Molecular Epidemiology Of HIV-1 Infection Research Articles

Characterization of Human Immunodeficiency Virus-1 Transmission Clusters and Transmitted Drug-Resistant Mutations in Croatia from 2019 to 2022.

Molecular epidemiology of HIV-1 infection is challenging due to the highly diverse HIV-genome. We investigated the genetic diversity and prevalence of transmitted drug resistance (TDR) followed by phylogenetic analysis in 270 HIV-1 infected, treatment-naïve individuals from Croatia in the period 2019-2022. The results of this research confirmed a high overall prevalence of TDR of 16.7%. Resistance to nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside RTIs (NNRTIs), and protease inhibitors (PIs) was found in 9.6%, 7.4%, and 1.5% of persons, respectively. No resistance to integrase strand-transfer inhibitors (INSTIs) was found. Phylogenetic analysis revealed that 173/229 sequences (75.5%) were part of transmission clusters, and the largest identified was T215S, consisting of 45 sequences. Forward transmission was confirmed in several clusters. We compared deep sequencing (DS) with Sanger sequencing (SS) on 60 randomly selected samples and identified additional surveillance drug resistance mutations (SDRMs) in 49 of them. Our data highlight the need for baseline resistance testing in treatment-naïve persons. Although no major INSTIs were found, monitoring of SDRMs to INSTIs should be continued due to the extensive use of first- and second-generation INSTIs.

Molecular epidemiology of HIV-1 infection in immigrant population in northern Italy.

Human immunodeficiency virus-1 (HIV-1) is characterised by a vast genetic diversity classified into distinct phylogenetic strains and recombinant forms. We describe the HIV-1 molecular epidemiology and evolution of 129 consecutive HIV-1 positive migrants living in Milan (northern Italy). Polymerase gene sequences of 116 HIV-1 subtype-B positive patients were aligned with HIV-1 reference sequences (https://www.ncbi.nlm.nih.gov/) by using MAFFT alignment and edited by using Bioedit software. A maximum likelihood (ML) phylogenetic tree was performed by MEGA7 and was visualised by using FigTree v1.4.3. Of 129 migrants, 35 were born in Europe (28 in Eastern Europe), 70 in the Americas (67 in South America), 15 in Africa and nine in Asia; 76.4% were men who have sex with men (MSM). The serotype HIV-1-B prevailed (89.9%), followed by -C, -F1, -D and -A. Compared with 116 HIV-B patients, the 13 with HIV-non-B showed lower Nadir of CD4+ cell/mmc (P = 0.043), more frequently had sub Saharan origin (38.5 vs. 1.72%, P = 0.0001) and less frequently were MSM (40 vs. 74.5%, P = 0.02). The ML phylogenetic tree of the 116 HIV-1 subtype-B positive patients showed 13 statistically supported nodes (bootstrap > 70%). Most of the sequences included in these nodes have been isolated from male patients from the Americas and the most common risk factor was MSM. The low number of HIV-1 non-B subtype patients did not allow to perform this analysis. These results suggest a shift of HIV-1 prevention projects' focus and a continuous monitoring of HIV-1 molecular epidemiology among entry populations. Prevention efforts based on HIV molecular epidemiology may improve public health surveillance setting.

Analysis of HIV-1 diversity, primary drug resistance and transmission networks in Croatia

Molecular epidemiology of HIV-1 infection in treatment-naive HIV-1 infected persons from Croatia was investigated. We included 403 persons, representing 92.4% of all HIV-positive individuals entering clinical care in Croatia in 2014–2017. Overall prevalence of transmitted drug resistance (TDR) was estimated at 16.4%. Resistance to nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside RTI (NNRTIs) and protease inhibitors (PIs) was found in 11.4%, 6.7% and 2.5% of persons, respectively. Triple-class resistance was determined in 2.2% of individuals. In addition, a single case (1.0%) of resistance to integrase strand-transfer inhibitors (InSTIs) was found. Deep sequencing was performed on 48 randomly selected samples and detected additional TDR mutations in 6 cases. Phylogenetic inference showed that 347/403 sequences (86.1%) were part of transmission clusters and identified forward transmission of resistance in Croatia, even that of triple-class resistance. The largest TDR cluster of 53 persons with T215S was estimated to originate in the year 1992. Our data show a continuing need for pre-treatment HIV resistance testing in Croatia. Even though a low prevalence of resistance to InSTI was observed, surveillance of TDR to InSTI should be continued.

