BF Recombinants Research Articles

Temporal Trends and Molecular Epidemiology of HIV Type 1 Infection in Rio de Janeiro, Brazil

HIV-1 molecular epidemiology studies carried out in Rio de Janeiro, Brazil have identified the prevalence of subtypes B, F1 and BF1 recombinants. A high percentage of HIV-1 subtype B isolates in Rio de Janeiro harbor the GWG motif at the V3 tip (B'' variant) instead of the canonical GPG motif (B variant). To trace the dynamics of the HIV-1 variants over time in different exposure categories in Rio de Janeiro, the HIV-1 proviral DNA from heterosexual men (HET) and men who have sex with men (MSM) from two distinct time periods (1990-1992 and 2008-2010) were extracted, and the env-gp120 region was amplified. Neighbor-joining phylogenetic analysis was performed to determine the viral subtype, and Bayesian analysis was used to trace the HIV-1 transmission networks. A predominance of subtype B was observed in both study periods, independent of the exposure risk category. An increase of non-B subtypes was observed in the HET group, but these subtypes were maintained among the MSM group. The distribution of HIV-1 subtype B signatures in the first and second periods studied were, respectively, HET (GPG) [44.8-51.5%], (GWG) [13.8-33.3%], and (GXG) [41.4-15.2%] and MSM (GPG) [34-50%], (GWG) [55.3-30.6%], and (GXG) [10.7-19.4%]. In the first period, an association between GWG and MSM was verified while a significant reduction of this association was observed during the second period. The phylogenetic tree and the BaTS program detected the clustering of isolates only according to the B signatures but not by exposure risk category. Our findings indicate a stable prevalence of HIV-1 subtypes B and F over time in Rio de Janeiro and further suggest that the B'' subclade of subtype B was possibly introduced into the MSM group in this area of Brazil.

Transmitted HIV Resistance Among Pregnant Young Women Infected with HIV-1 in Brazil

Transmitted HIV Resistance Among Pregnant Young Women Infected with HIV-1 in Brazil

Variability of HIV-1 Genomes among Children and Adolescents from São Paulo, Brazil

BackgroundGenetic variability is a major feature of the human immunodeficiency virus type 1 (HIV-1) and considered the key factor to frustrating efforts to halt the virus epidemic. In this study, we aimed to investigate the genetic variability of HIV-1 strains among children and adolescents born from 1992 to 2009 in the state of Sao Paulo, Brazil.MethodologyPlasma and peripheral blood mononuclear cells (PBMC) were collected from 51 HIV-1-positive children and adolescents on ART followed between September 1992 and July 2009. After extraction, the genetic materials were used in a polymerase chain reaction (PCR) to amplify the viral near full length genomes (NFLGs) from 5 overlapped fragments. NFLGs and partial amplicons were directly sequenced and data were phylogenetically inferred.ResultsOf the 51 samples studied, the NFLGs and partial fragments of HIV-1 from 42 PBMCs and 25 plasma were successfully subtyped. Results based on proviral DNA revealed that 22 (52.4%) patients were infected with subtype B, 16 (38.1%) were infected with BF1 mosaic variants and 4 (9.5%) were infected with sub-subtype F1. All the BF1 recombinants were unique and distinct from any previously identified unique or circulating recombinant forms in South America. Evidence of dual infections was detected in 3 patients coinfected with the same or distinct HIV-1 subtypes. Ten of the 31 (32.2%) and 12 of the 21 (57.1%) subjects with recovered proviral and plasma, respectively, protease sequences were infected with major mutants resistant to protease inhibitors. The V3 sequences of 14 patients with available sequences from PBMC/or plasma were predicted to be R5-tropic virus except for two patients who harbored an X4 strain.ConclusionsThe high proportion of HIV-1 BF1 recombinant, coinfection rate and vertical transmission in Brazil merits urgent attention and effective measures to reduce the transmission of HIV among spouses and sex partners.

