HIV Treatment Strategies Research Articles

Training rhesus macaques to take daily oral antiretroviral therapy for preclinical evaluation of HIV prevention and treatment strategies.

BackgroundMacaque models of simian or simian/human immunodeficiency virus (SIV or SHIV) infection are critical for the evaluation of antiretroviral (ARV)-based HIV treatment and prevention strategies. However, modelling human oral ARV administration is logistically challenging and fraught by limited adherence. Here, we developed a protocol for administering daily oral doses of ARVs to macaques with a high rate of compliance.MethodsParameters of positive reinforcement training (PRT), behavioral responses and optimal drug delivery foods were defined in 7 male rhesus macaques (Macaca mulatta). Animals were trained to sit in a specified cage location prior to receiving ARVs, emtricitabine (FTC) and tenofovir alafenamide (TAF), in a blended food mixture, which was followed immediately with a juice chaser. Consistency of daily oral adherence was evaluated in 4 trained macaques receiving clinically equivalent doses of FTC and TAF (20 and 1.5 mg/kg, respectively) in a short-term (1 month) and an extended (6 month) trial. Adherence was monitored using medication diaries and by quantifying intracellular FTC-triphosphate (FTC-TP) and tenofovir-diphosphate (TFV-DP) concentrations in peripheral mononuclear blood cells (PBMCs).ResultsTrained macaques quickly and consistently took daily oral ARVs for 1 month with an average 99.8% observed adherence. Intracellular concentrations of TFV-DP (median = 845.8 fmol/million cells [range, 620.8–1031.3]) and FTC-TP (median = 367.0 fmol/million cells [range, 289.5–413.5) in PBMCs were consistent with high adherence. Extended treatment with select subjects yielded similar observations for three months (99.5% adherence, 352/356 complete doses taken), although a sudden drop in adherence was observed after splenic biopsy surgery.ConclusionsWe demonstrate that trained macaques reliably adhere to a daily oral ARV regimen, although unexpected adherence issues are possible. Our approach, using clinical doses of oral FTC and TAF daily, further refines macaque models of HIV treatment and prevention by mimicking the human route and timing of ARV administration.

Prisons: ignore them at our peril.

People with HIV and HCV are concentrated within criminal justice settings globally, primarily related to criminalization of drug use. This review examines updated prevention and treatment strategies for HIV and HCV within prison with a focus on people who inject drugs and the challenges associated with the provision of these services within prisons and other closed settings and transition to the community. The prevalence of HIV and HCV are several-fold higher in the criminal justice system than within the broader community particularly in regions with high prevalence of injecting drug use, such as Asia, Eastern Europe and North America and where drug use is criminalized. Strategies to optimize management for these infections include routine screening linked to treatment within these settings and medication-assisted treatments for opioid dependence and access to syringe services programs. We build upon the 2016 WHO Consolidated Guidelines through the lens of the key populations of prisoners. Linkage to treatment postrelease, has been universally dismal, but is improved when linked to medication-assisted therapies like methadone, buprenorphine and overdose management. In many prisons, particularly in low-income and middle-income settings, provision of even basic healthcare including mental healthcare and basic HIV prevention tools remain suboptimal. In order to address HIV and HCV prevention and treatment within criminal justice settings, substantial improvement in the delivery of basic healthcare is needed in many prisons worldwide together with effective screening, treatment and linkage of treatment and prevention services to medication-assisted therapies within prison and linkage to care after release.

Structural Design and Data Requirements for Simulation Modelling in HIV/AIDS: A Narrative Review.

