Genotypic resistance mutations to antiretroviral drugs in HIV-1 B and non-B subtypes from Cuba

Ij, Ruibal-Brunet; Cuevas, María Teresa; Díaz-Torres, Héctor M; Ml, Villahermosa; Noa-Romero, E; E, Vázquez de Parga; M, Blanco de Armas; Pérez-Álvarez, Lucı́a

doi:10.1590/s1020-49892001000900005

Cited by 13 publications

(8 citation statements)

References 21 publications

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“…In Cuba, moderate TDR prevalence to NRTIs (7.4%) was reported in a small survey performed in 1999 in 27 ARV-naïve subjects as part of a multi-country UNAIDS HIVDR study [ 24 ]. Nevertheless, a second survey performed in Havana in 2003 in 250 ARV naïve individuals showed low prevalence of NRTI TDR, and no evidence of TDR to NNRTIs and PIs [ 25 ].…”

Section: Resultsmentioning

confidence: 99%

Surveillance of HIV Transmitted Drug Resistance in Latin America and the Caribbean: A Systematic Review and Meta-Analysis

Ávila‐Ríos¹,

Sued

Rhee

et al. 2016

PLoS ONE

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BackgroundHIV transmitted drug resistance (TDR) remains at moderate level in Latin America and the Caribbean (LAC). However, different epidemiologic scenarios could influence national and sub-regional TDR levels and trends.Methods and FindingsWe performed a systematic review of currently available publications on TDR in antiretroviral treatment-naïve adults in LAC. Ninety-eight studies published between January 2000 and June 2015 were included according to critical appraisal criteria and classified by sub-region: Brazil (50), Mesoamerica (17), Southern Cone (16), Andean (8) and Caribbean (7). From these, 81 studies encompassing 11,441 individuals with data on DR mutation frequency were included in a meta-analysis. Overall TDR prevalence in LAC was 7.7% (95% CI: 7.2%-8.2%). An increasing trend was observed for overall TDR when comparing 2000–2005 (6.0%) and 2006–2015 (8.2%) (p<0.0001), which was associated with significant NNRTI TDR increase (p<0.0001). NRTI TDR decreased (4.5% vs. 2.3%, p<0.0001). NNRTI TDR increase was associated mainly with K101E, K103N and G190A. NRTI TDR decrease was associated mainly with M184V, K70R and T215Y. All sub-regions reached moderate overall TDR levels. The rapid increase in TDR to all antiretroviral classes in the Caribbean is notable, as well as the significant increase in NNRTI TDR reaching moderate levels in the Southern Cone. NRTI TDR was dominant in 2000–2005, mainly in the Caribbean, Mesoamerica and Brazil. This dominance was lost in 2006–2015 in all sub-regions, with the Southern Cone and the Caribbean switching to NNRTI dominance. PI TDR remained mostly constant with a significant increase only observed in the Caribbean.ConclusionsGiven the high conceptual and methodological heterogeneity of HIV TDR studies, implementation of surveys with standardized methodology and national representativeness is warranted to generate reliable to inform public health policies. The observed increasing trend in NNRTI TDR supports the need to strengthen TDR surveillance and programme monitoring and evaluation in LAC.

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Section: Resultsmentioning

confidence: 99%

Surveillance of HIV Transmitted Drug Resistance in Latin America and the Caribbean: A Systematic Review and Meta-Analysis

Ávila‐Ríos¹,

Sued

Rhee

et al. 2016

PLoS ONE

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“…In one of the studies from Cuba 19 a prevalence of 5.3% of resistance-associated mutations to RTI was detected. In the other one, 13 including 103 HIV-1 samples obtained in 1999, the prevalence of resistance mutations was 27.6% to NRTI and 5.3% to NNRTI. These frequencies corresponded to a period in which antiretroviral treatment was not generalized in Cuba.…”

Section: Discussionmentioning

confidence: 98%

“…8,9 It has been recently reported that although subtype B continues to be predominant in this country, at least 10 genetic forms are circulating in Cuba, including subtypes A, C, F, G, and different RFs including CRF18_cpx (U pol ), CRF19_cpx (D pol ), BG (BG pol ), B/CRF19 (BD pol ), and B/CRF18 (BU pol ). [10][11][12] A previous study on plasma samples collected in 1999 in Cuba showed a low prevalence of resistance-associated mutations to reverse transcriptase and protease inhibitors (RTI and PRI) among B and non-B subtypes including 19 subtype A and 3 subtype C. 13 The introduction of highly active antiretroviral therapy (HAART) in 2001 was followed by a decrease in the AIDS mortality rate and in the incidence of opportunistic infections related to HIV/AIDS. At the end of 2003, a total of 1292 HIV-1 patients had received HAART, and consequently the emergence of HIV-1 drug resistance-associated mutations selected under treatment was probably occurring.…”

