Search Results (264)

Regional HIV-1 epidemics are evolving with distinct patterns in transmission routes, subtype distribution, and molecular transmission cluster (MTCs) characteristics. We analyzed 9500 HIV-1 cases diagnosed over 30 years using phylogenetic and network methods, integrating molecular, epidemiological, demographic, and behavioral data. Subtype A6 remains dominant nationally (80.6%), followed by 63_02A6 (7.9%), subtype B (5.6%), 02_AG_FSU (1.2%), 03_A6B (0.7%), and 14/73_BG (0.6%). Non-A6 infections were more common among males (OR 1.51) and men who have sex with men (OR 7.33). Network analysis identified 421 MTCs, with 256 active clusters. Clustering was more likely among young individuals (OR: 1.31), those not receiving antiretroviral therapy (OR: 2.70), and injecting drug users (OR: 1.28). Non-A6 subtypes showed a higher likelihood of clustering. Phylogenetic analysis revealed that local clusters of the major subtypes originated between the late 1970s (subtype B) and the mid-2000s (63_02A6) with links to populations in Eastern Europe, Central Asia (subtypes A6, 63_02A6, 02_AG_FSU, 03_A6B), and Western Europe and the Americas (subtype B, 14/73_BG). These findings indicate a complex, evolving regional epidemic transitioning from subtype A6 dominance to a more diverse mix of subtypes. The ability of non-A6 subtypes to form active MTCs suggests their establishment in the local population. Full article

The HIV-1 aspartic protease is an effective target for the treatment of HIV/AIDS. Current therapy utilizes a selection of nine protease inhibitors (PIs) in combination with other classes of antiretroviral drugs. Although PIs were originally developed based on the knowledge of the HIV-1 subtype B protease, the existence of other HIV-1 subtypes and the effects of drug resistance on currently available PIs have become a major challenge in the treatment of HIV/AIDS. Specifically, the HIV-1 subtype C accounts for more than half of the global HIV infections. Considering the importance and relevance of the subtype C virus, in this timely review we discuss the effect of polymorphisms in the HIV-1 subtype C protease on drug resistance, flap flexibility, and hinge region dynamics. We discuss novel paradigms of protease inhibition that attempt to overcome the limitations of currently available inhibitors which fall short considering genetic diversity and resistance mutations. Full article

Zoonotic opportunistic enteric protozoa represent a significant global health threat to immunocompromised populations, especially individuals with human immunodeficiency virus (HIV). Despite China’s severe HIV burden, molecular epidemiological data on enteric protozoa remain limited in this population. In this study, we investigated the occurrence and molecular characteristics of Cryptosporidium species, Giardia duodenalis, and Enterocytozoon bieneusi among 150 AIDS patients with severe immunodeficiency in Wuhan city, Hubei Province, China. The overall test-positive rate was 5.33% (8/150), comprising Cryptosporidium species (including C. hominis, C. parvum, and C. meleagridis) in 2.00% (3/150) and G. duodenalis (including assemblage A, B, and E) in 3.33% (5/150); E. bieneusi was not detected. Notably, this study reports the first identification of the C. parvum subtype IIcA5G3 in humans in China, certainly indicating possible cross-border transmission. Furthermore, the detection of C. meleagridis IIIbA22G1R1c provided additional molecular evidence for chicken-to-human transmission. The finding of G. duodenalis assemblage E highlights the underrecognized zoonotic spillover risks to immunocompromised populations. These findings emphasize the diversity of infectious reservoirs, and the need for enhanced national molecular surveillance of these neglected zoonotic enteric protozoa, alongside targeted interventions for vulnerable populations. Full article

