Resistance to Nonnucleoside Reverse-Transcriptase Inhibitors and Prevalence of HIV Type 1 Non-B Subtypes Are Increasing among Persons with Recent Infection in Spain

Mendoza, Carmen de; Rodrı́guez, Carmen; Colomina, Javier; Tuset, C.; García, Féderico; Eirós, José María; Corral, Angélica; Leiva, Pilar; Agüero, Jesús; Torre‐Cisneros, Julián; Pedreira, José; Viciana, Isabel; Romero, Jorge del; Sáez, Ana; Lejarazu, Raúl Ortíz de; Soriano, Vincent

doi:10.1086/496982

Cited by 49 publications

(24 citation statements)

References 14 publications

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“…11 They also were identified in 7.6% of recent HIV-1 seroconverters across our country. 13 In a prior report, we found that nearly two-thirds of HIV-1-infected immigrants in Las Palmas, the second largest island of the archipelago, were infected with non-B subtypes. 12 The objective of the current study was to assess the presence and nature of non-B subtypes in the native Spanish population newly diagnosed with HIV-1 infection in the island in the past 7 years.…”

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confidence: 84%

“…In fact, more than 25 million are in sub-Saharan Africa 3 from where they are spreading to other regions, including industrialized countries of the northern hemisphere. 1,[5][6][7][8][9][10][11][12][13][14][15] The strong relationships with former African colonies and illegal entrance have both contributed to a sharp rise in the number of African immigrants arriving into the European Union during the past two decades. Due to its geographical position, one gate of entrance of Africans into Europe is Spain.…”

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confidence: 99%

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Introduction of Non-B Subtypes among Spaniards Newly Diagnosed with HIV Type 1 in the Canary Islands

Holguín¹,

Peña²,

Troncoso³

et al. 2007

AIDS Research and Human Retroviruses

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The Spanish Canary Islands face the northwest coast of Africa, being one gate of entrance of African immigrants into Europe and of HIV-1 non-B strains, prevalent in most African regions. The presence and nature of HIV-1 non-B subtypes were examined in Spanish natives newly diagnosed with HIV-1 infection from 1998 to 2004 in a reference hospital located in one of the largest islands of the archipelago. Subtyping of HIV-1 pol genes was performed in 139 out of 429 individuals found to be HIV-1 positive during that period. Non-B strains infected 40 (28.8%) subjects, 12 (13.7%) out of 87 native Spaniards and 28 (53.8%) out of 52 immigrants (75% Africans) (p < 0.01). HIV-1 non-B subtypes, mostly recombinant forms, were present in Spaniards at least since 1998. HIV-1 non-B subtypes are frequently recognized in HIV+ Africans arriving in the Canary islands and continuously introduced into the newly diagnosed HIV-1+ native population living in the archipelago.

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confidence: 84%

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confidence: 99%

Introduction of Non-B Subtypes among Spaniards Newly Diagnosed with HIV Type 1 in the Canary Islands

Holguín¹,

Peña²,

Troncoso³

et al. 2007

AIDS Research and Human Retroviruses

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“…In Spain, the large immigration wave seen during the past decade has been followed by an increased proportion of circulating non-B subtypes in the HIV population. 5,6 Periodic surveillance of drug resistance mutational patterns among drug-naive as well among treatment-experienced patients is important since selection of the most adequate first-line regimens as well as rescue interventions, respectively, may largely be influenced by this information.…”

Section: Introductionmentioning

confidence: 99%

Changes in Drug Resistance Patterns following the Introduction of HIV Type 1 Non-B Subtypes in Spain