P7 - Molecular epidemiology of HIV-1 infection in Cyprus: onward transmission is predominantly driven by young adults

P7 - Molecular epidemiology of HIV-1 infection in Cyprus: onward transmission is predominantly driven by young adults

Molecular Epidemiology of HIV-1 Infection among Men who Have Sex with Men in Taiwan in 2012.

The number of men who have sex with men (MSM) infected with HIV-1 in Taiwan has increased rapidly in the past few years. The goal of this study was to conduct a molecular epidemiological study of HIV-1 infection among MSM in Taiwan to identify risk factors for intervention. Voluntary counseling program and anonymous testing were provided to patrons at 1 gay bar, 7 night clubs and 3 gay saunas in Taipei and New Taipei Cities in 2012. HIV-1 subtypes were determined using gag subtype-specific PCR and phylogenetic analysis by env sequences. Recent HIV-1 infection was determined using LAg-Avidity EIA. In-depth interviews and questionnaires were used to identify risk factors. The prevalence and incidence of HIV-1 among MSM in Taiwan were 4.38% (53/1,208) and 3.29 per 100 person-years, respectively. Of 49 cases genotyped, 48 (97.9%) were infected with subtype B and 1 with CRF01_AE (2%). Phylogenetic analysis of 46 HIV-1 strains showed that 25 (54.4%) subtype B strains formed 9 clusters with each other or with other local strains. The CRF01_AE case clustered with a reference strain from a Thai blood donor with bootstrap value of 99. Multivariate logistic regression analysis showed that risk factors associated with HIV-1 infection included use of oil-based solution as lubricant (vs. saliva or water-based lubricants, OR= 4.23; p <0.001); exclusively receptive role (vs. insertive role, OR= 9.69; p <0.001); versatile role (vs. insertive role, OR= 6.45; p= 0.003); oral sex (vs. insertive role, OR= 11.93; p= 0.044); times of sexual contact per week (2-3 vs. zero per week, OR= 3.41; p= 0.021); illegal drug use (OR= 4.12; p <0.001); and history of sexually transmitted diseases (OR= 3.65; p= 0.002). In conclusion, there was no new HIV-1 subtype or circulating recombinant form responsible for the increase of HIV-1 among MSM in Taiwan in 2012. Misuse of oil-based solution as lubricant is a new risk factor identified among MSM in Taiwan. The Taiwan’s Centers for Disease Control has created a video (www.youtube.com/watch?v=BinExvvOTMM&feature=iv&src_vid=BW81-PfmY3E&annotation_id=annotation_2436493705) to correct such misconception in its AIDS prevention campaign.

Molecular Epidemiology of HIV Type 1 Infection in Iran: Genomic Evidence of CRF35_AD Predominance and CRF01_AE Infection Among Individuals Associated with Injection Drug Use

To understand the molecular epidemiology of HIV-1 infection in Iran, we conducted the first study to analyze the genome sequence of Iranian HIV-1 isolates. For this cross-sectional study, we enrolled 10 HIV-1-infected individuals associated with injection drug use from Tehran, Shiraz, and Kermanshah. Near full-length genome sequences obtained from their plasma samples were used for phylogenetic tree and similarity plotting analyses. Among 10 isolates, nine were clearly identified as CRF35_AD and the remaining one as CRF01_AE. Interestingly, five of our Iranian CRF35_AD isolates made two clusters with 10 Afghan CRF35_AD isolates in a phylogenetic tree, indicating epidemiological connections among injection drug users in Iran and Afghanistan. In contrast, our CRF01_AE isolate had no genetic relationship with any other CRF01_AE isolates worldwide, even from Afghanistan. This study provides the first genomic evidence of HIV-1 CRF35_AD predominance and CRF01_AE infection among individuals associated with injection drug use in Iran.