Born out of a necessity for fiscal sustainability, simulation modeling is playing an increasingly prominent role in setting priorities for combination implementation strategies for HIV treatment and prevention globally. The design of a model and the data inputted into it are central factors in ensuring credible inferences. We executed a narrative review of a set of dynamic HIV transmission models to comprehensively synthesize and compare the structural design and the quality of evidence used to support each model. We included 19 models representing both generalized and concentrated epidemics, classified as compartmental, agent-based, individual-based microsimulation or hybrid in our review. We focused on four structural components (population construction; model entry, exit and HIV care engagement; HIV disease progression; and the force of HIV infection), and two analytical components (model calibration/validation; and health economic evaluation, including uncertainty analysis). While the models we reviewed focused on a variety of individual interventions and their combinations, their structural designs were relatively homogenous across three of the four focal components, with key structural elements influenced by model type and epidemiological context. In contrast, model entry, exit and HIV care engagement tended to differ most across models, with some health system interactions-particularly HIV testing-not modeled explicitly in many contexts. The quality of data used in the models and the transparency with which the data was presented differed substantially across model components. Representative and high-quality data on health service delivery were most commonly not accessed or were unavailable. The structure of an HIV model should ideally fit its epidemiological context and be able to capture all efficacious treatment and prevention services relevant to a robust combination implementation strategy. Developing standardized guidelines on evidence syntheses for health economic evaluation would improve transparency and help prioritize data collection to reduce decision uncertainty.

Understanding the role of resilience resources, antiretroviral therapy initiation, and HIV-1 RNA suppression among people living with HIV in South Africa: a prospective cohort study.

Failure to initiate antiretroviral therapy (ART) and achieve virologic suppression are significant barriers to the United Nations 90-90-90 goals. Identifying resilience resources, or modifiable strength-based factors, among people living with HIV is critical for successful HIV treatment and prevention. Prospective cohort study. From July 2014 to July 2015, 500 adults presenting for voluntary counseling and HIV testing who were diagnosed with HIV and were ART-eligible in South Africa (Soweto and Gugulethu) were enrolled and surveyed. Logistic regression models assessed resilience-related predictors of ART initiation within 6 months of voluntary counseling and HIV testing for HIV, and HIV-1 plasma RNA suppression within 9 months, adjusting for sociodemographic factors. Within 6 months, 62% initiated ART, and within 9 months, 25% had evidence of an undetectable HIV-1 plasma RNA (<50 copies/ml). Participants who initiated ART relied less on social support from friends [adjusted odds ratio (aOR) 0.94, 95% confidence interval (CI): 0.89-0.99], coped using self-distraction (aOR 1.05, 95% CI: 1.00-1.10) and avoided coping through substance use (aOR 0.79, 95% CI: 0.65-0.97), as compared with participants who did not initiate ART. Those who achieved plasma RNA suppression relied more on social support from a significant other/partner (aOR 1.04, 95% CI: 1.02-1.07), used positive religious coping (aOR 1.03, 95% CI: 1.00-1.07), and were less likely to engage in denial coping (aOR 0.84, 95% CI: 0.77-0.92), compared with those who initiated ART but did not achieve plasma RNA suppression. Interventions optimizing resilience resources and decreasing maladaptive coping strategies (e.g., substance use, denial) may present a feasible approach to maximizing ART-based HIV treatment strategies among South African people living with HIV.

HIV care cost in England: a cross-sectional analysis of antiretroviral treatment and the impact of generic introduction.

Reliable and timely HIV care cost estimates are important for policy option appraisals of HIV treatment and prevention strategies. As HIV clinical management and outcomes have changed, we aimed to update profiles of antiretroviral (ARV) usage pattern, patent/market exclusivity details and management costs in adults (≥18years old) accessing HIV specialist care in England. The data reported quarterly to the HIV and AIDS Reporting System in England was used to identify ARV usage pattern, and were combined with British National Formulary (BNF) prices, non-ARV care costs and patent/market exclusivity information to generate average survival-adjusted lifetime care costs. The cumulative budget impact from 2018 to the year in which all current ARVs were expected to lose market exclusivity was calculated for a hypothetical 85000 (± 5000) person cohort, which provided an illustration of potential financial savings afforded by bioequivalent generic switches. Price scenarios explored BNF70 (September 2015) prices and generics at 10/20/30/50% of proprietary prices. The analyses took National Health Service (NHS) England's perspective (as the payer), and results are presented in 2016/2017 British pounds. By 2033, most currently available ARVs would lose market exclusivity; that is, generics could be available. Average per person lifetime HIV cost was ~£200000 (3.5% annual discount) or ~£400000 (undiscounted), reducing to ~£70000 (3.5% annual discount; ~£120000 undiscounted) with the use of generics (assuming that generics cost 10% of proprietary prices). The cumulative budget to cover 85000 (± 5000) persons for 16years (2018-2033) was £10.5 (± 0.6) billion, reducing to £3.6 (± 0.2) billion with the use of generics. HIV management costs are high but financial efficiency could be improved by optimizing generic use for treatment and prevention to mitigate the high cost of lifelong HIV treatment. Earlier implementation of generics as they become available offers the potential to maximize the scale of the financial savings.

