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HIV-1 subtype C-infected individuals maintaining high viral load as potential targets for the "test-and-treat" approach to reduce HIV transmission.

ABSTRACT: The first aim of the study is to assess the distribution of HIV-1 RNA levels in subtype C infection. Among 4,348 drug-naïve HIV-positive individuals participating in clinical studies in Botswana, the median baseline plasma HIV-1 RNA levels differed between the general population cohorts (4.1-4.2 log(10)) and cART-initiating cohorts (5.1-5.3 log(10)) by about one log(10). The proportion of individuals with high (> or = 50,000 (4.7 log(10)) copies/ml) HIV-1 RNA levels ranged from 24%-28% in the general HIV-positive population cohorts to 65%-83% in cART-initiating cohorts. The second aim is to estimate the proportion of individuals who maintain high HIV-1 RNA levels for an extended time and the duration of this period. For this analysis, we estimate the proportion of individuals who could be identified by repeated 6- vs. 12-month-interval HIV testing, as well as the potential reduction of HIV transmission time that can be achieved by testing and ARV treating. Longitudinal analysis of 42 seroconverters revealed that 33% (95% CI: 20%-50%) of individuals maintain high HIV-1 RNA levels for at least 180 days post seroconversion (p/s) and the median duration of high viral load period was 350 (269; 428) days p/s. We found that it would be possible to identify all HIV-infected individuals with viral load > or = 50,000 (4.7 log(10)) copies/ml using repeated six-month-interval HIV testing. Assuming individuals with high viral load initiate cART after being identified, the period of high transmissibility due to high viral load can potentially be reduced by 77% (95% CI: 71%-82%). Therefore, if HIV-infected individuals maintaining high levels of plasma HIV-1 RNA for extended period of time contribute disproportionally to HIV transmission, a modified "test-and-treat" strategy targeting such individuals by repeated HIV testing (followed by initiation of cART) might be a useful public health strategy for mitigating the HIV epidemic in some communities.

SUBMITTER: Novitsky V

PROVIDER: S-EPMC2853582 | biostudies-literature | 2010 Apr

REPOSITORIES: biostudies-literature

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HIV-1 subtype C-infected individuals maintaining high viral load as potential targets for the "test-and-treat" approach to reduce HIV transmission.

Novitsky Vladimir V Wang Rui R Bussmann Hermann H Lockman Shahin S Baum Marianna M Shapiro Roger R Thior Ibou I Wester Carolyn C Wester C William CW Ogwu Anthony A Asmelash Aida A Musonda Rosemary R Campa Adriana A Moyo Sikhulile S van Widenfelt Erik E Mine Madisa M Moffat Claire C Mmalane Mompati M Makhema Joseph J Marlink Richard R Gilbert Peter P Seage George R GR DeGruttola Victor V Essex M M

PloS one 20100412 4

The first aim of the study is to assess the distribution of HIV-1 RNA levels in subtype C infection. Among 4,348 drug-naïve HIV-positive individuals participating in clinical studies in Botswana, the median baseline plasma HIV-1 RNA levels differed between the general population cohorts (4.1-4.2 log(10)) and cART-initiating cohorts (5.1-5.3 log(10)) by about one log(10). The proportion of individuals with high (> or = 50,000 (4.7 log(10)) copies/ml) HIV-1 RNA levels ranged from 24%-28% in the ge ...[more]

PMID: 20405044

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Project description:BACKGROUND:Access to HIV viral load is crucial to efficiently monitor patients on antiretroviral treatment (ART) and prevent HIV drug resistance acquisition. However, in some remote settings, access to viral load monitoring is still complex due to logistical and financial constraints. Use of dried blood spots (DBS) for blood collection could overcome these difficulties. This study aims to describe feasibility and operability of DBS use for routine viral load monitoring. METHODS:From June 2017 to April 2018, HIV-infected adults who initiated ART were enrolled in a prospective cohort in 43 clinical sites across 6 provinces in North Vietnam. Following national guidelines, the first viral load monitoring was planned 6 months after ART initiation. DBS were collected at the clinical site and sent by post to a central laboratory in Hanoi for viral load measurement. RESULTS:Of the 578 patients enrolled, 537 were still followed 6 months after ART initiation, of which DBS was collected for 397 (73.9%). The median (inter quartile range) delay between DBS collection at site level and reception at the central laboratory was 8 (6-19) days and for 70.0% viral load was measured ≤30 days after blood collection. The proportion of patients with viral load ≥1000 copies/mL at the 6 month evaluation was 15.9% (n = 59). Of these, a DBS was collected again to confirm virological failure in 15 (24.4%) of which virological failure was confirmed in 11 (73.3%). CONCLUSION:Delay of DBS transfer to the central laboratory was acceptable and most viral loads were measured in ≤30 days, in-line with routine follow-up. However, the level of DBS coverage and the proportion of patients in failure for whom a confirmatory viral load was available were suboptimal, indicating that integration of viral load monitoring in the field requires, among other things, careful training and strong involvement of the local teams. The proportion of patients experiencing virological failure was in line with other reports; interestingly those who reported being non-adherent and those with a low BMI were more at risk of failure.

Project description:HIV-1 downregulates HLA-A and HLA-B from the surface of infected cells primarily to evade CD8 T cell recognition. HLA-C was thought to remain on the cell surface and bind inhibitory killer immunoglobulin-like receptors, preventing NK cell-mediated suppression. However, a recent study found HIV-1 primary viruses have the capacity to downregulate HLA-C. The goal of this study was to assess the heterogeneity of HLA-A, HLA-B and HLA-C downregulation among full-length primary viruses from six chronically infected and six newly infected individuals from transmission pairs, and to determine whether transmitted/founder variants exhibit common HLA class I downregulation characteristics. We measured HLA-A, HLA-B, HLA-C and total HLA class I downregulation by flow cytometry of primary CD4 T cells infected with 40 infectious molecular clones. Primary viruses mediated a range of HLA class I downregulation capacities (1.3-6.1-fold), which could differ significantly between transmission pairs. Downregulation of HLA-C surface expression on infected cells correlated with susceptibility to in vitro NK cell suppression of virus release. Despite this, transmitted/founder variants did not share a common downregulation signature and instead were more similar to the quasispecies of matched donor partners. These data indicate that a range of viral abilities to downregulate HLA-A, HLA-B and HLA-C exist within and between individuals, which can have functional consequences on immune recognition.IMPORTANCE Subtype C HIV-1 is the predominant subtype involved in heterosexual transmission in Sub-Saharan Africa. Authentic subtype C viruses that contain natural sequence variations throughout the genome are often not used in experimental systems, due to technical constraints and sample availability. In this study, authentic full-length subtype C viruses, including transmitted/founder viruses, were examined for the ability to disrupt surface expression of human leukocyte antigen (HLA) class I molecules, which are central to both adaptive and innate immune responses to viral infections. We found that HLA class I downregulation capacity of primary viruses varied, and HLA-C downregulation capacity impacted viral suppression by natural killer cells. Transmitted viruses were not distinct in the capacity for HLA class I downregulation or natural killer cell evasion. These results enrich our understanding of the phenotypic variation existing among natural HIV-1 viruses, and how that might impact the ability of the immune system to recognize infected cells in acute and chronic infection.

Dataset Information

HIV-1 subtype C-infected individuals maintaining high viral load as potential targets for the "test-and-treat" approach to reduce HIV transmission.

Publications

HIV-1 subtype C-infected individuals maintaining high viral load as potential targets for the "test-and-treat" approach to reduce HIV transmission.

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