Background/Objectives: Since the World Health Organization (WHO) recommended HIV self-testing as an alternative to traditional facility-based testing in 2016, it has been increasingly adopted worldwide. This study aimed to evaluate the performance of the ConfiSign HIV Self-Test (GenBody Inc., Republic of Korea), a newly developed blood-based immunochromatographic assay for the qualitative detection of total antibodies (IgG and IgM) against HIV-1/HIV-2. Methods: The evaluation included four components: (1) retrospective analysis of 1400 archived serum samples (400 HIV-positive and 1000 HIV-negative samples), (2) prospective self-testing by 335 participants (112 HIV-positive participants and 223 individuals with an unknown HIV status, including healthy volunteers), (3) assessment using seroconversion panels and diverse HIV subtypes, and (4) analytical specificity testing for cross-reactivity and interference. The Elecsys HIV combi PT and Alinity I HIV Ag/Ab Combo assays were used as reference assays. Results: In retrospective testing, the ConfiSign HIV Self-Test achieved a positive percent agreement (PPA) of 100%, a negative percent agreement (NPA) of 99.2%, and a Cohen’s kappa value of 0.986, showing excellent agreement with the reference assays. In the prospective study, the test showed 100% sensitivity and specificity, with a low invalid result rate of 1.8%. All HIV-positive samples, including those with low signal-to-cutoff (S/Co) values in the Alinity I assay, were correctly identified. The test also reliably detected early seroconversion samples and accurately identified a broad range of HIV-1 subtypes (A, B, C, D, F, G, CRF01_AE, CRF02_AG, and group O) as well as HIV-2. No cross-reactivity or interference was observed with samples that were positive for hepatitis viruses, cytomegalovirus, Epstein–Barr virus, varicella zoster virus, influenza, HTLV-1, HTLV-2, or malaria. Conclusions: The ConfiSign HIV Self-Test demonstrated excellent sensitivity, specificity, and robustness across diverse clinical samples, supporting its reliability and practicality as a self-testing option for HIV-1/2 antibody detection. Full article

Background: With a high human immunodeficiency virus (HIV) adult prevalence, people living with HIV (PLHIV) in Botswana continue to experience a high burden of comorbid HIV and cancer. We sought to investigate the trends of acquired immunodeficiency syndrome (AIDS) defining cancers (ADCs), non-AIDS defining cancers (NADCs), and associated risk factors in PLHIV compared with those without HIV. Methods: We analyzed data from adults aged ≥18 years reported in Botswana National Cancer Registry and National Data Warehouse. The crude, age-standardized incidence rate (ASIR), standardized incidence ratios (SIRs) of cancers and time trends were computed. Risk factors were determined using the Cox-regression model. Results: Over a 30-year period, 27,726 cases of cancer were documented. Of these, 13,737 (49.5%) were PLHIV and 3505 (12.6%) were people without HIV and 10,484 (37.8%) had an unknown HIV status. Compared to the HIV-uninfected, the PLHIV had higher and increasing trends in the cancer incidence overall during the study period (from 44.2 to 1047.6 per 100,000; p-trend < 0.001) versus (from 1.4 to 27.2 per 100,000; p-trend < 0.001). The ASIRs also increased in PLHIV for overall ADCs, NADCs and other sub-types like cervical, lung, breast, and conjunctiva cancers (p-trend < 0.001). Further, PLHIV had elevated SIRs for cervical cancer, Kaposi sarcoma in males and some NADCs. The most common risk factors were HIV infection and female sex for ADCs incidence and advanced age and being HIV-uninfected for NADCs incidence. Conclusions: Increasing trends of ADCs and NADCs during ART expansion were observed among PLHIV compared to those without HIV highlighting a greater need for targeted effective prevention and screening strategies including the provision of access to timely HIV and cancer treatment. Full article

Acquired immunodeficiency syndrome (AIDS) is a chronic disease condition caused by the human immunodeficiency virus (HIV). The widespread availability of highly active antiretroviral therapies has helped to control HIV. There are ten FDA-approved protease inhibitors (PIs) that are used as part of antiretroviral therapies in HIV treatment. Importantly, all these drugs are designed and developed against the protease (PR) from HIV subtype B. On the other hand, HIV-1 PR subtype C, which is the most dominant strain in countries including South Africa and India, has shown resistance to PIs due to its genetic diversity and varied mutations. The emergence of resistance is concerning because the virus continues to replicate despite treatment; hence, it is necessary to develop drugs specifically against subtype C. This review focuses on the origin, genetic diversity, and mutations associated with HIV-1 PR subtype C. Furthermore, computational studies performed on HIV-1 PR subtype C and mutations associated with its resistance to PIs are highlighted. Moreover, potential research gaps and future directions in the study of HIV-1 PR subtype C are discussed. Full article