Disparities in Viral Suppression and Medication Adherence among Women in the USA, 2011-2016.

We assessed disparities in viral suppression (VS) and antiretroviral therapy (ART) adherence among women of the HIV Outpatient Study to inform HIV treatment strategies. We used adjusted prevalence ratios (aPR) with 95% confidence intervals (CI) to assess VS by race/ethnicity and generalized estimating equations to investigate factors associated with not achieving VS and ART non-adherence. Among 426 women (median age = 46years), at baseline, VS was less prevalent among black women (63%) compared with Hispanic women/Latinas (73%) and white women (78%). In the multivariable analysis, factors significantly associated with not achieving VS included the following social and behavioral determinants of care: using public insurance (aPR = 1.69, CI 1.01-2.82, p = 0.044) compared to using private insurance, seeking care in a public clinic (aPR = 1.60, CI 1.03-2.50, p = 0.037) compared to seeking care in a private clinic, and ART non-adherence (aPR = 2.79, CI 1.81-4.29), p < 0.001). Although race was not a significant factor in not achieving VS, race was associated with ART non-adherence; black women were more likely to miss a dose of ART medication (aPR = 2.07, CI 1.19-3.60, p = 0.010) when compared to white women and Hispanic women/Latinas. Interventions and resources disseminated to address social barriers to care and improve VS and ART adherence among HIV-positive women, particularly black women, are warranted.

Evaluating Physicians' Intention to Discriminate Against Patients Living with HIV in Malaysia.

People with HIV (PWH) in Malaysia experience high levels of stigma, which may act as a barrier to accessing healthcare. Stigma against PWH in medical settings is understudied in Malaysia. In the present study, we examine factors associated with physicians' intention to discriminate against PWH in Malaysia. A cross-sectional online survey was emailed to all 1431 physicians at two major university hospitals in Malaysia; 568 (39.6%) participants completed the survey and were included in this analysis. Measures included intention to discriminate against PWH, stigma-related constructs, and socio-demographic characteristics. Multivariate linear regression was used to identify factors associated with intention to discriminate against PWH. Participants were comprised of women (53.5%), Malays (43.1%), and Chinese (35.0%) with nearly 10years of clinical experience. Most participants were from non-surgical specialties (77.6%). The final multivariate linear regression showed that physicians who expressed greater discriminatory intent against PWH also expressed more negative feelings toward PWH, more HIV-related shame, were more fearful of HIV, and believed that PWH do not deserve good care. Physicians from surgical-based specialties were also significantly more likely to endorse discriminatory intent toward PWH. Stigma and intentions to discriminate against a class of patients, including PWH, can undermine engagement in care, which is central to international HIV prevention and treatment strategies. Interventions that reduce stigma toward PWH among physicians are crucial to ensuring equitable and stigma-free healthcare.

