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Oche Agbaji,
Chloe L Thio,
Seema Meloni,
Camilla Graham,
Mohammed Muazu,
Ladep Nimzing,
John Idoko, Jean-Louis Sankalé,
Ernest Ekong,
Robert Murphy,
Phyllis Kanki,
Claudia Hawkins
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ABSTRACT: The effect of HCV on ART response in patients in sub-Saharan Africa is unknown. We studied 1431 HIV-infected ART initiators in Jos, Nigeria of whom 6% were HCV co-infected. A similar proportion of HIV-HCV co-infected and HIV-mono-infected patients achieved HIV RNA <400 cp/ml after 24 and 48 weeks of ART (p values >0.05). Hepatotoxicity was uncommon (0.8% and 0.33% at 24 and 48 weeks, respectively), but was more common in the HIV-HCV co-infected group at 24 (aOR=19.3; 95% CI: 4.41-84.4) and 48 weeks (aOR=56.7; 95% CI: 5.03-636.92). HCV did not significantly impact ART response in this Nigerian cohort.
JAIDS Journal of Acquired Immune Deficiency Syndromes 11/2012; · 4.43 Impact Factor
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Holly E Rawizza,
Beth Chaplin,
Seema T Meloni,
Geoffrey Eisen,
Tara Rao, Jean-Louis Sankalé,
Abdoulaye Dieng-Sarr,
Oche Agbaji,
Daniel I Onwujekwe,
Wadzani Gashau,
Reuben Nkado,
Ernest Ekong,
Prosper Okonkwo,
Robert L Murphy,
Phyllis J Kanki
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ABSTRACT: Viral load (VL) quantification is considered essential for determining antiretroviral treatment (ART) success in resource-rich countries. However, it is not widely available in resource-limited settings where the burden of human immunodeficiency virus infection is greatest. In the absence of VL monitoring, switches to second-line ART are based on World Health Organization (WHO) clinical or immunologic failure criteria.
We assessed the performance of CD4 cell criteria to predict virologic outcomes in a large ART program in Nigeria. Laboratory monitoring consists of CD4 cell count and VL at baseline, then every 6 months. Failure was defined as 2 consecutive VLs >1000 copies/mL after at least 6 months of ART. Virologic outcomes were compared with the 3 WHO-defined immunologic failure criteria.
A total of 9690 patients were included in the analysis (median follow-up, 33.2 months). A total of 1225 patients experienced failure by both immunologic and virologic criteria, 872 by virologic criteria only, and 1897 by immunologic criteria only. The sensitivity of CD4 cell criteria to detect viral failure was 58%, specificity was 75%, and the positive-predictive value was 39%. For patients with both virologic and immunologic failure, VL criteria identified failure significantly earlier than CD4 cell criteria (median, 10.4 vs 15.6 months; P < .0001).
Because of the low sensitivity of immunologic criteria, a substantial number of failures are missed, potentially resulting in accumulation of resistance mutations. In addition, specificity and predictive values are low, which may result in large numbers of unnecessary ART switches. Monitoring solely by immunologic criteria may result in increased costs because of excess switches to more expensive ART and development of drug-resistant virus.
Clinical Infectious Diseases 12/2011; 53(12):1283-90. · 9.15 Impact Factor
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Kevin Robertson,
Jeff Liner,
James Hakim, Jean-Louis Sankalé,
Igor Grant,
Scott Letendre,
David Clifford,
Amadou Gallo Diop,
Assan Jaye,
Georgette Kanmogne, [......],
Michael Boivin,
Penny Holding,
Betsy Kammerer,
Annelies Van Rie,
Prudence Ive,
Avindra Nath,
Kathy Lawler,
Clement Adebamowo,
Walter Royal,
Jeymohan Joseph
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ABSTRACT: In July 2009, the Center for Mental Health Research on AIDS at the National Institute of Mental Health organized and supported the meeting "NeuroAIDS in Africa." This meeting was held in Cape Town, South Africa, and was affiliated with the 5th IAS Conference on HIV Pathogenesis, Treatment and Prevention. Presentations began with an overview of the epidemiology of HIV in sub-Saharan Africa, the molecular epidemiology of HIV, HIV-associated neurocognitive disorders (HANDs), and HAND treatment. These introductory talks were followed by presentations on HAND research and clinical care in Botswana, Cameroon, Ethiopia, The Gambia, Kenya, Malawi, Nigeria, Senegal, South Africa, Uganda, and Zambia. Topics discussed included best practices for assessing neurocognitive disorders, patterns of central nervous system (CNS) involvement in the region, subtype-associated risk for HAND, pediatric HIV assessments and neurodevelopment, HIV-associated CNS opportunistic infections and immune reconstitution syndrome, the evolving changes in treatment implementation, and various opportunities and strategies for NeuroAIDS research and capacity building in the region.