Background/Objectives: This study aimed to explore how HTLV-2 infection affects the production of broadly neutralizing antibodies (bNAbs) in persons with HIV-1 (PWH) and to assess the impact of boosted protease inhibitors (PIs). Methods: We evaluated broadly neutralizing antibody (bNAb) activity in 65 PWH, which included 27 who were also co-infected with HTLV-2. All participants were former injection drug users with HCV antibodies and were receiving suppressive antiretroviral therapy (ART). Neutralizing activity was assessed against six recombinant HIV-1 viruses that represent five different subtypes. B cell subsets were also analyzed. Results: HTLV-2 co-infection and the lack of ritonavir-boosted protease inhibitors (r-PIs) were both independently associated with higher neutralization scores (p = 0.017 and p = 0.005, respectively). Among those not on r-PIs, individuals co-infected with HTLV-2 showed significantly higher neutralization scores (p = 0.027) and a broader neutralization breadth (83.4% vs. 48.5%, p = 0.015) compared to those infected only with HIV-1. Additionally, HTLV-2 co-infected individuals had more resting memory B cells (p = 0.001) and fewer activated memory B cells (p = 0.017) than the HIV-1 mono-infected individuals. In our multivariate analysis, only HTLV-2 co-infection remained independently associated with neutralization scores (p = 0.027). Elite neutralizers (with a breadth score of ≥10) had more naive B cells and fewer resting memory B cells compared to those with weaker neutralization in both groups. Conclusions: Co-infection with HTLV-2 enhances bNAb production in PWH on suppressive ART and, in particular, in the absence of r-PI regimens. The prominent neutralizing activity corresponded with B cell subset distributions. The results suggest the complexity regarding the interaction between viral co-infections, antiretroviral regimens, and humoral immune compartments and may inform further H1V-1 pathogenesis inquiries or the appropriate design of a vaccine. Full article

In this study, we investigated the proportion of transmitted drug resistance (TDR) mutations and human immunodeficiency virus (HIV)-1 subtypes among 487 antiretroviral therapy (ART)-naïve individuals in South Korea from 2021 to 2024 to inform more effective treatment strategies. Consistent with previous reports, subtype B was most prevalent among HIV-1 subtypes at 50.7%; however, its proportion decreased annually (p = 0.047). Various subtypes of circulating recombinant forms (CRFs) were analyzed in this study, resulting in high genetic diversity. The subtype distributions of Korean and non-Korean patients differed, with subtype B (53.7%) and CRF01_AE (34.4%) being dominant in the former and latter, respectively. TDR across antiretroviral drug classes was approximately 3.5% in South Korea. Non-nucleoside reverse transcriptase inhibitors elicited the greatest drug resistance, which increased from 2021 to 2023, with a slight decrease in 2024. The integrase strand transfer inhibitor drugs, elvitegravir and raltegravir, most frequently exhibited high resistance scores. We provide a comprehensive overview of the HIV-1 genetic distribution and TDR patterns in South Korea from 2021 to 2024. Within the broader context of HIV-1 epidemiology in Asia and the Pacific, the findings contribute to a comprehensive understanding of the global distribution of HIV-1 resistance and genotypes, enabling the development of effective interventions. Full article

We investigated HIV-1 immune evasion mechanisms in a slow progressor (CBJC515) by constructing pseudoviruses expressing autologous Env proteins. Intriguingly, all pseudoviruses exhibited resistance to the broadly neutralizing antibody (bNAb) PGT135. Using site-directed mutagenesis and chimeric Env construction, we identified distinct escape mechanisms: early 2005 strains lost the N332 glycan site, while 2006/2008 strains retained key epitopes but developed resistance through structural modifications in the V1/V4/C2 regions or acquired novel N-glycosylation sites (N398/N611). These findings provide insights into how HIV-1 can escape from N332-directed bNAb responses without altering the epitope itself. Furthermore, chimeric experiments also elucidated regional co-evolution and functional maintenance: the V1V2 region broadly interfered with envelope protein function, while the V3 region may exhibit compensatory activity, restoring functionality and mitigating deleterious polymorphisms in other regions to keep Env antigenic diversity. These results offer valuable mechanistic clues that may inform the development of next-generation HIV-1 vaccines. Full article

Human immunodeficiency virus (HIV) type 2 (HIV-2) is less pathogenic than HIV-1. However, the factors responsible for the differences in pathogenicity are still not well defined. To investigate this issue, we performed infection of primary human monocyte-derived macrophages (MDMs) with individual HIV-1 or HIV-2 strains and compared the levels of M-CSF, a cytokine shown to promote HIV-1 infection and replication in our previous studies, and CXCL7, a chemokine identified as being expressed at levels correlated with HIV type by our preliminary gene-expression analysis. We tested several HIV-2 isolates able to replicate in human MDMs and observed that all of them induced the production of M-CSF at high levels similar to those previously established for HIV-1 infection. In addition, the production of M-CSF in MDMs infected with HIV-1 or HIV-2 isolates correlated with the extent of virus replication. In contrast to M-CSF, the chemokine CXCL7 was differentially expressed between MDMs infected with HIV-1 or HIV-2 isolates, as revealed by qPCR and ELISA testing. Together, these results suggest that M-CSF induction may play similar roles in promoting the replication of HIV-1 and HIV-2, while differential regulation of chemokine expression may be an important factor contributing to the differential pathogenicity of the two HIV subtypes. Full article

