Search

The article presents a study regarding the differences of CD4+ T-Cell decline rate in the HIV Seroincident Antiretroviral (ART)-naïve adults in Rakai District, Uganda. The study used the linear mixed effect models to determine the rates of CD4+ T-Cell decline among 312 HIV seroincident individuals by HIV-1 subtype. The result shows that rapid diseases progression is linked to higher rates of CD4+ loss rather than infections with subtype A.

Assesses knowledge and beliefs regarding vaccines and willingness to participate in HIV vaccine trials. Assessment of willingness to participate in HIV-preventive vaccine trials during a follow-up survey ten months later after providing community education on HIV vaccines; Necessity of education on the potential role of preventive HIV vaccines in the control of the epidemic and the importance of vaccination for men.

Objective: People with chronic HIV exhibit lower regional brain volumes compared to people without HIV (PWOH). Whether imaging alterations observed in chronic infection occur in acute HIV infection (AHI) remains unknown., Design: Cross-sectional study of Thai participants with AHI., Methods: One hundred and twelve Thai males with AHI (age 20-46) and 18 male Thai PWOH (age 18-40) were included. Individuals with AHI were stratified into early (Fiebig I-II; n  = 32) and late (Fiebig III-V; n  = 80) stages of acute infection using validated assays. T1-weighted scans were acquired using a 3 T MRI performed within five days of antiretroviral therapy (ART) initiation. Volumes for the amygdala, caudate nucleus, hippocampus, nucleus accumbens, pallidum, putamen, and thalamus were compared across groups., Results: Participants in late Fiebig stages exhibited larger volumes in the nucleus accumbens (8% larger; P  = 0.049) and putamen (19%; P  < 0.001) when compared to participants in the early Fiebig. Compared to PWOH, participants in late Fiebig exhibited larger volumes of the amygdala (9% larger; P  = 0.002), caudate nucleus (11%; P  = 0.005), nucleus accumbens (15%; P  = 0.004), pallidum (19%; P  = 0.001), and putamen (31%; P  < 0.001). Brain volumes in the nucleus accumbens, pallidum, and putamen correlated modestly with stimulant use over the past four months among late Fiebig individuals ( P s < 0.05)., Conclusions: Findings indicate that brain volume alterations occur in acute infection, with the most prominent differences evident in the later stages of AHI. Additional studies are needed to evaluate mechanisms for possible brain disruption following ART, including viral factors and markers of neuroinflammation., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: We examined individual differences in CD4/CD8 T-cell ratio trajectories and associated risk profiles from acute HIV infection (AHI) through 144 weeks of antiretroviral therapy (ART) using a data-driven approach., Methods: A total of 483 AHI participants began ART during Fiebig I-V and completed follow-up evaluations for 144 weeks. CD4+, CD8+, and CD4/CD8 T-cell ratio trajectories were defined followed by analyses to identify associated risk variables., Results: Participants had a median viral load (VL) of 5.88 copies/ml and CD4/CD8 T-cell ratio of 0.71 at enrollment. After 144 weeks of ART, the median CD4/CD8 T-cell ratio was 1.3. Longitudinal models revealed five CD4/CD8 T-cell ratio subgroups: group 1 (3%) exhibited a ratio >1.0 at all visits; groups 2 (18%) and 3 (29%) exhibited inversion at enrollment, with normalization 4 and 12 weeks after ART, respectively; and groups 4 (31%) and 5 (18%) experienced CD4/CD8 T-cell ratio inversion due to slow CD4+ T-cell recovery (group 4) or high CD8+ T-cell count (group 5). Persistent inversion corresponded to ART onset after Fiebig II, higher VL, soluble CD27 and TIM-3, and lower eosinophil count. Individuals with slow CD4+ T-cell recovery exhibited higher VL, lower white blood cell count, lower basophil percent, and treatment with standard ART, as well as worse mental health and cognition, compared with individuals with high CD8+ T-cell count., Conclusions: Early HIV disease dynamics predict unfavorable CD4/CD8 T-cell ratio outcomes after ART. CD4+ and CD8+ T-cell trajectories contribute to inversion risk and correspond to specific viral, immune, and psychological profiles during AHI. Adjunctive strategies to achieve immune normalization merit consideration., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Psychosomatic Society.)