Dolutegravir-rilpivirine: first 2-drug regimen for HIV-positive adults

ABSTRACTIntroduction: New strategies for HIV treatment are being investigated to reduce drug-exposure, toxicities, and costs. Dolutegravir (DTG) 50 mg/rilpivirine (RPV) 25 mg was approved in November 2017 by FDA and in May 2018 by the European Medicines Agency (EMA). It is indicated as a complete regimen for HIV-1 infected adults with undetectable plasmatic HIV-RNA for at least 6 months on their current HIV treatment combination. Its approval was based on the data of two randomized, multicenter, non-inferiority trials (SWORD-1 and SWORD-2).Areas covered: We reviewed data from literature about DTG and RPV. We mainly focused on the efficacy and on the safety of this new dual therapy. Its impact on renal function, its bone and cardiovascular profile, its reservoir penetration and its role on inflammation were also evaluated.Expert commentary: Dual therapies may be an attractive alternative to standard triple regimens in terms of tolerability and simplicity. Long-term efficacy of DTG and RPV dual regimen need to be confirmed, where only the extensive use of this new treatment and a longer follow-up will give us the answers.

Opioid Agonist Treatment and Improved Outcomes at Each Stage of the HIV Treatment Cascade in People Who Inject Drugs in Ukraine.

The HIV treatment cascade is a crucial tool to guide HIV prevention and treatment strategies. The extent to which opioid agonist treatments (OATs) such as methadone and buprenorphine influence this cascade was examined in a nationwide study of people who inject drugs (PWID) in Ukraine. Cross-sectional stratified survey of PWID followed by HIV and hepatitis C virus testing in 5 Ukrainian cities. Opioid-dependent PWID (N = 1613) were sampled from January 2014 to March 2015. Analysis was confined to 520 participants with HIV, with 184 (35.4%) prescribed OAT. Weighted logistic regression models were used to assess independent factors associated with the 5 steps in the HIV treatment cascade. Compared with PWID not on OAT (N = 336), participants who prescribed OAT (N = 184) were significantly more likely to be diagnosed (91% vs. 71%), linked (81% vs. 52%), and retained (69% vs. 35%) in HIV care, and prescribed (56% vs. 31%) and optimally (>95% of doses) adherent to antiretroviral therapy (41% vs. 22%). Receiving OAT contributed most as an independent factor with every step of the cascade. Other steps in the HIV treatment cascade were influenced by age, depression, and geographical variability. OAT remains an essential and effective strategy to not only treat patients with opioid use disorder, but also a crucial strategy to engage PWID in care to meet UNAIDS 90-90-90 targets. Geographical differences suggest local structural impediments. With low OAT coverage prescribed for 2.9% of the estimated 347,000 PWID in Ukraine, OAT expansion requires strategic interventions that target the individual, clinical care settings, policies, and funding.

Regional differences between people who inject drugs in an HIV prevention trial integrating treatment and prevention (HPTN 074): a baseline analysis.

IntroductionPeople who inject drugs (PWID) experience high HIV incidence and face significant barriers to engagement in HIV care and substance use treatment. Strategies for HIV treatment as prevention and substance use treatment present unique challenges in PWID that may vary regionally. Understanding differences in the risk structure for HIV transmission and disease progression among PWID is essential in developing and effectively targeting intervention strategies of HIV treatment as prevention.MethodsWe present a baseline analysis of HIV Prevention Trials Network (HPTN) 074, a two‐arm, randomized controlled trial among PWID in Indonesia (n = 258), Ukraine (n = 457) and Vietnam (n = 439). HPTN 074 was designed to determine the feasibility, barriers and uptake of an integrated intervention combining health systems navigation and psychosocial counselling for the early engagement of antiretroviral therapy (ART) and substance use treatment for PWID living with HIV. Discordant PWID networks were enrolled, consisting of an HIV‐positive index and their HIV‐negative network injection partner(s). Among the enrolled cohort of 1154 participants (502 index participants and 652 network partners), we examine regional differences in the baseline risk structure, including sociodemographics, HIV and substance use treatment history, and injection and sexual risk behaviours.ResultsThe majority of participants were male (87%), with 82% of the enrolled females coming from Ukraine. The overall mean age was 34 (IQR: 30, 38). Most commonly injected substances included illegally manufactured methadone in Ukraine (84.2%), and heroin in Indonesia (81.8%) and Vietnam (99.5%). Injection network sizes varied by region: median number of people with whom participants self‐reported injecting drugs was 3 (IQR: 2, 5) in Indonesia, 5 (IQR: 3, 10) in Ukraine and 3 (IQR: 2, 4) in Vietnam. Hazardous alcohol use, assessed using the Alcohol Use Disorders Identification Test – Alcohol Consumption Questions (AUDIT‐C), was prominent in Ukraine (54.7%) and Vietnam (26.4%). Reported sexual risk behaviours in the past month, including having two or more sex partners and giving/receiving money or drugs in exchange for sex, were uncommon among all participants and regions.ConclusionsWhile regional differences in risk structure exist, PWID particularly in Ukraine need immediate attention for risk reduction strategies. Substantial regional differences in risk structure will require flexible, tailored treatment as prevention interventions for distinct PWID populations.

