Viremia and drug resistance among HIV-1 patients on antiretroviral treatment: a cross-sectional study in Soweto, South Africa

El‐Khatib, Ziad; Ekström, Anna Mia; Ledwaba, Johanna; Mohapi, Lerato; Laher, Fatima; Karstaedt, Alan; Charalambous, Salome; Petzold, Max; Katzenstein, David; Morris, Lynn

doi:10.1097/qad.0b013e32833a097b

Cited by 110 publications

(131 citation statements)

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“…In the present study, we examined patients from the public health system and found a high rate of drug resistance mutations: 76.39% of the samples tested (55/72) had at least one drug resistance mutation after a median follow-up period of 40 months. This rate of drug resistance mutation is similar to that recently reported in studies in decentralized areas of Senegal (18) and in other countries such as the Central African Republic (19) and the Republic of South Africa using the same first-line regimens (20). In contrast, a relatively low prevalence of resistant viruses has been reported in Cameroon after 12 and 24 months, probably because of the shorter median follow-up period of 17 months (21).…”

Section: Discussionsupporting

confidence: 89%

HIV-1 Genetic Diversity and Drug Resistance among Senegalese Patients in the Public Health System

et al. 2013

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In this study, we investigated the prevalence of human immunodeficiency virus type 1 (HIV-1) drug resistance mutations and genetic variability among Senegalese patients undergoing highly active antiretroviral therapy (ART) in the public health system. We conducted a cross-sectional study of 72 patients with suspected therapeutic failure. HIV-1 genotyping was performed with Viroseq HIV-1 Genotyping System v2.0 or the procedure developed by the ANRS AC11 resistance study group, and a phylogenetic analysis was performed. The median follow-up visit was at 40 (range, 12 to 123) months, and the median viral load was 4.67 (range, 3.13 to 6.94) log 10 copies/ml. The first-line therapeutic regimen was nucleoside reverse transcriptase inhibitors (NRTIs) plus efavirenz (EFV) or NRTIs plus nevirapine (NVP) (54/72 patients; 75%), and the second-line therapy was NRTIs plus a protease inhibitor (PI/r) (18/72; 25%). Fifty-five patients (55/72; 76.39%) had at least one drug resistance mutation. The drug resistance rates were 72.22 and 88.89% for the first-line and second-line ARTs, respectively. In NRTI mutations, thymidine analog mutations (TAMs) were found in 50.79% and the M184V mutation was found in 34.92% of the samples. For non-NRTI resistance, we noted a predominance of the K103N mutation (46.27%). For PI/r, several cases of mutations were found with a predominance of M46I and L76V/F at 24% each. The phylogenetic analysis revealed CRF02_AG as the predominant circulating recombinant form (43/72; 59.72%). We found a high prevalence of resistance mutations and a high rate of TAMs among Senegalese patients in the public health system. These findings emphasize the need to improve virological monitoring in resource-limited settings.

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Section: Discussionsupporting

confidence: 89%

HIV-1 Genetic Diversity and Drug Resistance among Senegalese Patients in the Public Health System

et al. 2013

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“…Patient samples (n ϭ 38) from the South African Virological Evaluation (SAVE) study (9) and a workplace HIV program within the mining industry (26) and samples submitted for routine genotyping were selected for resistance phenotyping (27). Samples were selected on the basis of availability and the presence of one or more NNRTI resistance-associated mutations.…”

Section: Hiv-1 Subtype C Sequencesmentioning

confidence: 99%

“…Sequences were obtained from the South African Treatment and Resistance Network (SATuRN) database (http://www.bioafrica.net/regadb/) (n ϭ 766) (9) and the Stanford HIV Drug Resistance Database (HIVdb) (http://hivdb .stanford.edu/) (n ϭ 667). Only sequences with NNRTI resistance-associated mutations were included.…”

Section: Hiv-1 Subtype C Sequencesmentioning

confidence: 99%

“…The accumulation of EFV and NVP resistance-associated mutations is rapid, often occurring within 3 months of virologic failure (8). Recent studies in South Africa have shown that up to 80% of patients who fail EFV or NVP therapy develop NNRTI resistance-associated mutations (9)(10)(11)(12). Furthermore, the substantial cross-resistance between these two drugs makes their sequential use after virologic failure inappropriate.…”

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confidence: 99%

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Impact of Drug Resistance-Associated Amino Acid Changes in HIV-1 Subtype C on Susceptibility to Newer Nonnucleoside Reverse Transcriptase Inhibitors