Objective: To develop a predictive model of neurocognitive trajectories in children with perinatal HIV (pHIV)., Design: Machine learning analysis of baseline and longitudinal predictors derived from clinical measures utilized in pediatric HIV., Methods: Two hundred and eighty-five children (ages 2-14 years at baseline; Mage = 6.4 years) with pHIV in Southeast Asia underwent neurocognitive assessment at study enrollment and twice annually thereafter for an average of 5.4 years. Neurocognitive slopes were modeled to establish two subgroups [above (n = 145) and below average (n = 140) trajectories). Gradient-boosted multivariate regressions (GBM) with five-fold cross validation were conducted to examine baseline (pre-ART) and longitudinal predictive features derived from demographic, HIV disease, immune, mental health, and physical health indices (i.e. complete blood count [CBC])., Results: The baseline GBM established a classifier of neurocognitive group designation with an average AUC of 79% built from HIV disease severity and immune markers. GBM analysis of longitudinal predictors with and without interactions improved the average AUC to 87 and 90%, respectively. Mental health problems and hematocrit levels also emerged as salient features in the longitudinal models, with novel interactions between mental health problems and both CD4 cell count and hematocrit levels. Average AUCs derived from each GBM model were higher than results obtained using logistic regression., Conclusion: Our findings support the feasibility of machine learning to identify children with pHIV at risk for suboptimal neurocognitive development. Results also suggest that interactions between HIV disease and mental health problems are early antecedents to neurocognitive difficulties in later childhood among youth with pHIV.

Background: The HIV epidemic continues to grow among MSM in countries across sub-Saharan Africa including Nigeria. To inform prevention efforts, we used a phylogenetic cluster method to characterize HIV genetic clusters and factors associated with cluster formation among MSM living with HIV in Nigeria., Methods: We analyzed HIV-1 pol sequences from 417 MSM living with HIV enrolled in the TRUST/RV368 cohort between 2013 and 2017 in Abuja and Lagos, Nigeria. A genetically linked cluster was defined among participants whose sequences had pairwise genetic distance of 1.5% or less. Binary and multinomial logistic regressions were used to estimate adjusted odds ratios (AORs) and 95% confidence intervals (CIs) for factors associated with HIV genetic cluster membership and size., Results: Among 417 MSM living with HIV, 153 (36.7%) were genetically linked. Participants with higher viral load (AOR = 1.72 95% CI: 1.04-2.86), no female partners (AOR = 3.66; 95% CI: 1.97-6.08), and self-identified as male sex (compared with self-identified as bigender) (AOR = 3.42; 95% CI: 1.08-10.78) had higher odds of being in a genetic cluster. Compared with unlinked participants, MSM who had high school education (AOR = 23.84; 95% CI: 2.66-213.49), were employed (AOR = 3.41; 95% CI: 1.89-10.70), had bacterial sexually transmitted infections (AOR = 3.98; 95% CI: 0.89-17.22) and were not taking antiretroviral therapy (AOR = 6.61; 95% CI: 2.25-19.37) had higher odds of being in a large cluster (size > 4)., Conclusion: Comprehensive HIV prevention packages should include behavioral and biological components, including early diagnosis and treatment of both HIV and bacterial sexually transmitted infections to optimally reduce the risk of HIV transmission and acquisition.

While abundant sequence information is available from human immunodeficiency virus type 1 (HIV-1) subtypes A, B, C and CRF01&#95;AE for HIV-1 vaccine design, sequences from West Africa are less represented. We sought to augment our understanding of HIV-1 variants circulating in 6 Nigerian cities as a step to subsequent HIV-1 vaccine development.The G/CRF02&#95;AG multi-region hybridization assay (MHA) was developed to differentiate subtype G, CRF02&#95;AG and their recombinants from other subtypes based on 7 HIV-1 segments. Plasma from 224 HIV-1 infected volunteers enrolled in a cohort examining HIV-1 prevalence, risk factor, and subtype from Makurdi (30), Abuja (18), Enugu (11), Kaduna (12), Tafa (95), and Ojo/Lagos (58) was analyzed using MHA. HIV-1 genomes from 42 samples were sequenced to validate the MHA and fully explore the recombinant structure of G and CRF02&#95;AG variants.The sensitivity and specificity of MHA varied between 73-100% and 90-100%, respectively. The subtype distribution as identified by MHA among 224 samples revealed 38% CRF02&#95;AG, 28% G, and 26% G/CRF02&#95;AG recombinants while 8% remained nontypeable strains. In envelope (env) gp120, 38.84% of the samples reacted to a G probe while 31.25% reacted to a CRF02 (subtype A) probe. Full genome characterization of 42 sequences revealed the complexity of Nigerian HIV-1 variants.CRF02&#95;AG, subtype G, and their recombinants were the major circulating HIV-1 variants in 6 Nigerian cities. High proportions of samples reacted to a G probe in env gp120 confirms that subtype G infections are abundant and should be considered in strategies for global HIV-1 vaccine development.