Qualitative research on community experiences in large HIV research trials: what have we learned?

IntroductionVery few pragmatic and community‐level effectiveness trials integrate the use of qualitative research over all stages of the trial, to inform trial design, implementation optimization, results interpretation and post‐trial policy recommendations. This is despite the growing demand for mixed methods research from funding agencies and awareness of the vital importance of qualitative and mixed methods research for understanding trial successes and challenges.DiscussionWe offer examples from work we have been involved in to illustrate how qualitative research conducted within trials can reveal vital contextual factors that influence implementation and outcomes, can enable an informed adaptation of trials as they are being conducted and can lead to the formulation of theory regarding the social and behavioural pathways of intervention, while also enabling community engagement in trial design and implementation. These examples are based on published findings from qualitative studies embedded within two ongoing large‐scale studies demonstrating the population‐level impacts of universal HIV testing and treatment strategies in southern and eastern Africa, and a qualitative study conducted alongside a clinical trial testing the adaptation, acceptability and experience of short‐cycle therapy in children and adolescents living with HIV.ConclusionsWe advocate for the integration of qualitative with clinical and survey research methods in pragmatic clinical and community‐level trials and implementation studies, and for increasing visibility of qualitative and mixed methods research in medical journals. Qualitative research from trials ideally should be published along with clinical outcome data, either integrated into the “main” trial papers or published concurrently in the same journal issue. Integration of qualitative research within trials can help not only to understand the why behind success or failure of interventions in different contexts, but also inform the adaptation of interventions that can facilitate their success, and lead to new alternative strategies and to policy changes that may be vital for achieving public health goals, including the end of AIDS.

Modelling Optimal Control of In-Host HIV Dynamics Using Different Control Strategies.

HIV is one of the major causes of deaths, especially in Sub-Saharan Africa. In this paper, an in vivo deterministic model of differential equations is presented and analyzed for HIV dynamics. Optimal control theory is applied to investigate the key roles played by the various HIV treatment strategies. In particular, we establish the optimal strategies for controlling the infection using three treatment regimes as the system control variables. We have applied Pontryagin's Maximum Principle in characterizing the optimality control, which then has been solved numerically by applying the Runge-Kutta forth-order scheme. The numerical results indicate that an optimal controlled treatment strategy would ensure significant reduction in viral load and also in HIV transmission. It is also evident from the results that protease inhibitor plays a key role in virus suppression; this is not to underscore the benefits accrued when all the three drug regimes are used in combination.

2549 Characterizing the expression kinetics of HIV-1 envelope protein

OBJECTIVES/SPECIFIC AIMS: Characterize the expression kinetics of HIV-1 Envelope and their relationship to virus production at the cellular level. METHODS/STUDY POPULATION: In vitro and ex vivo laboratory analyses. RESULTS/ANTICIPATED RESULTS: Initial studies addressing the kinetics of cell surface. Envelope (Env) expression reveal that Env expression to peaks on day 2 post infection. Next steps include a series of experiments to compare the kinetics of Env cell surface expression with broadly neutralizing antibody (bNAb)-mediated ADCC and the characterization of virus production kinetics in this same context. To be maximally effective, ADCC elimination of infected cells should occur before peak Env expression. DISCUSSION/SIGNIFICANCE OF IMPACT: Potent bNAbs to HIV-1 recognize vulnerable sites on the HIV-1 Envelope (Env) protein and are of great clinical interest due to their potential use in the prevention and treatment of HIV-1 infection. Their effectiveness depends not only on the neutralization of viral infectivity, but also on the elimination of productively infected cells via antibody-dependent cellular cytotoxicity (ADCC). On a cellular level, ADCC dynamics are determined by the timing and level of Env expression on the surface of HIV-infected cells. This study aims to delineate the expression kinetics of HIV-1 Envelope and their relationship to virus production. We expect that it will provide new insights into the utility of bNAb-mediated ADCC in treating and possibly curing HIV-1 infection; therefore results might have substantial impact on future HIV treatment strategies.