Journal of NeuroVirology 05/2010; 16(3):189-202. · 2.31 Impact Factor
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John Idoko,
Seema Meloni,
Mohammed Muazu,
Ladep Nimzing,
Bitrus Badung,
Claudia Hawkins, Jean-Louis Sankalé,
Ernest Ekong,
Robert Murphy,
Phyllis Kanki,
Chloe L Thio
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ABSTRACT: As highly active antiretroviral therapy (ART) is introduced into areas of the world in which hepatitis B virus (HBV) infection is highly endemic, it is important to determine the influence of HBV on persons with human immunodeficiency virus (HIV) and HBV coinfection who are receiving ART.
We studied 1564 HIV-infected patients in Jos, Nigeria, who initiated ART. Participants with HIV-HBV coinfection had hepatitis B e antigen (HBeAg) and HBV DNA status determined. CD4+ T cell count and HIV load at ART initiation were compared between individuals with HIV monoinfection and those with HIV-HBV coinfection with use of univariate methods. Regression analyses were used to determine if HBeAg status or HBV DNA at ART initiation were associated with baseline HIV parameters or ART response.
The median CD4+ T cell count of the 262 participants with HIV-HBV coinfection (16.7%) was 107 cells/mL, compared with 130 cells/mL for participants with HIV monoinfection at ART initiation (P = .001). Participants with HIV-HBV coinfection also had higher HIV loads than did patients with HIV monoinfection (4.96 vs 4.75 log10 copies/mL; p = .02 ). Higher HBV DNA and detectable HBeAg levels were independently associated with lower CD4+ T cell counts at ART initiation but not with higher HIV loads. In a multivariable model, HBeAg-positive patients were less likely than HBeAg-negative patients to suppress HIV replication to <or= 400 copies/mL (odds ratio, 0.54; P = .03 ) at 24 weeks, but they had similar CD4+ T cell increases. At 48 weeks, there was no significant effect of HBeAg status on ART response.
Among HIV-infected Nigerian individuals, HBV coinfection, especially among those with high levels of HBV replication, was associated with lower CD4+ T cell counts at ART initiation, independent of HIV RNA level. Patients with HBeAg-positive status had a slower virological response to ART, compared with HBeAg-negative patients. Further work is needed to understand the effects of HBV on CD4+ T cells.
Clinical Infectious Diseases 10/2009; 49(8):1268-73. · 9.15 Impact Factor
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ABSTRACT: Abstract The gag p6 region of HIV-1 has various nonsubstitutionary mutations, including insertions, duplications, deletions, and premature stop codons. Studies have linked gag p6 mutations to reduced susceptibility to antiretroviral therapy in HIV-1 subtype B. This study examined the relationship between antiretroviral therapy and gag p6 diversity in HIV-1 CRF02_AG and subtype G. p6 data were generated for secondary analyses following Viroseq genotyping of pol gene sequences in plasma samples from HIV-1-infected Nigerians on reverse transcriptase inhibitor therapy, with virologic failure (repeat VL > 2000 copies/ml). p6 sequence chromatograms were available for 40 CRF02_AG and 43 subtype G-infected individuals. Subjects who had not received their supply of antiretroviral drugs for at least 2 months prior to the plasma sampling were classified as nonadherent. p6 sequences from therapy-adherent individuals had more nonsubstitutionary mutations than sequences from drug-naive individuals (p = 0.0005). The P5L/T mutation was inversely correlated with the presence of K27Q/N in p6, with each mutation being more prominent in subtype G and CRF02_AG, respectively. The data also suggested that P5L/T may be a compensatory mutation for the loss of an essential phosphorylation site in p6. In addition, there was an inverse association between P5L/T mutations in p6 and thymidine analog mutations in reverse transcriptase (p = 0.0001), and drug nonadherence was associated with an 8-fold lower risk of having a nonsubstitutionary mutation in p6 (95% CI = 1.27-52.57). Our data suggest that antiretroviral therapy influences gag p6 diversity, but further studies are needed to clarify these observations.