Molecular Epidemiology of HIV-1 Infection in Taiwan from 2005 to 2008

Molecular Epidemiology of HIV-1 Infection in Taiwan from 2005 to 2008

Molecular Epidemiology of HIV-1 Infection in Taiwan from 2005 to 2008

In 2004, HIV-1 infection among Taiwanese injection drug users (IDUs) started to surge. In 2007, a resurgence of HIV-1 epidemic among men having sex with men (MSM) occurred. We conducted a molecular epidemiological study of HIV-1 among different risk groups in Taiwan from 2005 to 2008. In total 1133 HIV-1-infected adults including 576 IDUs, 464 MSM, and 93 heterosexuals were recruited. HIV-1 subtypes were determined using nested multiplex polymerase chain reaction and phylogenetic analysis. Dual infection was confirmed using cloning, sequencing, and heteroduplex mobility assay. Among HIV-1/AIDS subjects, 96.1% MSM and 62.5% heterosexual males were infected with subtype B, whereas 66.7% female heterosexuals were infected with CRF01_AE. Most IDUs (84.5%) were infected with CRF07_BC. Four heterosexual males, 2 females and 2 MSM who were not IDUs had CRF07_BC. Forty-nine patients had CRF07_BC/subtype B dual infection and 44 (89.8%) were IDUs. Multivariate logistic regression showed that the odds ratio for dual infection among IDUs who shared syringes >5 times per month was 4.7 (95% confidence interval = 1.3 to 17.7). Phylogenetic analyses revealed that there were 2 main groups of CRF07_BC strains with sporadic transmission between different risk groups. Among 10 IDUs infected with CRF01_AE, 7 cases were clustered with an outbreak happened in 2005 and 3 cases were clustered with other strains from heterosexual population. In Taiwan, 7.8% of HIV-1-infected IDUs had dual infection. It may have important impact to their clinical management. Although CRF07_BC was still remained in IDUs, it has spread to MSM and heterosexual populations.

Near Full-Length Genetic Analysis of HIV Sequences Derived from Cyprus: Evidence of a Highly Polyphyletic and Evolving Infection

The molecular epidemiology of HIV-1 infection was previously studied in Cyprus but the degree of HIV-1 diversity has remained indefinable. The main objective of the present study is to examine HIV-1 strains isolated from 77 HIV-1-infected individuals representing 38% of the known infected population in Cyprus in the period 1986 to 2006. DNA of the near full-length genome encoding gag, pol, vif, vpr, vpu, tat, rev, env, and 5'-end of nef was amplified by nested PCR/RT-PCR from all HIV-1 seropositives and sequenced using a newly designed assay. Detailed phylogenetic and bootscanning analyses were performed to determine phylogenetic associations and subtype assignments. Phylogenetic analyses of the obtained viral sequences indicated that subtype B was the dominant subtype (61%), followed by subtype A (23.3%), subtype C (5.2%), CRF02_AG (3.9%), and subtype D, CRF01_AE, and CRF04_cpx (1.3% each). Two HIV-1 isolates (2.6%), originating from the Democratic Republic of Congo (DRC), were not classified in any pure (sub)subtype or circulating recombinant form (CRF). Complete phylogenetic and bootscanning analyses revealed that one of these isolates had a new, unique recombinant pattern, comprising segments of subtypes D and G, and is distinct from any other CRFs or URFs reported so far. Detailed analyses of the sequence of the second isolate, which could not be classified, reveal that it is close to subtype K reference sequences but clusters near the root of the clade. At least two epidemiologically unrelated HIV-1 seropositives with an HIV-1 variant similar to this isolate are required to designate this variant as a novel HIV-1 subtype or subsubtype of subtype K. Analogous to results of the earlier epidemiological studies, these data exhibit the extensive heterogeneity of HIV-1 infection in Cyprus, which is being fueled by a continuous entry of new strains from other countries, creating an evolving and polyphyletic infection.

