scholarly journals Evaluation of Phylogenetic Methods for Inferring the Direction of Human Immunodeficiency Virus (HIV) Transmission: HIV Prevention Trials Network (HPTN) 052

2020 ◽  
Author(s):  
Yinfeng Zhang ◽  
Chris Wymant ◽  
Oliver Laeyendecker ◽  
M Kathryn Grabowski ◽  
Matthew Hall ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Hiv Prevention ◽  
Hiv Transmission ◽  
Group Analysis ◽  
Whole Genome ◽  
Individual Sample ◽  
Immunodeficiency Virus ◽  
Prevention Trials ◽  
Ngs Data ◽  
Transmission Direction

Abstract Background Phylogenetic analysis can be used to assess human immunodeficiency virus (HIV) transmission in populations. We inferred the direction of HIV transmission using whole-genome HIV sequences from couples with known linked infection and known transmission direction. Methods Complete next-generation sequencing (NGS) data were obtained for 105 unique index–partner sample pairs from 32 couples enrolled in the HIV Prevention Trials Network (HPTN) 052 study (up to 2 samples/person). Index samples were obtained up to 5.5 years before partner infection; partner samples were obtained near the time of seroconversion. The bioinformatics method, phyloscanner, was used to infer transmission direction. Analyses were performed using samples from individual sample pairs, samples from all couples (1 sample/person; group analysis), and all available samples (multisample group analysis). Analysis was also performed using NGS data from defined regions of the HIV genome (gag, pol, env). Results Using whole-genome NGS data, transmission direction was inferred correctly (index to partner) for 98 of 105 (93.3%) of the individual sample pairs, 99 of 105 (94.3%) sample pairs using group analysis, and 31 of the 32 couples (96.9%) using multisample group analysis. There were no cases where the incorrect transmission direction (partner to index) was inferred. The accuracy of the method was higher with greater time between index and partner sample collection. Pol region sequences performed better than env or gag sequences for inferring transmission direction. Conclusions We demonstrate the potential of a phylogenetic method to infer the direction of HIV transmission between 2 individuals using whole-genome and pol NGS data.

scholarly journals Better Virological Outcomes Among People Living With Human Immunodeficiency Virus (HIV) Initiating Early Antiretroviral Treatment (CD4 Counts ≥500 Cells/µL) in the HIV Prevention Trials Network 071 (PopART) Trial in South Africa

2019 ◽  
Vol 70 (3) ◽  
pp. 395-403 ◽  
Author(s):  
Geoffrey Fatti ◽  
Ashraf Grimwood ◽  
Jean B Nachega ◽  
Jenna A Nelson ◽  
Kelsea LaSorda ◽  
...  
Keyword(s):  
South Africa ◽  
Human Immunodeficiency Virus ◽  
Hiv Prevention ◽  
Cd4 Count ◽  
Adjusted Relative Risk ◽  
Cd4 Counts ◽  
Immunodeficiency Virus ◽  
Virological Outcomes ◽  
Prevention Trials ◽  
Cd4 Cell

Abstract Background There have been concerns about reduced adherence and human immunodeficiency virus (HIV) virological suppression (VS) among clinically well people initiating antiretroviral therapy (ART) with high pre-ART CD4 cell counts. We compared virological outcomes by pre-ART CD4 count, where universal ART initiation was provided in the HIV Prevention Trials Network 071 (PopART) trial in South Africa prior to routine national and international implementation. Methods This prospective cohort study included adults initiating ART at facilities providing universal ART since January 2014. VS (<400 copies/mL), confirmed virological failure (VF) (2 consecutive viral loads >1000 copies/mL), and viral rebound were compared between participants in strata of baseline CD4 cell count. Results The sample included 1901 participants. VS was ≥94% among participants with baseline CD4 count ≥500 cells/µL at all 6-month intervals to 30 months. The risk of an elevated viral load (≥400 copies/mL) was independently lower among participants with baseline CD4 count ≥500 cells/µL (3.3%) compared to those with CD4 count 200–499 cells/µL (9.2%) between months 18 and 30 (adjusted relative risk, 0.30 [95% confidence interval, .12–.74]; P = .010). The incidence rate of VF was 7.0, 2.0, and 0.5 per 100 person-years among participants with baseline CD4 count <200, 200–499, and ≥500 cells/µL, respectively (P < .0001). VF was independently lower among participants with baseline CD4 count ≥500 cells/µL (adjusted hazard ratio [aHR], 0.23; P = .045) and 3-fold higher among those with baseline CD4 count <200 cells/µL (aHR, 3.49; P < .0001). Conclusions Despite previous concerns, participants initiating ART with CD4 counts ≥500 cells/µL had very good virological outcomes, being better than those with CD4 counts 200–499 cells/µL. Clinical Trials Registration NCT01900977.