AIDS research and human retroviruses 08/2008; 24(9):1167-74. · 2.18 Impact Factor
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ABSTRACT: Human immunodeficiency virus type 1 (HIV-1)-infected individuals with a high viral set point progress to acquired immunodeficiency syndrome (AIDS) more rapidly than those with a low viral set point. It is not entirely clear which host and viral factors are responsible for the viral set point. Host factors that affect virus replication are likely to influence the viral set point. Human APOBEC proteins have been shown to restrict HIV-1 replication.
This prospective study was conducted to determine the relationship between human APOBEC3G (hA3G) and APOBEC3F (hA3F) levels and the viral set point. Fourteen subjects were classified as having a high viral set point, and 16 were classified as having a low viral set point. We quantified the levels of hA3G and hA3F mRNA in HIV-1-infected, antiretroviral drug-naive individuals before and after infection.
We found a significant correlation between the hA3G mRNA level and the viral set point. The expression of hA3G and hA3F increased after infection, and the levels of hA3G and hA3F mRNA were significantly higher after infection in the low viral set point group, compared with the high viral set point group.
The results suggest that the level of hA3G expression affects the establishment of the viral set point and may therefore function as a host determinant in the pathogenesis of HIV-1 infection.
The Journal of Infectious Diseases 08/2008; 198(4):486-92. · 6.41 Impact Factor
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ABSTRACT: This study was carried out to characterize HIV-1 reverse transcriptase (RT) mutations in vertically infected infants in Jos, Nigeria. DNA was extracted from peripheral blood mononuclear cells of 102 infants, aged 0 to 6 months, born to HIV-1-infected mothers who had received peripartum single-dose nevirapine prophylaxis. PCR-based diagnosis revealed that 14 infants (13.7%) were infected with HIV-1. Phylogenetic analyses of RT revealed wide viral diversity, with CRF02_AG, subtype G, subsubtype A3, CRF06_cpx, and a subtype D recombinant present in the population. Four of 13 (31%) infants had NNRTI resistance mutations--V179I (2 infants), Y181C, and V179E. Intriguingly, subtype G sequences did not have NNRTI mutations but rather carried a Q207N mutation, which may undergo negative selection under drug pressure. Our data suggest wide diversity for vertically transmitted HIV-1 viruses in Nigeria and highlight the potential significance of transmitting rare mutations in subtype G.
AIDS Research and Human Retroviruses 01/2008; 23(12):1587-92. · 2.25 Impact Factor
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ABSTRACT: Over a 20-year period we have observed the dynamics of HIV-1 subtypes and HIV-2 infection in a prospective cohort of registered female sex workers (FSW) in Dakar, Senegal. Prevalence and incidence rates for HIV-1 and HIV-2 are described from 290 seroprevalent and 193 seroincident subjects who were among the 3,910 women enrolled between 1985 and 2004. We report a significant decrease of HIV-2 prevalence in the cohort, parallel to the introduction and rise of HIV-1 infection. In 328 HIV-1-infected women, a 385-bp C2-V3 fragment of the envelope gene was sequenced and classified into the following subtypes or recombinant forms: 239 (72%) were subtype A [of which 180 (55%) were CRF02_AG and 53 (16%) were A3], 10 (3%) were B, 12 (4%) were C, 11 (4%) were D, 18 (6%) were G, 24 (7%) were CRF06_cpx, and 7 (2%) were CRF09_cpx. We found an increasing proportion of CRF02_AG over many years, but recently subsubtype A3 has over-taken CRF02_AG, with the largest proportion of new infections. The predominance of existing HIV-1 subtypes did not preclude the emergence and increase of other closely related subtypes or recombinant forms. This 20-year prospective serological and sequence analysis of HIV viruses reveals a complex and changing HIV epidemic in Senegal.