Correction: Trends of racial and ethnic disparities in virologic suppression among women in the HIV Outpatient Study, USA, 2010-2015.

[This corrects the article DOI: 10.1371/journal.pone.0189973.].

Trends of racial and ethnic disparities in virologic suppression among women in the HIV Outpatient Study, USA, 2010-2015

In the United States, women accounted for 19% of new HIV diagnoses in 2015 and were less likely to reach virologic suppression when compared to men. We assessed trends and disparities in virologic suppression among HIV-positive women to inform HIV treatment strategies. Data were from a prospective cohort of the HIV Outpatient Study and collected at nine United States HIV clinics. We included women aged ≥18 years, with ≥1 visit, who were prescribed antiretroviral therapy, and had ≥1 viral load test performed between 2010 and 2015. We defined virologic suppression as viral load <50 copies/mL and calculated adjusted prevalence ratios (aPR) with 95% confidence intervals (CI) for virologic suppression by race/ethnicity and year of measure. Generalized estimating equations were used for multivariable analyses to assess factors associated with virologic suppression. Among 809 women (median age = 44 years), 482 (60%) were black, 177 (22%) white, 150 (19%) Hispanic/Latina. Virologic suppression was less prevalent among black women (73%) compared with Hispanic/Latina women (83%) and white women (91%). In multivariable analyses, not achieving virologic suppression was more likely among black women (aPR = 2.13; CI = 1.50–3.02) or Hispanic/Latina women (aPR = 1.66; CI = 1.08–2.56) compared with white women, and among women who attended public clinics (aPR = 1.42; CI = 1.07–1.87) compared with those who attended a private clinic. Between 2010 and 2015, virologic suppression among HIV-positive women increased from 68% to 83%, but racial/ethnic disparities persisted. Black and Hispanic/Latina women had significantly lower rates of virologic suppression than white women. Interventions targeting virologic suppression improvement among HIV-positive women of color, especially those who attend public clinics, are warranted.

Ibalizumab Targeting CD4 Receptors, An Emerging Molecule in HIV Therapy.

The HIV infection is responsible for the most devastating global pandemic of the last century. More than 39 million people have died of HIV/AIDS since 1981. The development of the antiretroviral (ARV) treatment begins with the discovery of zidovudine a nucleoside reverse transcriptase inhibitor. This breakthrough was followed by other ARV drug classes and representatives. Presently, HIV treatment employs 27 ARV representatives belonging to five different classes. Despite the proven benefits of ARV treatment and its long-term control of the HIV infection, there is an increasing concern about the numerous adverse effects and resistance to current ARV drugs. Therefore, the new HIV treatment strategies focus on the development of new ARV agents with a high genetic barrier to resistance and low toxicity. Monoclonal antibodies (MAbs) belong to a new drug class with encouraging results in the treatment of cancer, autoimmune disorders and most recently against HIV infection. The advantages of using MAbs for HIV treatment are related to their antiviral effect, lack of toxicity, good resistance profile, additional synergy with other ARV drug classes and ability to restore CD4 T-cell responses. The current article is a short summary of ibalizumab, an anti-CD4 monoclonal antibody that interferes with HIV viral entry. Current studies on ibalizumab have underlined its antiviral potential, minimal adverse effects, and lack of crossed resistance with other ARV agents thus supporting its further therapeutic use in multidrug resistant HIV-infected patients.