scholarly journals Targeted Pregnancy and Human Immunodeficiency Virus Prevention Risk-Reduction Counseling for Young Women: Lessons Learned from Biomedical Prevention Trials

2018 ◽  
Vol 218 (11) ◽  
pp. 1759-1766 ◽  
Author(s):  
Gita Ramjee ◽  
Reshmi Dassaye ◽  
Tarylee Reddy ◽  
Handan Wand
Keyword(s):  
Risk Factors ◽  
Human Immunodeficiency Virus ◽  
Hiv Prevention ◽  
Pregnant Women ◽  
Young Women ◽  
Cox Regression ◽  
Human Immunodeficiency Virus Prevention ◽  
Immunodeficiency Virus ◽  
Prevention Trials ◽  
Hiv Acquisition

Abstract Background Women enrolled in human immunodeficiency virus (HIV) prevention efficacy trials receive counseling on prevention of HIV, sexually transmitted infections (STIs), and pregnancy during every visit. Incident pregnancy has an impact on efficacy outcomes. Incidence rates of pregnancy and HIV/STIs among women who became pregnant and associated risk factors were assessed. Methods Data from 9165 women participating in HIV prevention trials in KwaZulu-Natal, South Africa from 2002–2012 were combined. Demographic and behavioral predictors of incidence pregnancy and incidence HIV and STIs were determined using Cox regression models. Results Overall pregnancy incidence was 9.6 per 100 person-year (py) (95% confidence interval [Cl], 9.1–10.3). Human immunodeficiency virus incidence among pregnant women was 5.93 per 100 py (95% Cl, 4.73–7.44). Incidence of STIs among pregnant women for Chlamydia trachomatis, Trichomonas vaginalis, Neisseria gonorrhoeae, and Treponema pallidum (syphilis) were 10.87, 7.42, 3.92, and 1.43 per 100 py, respectively. In the adjusted analyses, we observed overlapping risk factors for HIV acquisition during pregnancy, ie, young age, not married/not cohabitating, and low parity. The risk of pregnancy and HIV acquisition is more than 3 times higher among young women (<20 years of age). Conclusions We identified overlapping risk factors for pregnancy and HIV incidence, suggesting an urgent need for appropriate, targeted, individual-centred counseling for women participating in HIV prevention trials.

Human Immunodeficiency Virus Preexposure Prophylaxis in Adolescents and Young Adults

2021 ◽  
Vol 43 (1) ◽  
pp. 28-36
Author(s):  
Megan E. Brundrett
Keyword(s):  
Human Immunodeficiency Virus ◽  
Young Adults ◽  
Hiv Prevention ◽  
Hiv Transmission ◽  
Hiv Infections ◽  
Adolescents And Young Adults ◽  
Prevention Services ◽  
Preexposure Prophylaxis ◽  
Immunodeficiency Virus ◽  
Hiv Acquisition

Human immunodeficiency virus (HIV) prevention holds the promise of decreasing the burden of HIV infections worldwide. Access to HIV prevention services, including preexposure prophylaxis (PrEP), is a key strategy in reducing HIV transmission, but it continues to be underused. PrEP, a once-daily medication for HIV prevention, is approved for adolescents. A pediatrician’s role is critical in identifying and increasing access for adolescents and young adults to PrEP services and reducing HIV acquisition in youth.

scholarly journals Cabotegravir Is Not Associated With Weight Gain in Human Immunodeficiency Virus–uninfected Individuals in HPTN 077

2019 ◽  
Vol 70 (2) ◽  
pp. 319-322 ◽  
Author(s):  
Raphael J Landovitz ◽  
Sahar Z Zangeneh ◽  
Gordon Chau ◽  
Beatriz Grinsztejn ◽  
Joseph J Eron ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Weight Gain ◽  
Antiretroviral Therapy ◽  
Hiv Prevention ◽  
Integrase Inhibitor ◽  
Excess Weight ◽  
Metabolic Parameters ◽  
Excess Weight Gain ◽  
Immunodeficiency Virus ◽  
Prevention Trials