AIDS Research and Human Retroviruses 11/2007; 23(10):1189-96. · 2.25 Impact Factor
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ABSTRACT: Multiple HIV-1 subtypes and circulating recombinant forms (CRFs) are known to circulate in West Africa. We undertook a survey of HIVs in Oyo state, in southwestern Nigeria. We analyzed 71 samples from Ibadan, the capital city, and 33 samples from Saki, 100 miles west of Ibadan. We sequenced part of the gag gene and the envelope C2V3 region from 102 and 89 samples, respectively. In the 87 samples for which both genes were sequenced, subtype G and CRF02_AG were found in equal proportions (32.2% each). Other samples included CRF06_cpx (8.0%), subtype A (2.3%), C (1.1%), unclassified (1.1%), or discordant sequences suggesting the presence of a large number of recombinants involving CRF02_AG and/or subtype G (20.7%) or other subtypes (2.3%). The subtype/CRF designation was concordant in two gene fragments in the majority of samples evaluated. However, we observed differences in subtype distribution between the two locations with a predominance of subtype G in Ibadan and CRF02 in Saki. This is the first in-depth analysis of HIV variability at a state level in Nigeria. Our analysis revealed a significant level of viral heterogeneity and a geographical difference in subtype distribution, and demonstrated that CRF02_AG does not account for the majority of circulating strains.
AIDS Research and Human Retroviruses 09/2007; 23(8):1020-5. · 2.25 Impact Factor
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ABSTRACT: Since the discovery of HIV-2 in 1985, considerable progress has been made in understanding its virology and epidemiology.
The data suggest differences between HIV-2 and HIV-1 in geographic distribution, distinct epidemic trends, perinatal transmission
rates, and incubation periods to the development of AIDS. The virologic determination and mechanisms for these apparent biologic
differences are still unknown. However, understanding how HIV-2 differs from HIV-1 is essential to interpretations of comparative
virologic studies. We hope such comparative studies will yield important information on the pathogenic mechanisms employed
by HIV viruses and will lead the way to the development of effective interventions for the prevention of AIDS. This is best
exemplified in studies indicating that this close relative of HIV-1 infection, via its attenuated phenotype, may confer significant
protection from subsequent infection by HIV-1. This further suggests that understanding HIV-2 immunity and cross-immunity
may be useful for HIV vaccine design and development.
08/2007: pages 74-103;
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ABSTRACT: Studies have shown that human immunodeficiency virus type 2 (HIV-2) is less pathogenic than HIV-1, with a lower rate of disease progression. Similarly, plasma viral loads are lower in HIV-2 infection, suggesting that HIV-2 replication is restricted in vivo in comparison to that of HIV-1. However, to date, in vivo studies characterizing replication intermediates in the viral life cycle of HIV-2 have been limited. In order to test the hypothesis that HIV-2 has a lower replication rate in vivo than HIV-1 does, we quantified total viral DNA, integrated proviral DNA, cell-associated viral mRNA, and plasma viral loads in peripheral blood samples from groups of therapy-naïve HIV-1-infected (n = 21) and HIV-2-infected (n = 18) individuals from Dakar, Senegal, with CD4(+) T-cell counts of >200/microl. Consistent with our previous findings, total viral DNA loads were similar between HIV-1 and HIV-2 and plasma viral loads were higher among HIV-1-infected individuals. Proportions of DNA in the integrated form were also similar between these viruses. In contrast, levels of viral mRNA were lower in HIV-2 infection. Our study indicates that HIV-2 is able to establish a stable, integrated proviral infection in vivo, but that accumulation of viral mRNA is attenuated in HIV-2 infection relative to that in HIV-1 infection. The differences in viral mRNA are consistent with the differences in plasma viral loads between HIV-1 and HIV-2 and suggest that lower plasma viral loads, and possibly the attenuated pathogenesis of HIV-2, can be explained by lower rates of viral replication in vivo.
Journal of Virology 05/2007; 81(10):5325-30. · 5.40 Impact Factor
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ABSTRACT: 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.
AIDS Research and Human Retroviruses 09/2006; 22(8):770-9. · 2.25 Impact Factor
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ABSTRACT: 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.
Journal of Virology 09/2006; 80(15):7316-21. · 5.40 Impact Factor
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ABSTRACT: 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.
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.
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.
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.
The Journal of Infectious Diseases 06/2005; 191(9):1460-7. · 6.41 Impact Factor
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ABSTRACT: We compared two techniques for CD4 T-lymphocyte counting: flow cytometry (Cyflow) and magnetic beads (Dynabead). Similar results with good correlation were obtained from the 40 adult blood samples counted (P=0.057, r=0.93). The Cyflow technique is more precise and cost-effective than the Dynabead method ($3 to $5 versus $12 to $22 per test, respectively), since as many as 200 samples can be measured per day.
