Prevalence of HIV‐1 Drug Resistance after Failure of a First Highly Active Antiretroviral Therapy Regimen in KwaZulu Natal, South Africa

Marconi, Vincent C.; Sunpath, Henry; Lu, Zhigang; Gordon, Michelle; Koranteng-Apeagyei, Kofi; Hampton, Jane; Carpenter, Stephen M.; Giddy, Janet; Ross, Douglas S.; Holst, Helga; Losina, Elena; Walker, Bruce D.; Kuritzkes, Daniel R.

doi:10.1086/587109

Cited by 219 publications

(210 citation statements)

References 27 publications

Supporting

Mentioning

168

Contrasting

Order By: Relevance

“…The most common NRTI mutation was M184V (75%), with K103N (43%) and V106AM (26%) being the most common NNRTI mutations, similar to previously reported studies. 18,19 K65R was present in 11% of patients, 9% of whom were on a tenofovir-containing regimen, consistent with recent findings. 20 Thymidine analogue mutations (TAMs) were present in 35% of patient samples, with 10% possessing mutations associated with the TAM1 pathway, 19% with TAM2, and 6% with mutations common to both pathways.…”

supporting

confidence: 90%

See 1 more Smart Citation

Viral Tropism and Antiretroviral Drug Resistance in HIV-1 Subtype C-Infected Patients Failing Highly Active Antiretroviral Therapy in Johannesburg, South Africa

Ketseoglou

Lukhwareni²,

Steegen³

et al. 2014

AIDS Research and Human Retroviruses

View full text Add to dashboard Cite

Reports show that up to 30% of antiretroviral drug-naive patients in Johannesburg have CXCR4-utilizing HIV-1 subtype C. We assessed whether HIV-1 subtype C-infected individuals failing highly active antiretroviral therapy (HAART) have a higher proportion of CXCR4-utilizing viruses compared to antiretroviral drug-naive patients. The V3 loop was sequenced from plasma from 100 randomly selected HAART-failing patients, and tropism was established using predictive algorithms. All patients harbored HIV-1 subtype C with at least one antiretroviral drug resistance mutation. Viral tropism prediction in individuals failing HAART revealed similar proportions (29%) of X4-utilizing viruses compared to antiretroviral drug-naive patients (30%). Findings are in contrast to reports from Durban in which 60% of HAART-failing subjects harbored X4/dual/mixed-tropic viruses. Despite differences in proportions of X4-tropism within South Africa, the high proportion of thymidine analogue mutations (TAMs) and CXCR4-utilizing HIV-1 highlights the need for intensified monitoring of HAART patients and the predicament of diminishing drug options, including CCR5 antagonists, for patients failing therapy.

show abstract

supporting

confidence: 90%

“…The high proportion of TAMs (35%) is comparable to previous South African studies that reported 32.2% TAMs in adult patients from KwaZuluNatal. 18 By contrast, TAMs were reported in 58.5% of HAARTfailing children 21 and 55% of HAART-failing adults 19 from KwaZulu-Natal.…”

mentioning

confidence: 96%

Viral Tropism and Antiretroviral Drug Resistance in HIV-1 Subtype C-Infected Patients Failing Highly Active Antiretroviral Therapy in Johannesburg, South Africa

Ketseoglou

Lukhwareni²,

Steegen³

et al. 2014

AIDS Research and Human Retroviruses

View full text Add to dashboard Cite

show abstract

“…This suggested that subtype C could have a lower genetic barrier to resistance to NNRTIs than subtype B, and that this V106M mutation could be more frequent in subtype C infected patients failing therapy, than in subtype B infected patients. Indeed, the clinical importance of the V106M mutation in non-B subtypes has been confirmed in several studies showing that V106M is more frequently seen in subtype C (and CRF01_AE) after therapy with EFV or NVP (Deshpande et al, 2007;Hsu et al, 2005;Marconi et al, 2008;Rajesh et al, 2009). The G190A mutation was also relatively more frequent in subtype C Indian and Israeli patients failling NNRTI-based regimens than in subtype B (Deshpande et al, 2007;Grossman et al, 2004).…”

Section: Impact Of Hiv-1 Diversity In Drug Resistancementioning

confidence: 87%

HIV-1 Diversity and Its Implications in Diagnosis, Transmission, Disease Progression, and Antiretroviral Therapy

Bártolo¹,

Taveira²

2012

Genetic Diversity in Microorganisms

View full text Add to dashboard Cite

“…Existing literature points to associations between pretreatment patient characteristics (e.g., low CD4 and high pretreatment viral load) and ART regimen composition (e.g., inclusion of NNRTIs, inadequate number of active drugs) and the development of ARV resistance, but none investigated the role of prior toxicity-related regimen changes. [17][18][19][20][21][22] In our study, we found, for the first time in the published literature that prior regimen change owing to toxicity was associated with a significant risk of developing resistance. Individuals who experienced toxicity-related regimen changes had over a 3-fold increased risk of developing ARV resistance than those who did not undergo toxicity-related regimen changes.…”

mentioning

confidence: 80%

The Role of Toxicity-Related Regimen Changes in the Development of Antiretroviral Resistance

Nevin

Aban

et al. 2011

AIDS Research and Human Retroviruses

View full text Add to dashboard Cite

In an effort to evaluate factors associated with the development of antiretroviral (ARV) resistance, we assessed the prevalence of toxicity-related regimen changes and modeled its association to the subsequent development of ARV resistance in a cohort of treatment-naive individuals initiating ARV therapy (ART). A retrospective analysis of patients initiating ART was conducted at the UAB 1917 Clinic from 1 January 2000 to 30 September 2007. Cox proportional hazards models were fit to identify factors associated with the development of resistance to ‡ 1 ARV drug class. Among 462 eligible participants, 14% (n = 64) developed ARV resistance. Individuals with ‡ 1 toxicity-related regimen change (HR = 3.94, 95% CI = 1.09-14.21), initiating ART containing ddI or d4T (4.12, 1.19-14.26), and from a minority race (2.91, 1.16-7.28) had increased risk of developing resistance. Achieving virologic suppression within 12 months of ART initiation (0.10, 0.05-0.20) and higher pretreatment CD4 count (0.85 per 50 cells/mm 3 , 0.75-0.96) were associated with decreased hazards of resistance. Changes in ART due to drug intolerance were associated with the subsequent development of ARV resistance. Understanding the role of ARV drug selection and other factors associated with the emergence of ARV resistance will help inform interventions to improve patient care and ensure long-term treatment success.

show abstract

Prevalence of HIV‐1 Drug Resistance after Failure of a First Highly Active Antiretroviral Therapy Regimen in KwaZulu Natal, South Africa

Cited by 219 publications

References 27 publications

Viral Tropism and Antiretroviral Drug Resistance in HIV-1 Subtype C-Infected Patients Failing Highly Active Antiretroviral Therapy in Johannesburg, South Africa

Viral Tropism and Antiretroviral Drug Resistance in HIV-1 Subtype C-Infected Patients Failing Highly Active Antiretroviral Therapy in Johannesburg, South Africa

HIV-1 Diversity and Its Implications in Diagnosis, Transmission, Disease Progression, and Antiretroviral Therapy

The Role of Toxicity-Related Regimen Changes in the Development of Antiretroviral Resistance

Contact Info

Product

Resources

About