Mendoza¹,

Garrido²,

Poveda³

et al. 2009

AIDS Research and Human Retroviruses

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Natural genetic variability at the pol gene may account for differences in drug susceptibility and selection of resistance patterns across HIV-1 clades. Spread of non-B subtypes along with changes in antiretroviral drug use may have modified drug resistance patterns in recent years. All HIV-1 clinical samples sent to a reference laboratory located in Madrid for drug resistance testing since January 2000 were analyzed. The pol gene was sequenced and HIV-1 subtypes were assigned using the Stanford algorithm and phylogenetic analyses for non-B subtypes. Drug resistance mutations were recorded using the IAS-USA mutation list (April 2008). A total of 3034 specimens from 730 antiretroviral-naive individuals (92 with non-B subtypes) and 1569 antiretroviral-experienced patients (97 with non-B subtypes) were examined. The prevalence of HIV-1 non-B subtypes in the study period increased from 4.4% (2000-2003) to 10.1% (2004-2007) (p < 0.01). The most predominant variants were CRF02_AG (41.8%) and G (17.5%). Thymidine analogue mutations (TAMs) were more prevalent in B than non-B subtypes, in both drug-naive (6.2% vs. 1%; p < 0.01) and treatment-experienced patients (49% vs. 30%, p < 0.01). K103N was most frequent in B than non-B subtypes (34% vs. 21%; p < 0.01); conversely, 106A/M was more prevalent in non-B than B clades (11% vs. 5%). Codon 179 mutations associated with etravirine resistance were more frequent in non-B than B subtypes. Finally, secondary protease resistance mutations were more common in non-B than B clades, with a potentially significant impact at least on tipranavir. The prevalence of HIV-1 non-B subtypes has increased since the year 2000 in a large drug resistance database in Spain, determining changes in drug resistance patterns that may influence the susceptibility to new antiretroviral drugs and have an impact on genotypic drug resistance interpretation algorithms.

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“…Had this regimen been implemented on a wide scale without evaluation, significant resistance could have developed in the population. This, in turn, would lead to transmission of resistance mutations into populations never treated with antiretroviral agents as has been demonstrated in the US and Europe [2,3]. With limited drug formularies, transmission of drug resistance to nonnucleoside reverse transcriptase inhibitors or cytosine nucleoside analogs could lead to a lack of available treatment options for newly diagnosed HIV infected individuals in many regions.…”

Section: Commentarymentioning

confidence: 99%

Commentary on “Prevalence and evolution of drug resistance HIV-1 variants in Henan, China”

et al. 2005

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COMMENTARYCritical to the implementation and scale-up of successful antiretroviral therapy worldwide is an understanding of the efficacy, toxicities and durability of antiretroviral regimens in the specific populations, which they are utilized. In order to obtain this information monitoring and evaluation or operational research must be done in each country or population. The article by Li et al in this issue represents an outstanding example of the importance of data obtained in the populations treated [1]. The authors proactively evaluated the outcomes at 3 and 6 months of 118 and 124 HIV infected individuals, respectively, treated with zidovudine, didanosine and nevirapine in one region in China. This regimen was chosen from the available agents in this region. Surprisingly, there was minimal virologic response to this regimen at 3 and 6 months and there was a staggering 62.7% rate of drug resistance mutations in the group treated for 6 months. Had this regimen been implemented on a wide scale without evaluation, significant resistance could have developed in the population. This, in turn, would lead to transmission of resistance mutations into populations never treated with antiretroviral agents as has been demonstrated in the US and Europe [2,3]. With limited drug formularies, transmission of drug resistance to nonnucleoside reverse transcriptase inhibitors or cytosine nucleoside analogs could lead to a lack of available treatment options for newly diagnosed HIV infected individuals in many regions. Not aggressively evaluating agents and regimens in relevant populations prior to wide scale implementation could lead not only to treatment failure at the level of the individual patient, but also failure at the program level, negating the ability of treatment to reverse the impact of the growing AIDS epidemic on economic and geopolitical landscape of the world. Although this was a smaller study, the data, when examined in the context of and synthesized with data from the Chinese national surveillance programs and other regional studies, will provide useful evidence to help China develop the optimal national antiretroviral regimen.China and these investigators are to be congratulated for having the openness to rapidly evaluate the consequences of their treatment choices in order to modify their treatment regimens based on evidence based data. This study emphasizes the importance of operational research and the need to test drug combinations prior to wide scale implementation. It is reminiscent of the surprising high virologic failure rates seen with the combination of tenofovir, abacavir, and lamivudine, previously predicted to be a potent, safe regimen [4,5]. In addition, it reminds us all that drugs demonstrated to be efficacious in one population or country may not be as efficacious or tolerable in another. It is likely that the lack of adherence and success in this study was due largely to toxicities of the antiretroviral agents, which previously were used in other populations with more success. Other invest...

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Resistance to Nonnucleoside Reverse-Transcriptase Inhibitors and Prevalence of HIV Type 1 Non-B Subtypes Are Increasing among Persons with Recent Infection in Spain

Cited by 49 publications

References 14 publications

Introduction of Non-B Subtypes among Spaniards Newly Diagnosed with HIV Type 1 in the Canary Islands

Introduction of Non-B Subtypes among Spaniards Newly Diagnosed with HIV Type 1 in the Canary Islands

Changes in Drug Resistance Patterns following the Introduction of HIV Type 1 Non-B Subtypes in Spain

Commentary on “Prevalence and evolution of drug resistance HIV-1 variants in Henan, China”

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