Clinical and Diagnostic Laboratory Immunology 02/2005; 12(1):224-7. · 2.51 Impact Factor
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ABSTRACT: Phylogenetic analyses demonstrate significant diversity in worldwide circulating strains of human immunodeficiency virus type 1 (HIV-1). Detailed studies have revealed a complex pattern of intersubtype recombinations, as well as evidence of sub-subtypes circulating in various populations. In this study, we characterized an HIV-1 strain that had previously been identified as a distinct subcluster within the subtype A radiation based on partial sequence data. These viruses were of particular interest given that we recently found that their prevalence was significantly higher in dually infected individuals compared to women who were singly infected with HIV-1. Five viruses isolated from commercial sex workers in Dakar, Senegal, were full-length PCR amplified and sequenced. Phylogenetic analyses indicated that, whereas three of these viruses were closely related and clustered overall within the HIV-1 subtype A radiation, they were distinct from previously characterized sub-subtype A1 and A2 viruses. The clustering pattern was maintained in the individual gag, pol, and env regions of the genome. Distance calculations between these viruses, which we termed A3, and other reference sub-subtype A1 and A2 viruses fell in the range of distances between previously characterized sub-subtype groups. In addition, we found evidence of two A3-containing recombinants in our cohort. These recombinants are mosaics composed of sequence from both sub-subtype A3 and CRF02_AG, the major circulating recombinant form in this West African population. Based on phylogenetic analyses, we propose that the group of viruses found in the Dakar sex worker cohort, previously referred to as HIV-1 A subcluster 2, be referred to as HIV-1 sub-subtype A3.
Journal of Virology 12/2004; 78(22):12438-45. · 5.40 Impact Factor
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ABSTRACT: The global human immunodeficiency virus (HIV)epidemic is characterized by significant genetic diversity in circulating viruses. We have recently characterized a group of viruses that form a distinct sub-subtype within the subtype A radiation, which we have designated HIV type 1 (HIV-1) sub-subtype A, circulating in West Africa. A prospective study of a cohort of female sex workers (FSW) in Dakar, Senegal over an 18-year period indicated that an A3-specific sequence in the C2-V3 region of the env gene was found in 46 HIV-1-infected women. HIV-1 sub-subtype A3 appeared in the FSW population as early as 1988 and continued to be transmitted as of 2001. We also found that HIV-1 A3 is not confined to the FSW cohort in Senegal but is also circulating in the general population in Dakar. Furthermore, analyses of viral sequences from a few other West and Central African countries also demonstrated evidence of HIV-1 A3 sequence in isolates from HIV-1-infected people in Ivory Coast, Nigeria, Niger, Guinea Bissau, Benin, and Equatorial Guinea. Overall, because of the evidence of sub-subtype A3 in the general population in Senegal, as well as in a few neighboring West and Central African countries, along with the increasing incidence of infection with A3-containing viruses in the Dakar high-risk FSW population, we feel that HIV-1 sub-subtype A3 viruses are important to distinguish and monitor.
Journal of Virology 12/2004; 78(22):12455-61. · 5.40 Impact Factor
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ABSTRACT: HIV-related lipodystrophy is characterized by adipose redistribution, dyslipidemia, and insulin resistance. Adiponectin is an adipose-derived peptide thought to act as a systemic regulator of glucose and lipid metabolism. We investigated adiponectin concentrations in 10 HIV-infected patients during acute HIV infection (viral load, 2.0 x 10(6) +/- 1.0 x 10(6) copies/ml) and then 6-8 months later, as well as cross-sectionally in 41 HIV-infected patients (21 with evidence of fat redistribution and 20 without evidence of fat redistribution) in comparison with 20 age- and body mass index-matched healthy control subjects. Circulating adiponectin concentrations did not change with treatment of acute HIV infection (5.8 +/- 0.4 vs. 5.9 +/- 0.7 micro g/ml, P = 0.96) but were reduced in patients with chronic HIV infection and fat redistribution (7.8 +/- 0.9 micro g/ml), compared with age- and body mass index-matched HIV-infected patients without fat redistribution (12.7 +/- 1.7 micro g/ml) and healthy control subjects (11.9 +/- 1.7 micro g/ml, P < 0.05 vs. HIV-infected patients without fat redistribution and vs. control subjects). Adiponectin concentrations correlated with body composition [correlation coefficient (r) = -0.47, P = 0.002 vs. trunk fat:total fat; r = 0.51, P < 0.001 vs. extremity fat:total fat], insulin response to glucose challenge (r = -0.36, P = 0.03), triglyceride (r = -0.39, P = 0.01), and high-density lipoprotein (r = 0.37, P = 0.02) among the HIV-infected patients. Adiponectin remained a significant correlate of insulin response to GTT, controlling for medication use and body composition changes in HIV-infected patients. These data suggest a strong relationship between adiponectin and body composition in HIV-infected patients. Changes in adiponectin may contribute to the metabolic dysregulation in this group of patients.