Genetic Analysis of HIV Type 1 Strains from Newly Infected Untreated Patients in Cyprus: High Genetic Diversity and Low Prevalence of Drug Resistance

Abstract The molecular epidemiology of HIV-1 infection was first studied in Cyprus in the mid-1990s, but the extent of HIV-1 diversity and the prevalence of drug resistance have remained elusive. In an effort to address this issue, the present study examined HIV-1 strains isolated from 37 newly diagnosed untreated HIV-1 patients, representing 72% of the total number of newly diagnosed and drug-naive patients in the period 2003 to 2006. DNA sequences encoding the gag (p17, p24, p2, p7, p1, and p6), pol (protease and reverse transcriptase), and env (gp160) regions were amplified by RT-PCR from plasma HIV-1 RNA from all patients and sequenced using a newly designed methodology. All amplified products were studied according to established genetic methodologies to determine the genetic subtype and the prevalence of drug-resistance-associated mutations to currently available antiretroviral drugs. Analyses of the obtained viral sequences indicated that subtype A was the most common subtype present and accounted for 38% of the infections followed by subtype B (35%), subtype C (13%), CRF02_AG (8%), and subtypes D and CRF01_AE (3% each). One patient (2.7%) had an M41L/M and another patient (2.7%) an M184V amino acid substitution in the reverse transcriptase (RT) associated with high-level resistance to RT inhibitors. There were no patients with resistant mutations to protease inhibitors (PI). Additionally, one patient (2.7%) had an L44M amino acid substitution within the HR1 region of gp41 conferring resistance to the enfuvirtide (T20) fusion inhibitor. Similar to results of the 1994 molecular epidemiological study, these data demonstrate the extensive heterogeneity of HIV-1 infection in Cyprus and the low prevalence of transmitted resistance to current HIV-1 antiretroviral drugs. Taken together, these findings demonstrate that HIV-1 infection in Cyprus is being replenished by a continuous influx of new strains from many countries, establishing an ever-evolving and polyphyletic infection in the island.

Molecular Epidemiology of HIV-1 Infection in a Small Brazilian County

The AIDS epidemic in Brazil is spreading from the large urban centers to small counties and the innermost parts of the country; however, data on the features of HIV-1 infection in these places are scarce. To study the routes of HIV-1 spread and assess the existence of transmission networks in such a setting, we performed a genetic analysis of viral sequences from the small county of Miracema, Rio de Janeiro State. HIV-1 envelope and polymerase sequences recovered from 63 adult patients (from a cohort of 78 patients) were phylogenetically analyzed. A polyphyletic pattern ensued. Six clusters of sequences sharing close genetic relatedness were also recovered from 29 (46%) patients. Envelope and polymerase phylogenies yielded essentially the same results. The polyphyletic pattern suggests multiple viral introductions in the region. Intracluster cases, including those with no known direct epidemiologic link, probably took part in the same chain of viral transmission. Such a pattern suggests the existence of sexual networks and the emergence of multiple new infections within a relatively short period, a potential molecular marker of high incidence.

Temporal trends and molecular epidemiology of HIV-1 infection in Taiwan from 1988 to 1998.