Phylogenetic and demographic characterization of HIV-1 transmission in Madrid, Spain

BackgroundThe combination of phylogenetic analyses of HIV sequences with patients’ demographic data allows us to understand local HIV transmission, a necessary knowledge for designing prevention strategies. The Community of Madrid represents a challenge for the control of HIV epidemic in Spain given its high HIV prevalence and increasing proportion of immigrant people among HIV-infected population. MethodsWe applied maximum likelihood methods and Bayesian Markov chain Monte Carlo (MCMC) inference using the program BEAST to a set of HIV-1 pol sequences from 1293 patients diagnosed in 1995–2010 in Madrid, Spain. ResultsTwo-hundred and thirty six patients (18.2% of the cohort) were included in 100 transmission chains using phylogenetic criteria, 67 (67%) belonging to HIV-1 subtype B and 33 (33%) to 11 different non-B strains, especially BG and BF recombinants. Most networks involved transmission between MSM (48/100). Half of non-B clusters (15/33) included at least one Spaniard. Sub-Saharan African patients presented a low linkage rate (9%) in contrast to Spanish (21%) and Latin American (25%) patients. Three clusters involving treatment-independent transmission of drug-resistance mutations were found. ConclusionsOne out of five HIV-infected patients in our cohort in Madrid was epidemically linked, mainly by transmission pairs. The inclusion in transmission networks was more likely for MSM, Spaniards and patients from Latin America. We found no evidence of self-sustained non-B epidemics due to the absence of large transmission chains with the exception of Cuban BG recombinants and CRF47_BF. However, the differences in transmission across variants are probably determined by the patient profile, especially the infection route.

First report on HIV molecular epidemiology in a native community from Argentina reveals transmission clades in the context of a unique HLA background

Background The Department of Oran is located on the North of Argentina and is populated by native settlements and urbanized areas. During the last twelve years, an increasing number of HIV infections have been detected. We previously reported a highly limited HLA diversity with a reduced number of HLA-A and B alleles present at high prevalence. The objective of the present study was to characterize the HIV epidemic through full-length genome sequencing of the virus in this population. Methods Samples from 147 HIV positive individuals collected in three campaigns to Oran were analyzed. Viral load, CD4count and drug resistance were assessed and reported to the clinicians. Limiting-dilution full genome sequencing was performed from plasma on 65 of the samples. Viral diversity was analyzed by recombination (SimPlot) and Neighbor-Joining trees with bootstrap. HLA-A, B and C were characterized by SBT. Results HLA typing showed a limited genetic diversity even at the four-digits high-resolution typing. This allele distribution resembles the one reported previously for this community with two-digits and confirms that the individuals included were in fact native. SimPlot analysis of the 65 complete and nearly-complete genomes showed a high prevalence of BF recombinants(70.77%) and the presence of subtype B(23.08%), C(3.08%) and F(3.08%) virus. 7 main recombination structures were found repeatedly in not-epidemiologically-linked individuals within highly supported monophyletic clades suggesting transmission of these particular viral strains within the community. Conclusion This HIV epidemic seems to be characterized by a few

Characterization of Primary Isolates of HIV Type 1 CRF28_BF, CRF29_BF, and Unique BF Recombinants Circulating in São Paulo, Brazil

We report for the first time the genetic and biological characterization of 10 HIV-1 primary isolates representing CRF28_BF and CRF29_BF together with additional unique BF recombinant forms (URFs) obtained by PBMC cocultivation. Recombination is an important factor promoting the increase in the genetic diversity of HIV-1. Notably, more than 20% of HIV-1 sequences worldwide were recombinants. Several recombinant viruses were reported in Brazil, and six circulating recombinant forms (CRFs) have been identified (CRF28_BF, CRF29_BF, CRF31_BC, CRF39_BF, CRF40_BF, and CRF46_BF). CRF28_BF and CRF29_BF were found to infect almost 30% of the patients in São Paulo State. The near full-length genomes of these 10 primary isolates were amplified by nested PCR in three overlapping segments, purified, and sequenced. Three samples were related to CRF28_BF, three to CRF29_BF, and four were unique recombinant forms (URFs), as determined by their breakpoint profile determined with the jpHMM program. Additionally, the coreceptor usage of these isolates was investigated in vitro using GHOST assays, which revealed three dual-tropic (X4/R5) viruses, four lymphotropic (X4) viruses, and three macrophage-tropic (R5) viruses with different V3-loop motifs, which challenges the notion that GWGR-carrying viruses are macrophage-tropic only. In sum, we report a much-anticipated well-characterized panel of viruses representing CRF28_BF, CRF29_BF, and URFs from São Paulo State, Brazil.

