Evaluation of minority populations of HIV type-1 with K103N and M184V drug resistance mutations among children in Argentina.

BACKGROUND: The aim of this study was to describe the frequency of minority populations of viruses carrying mutations K103N and M184V in drug-naive HIV type-1 (HIV-1)-infected children, and to further evaluate their effect on the selection of drug-resistant viruses within highly active antiretroviral therapy (HAART). METHODS: Newly diagnosed vertically HIV-1-infected children were evaluated. The HIV-1 pol gene was sequenced for subtyping and antiretroviral drug resistance analysis. Standard genotypic sequencing and sequence-selective real-time PCR (SPCR) to quantify minority viral populations were used. RESULTS: From December 2004 to July 2006, we included 35 children who were studied at baseline and during their first HAART regimen (follow-up median time 29.4 months). Of them, 82.9% were infected with intersubtype B/F recombinant variants. At baseline, all children had a drug-susceptible viral population that was studied by bulk sequencing. SPCR showed that 4 children had between 2-10% of M184V, 11 had <0.7%, 18 had no detectable mutation and 2 could not be amplified. No K103N minority populations were found. Once under HAART, children who had 2-10% of M184V at baseline further selected it in percentages >20% in less time than those with -0.1-0.6% or without minority populations (P=0.01). CONCLUSIONS: It was shown that having 2-10% of M184V at baseline enhanced its selection in high percentages in a short time after HAART initiation. Further research regarding the presence of minority quasispecies before initiation of HAART in large paediatric populations should be undertaken to evaluate their clinical effect during HAART.

Análisis de mutaciones primarias asociadas a resistencia a los antirretrovirales en niños con diagnóstico reciente de HIV-1 / Analysis of antiretroviral resistance-associated primary mutations in recently HIV-1 diagnosed children

El objetivo de este estudio fue analizar prospectivamente los niveles de resistencia a las drogas antirretrovirales y el progreso de la carga viral plasmática (CV) en niños infectados verticalmente por HIV-1 antes y durante el tratamiento antirretroviral (TARV).(AU)

The aim of this study was to prospectively analyze antiretroviral drug resistance and plasma viral load in HIV-1 vertically-infected children beforme and during antiretroviral therapy (ART).(AU)

Análisis de mutaciones primarias asociadas a resistencia a los antirretrovirales en niños con diagnóstico reciente de HIV-1 / Analysis of antiretroviral resistance-associated primary mutations in recently HIV-1 diagnosed children

El objetivo de este estudio fue analizar prospectivamente los niveles de resistencia a las drogas antirretrovirales y el progreso de la carga viral plasmática (CV) en niños infectados verticalmente por HIV-1 antes y durante el tratamiento antirretroviral (TARV).

The aim of this study was to prospectively analyze antiretroviral drug resistance and plasma viral load in HIV-1 vertically-infected children beforme and during antiretroviral therapy (ART).

Low rate of emergence of nevirapine and lamivudine resistance after post-partum interruption of a triple-drug regimen.

INTRODUCTION: Emergence of nevirapine (NVP) resistance may be a consequence of its use in monotherapy to prevent HIV mother-to-child transmission (MTCT). The aim of this study was to evaluate the emergence of strains resistant to NVP and lamivudine (3TC) after discontinuation of antiretroviral therapy (ART) with 3TC/zidovudine (ZDV)/NVP. METHODS: Twenty pregnant women (ART-naive or preexposed only to ZDV), to whom 3TC/ZDV/NVP was prescribed as MTCT prophylaxis, were studied. They received ART for a median of 4 months with median viral load (VL) at labour <50 copies/ml. Samples were collected between 1 and 15 months (median: 3 months) after ART interruption. Sequence-selective real-time PCR (SPCR), which quantifies minority viral populations containing K103N, Y181C and M184V mutations, and standard genotypic sequencing were assayed. RESULTS: No mutations associated with resistance to 3TC or NVP were found by standard population sequencing. Analysis of K103N by SPCR showed that 35% of the patients contained < or =0.1% of viruses carrying either the AAC or AAT mutations. For Y181C mutation, 10% of the patients contained <0.5% of viruses with TGT codon change. For M184V mutation, one patient contained 6.2% of virus with GTG mutation and 13 patients (65%) contained <0.9% of mutated viruses. Four women were re-exposed to 3TC/ZDV/NVP and achieved HIV VL <50 copies/ml. No perinatal transmission occurred in any of the 22 births. CONCLUSIONS: NVP associated with ZDV/3TC as a regimen to prevent MTCT may involve a low risk for the selection of antiretroviral-resistant strains and may not jeopardize the use of these same drugs for future treatment.

High frequency of primary mutations associated with antiretroviral drug resistance in recently diagnosed HIV-infected children.

INTRODUCTION: The aim of our study was to analyse the frequency of primary mutations associated with HIV drug resistance in a population of children born to HIV-infected mothers. DESIGN: A prospective study included newly HIV-diagnosed children treated at two public paediatric hospitals. PATIENTS AND METHODS: Clinical and antiretroviral therapy (ART) data were collected in mother-child pairs. HIV-1 subtyping and ART resistance mutations were assayed in children by sequencing a region of HIV pol gene. RESULTS: A total of 67 children were enrolled: 22 less than 12 months of age, 20 between 1 and 5 years and 25 between 6 and 14 years. Six (9.0%) children had viral strains with at least one primary mutation associated with resistance to reverse transcriptase and protease inhibitors. A significantly (P = 0.019) higher frequency of resistance (22.7%, n = 5/22) was found among children aged < 12 months. Fourteen children (20.9%) had a subtype B HIV-1 strain and 53 (79.1%) had an inter-subtype B/F recombinant variant. DISCUSSION: A high percentage of recently diagnosed infants were found to carry primary ART resistance mutations. Limited options for ART of HIV-infected children might lead to increased HIV-associated morbidity and mortality. Thus, consideration should be given to mandatory screening for primary ART resistance before initiating therapy for infants aged < 12 months in countries where HIV mother-to-child transmission is still present, such as in Argentina. This will allow for the rationalized and individualized use of drugs and will contribute to the increased cost-effectiveness of local health systems.

