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1.
J Antimicrob Chemother ; 72(1): 210-219, 2017 01.
Article in English | MEDLINE | ID: mdl-27659733

ABSTRACT

BACKGROUND: Routine HIV-1 antiretroviral drug resistance testing for patients failing NNRTI-based regimens is not recommended in resource-limited settings. Therefore, surveys are required to monitor resistance profiles in patients failing ART. METHODS: A cross-sectional survey was conducted amongst patients failing NNRTI-based regimens in the public sector throughout South Africa. Virological failure was defined as two consecutive HIV-1 viral load results >1000 RNA copies/mL. Pol sequences were obtained using RT-PCR and Sanger sequencing and submitted to Stanford HIVdb v7.0.1. RESULTS: A total of 788 sequences were available for analysis. Most patients failed a tenofovir-based NRTI backbone (74.4%) in combination with efavirenz (82.1%) after median treatment duration of 36 months. K103N (48.9%) and V106M (34.9%) were the most common NNRTI mutations. Only one-third of patients retained full susceptibility to second-generation NNRTIs such as etravirine (36.5%) and rilpivirine (27.3%). After M184V/I (82.7%), K65R was the most common NRTI mutation (45.8%). The prevalence of K65R increased to 57.5% in patients failing a tenofovir regimen without prior stavudine exposure. Cross-resistance to NRTIs was often observed, but did not seem to affect the predicted activity of zidovudine as 82.9% of patients remained fully susceptible to this drug. CONCLUSIONS: The introduction of tenofovir-based first-line regimens has dramatically increased the prevalence of K65R mutations in the HIV-1-infected South African population. However, most patients failing tenofovir-based regimens remained fully susceptible to zidovudine. Based on these data, there is currently no need to change either the recommended first- or second-line ART regimens in South Africa.


Subject(s)
Anti-Retroviral Agents/pharmacology , Drug Resistance, Viral , HIV Infections/drug therapy , HIV Infections/virology , HIV-1/drug effects , Adolescent , Adult , Aged , Aged, 80 and over , Anti-Retroviral Agents/therapeutic use , Cross-Sectional Studies , Female , Genotype , Genotyping Techniques , HIV-1/genetics , HIV-1/isolation & purification , Humans , Male , Middle Aged , Reverse Transcriptase Polymerase Chain Reaction , Sequence Analysis, DNA , South Africa , Treatment Failure , Viral Load , Young Adult , pol Gene Products, Human Immunodeficiency Virus/genetics
2.
J Infect Dis ; 214(12): 1826-1830, 2016 Dec 15.
Article in English | MEDLINE | ID: mdl-27923946

ABSTRACT

Limited data exist on human immunodeficiency virus type 1 (HIV-1) resistance in patients who are not responding to protease inhibitor (PI)-based regimens in resource-limited settings. This study assessed resistance profiles in adults across South Africa who were not responding to PI-based regimens. pol sequencing was undertaken and submitted to the Stanford HIV Drug Resistance Database. At least 1 major PI mutation was detected in 16.4% of 350 participants. A total of 53.4% showed intermediate resistance to darunavir/ritonavir, whereas high-level resistance was not observed. Only 5.2% and 32.8% of participants showed high-level and intermediate resistance to etravirine, respectively. Although the prevalence of major PI mutations was within previously reported ranges, most patients will likely experience virological suppression during receipt of currently available South African third-line regimens.


Subject(s)
Anti-Retroviral Agents/therapeutic use , Drug Resistance, Viral , HIV Infections/drug therapy , HIV Infections/virology , HIV Protease Inhibitors/therapeutic use , HIV-1/drug effects , Adolescent , Adult , Aged , Anti-Retroviral Agents/pharmacology , Cross-Sectional Studies , Gene Products, pol/genetics , HIV Protease Inhibitors/pharmacology , HIV-1/isolation & purification , Humans , Middle Aged , Mutation, Missense , Prevalence , Sequence Analysis, DNA , South Africa/epidemiology , Treatment Failure , Young Adult
3.
Epidemiol Infect ; 143(7): 1451-6, 2015 May.
Article in English | MEDLINE | ID: mdl-25185583

ABSTRACT

A peptide library was used to screen for regions containing potential linear B-cell epitope sites in the glycoproteins and nucleoprotein of Crimean-Congo haemorrhagic fever virus (CCHFV) in an enzyme-linked immunosorbent assay (ELISA). The library consisted of 156 peptides, spanning the nucleoprotein and mature GN and GC proteins in a 19-mer with 9-mer overlap format. Using pooled serum samples from convalescent patients to screen the library, six peptides were identified as potential epitope sites. Further testing of these six peptides with individual patient sera identified two of these peptides as probable epitope sites, with peptide G1451-1469 reacting to 13/15 and peptide G1613-1631 to 14/15 human sera. These peptides are situated on the GC protein at amino acid positions 1451-1469 (relative to CCHFV isolate SPU103/97) (TCTGCYACSSGISCKVRIH) and 1613-1631 (FMFGWRILFCFKCCRRTRG). Identified peptides may have application in ELISA for diagnostic or serosurveillance purposes.


