Abstract:
:We investigate mutations and correlates according to HIV-1 subtype after virological failure (VF) of standard first-line antiretroviral therapy (ART) (non-nucleoside/nucleotide reverse transcriptase inhibitor [NNRTI] +2 nucleoside/nucleotide reverse transcriptase inhibitor [N(t)RTI]). SECOND-LINE study participants were assessed at baseline for HIV-1 subtype, demographics, HIV-1 history, ART exposure, viral load (VL), CD4(+) count, and genotypic ART resistance. We used backward stepwise multivariate regression (MVR) to assess associations between baseline variables and presence of ≥3 N(t)RTI mutations, ≥1 NNRTI mutation, ≥3 thymidine analog-N(t)RTI [ta-N(t)RTI] mutations (TAMs), the K65/K70 mutation, and predicted etravirine (ETV)/rilpivirine (RPV) activity. The inclusion p-value for MVR was p < .2. The exclusion p-value from stepwise elimination was p > .05. Of 541 participants, 491 (91%) had successfully characterized baseline viral isolates. Subtype distribution: B (n = 123, 25%), C (n = 202, 41%), CRF01_AE (n = 109, 22%), G (n = 25, 5%), and CRF02_AG (n = 27, 5%). Baseline CD4(+) 200-394 cells/mm(3) were associated with <3 N(t)RTI mutations (OR = 0.47; 95% CI 0.29-0.77; p = .003), absence of the K65/K70 mutation (OR = 0.43; 95% CI 0.26-0.73; p = .002), and higher ETV sensitivity (OR = 0.52; 95% CI 0.35-0.78; p = .002). Recent tenofovir (TDF) use was associated with K65/K70 mutations (OR = 8.91; 95% CI 5.00-15.85; p < .001). Subtype CRF01_AE was associated with ≥3 N(t)RTI mutations (OR = 2.34; 95% CI 1.31-4.17; p = .004) and higher RPV resistance (OR = 2.13; 95% CI 1.30-3.49; p = .003), and subtype C was associated with <3 TAMs (OR = 0.45; 95% CI 0.21-0.99; p = .015). Subtypes CRF01_AE (OR = 2.46; 95% CI 1.26-4.78; p = .008) and G (OR = 4.77; 95% CI 1.44-15.76; p = .01) were associated with K65/K70 mutations. Higher VL at confirmed first-line VF was associated with ≥3 N(t)RTI mutations (OR = 1.39; 95% CI 1.07-1.78; p = .013) and ≥3 TAMs (OR = 1.62; 95% CI 1.15-2.29; p = .006). The associations of first-line resistance mutations across the HIV-1 subtypes in this study are consistent with knowledge derived from subtype B, with some exceptions. Patterns of resistance after failure of a first-line ta-N(t)RTI regimen support using TDF in N(t)RTI-containing second-line regimens, or using N(t)RTI-sparing regimens.
journal_name
AIDS Res Hum Retrovirusesjournal_title
AIDS research and human retrovirusesauthors
Lam EP,Moore CL,Gotuzzo E,Nwizu C,Kamarulzaman A,Chetchotisakd P,van Wyk J,Teppler H,Kumarasamy N,Molina JM,Emery S,Cooper DA,Boyd MAdoi
10.1089/AID.2015.0331subject
Has Abstractpub_date
2016-09-01 00:00:00pages
841-50issue
9eissn
0889-2229issn
1931-8405journal_volume
32pub_type
杂志文章abstract::We studied plasma samples from 2082 Mataco Indians living in 22 different communities in the western part of Formosa Province, northern Argentina. Samples were screened for HTLV-I/II antibodies by particle agglutination assay. All positive or borderline samples were then tested by an immunofluorescence assay (IFA) on ...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/088922299311150
更新日期:1999-03-20 00:00:00
abstract::The mechanisms responsible for the hematopoietic failure in human immunodeficiency virus type 1 (HIV-1)-infected patients are still unknown. Several findings indicate that the in vitro proliferative potential of precursor cells from AIDS patients is reduced. The changes seen in bone marrow (BM) morphology and the defe...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/088922200750005994
更新日期:2000-10-10 00:00:00
abstract::We investigated whether V3-binding assays might be useful to analyze human immunodeficiency virus type 1 (HIV-1) variants in different geographic regions. We showed that strong cross-reactivity between subtype-specific V3 peptides is almost inevitable in standard indirect enzyme-linked immunosorbent assays (EIA), impa...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.1996.12.1279
更新日期:1996-09-01 00:00:00
abstract::An aqueous extract of Phyllanthus niruri (Euphorbiaceae) inhibited human immunodeficiency virus type-1 reverse transcriptase (HIV-1-RT). The inhibitor against HIV-1-RT in this plant was purified by combination of three column chromatographies, Sephadex LH-20, cellulose, and reverse-phase high-performance liquid chroma...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.1992.8.1937
更新日期:1992-11-01 00:00:00
abstract::We recently reported a novel adhesion pathway in lymphocytes that is mediated by cyclin-dependent kinase (Cdk) 4 activity and mediates lymphocyte interactions with endothelial matrix. We now demonstrate that HIV-infected lymphocytes also use Cdk4 to mediate spontaneous adhesion to fibronectin and endothelial matrix. W...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/AID.2011.0262
更新日期:2012-12-01 00:00:00
abstract::We have previously shown that the cell line 6D5(451) chronically infected with the HIV-1 isolate HTLV-III(451), secretes the HIV-1 envelope glycoproteins gp120 and gp160 in the extracellular medium. The HTLV-III(451) gp120 and gp160 were purified by sequential affinity chromatographic steps using a monoclonal antibody...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.1990.6.371
