Human Immunodeficiency Virus Model Research Articles

The Association between IL-1β and IL-18 Levels, Gut Barrier Disruption, and Monocyte Activation during Chronic Simian Immunodeficiency Virus Infection and Long-Term Suppressive Antiretroviral Therapy.

HIV-induced persistent immune activation is a key mediator of inflammatory comorbidities such as cardiovascular disease (CVD) and neurocognitive disorders. While a preponderance of data indicate that gut barrier disruption and microbial translocation are drivers of chronic immune activation, the molecular mechanisms of this persistent inflammatory state remain poorly understood. Here, utilizing the nonhuman primate model of Human Immunodeficiency Virus (HIV) infection with suppressive antiretroviral therapy (ART), we investigated activation of inflammasome pathways and their association with intestinal epithelial barrier disruption (IEBD). Longitudinal blood samples obtained from rhesus macaques with chronic SIV infection and long-term suppressive ART were evaluated for IEBD biomarkers, inflammasome activation (IL-1β and IL-18), inflammatory cytokines, and triglyceride (TG) levels. Activated monocyte subpopulations and glycolytic potential were investigated in peripheral blood mononuclear cells (PBMCs). During the chronic phase of treated SIV infection, elevated levels of plasma IL-1β and IL-18 were observed following the hallmark increase in IEBD biomarkers, intestinal fatty acid-binding protein (IFABP) and LPS-binding protein (LBP). Further, significant correlations of plasma IFABP levels with IL-1β and IL-18 were observed between 10 and 12 months of ART. Higher levels of sCD14, IL-6, and GM-CSF, among other inflammatory mediators, were also observed only during the long-term SIV + ART phase along with a trend of increase in the frequencies of activated CD14+CD16+ intermediate monocyte subpopulations. Lastly, we found elevated levels of blood TG and higher glycolytic capacity in PBMCs of chronic SIV-infected macaques with long-term ART. The increase in circulating IL-18 and IL-1β following IEBD and their significant positive correlation with IFABP suggest a connection between gut barrier disruption and inflammasome activation during chronic SIV infection, despite viral suppression with ART. Additionally, the increase in markers of monocyte activation, along with elevated TG and enhanced glycolytic pathway activity, indicates metabolic remodeling that could fuel metabolic syndrome. Further research is needed to understand the mechanisms by which gut dysfunction and inflammasome activation contribute to HIV-associated metabolic complications, enabling targeted interventions in people with HIV.

Understanding HIV/AIDS dynamics: insights from CD4+T cells, antiretroviral treatment, and country-specific analysis.

In this article, we present a mathematical model for human immunodeficiency virus (HIV)/Acquired immune deficiency syndrome (AIDS), taking into account the number of CD4+T cells and antiretroviral treatment. This model is developed based on the susceptible, infected, treated, AIDS (SITA) framework, wherein the infected and treated compartments are divided based on the number of CD4+T cells. Additionally, we consider the possibility of treatment failure, which can exacerbate the condition of the treated individual. Initially, we analyze a simplified HIV/AIDS model without differentiation between the infected and treated classes. Our findings reveal that the global stability of the HIV/AIDS-free equilibrium point is contingent upon the basic reproduction number being less than one. Furthermore, a bifurcation analysis demonstrates that our simplified model consistently exhibits a transcritical bifurcation at a reproduction number equal to one. In the complete model, we elucidate how the control reproduction number determines the stability of the HIV/AIDS-free equilibrium point. To align our model with the empirical data, we estimate its parameters using prevalence data from the top four countries affected by HIV/AIDS, namely, Eswatini, Lesotho, Botswana, and South Africa. We employ numerical simulations and conduct elasticity and sensitivity analyses to examine how our model parameters influence the control reproduction number and the dynamics of each model compartment. Our findings reveal that each country displays distinct sensitivities to the model parameters, implying the need for tailored strategies depending on the target country. Autonomous simulations highlight the potential of case detection and condom use in reducing HIV/AIDS prevalence. Furthermore, we identify that the quality of condoms plays a crucial role: with higher quality condoms, a smaller proportion of infected individuals need to use them for the potential eradication of HIV/AIDS from the population. In our optimal control simulations, we assess population behavior when control interventions are treated as time-dependent variables. Our analysis demonstrates that a combination of condom use and case detection, as time-dependent variables, can significantly curtail the spread of HIV while maintaining an optimal cost of intervention. Moreover, our cost-effectiveness analysis indicates that the condom use intervention alone emerges as the most cost-effective strategy, followed by a combination of case detection and condom use, and finally, case detection as a standalone strategy.

