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Transmission of HIV Strains with Resistance to PI and to Multiple Drug Classes Is Growing in Spain
Carmen de Mendoza*1, C Rodriguez2, F Gutierrez3, E Caballero4, J Colomina5, A Aguilera6, J Aguero7, C Tuset8, J Torre-Cisneros9, V Soriano1, and on behalf of the Spanish HIV Seroconverter Study Group.
1Hosp Carlos III, Madrid, Spain; 2Ctr Sanitario Sandoval, Madrid, Spain; 3Hosp Gen, Elche, Spain; 4Hosp Vall d'Hebron, Barcelona, Spain; 5Hosp de la Ribera, Valencia, Spain; 6Hosp Xeral, Santiago, Spain; 7Hosp Marques de Valdecilla, Santander, Spain; 8Hosp Gen, Valencia, Spain; and 9Hosp Reina Sofia, Cordoba, Spain
Background: The study of HIV recent seroconverters
provides critical information about the main characteristics of the epidemic in
a given region. Knowledge about the predominant HIV subtypes, proportion of
drug-resistant strains, and HIV co-receptor usage of viruses currently
transmitted is crucial for the optimal design of first line therapies.
Methods: All consecutive recent HIV seroconverters
(<12 months from exposure) seen since January 1997 to September 2006 at 15
different hospitals distributed across Spain were examined. Major drug
resistance mutations (International AIDS Society-USA list updated in September
2006), HIV subtype and estimation of co-receptor usage using V3 loop amino acid
sequences were performed.
Results: A total of 358 recent HIV-1 seroconverters were identified. Median time from initial
HIV exposure was 7 months; 69.5% were men who have sex with men (MSM). At the
time of first diagnosis, median plasma HIV RNA was 4.7 log and median CD4 count
569 cell/μL. Overall,
12.6% of patients carried viruses with drug resistance mutations. They were
9.9% for nucleoside reverse transcriptase inhibitors (NRTI), 4.5% for non-NRTI
(NNRTI), and 3.4% for protease inhibitors (PI). While a significant decline in
the transmission of drug-resistant viruses was seen comparing the periods
1997-1999 and 2000-2001 (29% vs 5.3%, p <0.001), a rebound was seen in the
period 2002-2004 (10.7%) and particularly in 2005-2006 (13.2%). Moreover, an
increased transmission of viruses with resistance to NNRTI and PI occurred
(5.4% and 6.2%, respectively). Furthermore, within the last 3 years, 5 patients
have acquired viruses containing resistance mutations to all the 3 drug
families—41L (5), 74V (1), 118I (3), 210W (3), 215N/S/D (5), 103N (5), 46L (1),
82A/T (2), and 90M (3). A total of 24 individuals (6.4%) carried non-B subtypes
(8 CRF14_BG, 4 CRF03_AG, 3 CRF12_BF, 3 C, 3 G, 2 F, and 1 A). Interestingly, they only began to be
recognized since 2001. X4 viruses, either as pure or dual/mixed population,
were recognized in 15.3%. Distinct HIV tropism (X4 vs
R5) was not associated with plasma HIV RNA (4.5 vs
4.4 log copies/mL), nor CD4 counts (594 vs 540 cells/mL), nor with drug-resistance
mutations.
Conclusions: A significant proportion
(13.2%) of recent HIV-1 seroconverters in 2005-2006
harbor drug-resistance mutations, which represents an increase with
respect to prior years. Moreover, PI-resistant and multidrug-resistant
viruses have become more frequent in recent years. The presence of X4 viruses
does not seem to be associated with transmission of drug-resistance mutations.
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