensable in trying to arrest the continuous spread the HIV infection.

Acquired Immunodeficiency Syndrome

Evidence of an in vitro association between human immunodeficiency virus antigen P24 and Epstein-Barr virus DNA.

To investigate the association between human immunodeficiency virus (HIV) and Epstein-Barr virus (EBV), simultaneous determinations of HIV antigen (HIV Ag) p24 and EBV DNA were performed in lymphocyte culture supernatants from 63 individuals at risk of HIV infection. In vitro data, together with HIV immune status results, were subjected to a statistical analysis. HIV infection was identified in 49 patients (78%); of these, in vitro EBV DNA was found in 44 individuals (90%), while in only 3 of the 14 non-infected ones (21%). Statistical analysis demonstrated a close relationship between evidence of HIV infection and in vitro detection of EBV DNA (87.3% concordant with 95% confidence interval: 76.5%-94.5%). Furthermore, a strong dependence was revealed between the presence of EBV DNA and HIV Ag in culture (p less than 0.00001). These results indicate the existence of in vitro viral interactions, with likely in vivo implications in the pathogenesis and evolution of HIV infection.

AIDS-Related Complex

Electrophysiologic study in peripheral neuropathy associated with HIV infection.

Clinical and electrophysiologic features in 22 patients with HIV infection are reported. Four cases had chronic demyelinating polyneuropathy, two mononeuropathy multiplex, and nine symmetrical sensory-motor polyneuropathy. Seven cases had normal clinical and electromyographic examination. Electrophysiological study had a higher diagnostic yield (68%) than clinical examination (50%) for peripheral neuropathy diagnosis. Thus, peripheral nerve abnormalities are frequent in patients with different stages of HIV infection, although their pathogenesis remains unclear. Symmetrical sensory-motor polyneuropathy is the main type of neuropathy seen in ouvert AIDS, whereas chronic demyelinating polyneuropathy was mainly diagnosed in patients with asymptomatic HIV infection as first manifestation of the disease. Axonal or demyelinating nerve damage was established according to electrophysiological criteria. Frequently a mixture of both lesions was found. Electrophysiologic study is also a good index of neuropathy evolution in HIV infection and to follow-up of nerve abnormalities after treatment.

Adult

HIV-1 in Ethiopia: phylogenetic divergence from other HIV-1 strains.

Phylogenetic tree analysis was performed on selected polymerase chain reaction (PCR)-amplified and sequenced regions of the gag and env reading frames of several Ethiopian and Swedish human immunodeficiency virus type 1 (HIV-1) strains. These regions are considered to be conserved parts of the HIV-1 genome and correspond to the p7 of the core (gag) and part of the carboxy terminal of the gp41 protein of env respectively. Comparisons were made with all available HIV-1 sequences. The tree analysis showed that gag sequences from nine and env sequences from four Ethiopian strains all grouped together in separate branches distinct from all other sequenced European, North American, and African HIV-1 isolates. Thus, the Ethiopian strains seem to represent a highly divergent group of HIV-1, which might have developed during a relatively early stage of HIV-1 evolution.

Base Sequence

The natural history of HIV-1 infection: staging classifications of disease.

We evaluated and compared four staging classification systems for HIV infection in a population-based cohort: (1) a staging based on prodromal clinical criteria; (2) the Walter Reed Staging Classification (WRSC); (3) the immunologic staging system (ISS), and (4) a simple staging based on oral disease and CD4+ T-cell depletion. The staging systems were applied to 386 HIV-infected men in the San Francisco Men's Health Study cohort who did not have AIDS at the baseline examination. After 48-56 months of follow-up the cumulative incidence of AIDS and the cumulative mortality by stage was determined for each staging. Unlike the other systems, the WRSC could not classify a substantial proportion of HIV-infected men (51.9%). The WRSC and ISS include one or more stages which did not appear to be associated with a prognosis substantially different from that of adjacent stages. The simplified staging system based on CD4+ T-cell depletion and oral disease may be the most effective of the systems studied. A more complete understanding of the pathophysiology during the evolution of HIV infection will be required to define a more detailed staging of this disease.

Acquired Immunodeficiency Syndrome