Genotypic Resistance at Viral Rebound Among Patients Who Received Lopinavir/Ritonavir-Based or Efavirenz-Based First Antiretroviral Therapy in South Africa

Office of Clinical Operation, Project Phidisa, South African Military Health Service (SAMHS), Pretoria, South Africa.
JAIDS Journal of Acquired Immune Deficiency Syndromes (Impact Factor: 4.56). 06/2011; 58(3):304-8. DOI: 10.1097/QAI.0b013e3182278c29
Source: PubMed


Nonnucleoside reverse transcriptase inhibitor-drug resistance mutations (DRM) are increasingly reported in Africans failing their first antiretroviral regimen. The Phidisa II trial randomized treatment-naive participants to lopinavir/ritonavir or efavirenz with stavudine + lamivudine or zidovudine + didanosine. We report the prevalence of DRM in subjects who achieved HIV RNA <400 copies per milliliter at 6 months, but subsequently had 2 consecutive HIV RNA >1000 copies per milliliter. Sixty-eight participants fulfilled the inclusion criteria. nonnucleoside reverse transcriptase inhibitor-DRM were found in 17 of 36 (47.2%) efavirenz recipients, and M184V/I mutation in 14 of 40 (35.0%) lamivudine recipients. No protease inhibitor mutation was identified in 38 lopinavir/ritonavir recipients. This is one of the first studies in Africa confirming the paucity of protease inhibitor-associated DRM despite virologic failure.

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    ABSTRACT: The treatment of HIV-1 infection with antiretroviral drugs has greatly improved the survival of those who are infected. However, HIV-1 diversity and drug resistance are major challenges in patient management, especially in resource-poor countries. To evaluate HIV-1 genetic diversity and drug resistance-associated mutations among drug-naive patients in Kenya prior to antiretroviral therapy (ART), a genetic analysis of HIV-1 pol-RT and env-gp41 was performed on samples collected from 53 (18 males and 35 females) consenting patients between April and June 2005. The average age, baseline CD4(+) T cell counts, and viral loads were 38 (range, 24-62) years, 475 (range, 203-799) cells/mm(3), and 4.7 (range, 3.4-5.9) log(10) copies/ml, respectively. Phylogenetic analysis revealed that 40 samples (75.5%) were concordant subtypes for the two genes and 13 (24.5%) were discordant, suggesting possible recombination and/or dual infections. Prevalent subtypes included A1/A1(pol-RT/env-gp41), 31 (58.5%); D/D, 9 (16.9%); A1/C, 2 (3.8%); A1/D, 4 (7.5%); G/A1, 2 (3.8%); A1/A2, 1 (1.9%); C/A1, 2 (3.8%); D/A1, 1(1.9%); and D/A2, 1 (1.9%). Major reverse transcriptase inhibitor (RTI) resistance-associated mutations were found in four patients (7.5%). Of these patients, three had nucleoside RTI resistance mutations, such as M184V, K65R, D67N, K70R, and K219Q. Nonnucleoside RTI resistance-associated mutations K103N and Y181C were detected in three patients and one patient, respectively. Multiple drug resistance mutations were observed in this drug-naive population. With increasing numbers of patients that require treatment and the rapid upscaling of ART in Kenya, HIV-1 drug resistance testing is recommended before starting treatment in order to achieve better clinical outcomes.
    Full-text · Article · Dec 2009 · AIDS research and human retroviruses
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    ABSTRACT: Following the rapid scale-up of the programme for universal access to antiretroviral therapy (ART) in southern Africa, resistance to antiretroviral medications will occur. A detectable viral load must be treated as an emergency and should trigger intensive patient tracking and adherence counselling. In contrast to the developed world, the incidence of transmitted resistance is still low in most areas in the region. Therefore, in this consensus statement we do not recommend resistance testing in HIV-infected adults upon diagnosis or ART initiation. However, baseline resistance testing is recommended for children who have been exposed to ART for prevention of mother-to-child-transmission therapy and subsequently become HIV-infected. Resistance testing is also recommended after virological failure of first- and second-line ART regimens.
    Full-text · Article · Nov 2012 · Southern African Journal of HIV Medicine
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    Full-text · Article · Nov 2012 · Journal of the International AIDS Society
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