Biomedical subjects

Abdoulaye Dieng Sarr

Publications and source records attributed to Abdoulaye Dieng Sarr.

7 recordsLinked to original sources

PubMed2006

The absence of anti-Tat antibodies is associated with risk of disease progression in HIV-2 infection.

The Tat protein of human immunodeficiency virus (HIV) is essential for viral replication and has extracellular pathogenic activity. We sought to determine whether the anti-Tat antibody response was predictive of disease progression in 144 HIV type 2 (HIV-2)-infected subjects observed longitudinally between 1985 and 2003. Sixty-eight percent of the subjects tested positive for anti-Tat antibodies, with reactivity notably established early after seroconversion and stably maintained over the course of infection. The risk and rate of progression to advanced HIV-2 AIDS was significantly higher in anti-Tat-negative subjects than in anti-Tat-positive subjects, extending the importance of this prognostic marker for HIV-2 AIDS.

Adult↗

PubMed2006

Subtype-specific patterns in HIV Type 1 reverse transcriptase and protease in Oyo State, Nigeria: implications for drug resistance and host response.

As the use of antiretroviral therapy becomes more widespread across Africa, it is imperative to characterize baseline molecular variability and subtype-specific peculiarities of drug targets in non-subtype B HIV-1 infection. We sequenced and analyzed 35 reverse transcriptase (RT) and 43 protease (PR) sequences from 50 therapy-naive HIV-1-infected Nigerians. Phylogenetic analyses of RT revealed that the predominant viruses were CRF02_AG (57%), subtype G (26%), and CRF06_cpx (11%). Six of 35 (17%) individuals harbored primary mutations for RT inhibitors, including M41L, V118I, Y188H, P236L, and Y318F, and curiously three of the six were infected with CRF06_cpx. Therefore, CRF06_cpx drug-naive individuals had significantly more drug resistance mutations than the other subtypes (p = 0.011). By combining data on quasisynonymous codon bias with the influence of the differential genetic cost of mutations, we were able to predict some mutations, which are likely to predominate by subtype, under drug pressure. Some subtype-specific polymorphisms occurred within epitopes for HLA B7 and B35 in the RT, and HLA A2 and A*6802 in PR, at positions implicated in immune evasion. Balanced polymorphism was also observed at predicted serine-threonine phosphorylation sites in the RT of subtype G viruses. The subtype-specific codon usage and polymorphisms observed suggest the involvement of differential pathways for drug resistance and host-driven viral evolution in HIV-1 CRF02_AG, subtype G, and CRF06_cpx, compared to subtype B. Subtype-specific responses to HIV therapy may have significant consequences for efforts to provide effective therapy to the populations infected with these HIV-1 subtypes.

Amino Acid Sequence↗

PubMed2006

Genomic sites of human immunodeficiency virus type 2 (HIV-2) integration: similarities to HIV-1 in vitro and possible differences in vivo.

Retroviruses have distinct preferences in integration site selection in the host cell genome during in vitro infection, with human immunodeficiency virus type 1 (HIV-1) integration strongly favoring transcriptional units. Additionally, studies with HIV-1 have shown that the genomic site of proviral integration may impact viral replication, with integration in heterochromatin associated with a block in viral transcription. HIV-2 is less pathogenic than HIV-1 and is believed to have a lower replication rate in vivo. Although differences in integration site selection between HIV-2 and HIV-1 could potentially explain the attenuated pathogenicity of HIV-2, no studies have characterized integration site selection by HIV-2. In this study, we mapped 202 HIV-2 integration sites during in vitro infection of peripheral blood mononuclear cells with a primary HIV-2 isolate. In addition, we assayed for in vivo proviral integration within heterochromatin in 21 HIV-1-infected subjects and 23 HIV-2-infected subjects, using an alphoid repeat PCR assay. During in vitro infection, HIV-2 displayed integration site preferences similar to those previously reported for HIV-1. Notably, 82% of HIV-2 integrations mapped to Refseq genes, and integration strongly favored regions of the genome with high gene density and high GC content. Though rare, the proportion of HIV-2 subjects with evidence of proviral integration within heterochromatin in vivo was higher than that of HIV-1-infected subjects. It is therefore possible that integration site selection may play a role in the differences in HIV-1 and HIV-2 in vivo pathogenesis.

Base Composition↗

PubMed2005

Viral dynamics of primary HIV-1 infection in Senegal, West Africa.

