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1.

Objective

To identify unique characteristics of recent versus established HIV infections and describe sexual transmission networks, we characterized circulating HIV-1 strains from two randomly selected populations of ART-naïve participants in rural western Kenya.

Methods

Recent HIV infections were identified by the HIV-1 subtype B, E and D, immunoglobulin G capture immunoassay (IgG BED-CEIA) and BioRad avidity assays. Genotypic and phylogenetic analyses were performed on the pol gene to identify transmitted drug resistance (TDR) mutations, characterize HIV subtypes and potential transmission clusters. Factors associated with recent infection and clustering were assessed by logistic regression.

Results

Of the 320 specimens, 40 (12.5%) were concordantly identified by the two assays as recent infections. Factors independently associated with being recently infected were age ≤19 years (P = 0.001) and history of sexually transmitted infections (STIs) in the past six months (P = 0.004). HIV subtype distribution differed in recently versus chronically infected participants, with subtype A observed among 53% recent vs. 68% chronic infections (p = 0.04) and subtype D among 26% recent vs. 12% chronic infections (p = 0.012). Overall, the prevalence of primary drug resistance was 1.16%. Of the 258 sequences, 11.2% were in monophyletic clusters of between 2–4 individuals. In multivariate analysis factors associated with clustering included having recent HIV infection P = 0.043 and being from Gem region P = 0.002.

Conclusions

Recent HIV-1 infection was more frequent among 13–19 year olds compared with older age groups, underscoring the ongoing risk and susceptibility of younger persons for acquiring HIV infection. Our findings also provide evidence of sexual networks. The association of recent infections with clustering suggests that early infections may be contributing significant proportions of onward transmission highlighting the need for early diagnosis and treatment as prevention for ongoing prevention. Larger studies are needed to better understand the structure of these networks and subsequently implement and evaluate targeted interventions.  相似文献   

2.

Background

Acquisition of more than one strain of human immunodeficiency virus type 1 (HIV-1) has been reported to occur both during and after primary infection, but the risks and repercussions of dual and superinfection are incompletely understood. In this study, we evaluated a longitudinal cohort of chronically HIV-infected men who were sexual partners to determine if individuals acquired their partners'' viral strains.

Methodology

Our cohort of HIV-positive men consisted of 8 couples that identified themselves as long-term sexual partners. Viral sequences were isolated from each subject and analyzed using phylogenetic methods. In addition, strain-specific PCR allowed us to search for partners'' viruses present at low levels. Finally, we used computational algorithms to evaluate for recombination between partners'' viral strains.

Principal Findings/Conclusions

All couples had at least one factor associated with increased risk for acquisition of new HIV strains during the study, including detectable plasma viral load, sexually transmitted infections, and unprotected sex. One subject was dually HIV-1 infected, but neither strain corresponded to that of his partner. Three couples'' sequences formed monophyletic clusters at the entry visit, with phylogenetic analysis suggesting that one member of the couple had acquired an HIV strain from his identified partner or that both had acquired it from the same source outside their partnership. The 5 remaining couples initially displayed no evidence of dual infection, using phylogenetic analysis and strain-specific PCR. However, in 1 of these couples, further analysis revealed recombinant viral strains with segments of viral genomes in one subject that may have derived from the enrolled partner. Thus, chronically HIV-1 infected individuals may become superinfected with additional HIV strains from their seroconcordant sexual partners. In some cases, HIV-1 superinfection may become apparent when recombinant viral strains are detected.  相似文献   

3.

Background

In Trinidad and the wider Caribbean, subtype B Human Immunodeficiency Virus-type 1 (HIV-1B) overwhelmingly accounts for HIV infection among heterosexuals; this contrasts with the association of HIV-1B with homosexual transmission and injecting drug use globally. The HIV envelope contains genetic determinants of cell tropism and evasion from immune attack. In this study we investigate the genetic properties of the env V1-C4 of HIV-1B soon after transmission to Trinidadian heterosexuals. This will reveal distinctive genetic features of the strains that cause the HIV-1B epidemic in Trinidad and generate insights to better understand their properties.