AbstractStudies in human immunodeficiency virus (HIV)–infected individuals suggest excess weight gain with integrase inhibitor–based antiretroviral therapy. The HIV Prevention Trials Network Study 077 evaluated changes in weight and fasting metabolic parameters in HIV-uninfected individuals randomized to cabotegravir or a placebo. No differences between arms were found for change in weight or fasting metabolic parameters overall or for subgroups.

scholarly journals Human Immunodeficiency Virus (HIV) Drug Resistance, Phylogenetic Analysis, and Superinfection Among Men Who Have Sex with Men and Transgender Women in Sub-Saharan Africa: HIV Prevention Trials Network (HPTN) 075 Study

2020 ◽  
Author(s):  
Mariya V Sivay ◽  
Philip J Palumbo ◽  
Yinfeng Zhang ◽  
Vanessa Cummings ◽  
Xu Guo ◽  
...  
Keyword(s):  
South Africa ◽  
Human Immunodeficiency Virus ◽  
Drug Resistance ◽  
Hiv Prevention ◽  
Transgender Women ◽  
Sub Saharan Africa ◽  
Immunodeficiency Virus ◽  
Prevention Trials ◽  
Sub Saharan ◽  
Sex With Men

Abstract Background The HIV Prevention Trials Network (HPTN) 075 study evaluated the feasibility of enrolling and retaining men who have sex with men (MSM) and transgender women (TWG) from Kenya, Malawi, and South Africa. During the study follow-up, 21 participants acquired human immunodeficiency virus (HIV) (seroconverters). We analyzed HIV subtype diversity, drug resistance, transmission dynamics, and HIV superinfection data among MSM and TGW enrolled in HPTN 075. Methods HIV genotyping and drug resistance testing were performed for participants living with HIV who had viral loads >400 copies/mL at screening (prevalent cases, n = 124) and seroconverters (n = 21). HIV pol clusters were identified using Cluster Picker. Superinfection was assessed by a longitudinal analysis of env and pol sequences generated by next-generation sequencing. Results HIV genotyping was successful for 123/124 prevalent cases and all 21 seroconverters. The major HIV subtypes were A1 (Kenya) and C (Malawi and South Africa). Major drug resistance mutations were detected in samples from 21 (14.6%) of 144 participants; the most frequent mutations were K103N and M184V/I. Phylogenetic analyses identified 11 clusters (2–6 individuals). Clusters included seroconverters only (n = 1), prevalent cases and seroconverters (n = 4), and prevalent cases only (n = 6). Superinfections were identified in 1 prevalent case and 2 seroconverters. The annual incidence of superinfection was higher among seroconverters than among prevalent cases, and was higher than the rate of primary HIV infection in the cohort. Conclusions This report provides important insights into HIV genetic diversity, drug resistance, and superinfection among MSM and TWG in sub-Saharan Africa. These findings may help to inform future HIV prevention interventions in these high-risk groups.

scholarly journals Counselors’ Knowledge about HIV Transmission and Prevention

2020 ◽  
pp. 1-9
Author(s):  
Joseph Campbell ◽  
Zachary Pietrantoni ◽  
Audrey Miller
Keyword(s):  
Human Immunodeficiency Virus ◽  
Hiv Prevention ◽  
Counselor Training ◽  
Online Survey ◽  
Hiv Transmission ◽  
Survey Study ◽  
Prevention Strategies ◽  
Related Factors ◽  
Hiv Prevention Strategies ◽  
Immunodeficiency Virus

This article presents the results of an online survey study of 80 counselors to explore counselors’ knowledge about Human Immunodeficiency Virus (HIV) transmission, HIV prevention strategies, potentially related factors, and where counselors obtained their knowledge. Results show that approximately 90% of counselors correctly identified knowledge about HIV transmission, 68% correctly identified knowledge about HIV prevention strategies, and 64% reported receiving no education regarding HIV/AIDS in their graduate counseling programs. Implications for counselor training and professional development are discussed.