BF Integrase Genes of HIV-1 Circulating in São Paulo, Brazil, with a Recurrent Recombination Region

Although some studies have shown diversity in HIV integrase (IN) genes, none has focused particularly on the gene evolving in epidemics in the context of recombination. The IN gene in 157 HIV-1 integrase inhibitor-naïve patients from the São Paulo State, Brazil, were sequenced tallying 128 of subtype B (23 of which were found in non-B genomes), 17 of subtype F (8 of which were found in recombinant genomes), 11 integrases were BF recombinants, and 1 from subtype C. Crucially, we found that 4 BF recombinant viruses shared a recurrent recombination breakpoint region between positions 4900 and 4924 (relative to the HXB2) that includes 2 gRNA loops, where the RT may stutter. Since these recombinants had independent phylogenetic origin, we argue that these results suggest a possible recombination hotspot not observed so far in BF CRF in particular, or in any other HIV-1 CRF in general. Additionally, 40% of the drug-naïve and 45% of the drug-treated patients had at least 1 raltegravir (RAL) or elvitegravir (EVG) resistance-associated amino acid change, but no major resistance mutations were found, in line with other studies. Importantly, V151I was the most common minor resistance mutation among B, F, and BF IN genes. Most codon sites of the IN genes had higher rates of synonymous substitutions (dS) indicative of a strong negative selection. Nevertheless, several codon sites mainly in the subtype B were found under positive selection. Consequently, we observed a higher genetic diversity in the B portions of the mosaics, possibly due to the more recent introduction of subtype F on top of an ongoing subtype B epidemics and a fast spread of subtype F alleles among the B population.

A clustering phenomenon among HCV‐1a strains among patients coinfected with HIV from Buenos Aires, Argentina

The human immunodeficiency virus (HIV) and hepatitis C virus (HCV) share the same transmission routes which lead to high coinfection rates. Among HIV-infected individuals such rates reached 21% in Argentina, being HCV-1a the most predominant subtype. In this work, 25 HCV subtype 1a (HCV-1a) strains from Argentinean patients coinfected with HIV were studied based on E2 and NS5A sequences. Phylogenetic analyses indicated that 12 strains were highly related to each other, constituting a highly supported (posterior probability = 0.95) monophyletic group that we called "M." The remaining HCV strains (group dispersed or "D") were interspersed along the phylogenetic trees. When comparing both groups of HCV-1a, 10 amino acid differences were located in functional domains of E2 and NS5A proteins that appeared to affect eventually the peptides binding to MHC-I molecules thus favoring immune escape and contributing to the divergence of HCV genotypes. Bayesian coalescent analyses for HCV-1a cluster M isolates indicated that the time to the most recent common ancestor (tMRCA) overlaps with the age estimated recently for the HIV-BF epidemic in Argentina. Furthermore, the genomic characterization based on pol gene analysis from HIV viremic patients showed that most HIV isolates from patients coinfected with HCV-1a cluster M were BF recombinants with identical recombination patterns. In conclusion, these results suggest the presence of an HCV-1a monophyletic cluster with a potential HIV co-transmission by phylogenetic analyses.

The HIV-1 epidemic in Bolivia is dominated by subtype B and CRF12_BF "family" strains

BackgroundMolecular epidemiological studies of HIV-1 in South America have revealed the occurrence of subtypes B, F1 and BF1 recombinants. Even so, little information concerning the HIV-1 molecular epidemiology in Bolivia is available. In this study we performed phylogenetic analyses from samples collected in Bolivia at two different points in time over a 10 year span. We analyzed these samples to estimate the trends in the HIV subtype and recombinant forms over time.Materials and methodsFifty one HIV-1 positive samples were collected in Bolivia over two distinct periods (1996 and 2005). These samples were genetically characterized based on partial pol protease/reverse transcriptase (pr/rt) and env regions. Alignment and neighbor-joining (NJ) phylogenetic analyses were established from partial env (n = 37) and all pol sequences using Mega 4. The remaining 14 env sequences from 1996 were previously characterized based on HMA-env (Heteroduplex mobility assay). The Simplot v.3.5.1 program was used to verify intragenic recombination, and SplitsTree 4.0 was employed to confirm the phylogenetic relationship of the BF1 recombinant samples.ResultsPhylogenetic analysis of both env and pol regions confirmed the predominance of "pure" subtype B (72.5%) samples circulating in Bolivia and revealed a high prevalence of BF1 genotypes (27.5%). Eleven out of 14 BF1 recombinants displayed a mosaic structure identical or similar to that described for the CRF12_BF variant, one sample was classified as CRF17_BF, and two others were F1pol/Benv. No "pure" HIV-1 subtype F1 or B" variant of subtype B was detected in the present study. Of note, samples characterized as CRF12_BF-related were depicted only in 2005.ConclusionHIV-1 genetic diversity in Bolivia is mostly driven by subtype B followed by BF1 recombinant strains from the CRF12_BF "family". No significant temporal changes were detected between the mid-1990s and the mid-2000s for subtype B (76.2% vs 70.0%) or BF1 recombinant (23.8% vs 30.0%) samples from Bolivia.