Methodology/Principal Findings

Quasispecies sampling was performed on the env V1-C4 of HIV-1B strains soon after transmission to heterosexual Trinidadians in a cohort of seroconverters. Phylogenetic relationships were determined for these quasispecies and the length and number of asparagine (N) linked glycosylation sites (NLGS) in their variable loops compared to that for HIV-1B globally. Signature amino acids within the constant domains of the env V1-C4 were identified for heterosexually transmitted HIV-1B from Trinidad relative to HIV-1B globally. HIV-1B obtained from Trinidadian heterosexuals soon after seroconversion had significantly longer V2 loops with one more glycosylation site, shorter V3 loops and no significant difference in V1 or V4 when compared to HIV-1B obtained soon after seroconversion from infected individuals in the rest of the world. HIV-1B soon after seroconversion and during chronic infection of Trinidadians was not significantly different, suggesting that distinctly long V2 loops are characteristic of HIV-1B in Trinidad. A threonine deletion at position 319 (T319-) along with the substitutions R315K and S440R were found to be distinctly associated with HIV-1B from Trinidad compared to HIV-1B globally.

Conclusions

This finding of distinctive genetic features that are characteristic of HIV-1B strains from Trinidad is consistent with the Trinidad epidemic being established by a founder strain or closely related founder strains of HIV-1B.  相似文献   

4.

Background

Harm reduction strategies for combating HIV epidemics among people who inject drugs (PWID) have been implemented in several countries. However, large-scale studies using sensitive measurements of HIV incidence and intervention exposures in defined cohorts are rare. The aim of this study was to determine the association between harm reduction programs and HIV incidence among PWID.

Methods and Findings

The study included two populations. For 3,851 PWID who entered prison between 2004 and 2010 and tested HIV positive upon incarceration, we tested their sera using a BED HIV-1 capture enzyme immunoassay to estimate HIV incidence. Also, we enrolled in a prospective study a cohort of 4,357 individuals who were released from prison via an amnesty on July 16, 2007. We followed them with interviews at intervals of 6–12 mo and by linking several databases. A total of 2,473 participants who were HIV negative in January 2006 had interviews between then and 2010 to evaluate the association between use of harm reduction programs and HIV incidence. We used survival methods with attendance at methadone clinics as a time-varying covariate to measure the association with HIV incidence. We used a Poisson regression model and calculated the HIV incidence rate to evaluate the association between needle/syringe program use and HIV incidence. Among the population of PWID who were imprisoned, the implementation of comprehensive harm reduction programs and a lower mean community HIV viral load were associated with a reduced HIV incidence among PWID. The HIV incidence in this population of PWID decreased from 18.2% in 2005 to 0.3% in 2010. In an individual-level analysis of the amnesty cohort, attendance at methadone clinics was associated with a significantly lower HIV incidence (adjusted hazard ratio: 0.20, 95% CI: 0.06–0.67), and frequent users of needle/syringe program services had lower HIV incidence (0% in high NSP users, 0.5% in non NSP users). In addition, no HIV seroconversions were detected among prison inmates.

Conclusions

Although our data are affected by participation bias, they strongly suggest that comprehensive harm- reduction services and free treatment were associated with reversal of a rapidly emerging epidemic of HIV among PWID. Please see later in the article for the Editors'' Summary  相似文献   

5.

Introduction

Primary HIV infection is usually caused by R5 viruses, and there is an association between the emergence of CCXR4-utilizing strains and faster disease progression. We characterized HIV-1 from a cohort of recently infected individuals in Brazil, predicted the virus''s co-receptor use based on the env genotype and attempted to correlate virus profiles with disease progression.

Methods

A total of 72 recently infected HIV patients were recruited based on the Serologic Testing Algorithm for Recent HIV Seroconversion and were followed every three to four months for up to 78 weeks. The HIV-1 V3 region was characterized by sequencing nine to twelve weeks after enrollment. Disease progression was characterized by CD4+ T-cell count decline to levels consistently below 350 cells/µL.

Results

Twelve out of 72 individuals (17%) were predicted to harbor CXCR4-utilizing strains; a baseline CD4<350 was more frequent among these individuals (p = 0.03). Fifty-seven individuals that were predicted to have CCR5-utilizing viruses and 10 individuals having CXCR4-utilizing strains presented with baseline CD4>350; after 78 weeks, 33 individuals with CCR5 strains and one individual with CXCR4 strains had CD4>350 (p = 0.001). There was no association between CD4 decline and demographic characteristics or HIV-1 subtype.