Global stability for age-infection-structured human immunodeficiency virus model with heterogeneous transmission

In this paper, we analyze the global asymptotic behaviors of a mathematical susceptible-infected(SI) age-infection-structured human immunodeficiency virus(HIV) model with heterogeneous transmission. Mathematical analysis shows that the local and global dynamics are completely determined by the basic reproductive number R0. If R0<1, disease-free equilibrium is globally asymptotically stable. If R0>1, it shows that disease-free equilibrium is unstable and the unique endemic equilibrium is globally asymptotically stable. The proofs of global stability utilize Lyapunov functions. Besides, the numerical simulations are illustrated to support these theoretical results and sensitivity analysis of each parameter for R0 is performed by the method of partial rank correlation coefficient(PRCC).

A novel approach to state estimation of HIV infection dynamics using fixed-time fractional order observer

This paper presents a novel approach to designing a fixed-time fractional order observer for estimating the states of the dynamic model of human immunodeficiency virus (HIV) infection. The proposed approach combines output injection terminal sliding mode and RBF neural network strategies to achieve a robust and efficient estimation of the states of the HIV model within a fixed time frame. The main contributions of this work are the introduction of an output injection observer that ensures the stability of the error system along with a novel nonlinear sliding surface that guarantees the fixed-time error convergence to the neighborhood of zero. Moreover, the closed-loop scheme of the observer design is proven to be bounded, and the fixed-time stability of the observer error is obtained using the fractional Lyapunov stability approach. Simulation results show that the proposed fixed-time fractional order observer design provides accurate and efficient estimation of the states of the HIV model.

Establishment of Transgenic Mouse Leukemia Cell Lines Expressing Human CD4/CCR5/CyclinT1 Infected with HIV-1.

Establishing a cross-species animal model of human immunodeficiency virus (HIV) infection is crucial for the study of HIV/acquired immunodeficiency syndrome (AIDS). However, due to the species-specific characteristics of HIV-1, the virus can only infect directly humans and a small number of non-human primates. It cannot directly infect mouse cells across species. A mouse leukemia cell line with high CD4 (clusters of differentiation 4)/CCR5 (CC-chemokine receptor 5)/CyclinT1 expression was constructed in this study. First, CD4/CCR5/CyclinT1 lentiviral vector was used to infect a murine leukemia cell line L1210 to express the receptor CD4, co-receptor CCR5 and tat protein driving factor CyclinT1, which are required to infect L1210 cells with HIV-1. The results of sequencing identification and fluorescence expression showed that the plasmid expressing CD4, CCR5, and CyclinT1 vector was successfully constructed and wrapped as the lentiviral vector. Moreover, it was observed that CD4, CCR5, and CyclinT1 proteins were highly expressed in mouse leukemia cells L1210 compared to empty lentiviral vector-transfected cells. Next, viral entry and replication were demonstrated when HIV-1 RNA was detected in body cells and cultured supernatants. Transgenic mice cells L1210 showed significantly greater content of HIV-1 RNA compared to control L1210 cells. Finally, CEMx174 was infected with cell culture supernatants to clarify that the progeny virus is an active virus with infection ability. HIV-1 RNA was highly expressed in CEMx174 cells. This study made the foundation for future studies evaluating HIV-1 cross-species infection in a murine animal model. The results provided new direction for studies investigating the development of vaccines, antiviral drugs screening, and HIV/AIDS pathogenesis.

The Incidence Rate of Sexual Behaviors Among Cisgender Men Who Have Sex with Men Attending a Sexual Health Clinic.

Although nuanced parameterization of sexual behavior may improve estimates from mathematical models of human immunodeficiency virus and sexually transmitted infection transmission, prospective estimates of the incidence of specific sexual behaviors among men who have sex with men (MSM) are limited. From December 2014 to July 2018, MSM with and without nongonococcal urethritis (NGU) completed weekly diaries over 3-12weeks. Incidence rates of any sex, receptive anal sex, insertive anal sex, insertive oral sex, receptive rimming, and receptive hand-penile contact were 1.19, 0.28, 0.66, 0.90, 0.24, and 0.85 episodes per person-week, respectively, among 104 MSM with NGU at baseline, and 1.33, 0.54, 0.32, 0.95, 0.44, and 0.88 episodes per person-week, respectively, among 25 MSM without NGU at baseline. Most receptive anal sex (NGU + 83%, NGU - 86%) and insertive anal sex (NGU + 85%, NGU - 76%) episodes were condomless. MSM engaged in sex just over once per week, and condom use was infrequent. Insertive oral sex and receptive hand-penile contact were the most common behaviors.