更新日期:1990-03-01 00:00:00
abstract::Studies have demonstrated that HIV-1 isolated from subjects experiencing virologic failure on stavudine (d4T)-containing regimens often contains thymidine analog mutations (TAMs), consisting of reverse transcriptase (RT) mutations M41L, D67N, K70R, L210W, T215Y/F, and K219Q/E, previously associated only with zidovudin...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章,多中心研究
doi:10.1089/088922201316912718
更新日期:2001-08-10 00:00:00
abstract::Even in the setting of maximally suppressive antiretroviral therapy (ART), HIV persists indefinitely. Several mechanisms might contribute to this persistence, including chronic inflammation and immune dysfunction. In this study, we have explored a preclinical model for the evaluation of potential interventions that mi...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/AID.2012.0162
更新日期:2013-02-01 00:00:00
abstract::The dichotomous effects of the protein kinase C (PKC) modulatory compounds 12-myristate 13-acetate (PMA), prostratin, and ingenol 3-angelate (I3A) on HIV-1 infection were investigated. PKC modulatory compounds were shown to be potent activators of cells latently infected with HIV-1 (I3A > prostratin). Conversely, PKC ...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.2006.22.854
更新日期:2006-09-01 00:00:00
abstract::A higher functionality of CD8(+) T cells might contribute to low-level HIV replication in long-term nonprogressors (LTNPs). However, the contrary could also be true, being the function of CD8(+) T cells modulated by HIV replication. We tested whether enhanced HIV replication following antiretroviral therapy interrupti...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.2008.0088
更新日期:2008-09-01 00:00:00
abstract::Six morphine-dependent and three control macaques were infected with a mixture of SIV/SHIV. Half of the animals in the morphine group developed accelerated disease (rapid progressor) and died within 20 weeks postinfection. The evolution of the envelope gene in the brain of the rapid progressor and morphine-dependent g...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.2008.0279
更新日期:2009-05-01 00:00:00
abstract::Data indicate the presence in the Seychelles Islands of a high level of human T cell leukemia/lymphoma virus type I (HTLV-I) endemicity as well as the presence of tropical spastic paraparesis/HTLV-I-associated myelopathy (TSP/HAM). We present here the results of an hospital survey performed since 1988 in La Réunion Is...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.1994.10.745
更新日期:1994-06-01 00:00:00
abstract::The gag-homologous region of the human endogenous retrovirus K10 (HERV-K10) was amplified by PCR from human genomic DNA and was analyzed by DNA cloning, sequencing, and expression of open reading frames in the prokaryotic pATH expression system. The analysis of genomic DNA of three donors provided evidence that HERV-K...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.1993.9.343
更新日期:1993-04-01 00:00:00
abstract::The HIV-1 subtype A epidemic affecting injecting drug users (IDU) in former Soviet Union (FSU) countries started dramatically in Odessa, southern Ukraine, in 1995, and is caused by a variant of monophyletic origin, often designated IDU-A. We phylogenetically analyzed one near full-length genome and two partial sequenc...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.2007.0166
更新日期:2007-12-01 00:00:00
abstract::This study reports on the drug resistance profiles for HIV-infected pediatrics in Jamaica who have been exposed to antiretroviral therapy (ART). The genetic diversity of HIV-1 found in these patients was also determined using phylogenetic analysis. The protease-reverse transcriptase (Pro-RT) region of the genome was a...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/AID.2015.0122
更新日期:2015-09-01 00:00:00
abstract::Enfuvirtide (ENF) is the first of a new class of antiretrovirals (ARVs) known as the HIV fusion inhibitors. Two phase III studies of ENF, TORO 1 and TORO 2, demonstrated that ENF given in combination with optimized background (OB) therapy significantly improved virological response, increased the time to virological f...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.2006.22.240
更新日期:2006-03-01 00:00:00
abstract::HIV-1 subtype C is the prevalent subtype in South Africa, with non-C subtypes being sporadically detected. The accessory genes of subtype C have not been well studied in South Africa. In this study the HIV-1 vpr region of 58 strains was amplified, sequenced, and subtyped. Phylogenetic analysis characterized 54 strains...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.2008.0251
更新日期:2009-03-01 00:00:00
abstract::To evaluate the efficacy, safety and tolerability of switching to a dolutegravir (DTG)-based regimen in a cohort of virological suppressed HIV-infected patients. The dynamics of total HIV-DNA and levels of high-sensitivity c-reactive protein (hsCRP), interleukin-6 (IL-6), soluble-CD14 (sCD14) and D-Dimer were also ana...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/AID.2020.0196