BACKGROUND: Few studies have addressed primary human immunodeficiency virus (HIV) type 1 infection in sub-Saharan Africa, where the epidemic is of a predominantly heterosexual character and is caused by different subtypes. The present study examines the dynamics of viral replication in subjects infected with various HIV-1 subtypes. METHODS: Seven hundred fifty-two HIV-negative Senegalese women at high risk for infection were monitored every 3 months for acute/early HIV infection; 26 infections were identified (23 HIV-1 and 3 HIV-2), with an HIV-1 incidence rate of 3.23 cases/person-years observation. Multiple viral-load measurements were taken for all seroconverters. RESULTS: The mean+/-standard deviation viral load for all subjects during the early stage of infection was 4.13+/-0.66 log10 copies/mL, with an overall decrease of 0.22 log10 copies/mL after the early stage; the viral set point was reached after 12 months of infection. Most subjects had relatively low viral loads during the early stage of infection. HIV-1 CRF02_AG-infected women had a significantly higher mean viral load during the early stage of infection (mean +/- SD, 4.45+/-0.60 log(10) copies/mL) than did non-HIV-1 CRF02_AG-infected women (mean+/-SD, 3.78+/-0.46 log(10) copies/mL) (P=.008). None of the subjects reported symptoms consistent with primary HIV-1 infection. CONCLUSION: Our findings in Senegalese women differ from what have been described for primary HIV-1 infection. Further investigations of primary infections with non-B subtypes are warranted, to better characterize their differences with primary infections with subtype B.

Acquired Immunodeficiency Syndrome↗

PubMed2005

Distinct profile of T cell activation in HIV type 2 compared to HIV type 1 infection: differential mechanism for immunoprotection.

The mechanism for the lower rate of disease progression in HIV-2 infection remains undefined. We evaluated T cell activation in a cohort of HIV-infected commercial sex workers in Dakar, Senegal. CD8+ T cell activation was significantly lower in HIV-2- compared to HIV-1-infected volunteers and both groups displayed higher activation levels compared to seronegative individuals. In contrast, CD4+ T cell activation was similar between the HIV-1 and HIV-2 groups and significantly higher compared to the seronegative group. Interestingly, HIV-2-positive volunteers with evidence of Gag-specific CD8+ T cell responses displayed lower CD4+ T cell activation. Our data suggest that the distinct T cell activation profile in HIV-2-positive individuals may reflect on the presence of effective host immune responses in HIV-2 infection.

CD4-Positive T-Lymphocytes↗

PubMed2004

Highly active antiretroviral therapy and viral response in HIV type 2 infection.

Human immunodeficiency virus type 2 (HIV-2), the second human retrovirus known to cause AIDS, is endemic to West Africa but is infrequently found outside this region. We present a case series of 10 HIV-2--infected individuals treated in the United States. Physicians applied the principles of highly active antiretroviral therapy (HAART), normally used in treating HIV type 1, with modifications considered appropriate for treating HIV-2. CD4+ cell count, HIV-2 virus load, and clinical status were found to correlate well, providing evidence that HIV-2 virus load is useful in managing treatment of patients with HIV-2 who are receiving therapy. However, HAART regimens with predicted efficacy for treatment of HIV type 1 infection are not as efficacious for treatment of HIV-2. Controlled clinical trials of HIV-2-infected patients receiving various HAART regimens are needed to provide therapeutic guidance to the medical community.

Adult↗

PubMedDate not supplied

Associations between MHC class I and susceptibility to HIV-2 disease progression.

OBJECTIVES: Human immunodeficiency virus type 2 (HIV-2) progression to disease is significantly slower than that of human immunodeficiency virus type 1 (HIV-1). Genetic determinants for susceptibility to disease progression were hypothesized to play a more significant role in this infection compared with HIV-1. We sought to identify common human lymphocyte antigen (HLA) alleles in the Senegalese population and to compare HLA profiles between HIV-2-infected individuals with low and high risk for disease progression. STUDY DESIGN/METHODS: We conducted a case-control study investigating possible associations between MHC class I genes and the risk of disease progression in HIV-2-infected individuals. The MHC class I genotype was molecularly defined using polymerase chain reaction with sequence specific primers (PCR-SSP) in 62 female sex workers from the Dakar, Senegal cohort. Lack of antibodies to the HIV-2 antigen p26 has been previously shown to predict disease progression and was used in this study as a surrogate marker. Twenty-one cases were identified lacking antibodies to p26, therefore at a higher risk of disease progression, and were compared with 41 p26 antibody-positive, randomly selected controls. RESULTS: Statistical analysis showed that HLA B35 was significantly associated with lack of p26 antibodies, and higher risk of disease progression ( < 0.05). The same association was found for the self-defined class I haplotypes B35-Cw4 and A23-Cw 7 ( < 0.05). The HLA B 53 allele was associated with slower disease progression; however, this association was not statistically significant. We observed a trend whereby heterozygotes were at lower risk for HIV-2 disease progression, as previously reported in HIV-1 disease. CONCLUSIONS: In this West African population, a distinct profile of HLA class I alleles was observed, and many of these appear to influence disease progression in HIV-2 infection.

Alleles↗