Prevalence and patterns of HIV transmitted drug resistance in Guatemala

To assess human immunodeficiency virus (HIV) diversity and the prevalence of transmitted drug resistance (TDR) in Guatemala. One hundred forty-five antiretroviral treatment-naïve patients referred to the Roosevelt Hospital in Guatemala City were enrolled from October 2010 to March 2011. Plasma HIV pol sequences were obtained and TDR was assessed with the Stanford algorithm and the World Health Organization (WHO) TDR surveillance mutation list. HIV subtype B was highly prevalent in Guatemala (96.6%, 140/145), and a 2.8% (4/145) prevalence of BF1 recombinants and 0.7% (1/145) prevalence of subtype C viruses were found. TDR prevalence for the study period was 8.3% (12/145) with the Stanford database algorithm (score > 15) and the WHO TDR surveillance mutation list. Most TDR cases were associated with non-nucleoside reverse transcriptase inhibitors (NNRTIs) (83.3%, 10/12); a low prevalence of nucleoside reverse transcriptase inhibitors and protease inhibitors was observed in the cohort (< 1% for both families). Low selection of antiretroviral drug resistance mutations was found, except for NNRTI-associated mutations. Major NNRTI mutations such as K101E, K103N, and E138K showed higher frequencies than expected in ART-naïve populations. Higher literacy was associated with a greater risk of TDR (odds ratio 4.14, P = 0.0264). This study represents one of the first efforts to describe HIV diversity and TDR prevalence and trends in Guatemala. TDR prevalence in Guatemala was at the intermediate level. Most TDR cases were associated with NNRTIs. Further and continuous TDR surveillance is necessary to gain more indepth knowledge about TDR spread and trends in Guatemala and to optimize treatment outcomes in the country.

Characterization of Partial and Near Full-Length Genomes of HIV-1 Strains Sampled from Recently Infected Individuals in São Paulo, Brazil

BackgroundGenetic variability is a major feature of human immunodeficiency virus type 1 (HIV-1) and is considered the key factor frustrating efforts to halt the HIV epidemic. A proper understanding of HIV-1 genomic diversity is a fundamental prerequisite for proper epidemiology, genetic diagnosis, and successful drugs and vaccines design. Here, we report on the partial and near full-length genomic (NFLG) variability of HIV-1 isolates from a well-characterized cohort of recently infected patients in São Paul, Brazil.MethodologyHIV-1 proviral DNA was extracted from the peripheral blood mononuclear cells of 113 participants. The NFLG and partial fragments were determined by overlapping nested PCR and direct sequencing. The data were phylogenetically analyzed.ResultsOf the 113 samples (90.3% male; median age 31 years; 79.6% homosexual men) studied, 77 (68.1%) NFLGs and 32 (29.3%) partial fragments were successfully subtyped. Of the successfully subtyped sequences, 88 (80.7%) were subtype B sequences, 12 (11%) BF1 recombinants, 3 (2.8%) subtype C sequences, 2 (1.8%) BC recombinants and subclade F1 each, 1 (0.9%) CRF02 AG, and 1 (0.9%) CRF31 BC. Primary drug resistance mutations were observed in 14/101 (13.9%) of samples, with 5.9% being resistant to protease inhibitors and nucleoside reverse transcriptase inhibitors (NRTI) and 4.9% resistant to non-NRTIs. Predictions of viral tropism were determined for 86 individuals. X4 or X4 dual or mixed-tropic viruses (X4/DM) were seen in 26 (30.2%) of subjects. The proportion of X4 viruses in homosexuals was detected in 19/69 (27.5%).ConclusionsOur results confirm the existence of various HIV-1 subtypes circulating in São Paulo, and indicate that subtype B account for the majority of infections. Antiretroviral (ARV) drug resistance is relatively common among recently infected patients. The proportion of X4 viruses in homosexuals was significantly higher than the proportion seen in other study populations.