Conclusions

Our findings confirm the presence of strains with higher in vitro pathogenicity during early HIV infection, suggesting that even among recently infected individuals, rapid progression may be a consequence of the early emergence of CXCR4-utilizing strains. Characterizing the HIV-1 V3 region by sequencing may be useful in predicting disease progression and guiding treatment initiation decisions.  相似文献   

6.

Background

It is perceived that little is known about the epidemiology of HIV infection among people who inject drugs (PWID) in the Middle East and North Africa (MENA). The primary objective of this study was to assess the status of the HIV epidemic among PWID in MENA by describing HIV prevalence and incidence. Secondary objectives were to describe the risk behavior environment and the HIV epidemic potential among PWID, and to estimate the prevalence of injecting drug use in MENA.

Methods and Findings

This was a systematic review following the PRISMA guidelines and covering 23 MENA countries. PubMed, Embase, regional and international databases, as well as country-level reports were searched up to December 16, 2013. Primary studies reporting (1) the prevalence/incidence of HIV, other sexually transmitted infections, or hepatitis C virus (HCV) among PWIDs; or (2) the prevalence of injecting or sexual risk behaviors, or HIV knowledge among PWID; or (3) the number/proportion of PWID in MENA countries, were eligible for inclusion. The quality, quantity, and geographic coverage of the data were assessed at country level. Risk of bias in predefined quality domains was described to assess the quality of available HIV prevalence measures. After multiple level screening, 192 eligible reports were included in the review. There were 197 HIV prevalence measures on a total of 58,241 PWID extracted from reports, and an additional 226 HIV prevalence measures extracted from the databases.We estimated that there are 626,000 PWID in MENA (range: 335,000–1,635,000, prevalence of 0.24 per 100 adults). We found evidence of HIV epidemics among PWID in at least one-third of MENA countries, most of which are emerging concentrated epidemics and with HIV prevalence overall in the range of 10%–15%. Some of the epidemics have however already reached considerable levels including some of the highest HIV prevalence among PWID globally (87.1% in Tripoli, Libya). The relatively high prevalence of sharing needles/syringes (18%–28% in the last injection), the low levels of condom use (20%–54% ever condom use), the high levels of having sex with sex workers and of men having sex with men (15%–30% and 2%–10% in the last year, respectively), and of selling sex (5%–29% in the last year), indicate a high injecting and sexual risk environment. The prevalence of HCV (31%–64%) and of sexually transmitted infections suggest high levels of risk behavior indicative of the potential for more and larger HIV epidemics.

Conclusions

Our study identified a large volume of HIV-related biological and behavioral data among PWID in the MENA region. The coverage and quality of the data varied between countries. There is robust evidence for HIV epidemics among PWID in multiple countries, most of which have emerged within the last decade and continue to grow. The lack of sufficient evidence in some MENA countries does not preclude the possibility of hidden epidemics among PWID in these settings. With the HIV epidemic among PWID in overall a relatively early phase, there is a window of opportunity for prevention that should not be missed through the provision of comprehensive programs, including scale-up of harm reduction services and expansion of surveillance systems. Please see later in the article for the Editors'' Summary  相似文献   

7.
8.
Khoja S  Ojwang P  Khan S  Okinda N  Harania R  Ali S 《PloS one》2008,3(9):e3191

Background

Genetic analysis of a viral infection helps in following its spread in a given population, in tracking the routes of infection and, where applicable, in vaccine design. Additionally, sequence analysis of the viral genome provides information about patterns of genetic divergence that may have occurred during viral evolution.

Objective

In this study we have analyzed the subtypes of Human Immunodeficiency Virus -1 (HIV-1) circulating in a diverse sample population of Nairobi, Kenya.

Methodology

69 blood samples were collected from a diverse subject population attending the Aga Khan University Hospital in Nairobi, Kenya. Total DNA was extracted from peripheral blood mononuclear cells (PBMCs), and used in a Polymerase Chain Reaction (PCR) to amplify the HIV gag gene. The PCR amplimers were partially sequenced, and alignment and phylogenetic analysis of these sequences was performed using the Los Alamos HIV Database.