scholarly journals Novel Strategy To Adapt Simian-Human Immunodeficiency Virus E1 Carryingenvfrom an RV144 Volunteer to Rhesus Macaques: Coreceptor Switch and Final Recovery of a Pathogenic Virus with Exclusive R5 Tropism

2018 ◽  
Vol 92 (14) ◽  
Author(s):  
Hanna B. Scinto ◽  
Sandeep Gupta ◽  
Swati Thorat ◽  
Muhammad M. Mukhtar ◽  
Anthony Griffiths ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Placebo Recipient ◽  
T Cell ◽  
Hiv Transmission ◽  
Rhesus Macaques ◽  
Phase Iii ◽  
Immunodeficiency Virus ◽  
Coreceptor Switch ◽  
Novel Strategy ◽  
Hiv Acquisition

ABSTRACTThe phase III RV144 human immunodeficiency virus (HIV) vaccine trial conducted in Thailand remains the only study to show efficacy in decreasing the HIV acquisition risk. In Thailand, circulating recombinant forms of HIV clade A/E (CRF01_AE) predominate; in such viruses,envoriginates from clade E (HIV-E). We constructed a simian-human immunodeficiency virus (SHIV) chimera carryingenvisolated from an RV144 placebo recipient in the SHIV-1157ipd3N4 backbone. The latter contains long terminal repeats (LTRs) with duplicated NF-κB sites, thus resembling HIV LTRs. We devised a novel strategy to adapt the parental infectious molecular clone (IMC), R5 SHIV-E1, to rhesus macaques: the simultaneous depletion of B and CD8+cells followed by the intramuscular inoculation of proviral DNA and repeated administrations of cell-free virus. High-level viremia and CD4+T-cell depletion ensued. Passage 3 virus unexpectedly caused acute, irreversible CD4+T-cell loss; the partially adapted SHIV had become dual tropic. Virus and IMCs with exclusive R5 tropism were reisolated from earlier passages, combined, and used to complete adaptation through additional macaques. The final isolate, SHIV-E1p5, remained solely R5 tropic. It had a tier 2 neutralization phenotype, was mucosally transmissible, and was pathogenic. Deep sequencing revealed 99% Env amino acid sequence conservation; X4-only and dual-tropic strains had evolved independently from an early branch of parental SHIV-E1. To conclude, our primate model data reveal that SHIV-E1p5 recapitulates important aspects of HIV transmission and pathobiology in humans.IMPORTANCEUnderstanding the protective principles that lead to a safe, effective vaccine against HIV in nonhuman primate (NHP) models requires test viruses that allow the evaluation of anti-HIV envelope responses. Reduced HIV acquisition risk in RV144 has been linked to nonneutralizing IgG antibodies with a range of effector activities. Definitive experiments to decipher the mechanisms of the partial protection observed in RV144 require passive-immunization studies in NHPs with a relevant test virus. We have generated such a virus by insertingenvfrom an RV144 placebo recipient into a SHIV backbone with HIV-like LTRs. The final SHIV-E1p5 isolate, grown in rhesus monkey peripheral blood mononuclear cells, was mucosally transmissible and pathogenic. Earlier SHIV-E passages showed a coreceptor switch, again mimicking HIV biology in humans. Thus, our series of SHIV-E strains mirrors HIV transmission and disease progression in humans. SHIV-E1p5 represents a biologically relevant tool to assess prevention strategies.

scholarly journals DC-SIGN Interactions with Human Immunodeficiency Virus: Virus Binding and Transfer Are Dissociable Functions

2001 ◽  
Vol 75 (21) ◽  
pp. 10523-10526 ◽  
Author(s):  
Stefan Pöhlmann ◽  
George J. Leslie ◽  
Terri G. Edwards ◽  
Todd Macfarlan ◽  
Jacqueline D. Reeves ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Cell Surface ◽  
Hiv Transmission ◽  
Virus Transmission ◽  
Underlying Mechanism ◽  
Virus Binding ◽  
Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Virus

ABSTRACT The C-type lectins DC-SIGN and DC-SIGNR capture and transfer human immunodeficiency virus (HIV) to susceptible cells, although the underlying mechanism is unclear. Here we show that DC-SIGN/DC-SIGNR-mediated HIV transmission involves dissociable binding and transfer steps, indicating that efficient virus transmission is not simply due to tethering of virus to the cell surface.

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