Detection of HIV-1 dual infections in highly exposed treated patients

BackgroundGenetic characterization of HIV-1 in Argentina has shown that BF recombinants predominate among heterosexuals and injecting drug users, while in men who have sex with men the most prevalent form is subtype B.ObjectivesThe aim of this work was to investigate the presence of HIV dual infections in HIV-infected individuals with high probability of reinfectionStudy designBlood samples were collected from 23 HIV positive patients with the risk of reinfection from Buenos Aires. A fragment of the HIV gene pol was amplified and phylogenetic analyses were performed. Antiretroviral drug resistance patterns of all the sequences were analyzed.ResultsFive dual infections were detected with four patients coinfected with subtype B and BF recombinants and one patient was coinfected with two BF recombinants presenting different recombination patterns. Prolonged infection with a stable clinical condition was observed in the five individuals. Resistance mutation patterns were different between the predominant and the minority strains.ConclusionsOur results show that HIV dual infection can occur with closely related subtypes, and even with different variants of the same recombinant form in certain populations. Clinical observations showed neither aggressive disease progression nor impact on the resistance patterns in the dually-infected patients.

Near Full-Length Sequence Analysis of HIV Type 1 BF Recombinants from Italy

Recombination between HIV-1 subtypes B and F has generated several circulating and unique recombinant forms, particularly in Latin American areas. In Italy, subtype B is highly prevalent while subtype F is the most common pure non-B subtype. To investigate the recombination pattern in Italian BF recombinant viruses, we characterized full-length sequences derived from 15 adult patients, mostly Italian and infected by the heterosexual route. One of the BF mosaics was a CRF29, three sequences clustered with low bootstrap values with CRF39, CRF40, and CRF42. With the exception of the CRF29-like sequence, the other recombination patterns were unique, but two possible clusters were identified. Analysis of the gp120 V3 domain suggested a possible link with subtype F from Eastern Europe rather than from Latin America, favoring the hypothesis of local recombination between clade B and F viruses over that of import of BF recombinants from Latin America. HIV-1 subtypes B and F appear prone to generation of unique recombinants in Italy, warranting epidemiological surveillance and investigation of a possible clinical significance.

Analysis of the origin and evolutionary history of HIV-1 CRF28_BF and CRF29_BF reveals a decreasing prevalence in the AIDS epidemic of Brazil.

BackgroundHIV-1 subtype B and subtype F are prevalent in the AIDS epidemic of Brazil. Recombinations between these subtypes have generated at least four BF circulating recombinant forms (CRFs). CRF28_BF and CRF29_BF are among the first two BF recombinants being identified in Brazil and they contributed significantly to the epidemic. However, the evolution and demographic histories of the CRFs are unclear.Methodology/Principal FindingsA collection of gag and pol sequences sampled within Brazil was screened for CRF28_BF-like and CRF29_BF-like recombination patterns. A Bayesian coalescent framework was employed to delineate the phylogenetic, divergence time and population dynamics of the virus having CRF28_BF-like and CRF29_BF-like genotype. These recombinants were phylogenetically related to each other and formed a well-supported monophyletic clade dated to 1988–1989. The effective number of infections by these recombinants grew exponentially over a five-year period after their emergence, but then decreased toward the present following a logistic model of population growth. The demographic pattern of both recombinants closely resembles those previously reported for CRF31_BC.ConclusionsWe revealed that HIV-1 recombinants of the CRF28_BF/CRF29_BF clade are still circulating in the Brazilian population. These recombinants did not exhibit a strong founder effect and showed a decreasing prevalence in the AIDS epidemic of Brazil. Our data suggested that multiple URFs may also play a role in shaping the epidemic of recombinant BF HIV-1 in the region.