HIV seroincidence estimates among at-risk populations in Buenos Aires and Montevideo: use of the serologic testing algorithm for recent HIV seroconversion.

Using the serological testing algorithm for recent HIV seroconversion, we estimated annualized incidences (per 100 person-years) of HIV-1 infection in different at-risk groups in Buenos Aires and Montevideo, during a 5-year period between 1998 and 2003. HIV-positive serum samples from 9 serosurveys conducted among men who have sex with men, patients attending clinics for a sexually transmitted infections consult (STIs), female commercial sex workers, injecting drug users (IDUs), noninjecting cocaine users (NICUs), asymptomatic women screened for HIV infection, and patients with tuberculosis were used. HIV incidences were as follows: 6.7 for men who have sex with men, 2.0 for STIs, 1.3 for female commercial sex workers, 0.0 for Argentinean IDUs, 10.3 for Uruguayan IDUs, 3.1 for Argentinean NICUs, 4.4 for Uruguayan NICUs, and 2.4 for patients with tuberculosis. Among asymptomatic women screened for HIV infection, incidence rose from 0.4 in 1998 to 4.6 in 1999 and to a high of 10.2 in the year 2000. Unexpectedly, high HIV incidences were detected among at-risk groups in Buenos Aires and Montevideo. This pattern shows an emerging HIV epidemic among heterosexuals stemming from core HIV-infected at-risk groups. There is an urgent need for development and implementation of specific prevention strategies to address this burgeoning epidemic.

Epidemiology of human immunodeficiency virus, viral hepatitis (B and C), treponema pallidum, and human T-cell lymphotropic I/II virus among men who have sex with men in Buenos Aires, Argentina.

BACKGROUND: Human immunodeficiency virus (HIV) and sexually transmitted infections (STI) are prevalent among men who have sex with men (MSM). GOAL: To estimate the prevalence of HIV and STIs in this group. STUDY: A total of 694 MSM were tested for HIV, hepatitis B (HBV), hepatitis C (HCV), human T-cell lymphotropic (HTLV-I/II) viruses and Treponema pallidum infection. RESULTS: HIV, HBV, and T pallidum were detected in 13.8%, 37.7%, and 16.9% of subjects, respectively. Prevalences of 1.9% and 0.3% were detected for HCV and HTLV-I/II. A prior history of STI was the most predictor for HIV, HBV, and T pallidum. Use of illegal drugs, blood transfusion history, and multiple sexual partners were associated with HCV. The 2 most common co-infections were HBV/T pallidum and HIV/HBV. CONCLUSIONS: Infection with HIV, HBV, and T pallidum was elevated among MSM. Routine testing, education, vaccine-based prevention, and control programs need to be implemented in this high-risk population.

HIV type 1 BF recombinant strains exhibit different pol gene mosaic patterns: descriptive analysis from 284 patients under treatment failure.

Different complex structures of the pol gene have been identified in 284 HIV-1 B/F recombinant sequences obtained from a group of 587 patients under treatment failure from Argentina. To analyze the mosaic structures of these viral sequences and to determine their phylogenetic relationship, the 284 partial pol gene sequences of BF recombinant viruses were amplified by RT-PCR and sequenced. Intersubtype breakpoints were analyzed by bootscanning. Phylogenetic relationships were determined by means of neighbor-joining trees. The analysis of the sequences showed multiple phylogenetic topologies clustering within intersubtype BF reference sequences. At least three different mosaic patterns were found compared to previously described BF-type viruses with unequal distribution in the studied population. The analysis also showed that HIV-1 BF recombinant viruses with diverse mosaic structures are phylogenetically related in their F segments and in selected B fragments with the F1 subtype and with BF recombinant viruses from Brazil, respectively, suggesting a common recombinant ancestor. No association was observed between the prevalence of each mosaic pattern and the frequency of major drug-resistance mutations in PR and RT.

Intersubtype BF recombinants of HIV-1 in a population of injecting drug users in Argentina.

The presence of recombinant intersubtypes of HIV-1 in Argentina has been reported since the mid-1990s. In this study, sequences of a region of the gag, pol, and vpu genes of HIV-1 were analyzed in samples of 21 injection drug users (IDUs) residing in the suburbs of the city of Buenos Aires. Genomic characterization and identification of recombination sites were made comparing the 3 regions with reference isolation sequences of subtypes B, F, C, A, and B/F recombinants: CRF12_BF and non-CRF12_BF sequences. Subtype assignment of the analyzed segments was phylogenetically confirmed. All the samples turned out to be BF recombinants in at least 1 of the 3 studied genes. Twelve samples (57%) had the same pattern as the Argentinean CRF12_BF, whereas in the rest, the pattern differed in at least 1 of the 3 genes. The relation of these fragments to the CRF12_BF was phylogenetically verified. These results indicate the predominance of BF recombinants and the presence of a high percentage of sequences closely related to the CRF12_BF in the IDU population in Argentina and suggest a possible association between viral variants and the transmission route.