Eight hundred and seventy-nine HIV-1-infected patients (comprising 46% of reported HIV-1/AIDS cases in Taiwan) were recruited for this study of the molecular epidemiology of HIV-1 in Taiwan from 1988 to 1998. HIV-1 subtypes were determined using a modified peptide-enzyme immunoassay complemented with DNA sequencing and phylogenetic analysis. Of the 807 HIV-1 infected men, 68.2% were infected with HIV-1B, 29.5% with HIV-1 circulating recombinant form (CRF)01_AE and 2.3% with other subtypes. Of the 72 HIV-1-infected women, 72.2% were infected with HIV-1 CRF01_AE, 13.9% with HIV-1B, and 13.9% with other subtypes. All of 8 foreign-born, Southeast Asian women and 6 of 7 (85.7%) Taiwan-native female commercial sex workers were infected with HIV-1 CRF01_AE. Fourteen of the 33 (42.4%) heterosexual married men with CRF01_AE had transmitted HIV-1 to their wives, whereas only 1 of 17 (5.9%) men with HIV-1 B had transmitted HIV-1 to their spouses (p < .01). Of 18 heterosexual male injecting drug users, 1 of 12 (8.5%) with HIV-1B and 5 of 6 (83.3%) with HIV-1 CRF01_AE had had sexual contact with female commercial sex workers (p < .01). Therefore, in this population, CRF01_AE was preferentially associated with heterosexual risk groups, a finding compatible with differences in transmission capability between B and non-B subtypes.

Temporal Trends and Molecular Epidemiology of HIV-1 Infection in Taiwan From 1988 to 1998

Objective: To examine the influence of country/region of birth on spectrum of AIDS-defining illness. Methods: National surveillance data for 4,629 adolescents and adults diagnosed with AIDS from 1992 through 1998 were analyzed. Country of birth was grouped into five broad categories (Australia, other predominantly industrialized country regions, sub-Saharan Africa, Asia-Pacific, and other regions with predominantly developing countries). Proportions of AIDS-defining illnesses were calculated and compared by country/region of birth. Role of country/region of birth in the distribution of AIDS-defining illnesses was further assessed using logistic models. Results: Of the 4,488 (97.0%) AIDS cases with country of birth recorded, 1,120 (25.0%) were born outside Australia. In multivariate analyzes, AIDS cases born in sub-Saharan Africa had an increased risk of tuberculosis (odds ratio [OR], 18.7; confidence interval [CI], 9.2-38.2) and cryptococcosis (OR, 2.4; CI, 1.1-5.4), but a decreased risk of esophageal candidiasis (OR, 0.3; 0.1-0.8) and Pneumocystis carinii pneumonia (OR, 0.5; 0.3-0.9) compared with AIDS cases born in Australia. Tuberculosis risk was also elevated among AIDS cases born in Asia-Pacific (OR, 9.6; 5.3-17.5) and other developing country regions (OR, 3.1; 0.9-10.4). Risk of AIDS-defining illnesses was similar for AIDS patients born in Australia and other industrialized country regions. Country of birth had no influence on risk of cytomegalovirus (CMV)-related disease and Mycobacterium avium complex (MAC) infection. Differential AIDS-defining illness risk was more pronounced among AIDS patients born in developing countries who had resided in Australia for less time. Conclusions: Differential risk by country/region of birth for some AIDS-defining illnesses, especially among more recent arrivals from developing countries, suggests that environmental microbial habitats are important determinants of opportunistic infection risk. Similar risk of CMV disease and MAC infection is consistent with the ubiquitous nature of these microbial agents and suggests that previously reported low prevalence from developing countries may reflect poor diagnostic capacity rather than level of risk.

Diversification of subtype E human immunodeficiency virus type 1 env in heterosexual seroconverters from Northern Thailand.

The C2-V3 region of the human immunodeficiency virus (HIV)-1 env was determined from 15 northern Thailand seroconverters between 1993 and 1995. Similar sequences were also determined from 18 seroconverting injection drug users in Baltimore. All seroconverters from northern Thailand were infected with subtype E HIV-1 on the basis of env sequences. Intersubject viral DNA distances increased from 2.3% in asymptomatic HIV-1-infected subjects characterized between 1990 and 1992 to 7.8% in these more recent seroconverters from Thailand. On the other hand, sequences from 18 seroconverters from Baltimore had a mean intersubject distance of 13.2%. The genetic diversity within HIV-1 subtype E in seroconverters in Thailand has increased significantly but is still less than that observed in HIV-1 from seroconverters in the United States, where the epidemic of HIV-1 infection is more mature. These results suggest that continued monitoring of the molecular epidemiology of HIV-1 infection in Thailand will be important for HIV vaccine development and evaluation.