Lack of High-Level Resistance Mutations in HIV Type 1 BF Recombinant Strains Circulating in Northeast Brazil

Abstract The genetic variability and the prevalence of drug resistance-associated mutations (DRAM) of HIV-1 isolates from 50 women and 8 children from Feira de Santana, Bahia, Brazil were investigated. DNA samples were obtained and pol sequences were generated by PCR and direct sequencing. Phylogenetic analysis showed that 39 (67.2%) samples were subtype B, four (6.9%) F, one (1.7%) C, and 14 (24.1%) BF recombinants. Four different BF recombination patterns were detected. Twelve (20.7%) samples shared the same breakpoint within the reverse transcriptase (RT) sequence. Fifty-five (94.8%) isolates showed several resistance-associated mutations in the RT and the protease (PR) genes. Ten (17.2%) isolates presented mutations associated with a high level of resistance: nine (15.5%) to nucleoside RT inhibitors (NRTI), four (6.9%) to nonnucleoside RT inhibitors (NNRTI), and three (5.2%) to PR inhibitors (PIs). Subtype B-infected patients had, on average, 0.5 high-level DRAM per sequence while no mutations were observed in BF recombinants, although the two groups were under ARV for a similar period of time. Our data indicate the predominance of the subtype B, followed by BF recombinants in this population, and the dissemination of a recombinant strain in Bahia, which could be related to adaptive advantages of these variants over the predominant subtype B.

Analysis of HIV type 1 BF recombinant sequences from South America dates the origin of CRF12_BF to a recombination event in the 1970s.

HIV-1 epidemics in South America are believed to have originated in part from the subtype B epidemic initiated in the Caribbean/North America region. However, circulation of BF recombinants in similar proportions was extensively reported. Information currently shows that many BF recombinants share a recombination structure similar to that found in the CRF12_BF. In the present study, analyzing a set of 405 HIV sequences, we identified the most likely origin of the BF epidemic in an early event of recombination. We found that the subtype B epidemics in South America analyzed in the present study were initiated by a founder event that occurred in the early 1970s, a few years after the introduction of these strains in the Americas. Regarding the F/BF recombinant epidemics, by analyzing a subtype F genomic segment within the viral gene gag present in the majority of the BF recombinants, we found evidence of a geographic divergence very soon after the introduction of subtype F strains in South America. Moreover, through analysis of a subtype B segment present in all the CRF12_BF-like recombination structure, we estimated the circulation of the subtype B strain that gave rise to that recombinant structure around the same time period estimated for the introduction of subtype F strains. The HIV epidemics in South America were initiated in part through a founder event driven by subtype B strains coming from the previously established epidemic in the north of the continent. A second introduction driven by subtype F strains is likely to have encountered the incipient subtype B epidemic that soon after their arrival recombined with them, originating the BF epidemic in the region. These results may explain why in South America the majority of F sequences are found as BF recombinants.

Longitudinal analysis of HIV-1 BF1 recombinant strains in vertically infected children from Argentina reveals a decrease in CRF12_BF pol gene mosaic patterns and high diversity of BF unique recombinant forms

The HIV-1 epidemic associated to BF1 recombinants in South America is both complex and intriguing, with an underestimated diversity of recombinant structures. Our aim was to explore the characteristics and temporal dynamics of the HIV-1 BF1 epidemic in Argentina, through the study of 172 HIV-1 pol BF1 recombinant sequences obtained from HIV-1 vertically infected patients born from 1986 to 2008. Recombination patterns were characterized by bootscanning, subtype signature analysis, and phylogenetic approaches. Proportion of sequences sharing common ancestry and recombination breakpoints with the Circulating Recombinant Form (CRF) CRF12_BF was compared against sequences with a non-CRF12_BF pattern in three study periods, and by fitting the data to a logistic model. Twenty-eight HIV-1 pol BF1 mosaic structures were identified, including four of the seven South-American CRF_BF-like patterns. However, common ancestry of these sequences with reference CRF strains only confirmed the presence of CRF12_BF (51.1%) and CRF17_BF (1.2%) among the Argentine BF pol sequences. Most non-CRF_BF-like recombinant patterns shared at least one common recombination breakpoint with CRF12_BF. The number of transmissions caused by CRF12_BF viruses decreased in a linear way over time, from 69% in the period 1986–1993 to 46% in 2001–2008. In conclusion, the diversity of HIV-1 pol BF1 recombinant structures in Argentina is much more complex than previously described, with at least two CRFs_BF and 26 BF1 unique recombinant forms. For the first time, we provide evidence of a decrease in the proportion of CRF12_BF viruses transmitted from mother-to-child since the start of the epidemic to the present time in Argentina.