Dynamic analysis of humoral immunity HIV for both virus-to-cell and cell-to-cell transmissions with RTI

In this paper, we have fabricated an HIV RTI model accompanied with humoral immunity. Positivity solution for the model and boundedness of the model were derived. Stability analysis of the constructed model about its steady states has been deliberated. Sensitivity analysis is performed on a delay differential equation model for human immunodeficiency virus (HIV) with reverse transcription inhibitors (RTI) model.

A fuzzy generalized predictive controller to optimal drug dosage therapy of mathematical modeling of HIV

This paper proposes a fuzzy-GPC based on a mathematical model of human immunodeficiency virus (HIV) to determine the drug dosage and control the progression of the illness. For this purpose, a Takagi-Sugeno (TS) fuzzy model is generated to identify the nonlinear behavior of HIV. The parameters of HIV are estimated by the least square error (LSE) estimation method. Moreover, three scenarios are proposed to control HIV. In scenario 1, according to TS fuzzy model, generalized Predictive Control (GPC) is designed for a daily base drug therapy. Scenario 2 and 3 are more practical. In scenario 2, since the biological behavior of patients are different, the variation in the patients biology is taken into account by generating data according to a group of patients with varying parameters in their mathematical model. In senario3, since daily diagnosis of patient’s health is costly, it is assumed that a patient information is available every month, and drug dosage is determined each month. As a result of which, the sample time of the measurement increases to 30 make it a multi-rate system. The result shows that the TS fuzzy models the mathematical model of HIV very well, and in all scenarios, the proposed controller has a good performance and the number of healthy cells are controlled in acceptable amount.

Modelling the impact of prevention strategies on cervical cancer incidence in South Africa.

In 2020, the World Health Organisation (WHO) published a strategy to eliminate cervical cancer as a public health concern. In South Africa, despite having a national screening policy in place since 2000, diagnosed cervical cancer incidence has shown no signs of decline. We extend a previously developed individual-based model for human immunodeficiency virus (HIV) and human papillomavirus (HPV) infection to include progression to cervical cancer. The model accounts for future reductions in HIV incidence and prevalence and includes a detailed cervical cancer screening algorithm, based on individual-level data from the public health sector. We estimate the impact of the current prevention programme and alternative screening scenarios on cervical cancer incidence. The South African screening programme prevented 8600 (95%CI 4700-12 300) cervical cancer cases between 2000 and 2019. At current levels of prevention (status quo vaccination, screening, and treatment), age-standardised cervical cancer incidence will reduce from 49.4 per 100 000 women (95%CI 36.6-67.2) in 2020, to 12.0 per 100 000 women (95%CI 8.0-17.2) in 2120. Reaching WHO's prevention targets by 2030 could help South Africa reach elimination (at the 10/100 000 threshold) by 2077 (94% probability of elimination by 2120). Using new screening technologies could reduce incidence to 4.7 per 100 000 women (95%CI 2.8-6.7) in 2120 (44% probability of elimination at the 4/100 000 threshold). HPV vaccination and decreasing HIV prevalence will substantially reduce cervical cancer incidence in the long term, but improvements to South Africa's current screening strategy will be required to prevent cases in the short term. Switching to new screening technologies will have the greatest impact.

Psychosocial Stress Alters the Immune Response and Results in Higher Viral Load During Acute Simian Immunodeficiency Virus Infection in a Pigtailed Macaque Model of Human Immunodeficiency Virus.

Although social distancing is a key public health response during viral pandemics, psychosocial stressors, such as social isolation, have been implicated in adverse health outcomes in general [1] and in the context of infectious disease, such as human immunodeficiency virus (HIV) [2, 3]. A comprehensive understanding of the direct pathophysiologic effects of psychosocial stress on viral pathogenesis is needed to provide strategic and comprehensive care to patients with viral infection. To determine the effect of psychosocial stress on HIV pathogenesis during acute viral infection without sociobehavioral confounders inherent in human cohorts, we compared commonly measured parameters of HIV progression between singly (n = 35) and socially (n = 41) housed simian immunodeficiency virus (SIV)-infected pigtailed macaques (Macaca nemestrina). Singly housed macaques had a higher viral load in the plasma and cerebrospinal fluid and demonstrated greater CD4 T-cell declines and more CD4 and CD8 T-cell activation compared with socially housed macaques throughout acute SIV infection. These data demonstrate that psychosocial stress directly impacts the pathogenesis of acute SIV infection and imply that it may act as an integral variable in the progression of HIV infection and potentially of other viral infections.