The human immunodeficiency virus (HIV-1) infiltrates the central nervous system (CNS) early in infection, leading to HIV-associated neurocognitive impairments, particularly pronounced in children who exhibit neurodevelopmental delay. Viral proteins, including the transactivator of transcription protein (Tat) and viral protein R (Vpr) are pivotal in HIV-1 neuropathogenesis, with their amino acid sequence variation influencing disease progression. Due to the difficulty of collecting cerebrospinal fluid from children, few studies have examined whether key Tat and Vpr neuropathogenic signatures found in blood are also present in the cerebrospinal fluid (CSF) of children with HIV. We employed Sanger sequencing for Tat and Vpr sequence analysis using retrospectively collected CSF samples from a South African pediatric HIV-1 subtype C cohort (n = 4). We compared our CSF-derived sequences with pediatric blood-derived sequences (n = 43) from various geographical regions, sourced from the Los Alamos database. Neuropathogenic amino acid variants were identified in Tat and Vpr sequences derived from CSF samples of South African pediatric participants No significant differences were found between subtype C sequences from CSF and blood. Regional analysis highlighted unique amino acid signatures. Obtaining pediatric CSF for HIV-1 sequencing is highly challenging. Despite a small sample size, this study offers rare insights into Tat and Vpr sequences in children, improving understanding of the potential HIV-1 brain pathogenesis in pediatric populations. Full article

Background: Anti-HIV neutralizing antibodies (anti-HIV-nAbs) play a critical role in the immune defense against HIV by preventing viral entry and limiting replication. This study longitudinally evaluated the titers and variability of anti-HIV-nAbs in individuals coinfected with HIV and HCV. Samples were collected at three time points: before starting HCV treatment, one year after completion, and five years post-treatment. Methods: A retrospective analysis was conducted on 71 HIV/HCV-coinfected patients who achieved a sustained virologic response following antiviral therapy for HCV. A control group of 41 HIV-monoinfected individuals was also included. Anti-HIV-nAb titers were evaluated by HIV neutralization assays using a panel of six recombinant HIV viruses representing multiple genetic subtypes. Generalized Linear Mixed Models and Generalized Linear Models were used for statistical analysis. p-values were adjusted using the Benjamini–Hochberg procedure (q-value). Results: HIV-neutralizing antibody responses in HIV/HCV-coinfected individuals remained stable over five years following HCV therapy without significant changes (q-value > 0.05). The mean neutralization scores remained stable, with baseline scores of 6.1 (95% CI: 5.4–6.7), 6.2 (95% CI: 5.5–6.8) at one year post-HCV therapy, and 6.0 (95% CI: 5.3–6.7) at five years post-HCV therapy. HIV/HCV-coinfected individuals consistently showed lower neutralization scores compared to the control group throughout the follow-up (q-value < 0.05). Regression analyses adjusted for age, gender, nadir CD4⁺, and baseline CD4⁺ counts confirmed that the observed differences between HIV-monoinfected and HIV/HCV-coinfected individuals persisted (q-value < 0.05) at both the baseline and after HCV therapy completion. Conclusions: Successful HCV eradication in HIV/HCV-coinfected individuals did not normalize anti-HIV-nAb titers, which remained consistently lower than those in HIV-monoinfected controls over five years. Full article

