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Molecular characteristics of human immunodeficiency virus type 1 subtype C viruses from KwaZulu-Natal, South Africa: implications for vaccine and antiretroviral control strategies.

ABSTRACT: The KwaZulu-Natal region of South Africa is experiencing an explosive outbreak of human immunodeficiency virus type 1 (HIV-1) subtype C infections. Understanding the genetic diversity of C viruses and the biological consequences of this diversity is important for the design of effective control strategies. We analyzed the protease gene, the first 935 nucleotides of reverse transcriptase, and the C2V5 envelope region of a representative set of 72 treatment-naïve patients from KwaZulu-Natal and correlated the results with amino acid signature and resistance patterns. Phylogenetic analysis revealed multiple clusters or "lineages" of HIV-1 subtype C that segregated with other C viruses from southern Africa. The same pattern was observed for both black and Indian subgroups and for retrospective specimens collected prior to 1990, indicating that multiple sublineages of HIV-1 C have been present in KwaZulu-Natal since the early stages of the epidemic. With the exception of three nonnucleoside reverse transcriptase inhibitor mutations, no primary resistance mutations were identified. Numerous accessory polymorphisms were present in the protease, but none were located at drug-binding or active sites of the enzyme. One frequent polymorphism, I93L, was located near the protease/reverse transcriptase cleavage site. In the envelope, disruption of the glycosylation motif at the beginning of V3 was associated with the presence of an extra protein kinase C phosphorylation site at codon 11. Many polymorphisms were embedded within cytotoxic T lymphocyte or overlapping cytotoxic T-lymphocyte/T-helper epitopes, as defined for subtype B. This work forms a baseline for future studies aimed at understanding the impact of genetic diversity on vaccine efficacy and on natural susceptibility to antiretroviral drugs.

SUBMITTER: Gordon M

PROVIDER: S-EPMC141090 | biostudies-literature | 2003 Feb

REPOSITORIES: biostudies-literature

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Molecular characteristics of human immunodeficiency virus type 1 subtype C viruses from KwaZulu-Natal, South Africa: implications for vaccine and antiretroviral control strategies.

Gordon M M De Oliveira T T Bishop K K Coovadia H M HM Madurai L L Engelbrecht S S Janse van Rensburg E E Mosam A A Smith A A Cassol S S

Journal of virology 20030201 4

The KwaZulu-Natal region of South Africa is experiencing an explosive outbreak of human immunodeficiency virus type 1 (HIV-1) subtype C infections. Understanding the genetic diversity of C viruses and the biological consequences of this diversity is important for the design of effective control strategies. We analyzed the protease gene, the first 935 nucleotides of reverse transcriptase, and the C2V5 envelope region of a representative set of 72 treatment-naïve patients from KwaZulu-Natal and co ...[more]

PMID: 12551997

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Project description:Antimicrobial resistance (AMR) is a serious global public-health threat. Evidence suggests that antimicrobial stewardship (AMS) is a valuable tool to facilitate rational antibiotic use within healthcare facilities. A cross-sectional situational analysis using a questionnaire was conducted to determine the current status of antimicrobial stewardship (AMS) activities in all public-sector hospitals in KwaZulu-Natal (KZN). The survey had a 79% (57, N = 72) response rate. A total of 75% of hospitals had an antimicrobial stewardship committee (AMSC), 47% (20, N = 43) had a formal written statement of support from leadership, and 7% (3, N = 43) had budgeted financial support. Only 37% (16, N = 43) had on-site or off-site support from a clinical microbiologist, and 5% (2, N = 43) had an on-site infectious disease (ID) physician. Microbiologist input on pathogen surveillance data (aOR: 5.12; 95% CI: 4.08-22.02; p-value = 0.001) and microbiological investigations prior to the commencement of antibiotics (aOR: 5.12; 95% CI: 1.08-42.01; p-value = 0.041) were significantly associated with having either on- or off-site microbiology support. Respondents that had a representative from microbiology on the AMSC were significantly associated with having and interrogating facility-specific antibiograms (P = 0.051 and P = 0.036, respectively). Those facilities that had access to a microbiologist were significantly associated with producing an antibiogram (aOR: 4.80; 95% CI: 1.25-18.42; p-value = 0.022). Facilities with an ID physician were significantly associated with having a current antibiogram distributed to prescribers within the facility (P = 0.010) and significantly associated with sending prescribers personalized communication regarding improving prescribing (P = 0.044). Common challenges reported by the facilities included suboptimal hospital management support; a lack of clinicians, pharmacists, nurses, microbiologists, and dedicated time; the lack of a multidisciplinary approach; low clinician buy-in; inadequate training; a lack of printed antibiotic guidelines; and financial restrictions for microbiological investigations. The survey identified the need for financial, IT, and management support. Microbiology and infectious disease physicians were recognized as scarce human resources.

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Dataset Information

Molecular characteristics of human immunodeficiency virus type 1 subtype C viruses from KwaZulu-Natal, South Africa: implications for vaccine and antiretroviral control strategies.

Publications

Molecular characteristics of human immunodeficiency virus type 1 subtype C viruses from KwaZulu-Natal, South Africa: implications for vaccine and antiretroviral control strategies.

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