COMPLEX FRACTIONAL-ORDER HIV DIFFUSION MODEL BASED ON AMPLITUDE EQUATIONS WITH TURING PATTERNS AND TURING INSTABILITY

A weakly nonlinear analysis provides a system constituting amplitude equations and its related analysis is capable of predicting parameter regimes with different patterns expected to co-exist in dynamical circumstances that exhibit complex fractional-order system characteristics. The Turing mechanism of pattern formation as a result of diffusion-induced instability of the homogeneous steady state is concerned with unpredictable conditions. The Turing instability caused by fractional diffusion in a Human Immunodeficiency Virus model has been addressed in this study. It is important that the effect of the Human Immunodeficiency Virus to the immune system can be modeled by the interaction of uninfected cells, unhealthy cells, virus particles and antigen-specific. Initially, all potential equilibrium points are defined and the stability of the interior equilibrium point is then evaluated using the Routh–Hurwitz criteria. The conditions for Turing instability are obtained by local equilibrium points with stability analysis. In the neighborhood of the Turing bifurcation point, weakly nonlinear analysis is employed to deduce the amplitude equations. After applying amplitude equations, it is observed that this system has a very rich dynamical behavior. The constraints for the formation of the patterns like a hexagon, spot, mixed and stripe patterns are identified for the amplitude equations by dynamic analysis. Furthermore, by using the numerical simulations, the theoretical results are verified. Within this framework, this study through the dynamical behavior of the complex system perspective and bifurcation point based on the viral death rate can provide the basis for several researchers working on Human Immunodeficiency Virus model through various aspects. Accordingly, the Turing bifurcation point and weakly nonlinear analysis employed within the complex fractional-order dynamics addressed herein are highly relevant experimentally since the related effects can be studied and applied concerning different mathematical, physical, engineering and biological models.

Stochastic global exponential stability of disease-free equilibrium of HIV/AIDS model

This paper investigates the dynamics behavior of the mathematical model of Human Immunodeficiency Virus (HIV) influenced by stochastic perturbations. This paper is involved in exploring the disease-free equilibrium’s stochastic global exponential stability with a basic reproductive number $$R_{0} < 1$$ . Necessary and sufficient conditions for stochastic global exponential stability of the disease-free equilibrium $$E^{0}$$ of the nonlinear HIV stochastic system are derived. This can be accomplished by the exponential analysis of the global mean square stability of trivial equilibrium of the corresponding linear system. Finally, we provide areas of stability of $$E^{0}$$ and numerical simulations to confirm the analytical results by using the fundamental Euler–Maruyama (EM) algorithm.

The impact of infected T lymphocyte burst rate and viral shedding rate on optimal treatment scheduling in a human immunodeficiency virus infection

We consider a mathematical model of human immunodeficiency virus (HIV) infection dynamics of T lymphocyte (T cell), infected T cell, and viral populations under reverse transcriptase inhibitor (RTI) andprotease inhibitor (PI) treatment. Existence, uniqueness, and characterization of optimal treatment profiles which minimize total amount of drug used, viral, and infected T cell populations, while maximizing levels of T cells are determined analytically. Numerical optimal control experiments are also performed to illustrate how burst rate of infected T cells and shedding rate of virions impact optimal treatment profiles. Finally, a sensitivity analysis is performed to detect how model input parameters contribute to output variance.

A novel method to estimate the indirect community benefit of HIV interventions using a microsimulation model of HIV disease.