Objective: To determine whether heterosexual transmission of HIV differs according to HIV-1 subtype., Design: A retrospective observational cohort., Methods: HIV-1 subtype effects on heterosexual HIV-1 transmission were determined among 268 HIV-discordant couples retrospectively identified from a population cohort in Rakai, Uganda. HIV-1 subtype (gag and gp41 sequencing and multiregion hybridization assay) and viral loads (reverse transcriptase PCR) were determined. Adjusted incidence rate ratios (adj IRR) of HIV transmission by subtype were estimated by multivariable Poisson regression adjusting for characteristics of index HIV-positive and HIV-negative partners., Results: Adjusting for index HIV-positive partners' age, viral load, stage of disease, genital ulcer disease, and HIV-negative partners' genital ulcer disease and nonuse of condoms, subtype A viruses were associated with a higher rate of transmission than subtype D [adj.IRR 1.98, 95% confidence interval (CI) 1.17-3.34], but no differences in transmission were observed between recombinant viruses and subtype D (aIRR 1.53, P = 0.25). Index-positive partners' age less than 30 years (adj.IRR 3.44, 95% CI 1.75-6.78) and viral load (adj.IRR 2.37, 95% CI 1.75-3.21), and index-negative partners' genital ulcer disease (adj.IRR 1.71, 95% CI 1.08-2.70) and nonuse of condoms (adj.IRR 1.94, 95% CI 1.15-3.28) were significant determinants of HIV transmission., Conclusion: In Rakai, Uganda, subtype A viruses have a significantly higher rate of heterosexual transmission than subtype D viruses. Differential subtype transmission efficiency may be important for HIV vaccine evaluation and could contribute to subtype-specific HIV epidemics in sub-Saharan Africa.

Molecular characterization of C2-V5 envelope sequences from maternal plasma, peripheral blood mononuclear cells (PBMC), cervical secretions and infant PBMC was performed in eight CRF01&#95;AE-infected mother/infant pairs. Maternal viruses were relatively homogeneous within a compartment but distinct in different compartments in mothers with high CD4 cell counts. Infant viruses were almost distinct, but phylogenetically related, to maternal viruses, mostly from the maternal PBMC compartment, reflecting the frequent transmission of HIV-1 from maternal cells rather than free viruses.

Objective: To enable more rapid and efficient genotyping of HIV-1 in East Africa, where subtypes A, C, and D and their recombinants are co-circulating., Design: Full-genome sequencing of HIV-1 provides complete discrimination of subtypes and recombinant forms but is costly and low-throughput compared to other genotyping approaches. Here we describe the development and evaluation of a Multi-region Hybridization Assay (MHA) for the efficient determination of HIV-1 subtypes A, C, D, recombinants, and dual infections., Methods: Five genome regions containing clustered mutations distinguishing subtypes A, C, and D were identified and used to design subtype-specific probes. DNA from primary peripheral blood mononuclear cells was used as template for real-time PCR using the fluorescent, subtype-specific probes., Results: A panel of 45 clinical samples from Uganda, Kenya, and Tanzania, previously characterized by full-genome sequencing and including 26 pure subtypes and 19 recombinant strains, was evaluated by MHA. The MHA provided 90% sensitivity and 98% specificity for the three subtypes, efficiently discriminated subtypes from recombinant forms, and detected several dual infections., Conclusions: Accurate and efficient genotyping of HIV-1 strains in vaccine trial populations in East Africa, ascertainment of dual infections, and elucidation of the genesis of recombinant forms in individuals can be facilitated by the application of MHA., (Copyright 2002 Lippincott Williams & Wilkins)

Objective: To further define the genetic diversity of HIV-1 in Kenya using approaches that clearly distinguish subtypes from inter-subtype recombinants., Design: Near full genome sequencing and analysis were used, including sensitive new tools for detection and mapping of recombinants., Methods: Purified peripheral blood mononuclear cell DNA from 41 HIV-1 positive blood donations collected from six hospitals across southern Kenya was used to amplify near full-length genomes by nested PCR. These were sequenced on an ABI 3100 automated sequencer and analyzed phylogenetically., Results: Among 41 near full-length genomes, 25 were non-recombinant (61%) and 16 were recombinant (39%). Of the 25 pure subtypes, 23 were subtype A, one was subtype C and one was subtype D. Most recombinants consisted of subtype A and either subtype C or subtype D; a few contained A2, a recently identified sub-subtype. Two A2/D recombinants had identical breakpoints and may represent a circulating recombinant form. A third A2/D recombinant had the same structure as a previously described Korean isolate, and these may constitute a second A2-containing circulating recombinant form., Conclusions: In Kenya, 93% of HIV-1 genomes were subtype A or A-containing recombinant strains. Almost 40% of all strains were recombinant. Vaccine candidates tested in Kenya should be based on subtype A strains, but the methods used for evaluation of breakthrough infections during future vaccine trials should be capable of identifying non-A subtypes, the A2 sub-subtype, and recombinants., (Copyright 2002 Lippincott Williams & Wilkins)