Journal of Clinical Endocrinology & Metabolism 04/2003; 88(4):1559-64. · 6.50 Impact Factor
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ABSTRACT: The human immunodeficiency virus type 1 (HIV-1) viral setpoint during the disease-free interval has been strongly associated with future risk of disease progression. An awareness of the correlation between viral setpoint and HIV-1 genetic evolution over time is important in the understanding of viral dynamics and infection. We examined genetic diversity in HIV-1 CRF02_A/G-IbNG-infected seroincident women in Dakar, Senegal; determined whether a viral setpoint kinetic pattern existed for CRF02_A/G-IbNG during the disease-free interval; and correlated viral load level and diversity. Samples were drawn during the disease-free interval from consenting CRF02_A/G-IbNG-infected, antiretroviral therapy-naïve female commercial sex workers in Dakar, Senegal. Based on sequential plasma RNA values, low and high viral setpoint groups were established. Intrapatient diversity and divergence over time was determined from earlier and later time point DNA samples from each person. Most individuals followed the viral setpoint paradigm. For each 1/-/log(10) copy/ml of plasma increase in viral load, intrapatient diversity increased by 1.4% (P = 0.028). A greater diversification rate was observed in the high viral setpoint group than in the low viral setpoint group (P = 0.01). Greater nucleotide (P = 0.015) and amino acid (P = 0.048) divergences and a greater nucleotide divergence rate (P = 0.03) were found in the high viral setpoint group. There was no difference between the groups in the ratio of the number of nonsynonymous substitutions per nonsynonymous site to the number of synonymous substitutions per synonymous site. The greater intrapatient diversity, divergence, and diversification rates observed in the high viral setpoint group supports the notion that diversity is driven by cycles of viral replication resulting in accumulated mutations. Recognizing diversity potential based on viral load levels in individuals may inform the design of vaccines and therapies.
Journal of Virology 12/2002; 76(21):10745-55. · 5.40 Impact Factor
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Abdoulaye Dieng Sarr,
Donald J. Hamel,
Ibou Thior,
Efi Kokkotou, Jean-Louis Sankalé,
Richard G. Marlink,
Eva-Marie Coll-Seck,
Myron E. Essex,
Tidiane Siby,
Ibrahima NDoye,
Souleymane Mboup,
Phyllis J. Kanki
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ABSTRACT: Objective: We conducted this study to genetically characterize dual infection in individuals demonstrating a dual serological profile.
Methods: All subjects were first evaluated by immunoblot for antibody reactivity to the major viral antigens for HIV-1 and HIV-2. Sera were judged to be dual-seropositive if they reacted with strong and equal intensity with the envelope antigens of both HIV-1 and HIV-2 and were confirmed with type-specific recombinant env peptides. We used nested polymerase chain reaction (PCR) to amplify proviral gag and env sequence from peripheral blood mononuclear cell (PBMC) DNA from HIV-1- and HIV-2-infected individuals. Positive amplification was detected after Southern blot hybridization.
Results: Plasmid dilution and mixing showed equivalent sensitivity of HIV-1 and HIV-2 primers that was not altered by heterologous target sequences. The DNA PCR showed 100% sensitivity and specificity for detection of monotypic HIV infection. Serologically defined HIV-dual reactives were evaluated by this assay, with 100% detection in female sex workers (21 out of 21), but only 38.5% detection (five out of 13) in hospitalized patients; all being HIV-1 positive only. The lack of HIV-2 proviral signal was significantly correlated with low CD4+ lymphocyte counts (P value = 0.04).
Conclusion: The results suggest that HIV dual infection may not be a static condition. Levels of HIV-2 may decrease with disease progression or sequester in tissue reservoirs; our results may also suggest that HIV-1 effectively overgrows HIV-2 in the dually exposed host individual.
AIDS 01/1998; 12(2):131-137. · 6.24 Impact Factor