The Association Between Primary Antiretroviral Resistance and HAART Virologic Failure in a Developing Set

Santos is a Brazilian port city with high HIV incidence, high primary antiretroviral resistance levels, high HIV-1 BF recombinants prevalence, and high rates of antiretroviral virologic failure. We evaluated factors related to virologic failure after 48 weeks of HAART in this population. We compared demographic and HIV profiles among 43 individuals with virologic failure (group 1) and 37 with virologic success (group 2) after 48 weeks of HAART initiation. The overall primary antiretroviral resistance prevalence was 31.2%; 46.5% in group 1 and 13.5% in group 2 (p < 0.005). Nine patients from group 1 and seven from group 2 were infected by F or BF strains. Fifteen individuals presented with NRTI mutations, 13 with NNRTI mutations, three with PI mutations, and five with NRTI and NNRTI mutations. No significant differences were observed in baseline viral load, CD4, clade assignment, antiretrovirals used, or demographics among groups or patients harboring resistant versus wild-type viruses. In this region, there was a high prevalence of antiretroviral resistance among long standing infected patients whose disease had progressed. This finding supports the concept that resistance testing prior to ART initiation is cost effective. The association between primary antiretroviral resistance and virologic failure may suggest that primary resistance greatly impairs antiretroviral activity.

Incidence of HIV Type 1 Infection, Antiretroviral Drug Resistance, and Molecular Characterization in Newly Diagnosed Individuals in Argentina: A Global Fund Project

An HIV incidence estimation was performed among men who have sex with men (MSM), drug users (DUs), sex workers (SWs), and pregnant women (PW) from Argentina. Volunteers older than 18 years old without a previous HIV-positive diagnosis were included. HIV-positive samples were analyzed by the Serological Testing Algorithm for Recent HIV Seroconversion (STARHS) to estimate incidence. By partial RT-PCR and sequencing of the HIV pol gene, an HIV subtype and resistance profile were determined. A total of 12,192 volunteers were recruited from October 2006 to September 2008. A higher HIV prevalence was detected among trans SWs (33.9%, 38/112), male SWs (10.8%, 12/111), and MSM 10.4% (161/1549). HIV incidence estimates by STARHS was also higher on trans SWs (11.31 per 100 person-years), male SWs (6.06 per 100 person-years), and MSM (6.36 per 100 person-years). Antiretroviral primary resistant mutations were detected in 8.4% of the study group, with a higher frequency in female DUs (33.3%). Phylogenetic analysis showed that 124 (57.9%) samples were subtype B, 84 (39.3%) intersubtype BF recombinants, 5 (2.3%) subtype C, and 1 (0.5%) subtype F in the pol region. Subtype B was most commonly found in MSM and male SWs whereas the intersubtype BF recombinant was more prevalent in female DUs, female SWs, and PW. Given the high HIV prevalence and incidence found in most of these groups, monitoring the continuing spread of the HIV epidemic is essential for determining public health priorities, assessing the impact of interventions, and estimating current and future health care needs.

Lower Prevalence of Human Immunodeficiency Virus Type 1 Brazilian Subtype B Found in Northeastern Brazil with Slower Progression to AIDS

Besides being extremely useful in measuring the level of HIV-1 diversity and prevalence in populations, the molecular analysis of genomic sequences provides crucial surveillance support and aids in the development of new therapies and effective vaccines. The present study focused on gag and env DNA and amino acid sequences that were generated from samples taken from 61 infected patients in the City of Salvador, Bahia, located in northeastern Brazil. In order to determine selective pressure and predict coreceptor usage, Bioinformatics tools were employed in phylogeny reconstruction. Fifty-six (91.8%) viruses were classified as belonging to subtype B, three (4.9%) from F1, and two (3.3%) from BF1 recombinants. Based on the characterization of the V3 region, the subtype B strains were represented by eight (18.2%) Brazilian variants (B'-GWGR), 20 (46.5%) European/EUA B variants (GPGR), and 15 (34.9%) GXGX variants. The mean time elapsed since diagnosis was 13 years among subtype B' and 9 years in subtype B. The mean dN/dS ratios from the GWGR, GPGR, and GXGX groups, when compared to an HXB2 reference, were 0.72, 0.77, and 0.67, respectively. Seventy-six percent of the viruses studied were predicted to use the CCR5 coreceptor for cell entry (R5 viruses), while 24% were predicted to use the CXCR4 or were classified as dual tropic viruses. The prevalence of subtypes B' and recombinant B/F1 was shown to be lower than findings from previous studies performed both in Brazil (B') and in Bahia (B/F1). The association between subtype B' and a lengthy period of time since diagnosis can be correlated with a slower disease progression in infected patients, when compared with those infected with subtype B.