Microsimulation models of human immunodeficiency virus (HIV) disease that simulate individual patients one at a time and assess clinical and economic outcomes of HIV interventions often provide key details regarding direct individual clinical benefits ("individual benefit"), but they may lack detail on transmissions, and thus may underestimate an intervention's indirect benefits ("community benefit"). Dynamic transmission models can be used to simulate HIV transmissions, but they may do so at the expense of the clinical detail of microsimulations. We sought to develop, validate, and demonstrate a practical, novel method that can be integrated into existing HIV microsimulation models to capture this community benefit, integrating the effects of reduced transmission while keeping the clinical detail of microsimulations. We developed a new method to capture the community benefit of HIV interventions by estimating HIV transmissions from the primary cohort of interest. The method captures the benefit of averting infections within the cohort of interest by estimating a corresponding gradual decline in incidence within the cohort. For infections averted outside the cohort of interest, our method estimates transmissions averted based on reductions in HIV viral load within the cohort, and the benefit (life-years gained and cost savings) of averting those infections based on the time they were averted. To assess the validity of our method, we paired it with the Cost-effectiveness of Preventing AIDS Complications (CEPAC) Model - a validated and widely-published microsimulation model of HIV disease. We then compared the consistency of model-estimated outcomes against outcomes of a widely-validated dynamic compartmental transmission model of HIV disease, the HIV Optimization and Prevention Economics (HOPE) model, using the intraclass correlation coefficient (ICC) with a two-way mixed effects model. Replicating an analysis done with HOPE, validation endpoints were number of HIV transmissions averted by offering pre-exposure prophylaxis (PrEP) to men who have sex with men (MSM) and people who inject drugs (PWID) in the US at various uptake and efficacy levels. Finally, we demonstrated an application of our method in a different setting by evaluating the clinical and economic outcomes of a PrEP program for MSM in India, a country currently considering PrEP rollout for this high-risk group. The new method paired with CEPAC demonstrated excellent consistency with the HOPE model (ICC=0.98 for MSM and 0.99 for PWID). With only the individual benefit of the intervention incorporated, a PrEP program for MSM in India averted 43,000 transmissions over a 5-year period and resulted in a lifetime incremental cost-effectiveness ratio (ICER) of US$2,300/year-of-life saved (YLS) compared to the status quo. After applying both the direct (individual) and indirect (community) benefits, PrEP averted 86,000 transmissions over the same period and resulted in an ICER of US$600/YLS. Our method enables HIV microsimulation models that evaluate clinical and economic outcomes of HIV interventions to estimate the community benefit of these interventions (in terms of survival gains and cost savings) efficiently and without sacrificing clinical detail. This method addresses an important methodological gap in health economics microsimulation modeling and allows decision scientists to make more accurate policy recommendations.

Role of rhesus macaque IFITM3(2) in simian immunodeficiency virus infection of macaques.

The experimental infection of rhesus macaques (rh) with simian immunodeficiency virus (SIV) is an important model for human immunodeficiency virus (HIV) infection of humans. The interferon-induced transmembrane protein 3 (IFITM3) inhibits HIV and SIV infection at the stage of host cell entry. However, it is still unclear to what extent the antiviral activity of IFITM3 observed in cell culture translates into inhibition of HIV/SIV spread in the infected host. We have shown previously that although rhIFITM3 inhibits SIV entry into cultured cells, polymorphisms in the rhIFITM3 gene are not strongly associated with viral load or disease progression in SIV infected macaques. Here, we examined whether rhIFITM3(2), which is closely related to rhIFITM3 at the sequence level, exerts antiviral activity and whether polymorphisms in the rhIFITM3(2) gene impact the course of SIV infection. We show that expression of rhIFITM3(2) is interferon-inducible and inhibits SIV entry into cells, although with reduced efficiency as compared to rhIFITM3. We further report the identification of 19 polymorphisms in the rhIFITM3(2) gene. However, analysis of a well characterized cohort of SIV infected macaques revealed that none of the polymorphisms had a significant impact upon the course of SIV infection. These results and our previous work suggest that polymorphisms in the rhIFITM3 and rhIFITM3(2) genes do not strongly modulate the course of SIV infection in macaques.

Global stability of a fractional order HIV infection model with cure of infected cells in eclipse stage

Modeling by fractional order differential equations has more advantages to describe the dynamics of phenomena with memory which exists in many biological systems. In this paper, we propose a fractional order model for human immunodeficiency virus (HIV) infection by including a class of infected cells that are not yet producing virus, i.e., cells in the eclipse stage. We first prove the positivity and bound-edness of solutions in order to ensure the well-posedness of the proposed model. By constructing appropriate Lyapunov functionals, the global stability of the disease-free equilibrium and the chronic infection equilibrium is established. Numerical simulations are presented in order to validate our theoretical results.