Basson

Rhee

Parry

et al. 2015

Antimicrob Agents Chemother

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The objective of this study was to assess the phenotypic susceptibility of HIV-1 subtype C isolates, with nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance-associated amino acid changes, to newer NNRTIs. A panel of 52 site-directed mutants and 38 clinically derived HIV-1 subtype C clones was created, and the isolates were assessed for phenotypic susceptibility to etravirine (ETR), rilpivirine (RPV), efavirenz (EFV), and nevirapine (NVP) in an in vitro single-cycle phenotypic assay. The amino acid substitutions E138Q/R, Y181I/V, and M230L conferred high-level resistance to ETR, while K101P and Y181I/V conferred high-level resistance to RPV. Y181C, a major NNRTI resistance-associated amino acid substitution, caused decreased susceptibility to ETR and, to a lesser extent, RPV when combined with other mutations. These included N348I and T369I, amino acid changes in the connection domain that are not generally assessed during resistance testing. However, the prevalence of these genotypes among subtype C sequences was, in most cases, <1%. The more common EFV/NVP resistance-associated substitutions, such as K103N, V106M, and G190A, had no major impact on ETR or RPV susceptibility. The low-level resistance to RPV and ETR conferred by E138K was not significantly enhanced in the presence of M184V/I, unlike for EFV and NVP. Among patient samples, 97% were resistant to EFV and/or NVP, while only 24% and 16% were resistant to ETR and RPV, respectively. Overall, only a few, relatively rare NNRTI resistance-associated amino acid substitutions caused resistance to ETR and/or RPV in an HIV-1 subtype C background, suggesting that these newer NNRTIs would be effective in NVP/EFV-experienced HIV-1 subtype C-infected patients. Highly active antiretroviral therapy (HAART), which comprises the concomitant use of multiple potent antiretroviral drugs, has contributed to a significant decrease in the morbidity and mortality of people infected with HIV-1 (1). The failure of HAART through the acquisition of HIV drug resistance-associated substitutions that cause a decrease in viral susceptibility is usually due to poor adherence and insufficient drug concentrations. Although more than two-thirds of the global HIV-1 infections occur in sub-Saharan African countries, where HIV-1 infections are dominated by non-B subtypes, HAART regimens have largely been developed and tested against HIV-1 subtype B isolates (2). Subtype C accounts for almost half of all global infections and dominates the epidemic in southern Africa (3). While HAART agents are effective against all subtypes (4), greatly aiding the global response to HIV infection, specific resistance mutations and disparities in drug susceptibilities can differ by subtype (5). Examples include the K65R (6) and V106M (7) resistance-associated amino acid substitutions, which develop more frequently under drug pressure in HIV-1 subtype C than subtype B.Nonnucleoside reverse transcriptase (RT) inhibitors (NNRTIs) are a component of most first-line HAART regimens. For efavirenz (EF...

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“…In one study conducted in Soweto, SA, about one-third of patients receiving the second-line lopinavir/ritonavir (LPV/r)-based regimen were found to be viraemic. [7] In another study in Khayelitsha, SA, patients receiving second-line ART were less likely to be virologically suppressed than patients remaining on first-line ART at equivalent durations of treatment (odds ratio (OR) 0.51; 95% confidence interval (CI) 0.26 -1.01). [8] North American and European ART guidelines recommend that genotyping governs decisions on the appropriate treatment for patients failing second-line ART.…”

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confidence: 99%

High rate of virological re-suppression among patients failing second-line antiretroviral therapy following enhanced adherence support: A model of care in Khayelitsha, South Africa

Garone

Conradie

Patten

et al. 2013

South. Afr. j. HIV med.

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Objective. To describe and evaluate the outcomes of a support programme for patients with virological failure while receiving second-line antiretroviral therapy (ART) in South Africa. Method. We described a comprehensive medical and counselling patient support programme for patients receiving secondline ART and with two consecutive viral loads (VLs) >1 000 copies/ml. Patients with >3 months follow-up and at least one VL measurement after inclusion in the programme were eligible for analysis. Results. Of 69 patients enrolled in the programme, 40 had at least one follow-up VL and no known drug resistance at enrolment; 27 (68%) of these re-suppressed while remaining on second-line ART following enhanced adherence support. The majority (18/27; 67%) achieved re-suppression within the first 3 months in the programme. Five patients with diagnosed second-line drug resistance achieved viral re-suppression (<400 copies/ml) after being switched to third-line ART. Seven patients (7/40; 18%) did not achieve viral re-suppression after 9 months in the programme: 6 with known adherence problems (4 without drug resistance on genotype) and 1 with a VL <1 000 copies/ml. Overall, 3 patients (4%) died, 3 (4%) were lost to follow-up and 2 (3%) were transferred out. Conclusion. Our experience from a routine programme demonstrates that with targeted adherence support, the majority of patients who were viraemic while receiving second-line ART returned to an undetectable VL within 3 months. By increasing the time receiving second-line ART and decreasing the need for genotypes and/or third-line ART, this intervention may reduce costs.

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Viremia and drug resistance among HIV-1 patients on antiretroviral treatment: a cross-sectional study in Soweto, South Africa

Abstract: Background: We assessed risk factors for viremia and drug resistance (DR) among long-term recipients of antiretroviral therapy (ART) in South Africa.

Cited by 110 publications

References 37 publications

HIV-1 Genetic Diversity and Drug Resistance among Senegalese Patients in the Public Health System

HIV-1 Genetic Diversity and Drug Resistance among Senegalese Patients in the Public Health System

Impact of Drug Resistance-Associated Amino Acid Changes in HIV-1 Subtype C on Susceptibility to Newer Nonnucleoside Reverse Transcriptase Inhibitors

High rate of virological re-suppression among patients failing second-line antiretroviral therapy following enhanced adherence support: A model of care in Khayelitsha, South Africa

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