Results

Blood samples from 69 HIV-1 infected subjects from varying ethnic backgrounds were analyzed. Sequence alignment and phylogenetic analysis showed 39 isolates to be subtype A, 13 subtype D, 7 subtype C, 3 subtype AD and CRF01_AE, 2 subtype G and 1 subtype AC and 1 AG. Deeper phylogenetic analysis revealed HIV subtype A sequences to be highly divergent as compared to subtypes D and C.

Conclusion

Our analysis indicates that HIV-1 subtypes in the Nairobi province of Kenya are dominated by a genetically diverse clade A. Additionally, the prevalence of highly divergent, complex subtypes, intersubtypes, and the recombinant forms indicates viral mixing in Kenyan population, possibly as a result of dual infections.  相似文献   

9.
10.

Introduction

The design of a globally effective vaccine rests on the identification of epitopes capable of eliciting effective cytotoxic T lymphocyte (CTL) responses across multiple HIV clades in different populations. This study aims to discern the effect of HLA polymorphisms and the cross-clade reactivity or clade-specificity of epitopes in Thailand where HIV-1 CRF01_AE is circulating.

Materials and Methods

14 peptides based on consensus HIV-1 CRF01_AE amino acid sequences were designed for use in IFN-γ ELISpot assays and 51Cr release assays among 66 HIV-1 CRF01_AE-infected Thai patients. For ELISpot responders carrying HLA alleles currently unknown to restrict CRF01_AE epitopes, in silico epitope-HLA prediction was performed.

Results

29/66 (43.9%) patients recognized at least one peptide. In total 79 responses were seen against all 14 peptides. 28/79 (35.4%) of the responses were in patients with HLA alleles previously reported to restrict CRF01_AE epitopes, 24/79 (30.4%) responses were in individuals with HLA alleles previously reported to restrict epitopes of HIV clades other than CRF01_AE, and the remaining 27/79 (34.2%) responses were not associated with HLA alleles previously known to restrict HIV epitopes. In silico epitope prediction detected 19 novel, epitope-HLA combinations, and 11/19 (57.9%) were associated with HLA-C alleles. We further confirmed a novel HLA restriction of a previously identified HIV-1 Gag epitope [p24122–130: PPIPVGDIY (PY9)] by HLA-B*40:01 with a standard 51Cr release assay.

Discussion

CTL recognition sites in HIV-1 Gag were similar among different clades but the HLA restriction differed in Thai patients. This disparity in HLA restriction along different populations illustrated the importance of clade- and population-specific HLA analysis prior to CTL vaccine design.  相似文献   

11.

Objective

To investigate the HIV-1 molecular epidemiology among newly diagnosed HIV-1 infected persons living in the Jilin province of northeastern China.

Methods

Plasma samples from 189 newly diagnosed HIV-1 infected patients were collected between June 2010 and August 2011 from all nine cities of Jilin province. HIV-1 nucleotide sequences of gag P17–P24 and env C2–C4 gene regions were amplified using a multiplex RT-PCR method and sequenced. Phylogenetic and recombination analyses were used to determine the HIV-1 genotypes.

Results

Based on all sequences generated, the subtype/CFR distribution was as follows: CRF01_AE (58.1%), CRF07_BC (13.2%), subtype B’ (13.2%), recombinant viruses (8.1%), subtype B (3.7%), CRF02_AG (2.9%), subtype C (0.7%). In addition to finding CRF01_AE strains from previously reported transmission clusters 1, 4 and 5, a new transmission cluster was described within the CRF07_BC radiation. Among 11 different recombinants identified, 10 contained portions of gene regions from the CRF01_AE lineage. CRF02_AG was found to form a transmission cluster of 4 in local Jilin residents.

Conclusions

Our study presents a molecular epidemiologic investigation describing the complex structure of HIV-1 strains co-circulating in Jilin province. The results highlight the critical importance of continuous monitoring of HIV-infections, along with detailed socio-demographic data, in order to design appropriate prevention measures to limit the spread of new HIV infections.  相似文献   

12.
13.
14.

Background

worldwide, hepatitis C and B virus infections (HCV and HCV), are the two most common coinfections with human immunodeficiency virus (HIV) and has become a major threat to the survival of HIV-infected persons. The review aimed to estimate the prevalence of HIV, HBV, HCV, HIV/HCV and HIV/HBV and triple coinfections in different subpopulations in Iran.