Subject(s)
Epitopes, B-Lymphocyte/genetics , Hemorrhagic Fever Virus, Crimean-Congo/genetics , Nucleoproteins/genetics , Viral Envelope Proteins/genetics , Amino Acid Sequence , Enzyme-Linked Immunosorbent Assay , Epitopes, B-Lymphocyte/metabolism , Hemorrhagic Fever Virus, Crimean-Congo/metabolism , Humans , Molecular Sequence Data , Nucleoproteins/metabolism , Sequence Alignment , Viral Envelope Proteins/metabolism
4.
Epidemiol Infect ; 142(9): 1952-62, 2014 Sep.
Article in English | MEDLINE | ID: mdl-24786748

ABSTRACT

Crimean Congo haemorrhagic fever virus (CCHFV) is a bunyavirus with a single-stranded RNA genome consisting of three segments (S, M, L), coding for the nucleocapsid protein, envelope glycoproteins and RNA polymerase, respectively. To date only five complete genome sequences are available from southern African isolates. Complete genome sequences were generated for 10 southern African CCHFV isolates using next-generation sequencing techniques. The maximum-likelihood method was used to generate tree topologies for 15 southern African plus 26 geographically distinct complete sequences from GenBank. M segment reassortment was identified in 10/15 southern African isolates by incongruencies in grouping compared to the S and L segments. These reassortant M segments cluster with isolates from Asia/Middle East, while the S and L segments cluster with strains from South/West Africa. The CCHFV M segment shows a high level of genetic diversity, while the S and L segments appear to co-evolve. The reason for the high frequency of M segment reassortment is not known. It has previously been suggested that M segment reassortment results in a virus with high fitness but a clear role in increased pathogenicity has yet to be shown.


Subject(s)
Hemorrhagic Fever Virus, Crimean-Congo/genetics , Hemorrhagic Fever Virus, Crimean-Congo/isolation & purification , Hemorrhagic Fever, Crimean/virology , Reassortant Viruses/genetics , Genetic Variation , Genome, Viral , Hemorrhagic Fever, Crimean/epidemiology , Humans , Phylogeny , Protein Structure, Tertiary , RNA, Viral/genetics , South Africa/epidemiology
5.
Int J Pediatr Otorhinolaryngol ; 74(3): 255-9, 2010 Mar.
Article in English | MEDLINE | ID: mdl-20018386

ABSTRACT

OBJECTIVES: To identify human papillomavirus (HPV) types associated with juvenile onset recurrent laryngeal papillomatosis (RLP) in southern Africa, to determine if there is a correlation between HPV type and disease aggressiveness and to determine the diagnostic and prognostic value of rapid molecular techniques for detection and typing of HPV using laryngeal biopsies. METHODS: Laryngeal biopsies from patients undergoing surgery for RLP were screened for HPV using conventional and real-time PCR techniques. Amplicons were sequenced to determine the HPV type involved. Clinical features were correlated with HPV type. RESULTS: HPV was identified in papillomata from 18 out of 19 patients. Only HPV-6 and HPV-11 were identified, with no co-infections. There was 100% concordance between conventional and real-time PCR techniques. Patients with HPV-11 disease required more procedures and tended to have higher Derkay scores than those with HPV-6 disease. The HPV types identified in our patients were genetically similar to HPV types from geographically distinct regions. CONCLUSIONS: RLP in our patient population appears to be exclusively due to HPV-6 or HPV-11. HPV-11 disease appears to be more aggressive than HPV-6 disease. Identification of the HPV types provides motivation for inclusion of vaccines against these types in vaccination programs to protect women against infection and subsequently reduce the incidence of RLP.


Subject(s)
Human papillomavirus 11/isolation & purification , Human papillomavirus 6/isolation & purification , Laryngeal Neoplasms/pathology , Laryngeal Neoplasms/virology , Papilloma/pathology , Papilloma/virology , Papillomaviridae/classification , Adolescent , Age of Onset , Biopsy , Child , Child, Preschool , Female , Humans , Infant , Laryngeal Neoplasms/epidemiology , Male , Neoplasm Recurrence, Local , Neoplasm Staging , Papilloma/epidemiology , Papillomavirus Vaccines/administration & dosage , Polymerase Chain Reaction , Severity of Illness Index , South Africa/epidemiology
6.
J Clin Virol ; 43(2): 216-8, 2008 Oct.
Article in English | MEDLINE | ID: mdl-18619898

ABSTRACT

BACKGROUND: Although human cytomegalovirus (HCMV) infection in infants has been associated with liver disease, the role of HCMV in infants presenting with prolonged neonatal jaundice is unclear as this clinical picture can be caused by a broad spectrum of underlying conditions. OBJECTIVES: This study aimed to determine a possible role for HCMV infection in infants with prolonged cholestatic neonatal jaundice that could facilitate the appropriate use of diagnostic assays and specific treatment in this condition. STUDY DESIGN: HCMV immunohistochemical staining was performed on liver biopsy specimens received for histopathological examination from 85 infants (mean age 3 months) with a clinical history of prolonged neonatal jaundice. HCMV serology was also performed. RESULTS: One infant with a histological diagnosis of HCMV hepatitis was also positive by immunohistochemical staining, while all other tissue specimens were negative for HCMV. HCMV IgG was positive in 92.3% and HCMV IgM in 39.7% of the infants (n=78). CONCLUSIONS: The serological results confirm the ubiquitous nature of HCMV with many primary infections occurring within the first year of life. Despite this, HCMV hepatitis was uncommon in this cohort.


Subject(s)
Cytomegalovirus Infections , Cytomegalovirus/immunology , Jaundice, Obstructive/complications , Biopsy , Cytomegalovirus/isolation & purification , Cytomegalovirus Infections/diagnosis , Cytomegalovirus Infections/epidemiology , Cytomegalovirus Infections/immunology , Cytomegalovirus Infections/virology , Female , Hepatitis, Viral, Human/diagnosis , Hepatitis, Viral, Human/epidemiology , Hepatitis, Viral, Human/immunology , Hepatitis, Viral, Human/virology , Humans , Immunoglobulin G/blood , Immunoglobulin M/blood , Immunohistochemistry , Infant , Liver/pathology , Liver/virology , Male
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