Background: Vietnam has made significant strides in reducing the prevalence of HIV infection and achievements in its antiretroviral treatment program. However, the COVID-19 pandemic and financial challenges in the healthcare system have posed significant obstacles to maintaining effective HIV treatment and monitoring, particularly among vulnerable populations. This study aims to evaluate the situation of HIV drug resistance among patients who have experienced treatment failure in the Mekong Delta region and to compare data from 2019 to 2022. Methods: The study material was blood plasma samples from HIV-infected individuals with ART failure: 316 collected in 2019 and 326 collected in 2022. HIV-1 genotyping and mutation detection were performed based on an analysis of the nucleotide sequences of the Pol gene region. A total of 116 HIV-infected individuals with virological failure in 2019 and 2022 were assessed for HIV drug resistance. Results: The study revealed a high proportion of participants with viral loads exceeding 1000 copies/mL, significantly increasing from 12.0% in 2019 to 23.9% in 2022 (OR = 2.3; p = 0.0001). HIV drug resistance mutations were detected in 84.21% of cases in 2019 and 92.59% in 2022. The prevalence of concurrent resistance to NRTIs and NNRTIs was 37.5% and 30.13% in 2019 and 2022, respectively. There was a statistically significant decrease in NNRTI resistance (OR = 0.32, χ² = 5.43, p < 0.05). In contrast, multi-drug resistance to protease inhibitors rose from 18.52% to 45.21% (φ* = 0.00403, p < 0.05). Triple-class resistance was identified only in 2022 (17.81%). The most common mutations included M184I/V, D67N, K103N, Y181C, and V82A/S/T, with D67N rising significantly from 3.13% to 21.92%. The predominant subtype was CRF01_AE. Conclusion: A high prevalence of viral non-suppression and HIV drug resistance was observed among patients in the Mekong Delta region, particularly after the onset of the COVID-19 pandemic. Our study highlights the ongoing challenges that the HIV/AIDS treatment program in Vietnam must address in the post-pandemic period to sustain its success and achieve the goals of the country’s HIV prevention strategies. Full article

In 2023, the HIV-1 pandemic claimed around 630,000 lives worldwide due to AIDS-related complications. Its burden is significantly heavier in Sub-Saharan Africa, where an increased HIV-1 genetic diversity is common, which increases the risk of resistance to antiretroviral (ARV) drugs. This study aims to update the molecular epidemiology of HIV-1 in Angola, focusing specifically on the gag gene, which is often overlooked, and to assess the potential viability of lenacapavir (LEN)-based ARV therapy in the region. A total of 243 blood samples were collected from ARV-naïve, HIV-infected patients at the General Hospital of Benguela, city of Benguela, Angola. The capsid-encoding region of HIV-1 proviral DNA was amplified by PCR and sequenced. Phylogenetic analysis was performed using the maximum likelihood method, and genome recombinant forms were characterised through bootscanning analysis. Primary resistance mutations to LEN were identified using Stanford University’s HIVdb algorithm. Among the 80 successfully sequenced samples, 13 different genetic forms/subtypes were identified, with unique recombinant forms (URFs) (37.5%, 30/80) and subtype C (31.25%, 25/80) being the most prevalent. Regarding resistance mutations, none were detected, apart from four polymorphic mutations. These findings reinforce Angola’s position as a transitional HIV-1 hotspot between the genetically highly diverse Central Africa and the subtype C-dominated Southern Africa, while also supporting the potential effectiveness of LEN-based regimens for treatment and prevention of HIV-1 infections in the future. Full article

By 2022, Bulgaria’s National Reference Laboratory had confirmed 4024 HIV cases. We analyzed 132 pol gene sequences to characterize the molecular epidemiology of HIV-1 subtypes A1, A6, and A7 (2001–2022). A1 accounted for 50.0% (66/132) of cases, increasing after 2014, with peaks in 2019 and 2022. A6 comprised 48.5% (64/132), dominating from 2005 to 2014 before stabilizing. A7 was rare (1.5%, 2/132), detected in 2003 and 2011. Transmission patterns varied: A1 was linked to men who have sex with men (MSM) (62.1%), while A6 was primarily heterosexual (HET) (82.8%) with a balanced gender distribution (56.3% male, 43.8% female). Resistance mutations were identified in 29.6% of cases, with A6 showing higher rates of nucleoside reverse transcriptase inhibitor (NRTI) (20.3%) and non-nucleoside reverse transcriptase inhibitor (NNRTI) (7.8%) resistance than A1. Phylogenetic analysis revealed that 13 Bulgarian sequences (9.8%) were involved in transmission clusters, including 10 (7.6%) from sub-subtype A1 and 3 (2.3%) from sub-subtype A6, highlighting distinct genetic diversity and transmission patterns. Despite significant migration from Ukraine in 2022, A6 prevalence remained unchanged, suggesting localized transmission dynamics. These findings highlight a shifting HIV-1 sub-subtype distribution in Bulgaria and emphasize the need for targeted prevention, diagnosis, and treatment strategies tailored to the evolving molecular landscape. Full article