Method

Following PRISMA guidelines, we conducted a systematic review and meta-analysis of reports on prevalence of HIV, HBV, HCV and HIV coinfections in different subpopulations in Iran. We systematically reviewed the literature to identify eligible studies from January 1996 to March 2012 in English or Persian/Farsi databases. We extracted the prevalence of HIV antibodies (diagnosed by Elisa confirmed with Western Blot test), HCV antibodies and HBsAg (with confirmatory laboratory test) as the main primary outcome. We reported the prevalence of the three infections and coinfections as point and 95% confidence intervals.

Findings

HIV prevalence varied from %0.00 (95% CI: 0.00–0.003) in the general population to %17.25 (95% CI: 2.94–31.57) in people who inject drugs (PWID). HBV prevalence ranged from % 0.00 (95% CI: 0.00–7.87) in health care workers to % 30.9 (95% CI: 27.88–33.92) in PWID. HCV prevalence ranged from %0.19 (95% CI: 0.00–0.66) in health care workers to %51.46 (95% CI: 34.30–68.62) in PWID. The coinfection of HIV/HBV and also HIV/HCV in the general population and in health care workers was zero, while the most common coinfections were HIV/HCV (10.95%), HIV/HBV (1.88%) and triple infections (1.25%) in PWID.

Conclusions

We found that PWID are severely and disproportionately affected by HIV and the other two infections, HCV and HBV. Screenings of such coinfections need to be reinforced to prevent new infections and also reduce further transmission in their community and to others.  相似文献   

15.
With ongoing generation of viral genetic diversity and increasing levels of migration, the global human immunodeficiency virus type 1 (HIV-1) epidemic is becoming increasingly heterogeneous. In this study, we investigate the epidemiological characteristics of 5,675 HIV-1 pol gene sequences sampled from distinct infections in the United Kingdom. These sequences were phylogenetically analyzed in conjunction with 976 complete-genome and 3,201 pol gene reference sequences sampled globally and representing the broad range of HIV-1 genetic diversity, allowing us to estimate the probable geographic origins of the various strains present in the United Kingdom. A statistical analysis of phylogenetic clustering in this data set identified several independent transmission chains within the United Kingdom involving recently introduced strains and indicated that strains more commonly associated with infections acquired heterosexually in East Africa are spreading among men who have sex with men. Coalescent approaches were also used and indicated that the transmission chains that we identify originated in the late 1980s to early 1990s. Similar changes in the epidemiological structuring of HIV epidemics are likely to be taking in place in other industrialized nations with large immigrant populations. The framework implemented here takes advantage of the vast amount of routinely generated HIV-1 sequence data and can provide epidemiological insights not readily obtainable through standard surveillance methods.  相似文献   

16.

Background

HIV infection in Cameroon is characterized by a great viral diversity with all HIV-1 groups (M, N, O, and P) and HIV-2 in circulation. HIV group determination is very important if tailored viral load analysis and treatments are to be applied. In our laboratory, HIV viral load is carried out using two platforms; Biocentric and Abbott depending on the HIV group identified. Biocentric which quantifies HIV-1 group M is a cheap and open system useful in resource limited settings. The objective of this study was to compare the viral load analyses of serologically group-indeterminate HIV samples using the two platforms with the view of reducing cost.

Methods

Consecutive samples received between March and May 2014, and between August and September 2014 in our laboratory for HIV viral load analysis were included. All these samples were analyzed for their HIV groups using an in-house ELISA serotyping test. All HIV-1 group M samples were quantified using the Biocentric test while all other known atypical samples (HIV-1 groups N, O and P) were analyzed using the Abbott technique. HIV group-indeterminate samples (by serotyping) were quantified with both techniques.

