Drug resistance and viral tropism in HIV-1 subtype C-infected patients in KwaZulu-Natal, South Africa

Implications for future treatment options

Ashika Singh, Henry Sunpath, Taryn N. Green, Nagavelli Padayachi, Keshni Hiramen, Yolanda Lie, Elizabeth D. Anton, Richard Murphy, Jacqueline D. Reeves, Daniel R. Kuritzkes, Thumbi Ndung'U

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Background: Drug resistance poses a significant challenge for the successful application of highly active antiretroviral therapy (HAART) globally. Furthermore, emergence of HIV-1 isolates that preferentially use CXCR4 as a coreceptor for cell entry, either as a consequence of natural viral evolution or HAART use, may compromise the efficacy of CCR5 antagonists as alternative antiviral therapy. Methods: We sequenced the pol gene of viruses from 45 individuals failing at least 6 months of HAART in Durban, South Africa, to determine the prevalence and patterns of drug-resistance mutations. Coreceptor use profiles of these viruses and those from 45 HAART-naive individuals were analyzed using phenotypic and genotypic approaches. Results: Ninety-five percent of HAART-failing patients had at least one drug-resistant mutation. Thymidine analog mutations (TAMs) were present in 55% of patients with 9% of individuals possessing mutations indicative of the TAM1 pathway, 44% had TAM2, whereas 7% had mutations common to both pathways. Sixty percent of HAART-failing subjects had X4/dual//mixed-tropic viruses compared with 30% of HAART-naïve subjects (P < 0.02). Genetic coreceptor use prediction algorithms correlated with phenotypic results with 60% of samples from HAART-failing subjects predicted to possess CXCR4-using (X4/dual/mixed viruses) versus 15% of HAART-naïve patients. Conclusions: The high proportion of TAMs and X4/dual/mixed HIV-1 viruses among patients failing therapy highlight the need for intensified monitoring of patients taking HAART and the problem of diminished drug options (including CCR5 antagonists) for patients failing therapy in resource-poor settings.

Original languageEnglish (US)
Pages (from-to)233-240
Number of pages8
JournalJournal of Acquired Immune Deficiency Syndromes
Volume58
Issue number3
DOIs
StatePublished - Nov 1 2011
Externally publishedYes

Fingerprint

Viral Tropism
Highly Active Antiretroviral Therapy
South Africa
Drug Resistance
HIV-1
Mutation
Viruses
Therapeutics
Thymidine
pol Genes
Physiologic Monitoring
Complementary Therapies
Pharmaceutical Preparations
Antiviral Agents

Keywords

  • antiretroviral drug resistance
  • coreceptor use
  • HAART-failing patients
  • HAART-naïve patients
  • viral tropism

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)

Cite this

Drug resistance and viral tropism in HIV-1 subtype C-infected patients in KwaZulu-Natal, South Africa : Implications for future treatment options. / Singh, Ashika; Sunpath, Henry; Green, Taryn N.; Padayachi, Nagavelli; Hiramen, Keshni; Lie, Yolanda; Anton, Elizabeth D.; Murphy, Richard; Reeves, Jacqueline D.; Kuritzkes, Daniel R.; Ndung'U, Thumbi.

In: Journal of Acquired Immune Deficiency Syndromes, Vol. 58, No. 3, 01.11.2011, p. 233-240.

Research output: Contribution to journalArticle

Singh, A, Sunpath, H, Green, TN, Padayachi, N, Hiramen, K, Lie, Y, Anton, ED, Murphy, R, Reeves, JD, Kuritzkes, DR & Ndung'U, T 2011, 'Drug resistance and viral tropism in HIV-1 subtype C-infected patients in KwaZulu-Natal, South Africa: Implications for future treatment options', Journal of Acquired Immune Deficiency Syndromes, vol. 58, no. 3, pp. 233-240. https://doi.org/10.1097/QAI.0b013e318228667f
Singh, Ashika ; Sunpath, Henry ; Green, Taryn N. ; Padayachi, Nagavelli ; Hiramen, Keshni ; Lie, Yolanda ; Anton, Elizabeth D. ; Murphy, Richard ; Reeves, Jacqueline D. ; Kuritzkes, Daniel R. ; Ndung'U, Thumbi. / Drug resistance and viral tropism in HIV-1 subtype C-infected patients in KwaZulu-Natal, South Africa : Implications for future treatment options. In: Journal of Acquired Immune Deficiency Syndromes. 2011 ; Vol. 58, No. 3. pp. 233-240.
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AU - Padayachi, Nagavelli

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