Section: Introductionmentioning

confidence: 99%

Genotypic Resistance to Antiretroviral Drugs in Patients Infected with Several HIV Type 1 Genetic Forms in Cuba

Pérez

Alvarez²,

Carmona³

et al. 2007

AIDS Research and Human Retroviruses

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The main objective of this study is to evaluate the prevalence of resistance-associated mutations to reverse transcriptase (RT) and protease (PR) inhibitors (I) 2 years after the introduction of antiretroviral treatment in Cuba, analyzing the mutations corresponding to different HIV-1 genetic forms circulating in Cuba. A total of 425 plasma samples were collected in 2003, corresponding to 175 (41.2%) subtype B and 250 (58.8%) non-B genetic forms, including 56 (22.4 %) non-B subtypes, 112 (44.8%) circulating recombinant forms (CRFs), and 82 (32.8%) unique RFs (URFs). Of these, 175 (41.2%) patients were under highly active antiretroviral therapy (HAART) and 250 (58.8%) were treatment-naive. The presence of RT and PR resistance-associated mutations was established by sequencing. Levels of resistance were evaluated according to the Stanford Database program (http://hivdb.stanford.edu). The prevalence of resistance to RTI was 52.2% among RTI-treated patients, 51.5% for subtype B, and 53.2% for non-B genetic forms, including CRF18_cpx, CRF19_cpx, subtype C, and BG URF. In treatment-naive patients it was 6.4% in subtype B and 4.2% in non-B subtypes and RFs. The prevalence of resistance to PRI was 30% among PRI-treated patients, 28% in subtype B and 31% in non-B genetic forms, and 3.2% among treatment-naive subjects, mostly BG recombinants. In conclusion, significant differences in the prevalence of resistance to RTI and PRI were not detected among the most frequent genetic forms from treated patients, suggesting that the genetic diversity of HIV-1 in Cuba does not play a main role in the development of resistance to antiretroviral drugs. The presence of transmitted resistance mutations supports the study of resistance at baseline of treatment.

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“…For example, two Brazilian studies found NRTI resistance rates greater than 10%. 6,7 High baseline NRTI resistance rates have also been reported in Caribbean islands such as Martinique 20 and Cuba 21 where NRTI mutations were found in 24% and 7.4%, respectively. Equally high resistance rates have also been found in several drug-naive cohorts across the globe including the United States, [22][23][24][25] Switzerland, 26 Poland, 27 Germany, 28 Canada, 29 and Israel.…”

Section: Discussionmentioning

confidence: 99%

Prevalence of Resistance Mutations in HIV-1-Infected Hondurans at the Beginning of the National Antiretroviral Therapy Program

Lloyd

O’Connell

Michael

et al. 2008

AIDS Research and Human Retroviruses

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The Honduran Ministry of Health (MOH) HIV antiretroviral treatment program began widespread treatment in 2003. We investigated the prevalence of antiretroviral genotypic resistance in specimens collected and archived from HIV-1-infected antiretroviral-naive patients presenting to initiate treatment between 1 July, 2002 and 30 June, 2003 in San Pedro Sula and Tegucigalpa, Honduras. Of 416 specimens collected, 336 (80.8%) were successfully genotyped. All genotypes were HIV-1, group M and 99.1% were subtype B. The prevalence of nucleoside reverse transcriptase inhibitor mutations was 7.7% with M184V and T215F/Y present in 6.0% and 3.0%, respectively. The prevalence of nonnucleoside reverse transcriptase inhibitor mutations was 7.1%. K103N mutations were present in 3.0% of study specimens. The prevalence of major protease inhibitor mutations was 2.7%. Overall, 9.2% of the specimens harbored clinically significant mutations that predict at least intermediate resistance to the Honduran first-line antiretroviral medications. These mutations were more common in San Pedro Sula (14.0%) than in Tegucigalpa (6.5%, p = 0.02). A significant number of patients presenting to initiate antiretroviral therapy in Honduran MOH clinics harbored HIV-1 isolates resistant to the MOH's first-line regimen and resistance varied by region. Further studies to assess the impact of the Honduran antiretroviral program on genotypic resistance are warranted.

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Genotypic resistance mutations to antiretroviral drugs in HIV-1 B and non-B subtypes from Cuba

Cited by 13 publications

References 21 publications

Surveillance of HIV Transmitted Drug Resistance in Latin America and the Caribbean: A Systematic Review and Meta-Analysis

Surveillance of HIV Transmitted Drug Resistance in Latin America and the Caribbean: A Systematic Review and Meta-Analysis

Genotypic Resistance to Antiretroviral Drugs in Patients Infected with Several HIV Type 1 Genetic Forms in Cuba

Prevalence of Resistance Mutations in HIV-1-Infected Hondurans at the Beginning of the National Antiretroviral Therapy Program

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