Results

Among the 6355 plasma samples received, HIV-1 group M was identified in 6026 (94.82%) cases; HIV-1 group O, in 20 (0.31%); HIV-1 group M?+?O, in 3 (0.05%) and HIV-2, in 3 (0.05%) case. HIV-group indeterminate samples represented about 4.76% (303/6355) and only 231 of them were available for analysis by Abbott Real-Time HIV-1 and Generic HIV Viral Load techniques. Results showed that 188 (81.39%) samples had undetectable viral load in both techniques. All the detectable samples showed high viral load, with a mean of 4.5 log copies/ml (range 2.1–6.5) for Abbott Real-Time and 4.5 log copies/ml (range 2–6.4) for Generic HIV Viral Load. The mean viral load difference between the two techniques was 0.03 log10 copies/ml and a good correlation was obtained (r 2 ?=?0.89; P?<?0.001).

Conclusion

Our results suggest that cheaper and open techniques such as Biocentric could be useful alternatives for HIV viral load follow-up quantification in resource limited settings like Cameroon; even with its high viral diversity.
  相似文献   

17.

Background

The findings of frequent circulation of HIV-1 subclade F1 viruses and the scarcity of BF1 recombinant viruses based on pol subgenomic fragment sequencing among blood donors in Pernambuco (PE), Northeast of Brazil, were reported recently. Here, we aimed to determine whether the classification of these strains (n = 26) extends to the whole genome sequences.

Methods

Five overlapping amplicons spanning the HIV near full-length genomes (NFLGs) were PCR amplified from peripheral blood mononuclear cells (PBMCs) of 26 blood donors. The amplicons were molecularly bar-coded, pooled, and sequenced by Illumina paired-end protocol. The prevalence of viral variants containing drug resistant mutations (DRMs) was compared between plasma and PBMCs.

Results

Of the 26 samples studied, 20 NFLGs and 4 partial fragments were de novo assembled into contiguous sequences and successfully subtyped. Two distinct BF1 recombinant profiles designated CRF70_BF1 and CRF71_BF1, with 4 samples in profile I and 11 in profile II were detected and thus constitute two novel recombinant forms circulating in PE. Evidence of dual infections was detected in four patients co-infected with distinct HIV-1 subtypes. According to our estimate, the new CRF71_BF1 accounts for 10% of the HIV-1 circulating strains among blood donors in PE. Discordant data between the plasma and PBMCs-virus were found in 15 of 24 donors. Six of these strains displayed major DRMs only in PBMCs and four of which had detectable DRMs changes at prevalence between 1-20% of the sequenced population.

Conclusions

The high percentage of the new RF71_BF1 and other BF1 recombinants found among blood donors in Pernambuco, coupled with high rates of transmitted DRMs and dual infections confirm the need for effective surveillance to monitor the prevalence and distribution of HIV variants in a variety of settings in Brazil.  相似文献   

18.

Background

The rate of human immunodeficiency virus type 1 (HIV-1) infection in Iran has increased dramatically in the past few years. While the earliest cases were among hemophiliacs, injection drug users (IDUs) fuel the current epidemic. Previous molecular epidemiological analysis found that subtype A was most common among IDUs but more recent studies suggest CRF_35AD may be more prevalent now. To gain a better understanding of the molecular epidemiology of HIV-1 infection in Iran, we analyzed all Iranian HIV sequence data from the Los Alamos National Laboratory.

Methods

All Iranian HIV sequences from subtyping studies with pol, gag, env and full-length HIV-1 genome sequences registered in the HIV databases (www.hiv.lanl.gov) between 2006 and 2013 were downloaded. Phylogenetic trees of each region were constructed using Neighbor-Joining (NJ) and Maximum Parsimony methods.

Results

A total of 475 HIV sequences were analyzed. Overall, 78% of sequences were CRF_35AD. By gene region, CRF_35AD comprised 83% of HIV-1 pol, 62% of env, 78% of gag, and 90% of full-length genome sequences analyzed. There were 240 sequences re-categorized as CRF_AD. The proportion of CRF_35AD sequences categorized by the present study is nearly double the proportion of what had been reported.

Conclusions

Phylogenetic analysis indicates HIV-1 subtype CRF_35AD is the predominant circulating strain in Iran. This result differed from previous studies that reported subtype A as most prevalent in HIV- infected patients but confirmed other studies which reported CRF_35AD as predominant among IDUs. The observed epidemiological connection between HIV strains circulating in Iran and Afghanistan may be due to drug trafficking and/or immigration between the two countries. This finding suggests the possible origins and transmission dynamics of HIV/AIDS within Iran and provides useful information for designing control and intervention strategies.  相似文献   

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