Simian immunodeficiency virus transiently increases brain temperature in rhesus monkeys: detection with magnetic resonance spectroscopy thermometry.

To evaluate brain temperature effects of early simian immunodeficiency virus (SIV) infection in rhesus macaques using proton magnetic resonance spectroscopy (MRS) thermometry (MRSt) and to determine whether temperature correlates with brain choline or myo-inositol levels. Brain temperature was retrospectively determined in serial MRS scans that had been acquired at baseline and at 2 and 4 weeks post-SIV infection (wpi) in 16 monkeys by calculating the chemical shift difference between N-acetylaspartate (NAA) and water peaks in sequentially acquired water-suppressed and unsuppressed point-resolved spectroscopy (PRESS) spectra. Frontal and parietal cortex, basal ganglia, and white matter spectra were analyzed. At 2 wpi, brain and rectal temperatures increased relative to baseline and normalized at 4 wpi. Brain temperatures correlated with choline levels in several brain areas, but not with myo-inositol levels. These data indicate that SIV transiently increases brain temperature soon after infection and that temperature is correlated with transient changes in choline levels. Given that choline levels are associated with brain inflammation in SIV-infected monkeys, our findings suggest that the SIV-induced temperature increase reflects brain inflammation. We conclude that MRSt may be informative in human immunodeficiency virus models and may be useful for assessing effects of treatments that reduce inflammation. This study also illustrates that existing MRS data sets containing unsuppressed water spectra can be used to measure tissue temperature, an important physiological parameter.

A Non‐Integer Variable Order Mathematical Model of Human Immunodeficiency Virus and Malaria Coinfection with Time Delay

The purpose of this paper is to propose a variable fractional‐order model with a constant time delay of the coinfection of HIV/AIDS and malaria. The proposed model describes the interaction between HIV/AIDS and malaria. This model is presented by using variable fractional‐order derivative which is an extension of the constant fractional‐order derivative to explain a certain pattern in the development of infection of several patients. The presented model has been solved numerically via the predictor‐corrector scheme. The local and global stability conditions of the disease‐free equilibrium are investigated. Also, numerical simulations are presented for different variable fractional‐order derivatives in Caputo sense.

Modelling In Vivo HIV Dynamics under Combined Antiretroviral Treatment

In this paper a within host mathematical model for Human Immunodeficiency Virus (HIV) transmission incorporating treatment is formulated. The model takes into account the efficacy of combined antiretroviral treatment on viral growth and T cell population in the human blood. The existence of an infection free and positive endemic equilibrium is established. The basic reproduction number R0 is derived using the method of next generation matrix. We perform local and global stability analysis of the equilibria points and show that if R0&lt;1, then the infection free equilibrium is globally asymptotically stable and theoretically the virus is cleared and the disease dies out and if R0&gt;1, then the endemic equilibrium is globally asymptotically stable implying that the virus persists within the host. Numerical simulations are carried out to investigate the effect of treatment on the within host infection dynamics.

Influence of Biological Sex, Age, and HIV Status in an In Vitro Primary Cell Model of HIV Latency Using a CXCR4 Tropic Virus.

Primary cell models of human immunodeficiency virus (HIV) latency have become tools to both understand the mechanisms involved in establishment of latency and test preclinical strategies toward HIV-1 cure. These models rely on infection of CD4 T cells from healthy donors. As such, these models provide an opportunity to explore the role of biological sex, age, and HIV status on establishment and reactivation of latent HIV in vitro. We have used an established primary cell model of latency based on the generation of latently infected central memory CD4 T cells with the CXCR4 strain HIV-1NL4-3 to address whether these variables influence (i) HIV-1NL4-3 replication, (ii) establishment of latency, and (iii) latency reversal in CD4 T cells. Our results indicate that replication of HIV-1NL4-3, but not establishment of latency, is influenced by the age of female, but not male, donors. Moreover, the frequency of latently infected cells in this model is directly correlated with levels of productive infection in both male and female donors independent of age. We did not find differences in the ability of five different latency-reversing agents to reactivate latent HIV-1NL4-3. Finally, we have found that this model can be generated using cells from aviremic participants. In conclusion, we have further characterized the central memory T cell model of latency regarding biological sex and age and demonstrated that this model is suitable for use with cells isolated from aviremic participants, opening the opportunity to use this primary cell model to address cure approaches, including shock and kill, in HIV-infected individuals.