更新日期:2021-01-24 00:00:00
abstract::In Taiwan, sexual transmission is responsible for most HIV-1 infections with two dominant subtypes, subtype B and CRF01_AE, distributing among homosexual and heterosexual groups, respectively. Recently, intravenous drug use has become an emerging route of HIV-1 transmission and contributed to a significant increase of...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.2006.22.1055
更新日期:2006-11-01 00:00:00
abstract::Heparin (Hep) and sulfated polysaccharides (SPs) have been reported to inhibit HIV infection in vitro. In vivo, anticoagulant activity and reduced bioavailability were found to limit the antiviral effects of Hep. In this investigation, three nonanticoagulant N-acylated Hep conjugates [OI1:3Hep, Pal1:5Hep, and Pal1:5He...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.1996.12.63
更新日期:1996-01-01 00:00:00
abstract::Combinations of drugs targeting viral proteins have been used to limit or control drug resistance, which is the most important cause of treatment failure in HIV-1-infected individuals. We suggest an alternative approach, namely to target cellular proteins, which are less prone to mutations than viral proteins. Here we...
journal_title:AIDS research and human retroviruses
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1089/aid.1997.13.1403
更新日期:1997-11-01 00:00:00
abstract::Antigenic properties of the V3 region are reflected by HIV-1 serotypes. These may represent biological properties of the virus. We serotyped HIV-1 in 142 serum samples from participants in a rural Uganda cohort who seroconverted between August 1991 and December 2001. Clinical progression was assessed using Cox proport...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.2004.20.932
更新日期:2004-09-01 00:00:00
abstract::Human immunodeficiency virus type 1 (HIV-1) proviral DNA sequences in the 5' long terminal repeat (LTR) were examined among 28 drug-naive individuals. Twenty-four subjects had highly conserved LTR sequences, however, more significant changes were observed in the remaining four LTR sequences. These included a 9-bp dele...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.2004.20.1019
更新日期:2004-09-01 00:00:00
abstract::Human immunodeficiency virus type 1 (HIV-1) isolates differ in their use of coreceptors to enter target cells. This has important implications for both viral pathogenicity and susceptibility to entry inhibitors, recently approved or under development. Predicting HIV-1 coreceptor usage on the basis of sequence informat...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.2008.0039
更新日期:2009-03-01 00:00:00
abstract::SIVsmmFGb is a lentivirus swarm that induces neuropathology in over 90% of infected pigtailed macaques and reliably models central nervous system HIV infection in people. We have previously studied SIVsmmFGb genetic diversity and compartmentalization during acute infection, but little is understood about diversity and...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.2009.0168
更新日期:2010-06-01 00:00:00
abstract::To provide a better understanding of the role of placenta in vertical human immunodeficiency virus (HIV) transmission, we have studied the infection of placental trophoblast in a group of 15 mother-neonate pairs. By nested PCR amplification of the C2V3 env gene region, HIV-1 has been found to infect the placenta in fi...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/088922299309711
更新日期:1999-12-10 00:00:00
abstract::Human immunodeficiency virus type 1 (HIV-1) spends a significant part of its life cycle as latent provirus in nonactivated cells. It induction requires mitogen stimulation. TPA treatment induces HIV-1 transcription by protein kinase C (PKC)-mediated activation of the cellular transcription factor NF-kB. PKC activation...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.1992.8.245
更新日期:1992-02-01 00:00:00
abstract::Natural polymorphisms of HIV-1, often associated with drug resistance, are widely described in protease and reverse transcriptase regions but data on their presence in the integrase region, especially in non-B subtypes, are still very limited. We aimed to characterize naturally occurring polymorphisms in the integrase...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.2010.0097
更新日期:2010-10-01 00:00:00
abstract::The advent of antiretroviral treatment (ART) has resulted in a dramatic reduction in AIDS-related morbidity and mortality. However, the emergence and spread of antiretroviral drug resistance (DR) threaten to negatively impact treatment regimens and compromise efforts to control the epidemic. It is recommended that sur...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/AID.2015.0039
更新日期:2015-12-01 00:00:00
abstract::The humoral immune response is a mechanism that potently suppresses or prevents viral infections. However, genetic diversity and resistance to antibody-mediated neutralization are serious obstacles in controlling HIV-1 infection. In this study, we isolated monoclonal antibodies from an SIV-infected macaque by using th...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/AID.2010.0191
更新日期:2011-05-01 00:00:00