Implementing Generalized Additive Models to Estimate the Expected Value of Sample Information in a Microsimulation Model: Results of Three Case Studies.

The expected value of sample information (EVSI) can help prioritize research but its application is hampered by computational infeasibility, especially for complex models. We investigated an approach by Strong and colleagues to estimate EVSI by applying generalized additive models (GAM) to results generated from a probabilistic sensitivity analysis (PSA). For 3 potential HIV prevention and treatment strategies, we estimated life expectancy and lifetime costs using the Cost-effectiveness of Preventing AIDS Complications (CEPAC) model, a complex patient-level microsimulation model of HIV progression. We fitted a GAM-a flexible regression model that estimates the functional form as part of the model fitting process-to the incremental net monetary benefits obtained from the CEPAC PSA. For each case study, we calculated the expected value of partial perfect information (EVPPI) using both the conventional nested Monte Carlo approach and the GAM approach. EVSI was calculated using the GAM approach. For all 3 case studies, the GAM approach consistently gave similar estimates of EVPPI compared with the conventional approach. The EVSI behaved as expected: it increased and converged to EVPPI for larger sample sizes. For each case study, generating the PSA results for the GAM approach required 3 to 4 days on a shared cluster, after which EVPPI and EVSI across a range of sample sizes were evaluated in minutes. The conventional approach required approximately 5 weeks for the EVPPI calculation alone. Estimating EVSI using the GAM approach with results from a PSA dramatically reduced the time required to conduct a computationally intense project, which would otherwise have been impractical. Using the GAM approach, we can efficiently provide policy makers with EVSI estimates, even for complex patient-level microsimulation models.

Engaging HIV-positive clients in care: acceptability and mechanisms of action of a peer navigation program in South Africa

ABSTRACTAntiretroviral therapy (ART) could curtail the HIV epidemic, but its impact is diminished by low uptake. We developed a peer navigation program to enhance engagement in HIV care, ART adherence, and behavioral prevention. In preparation for a randomized controlled trial, the program was piloted over four months at two primary health clinics in South Africa’s North West Province. Newly diagnosed, HIV-positive clients met regularly with navigators to address barriers to care, adherence, and prevention. To assess program acceptability and feasibility and characterize the mechanisms of action, we surveyed 25 clients who completed navigation services and conducted interviews with 10 clients, four navigators, and five clinic providers. Clients expressed near universal approval for the program and were satisfied with the frequency of contact with navigators. HIV stigma emerged as a primary driver of barriers to care. Navigators helped clients overcome feelings of shame through education and by modeling how to live successfully with HIV. They addressed discrimination fears by helping clients disclose to trusted individuals. These actions, in turn, facilitated clients’ care engagement, ART adherence, and HIV prevention efforts. The findings suggest peer navigation is a feasible approach with potential to maximize the impact of ART-based HIV treatment and prevention strategies.

Meeting the goal of concurrent adolescent and adult licensure of HIV prevention and treatment strategies

The ability of adolescents to access safe and effective new products for HIV prevention and treatment is optimised by adolescent licensure at the same time these products are approved and...

PolyICLC Exerts Pro- and Anti-HIV Effects on the DC-T Cell Milieu In Vitro and In Vivo.

Myeloid dendritic cells (mDCs) contribute to both HIV pathogenesis and elicitation of antiviral immunity. Understanding how mDC responses to stimuli shape HIV infection outcomes will inform HIV prevention and treatment strategies. The long double-stranded RNA (dsRNA) viral mimic, polyinosinic polycytidylic acid (polyIC, PIC) potently stimulates DCs to focus Th1 responses, triggers direct antiviral activity in vitro, and boosts anti-HIV responses in vivo. Stabilized polyICLC (PICLC) is being developed for vaccine adjuvant applications in humans, making it critical to understand how mDC sensing of PICLC influences HIV infection. Using the monocyte-derived DC (moDC) model, we sought to describe how PICLC (vs. other dsRNAs) impacts HIV infection within DCs and DC-T cell mixtures. We extended this work to in vivo macaque rectal transmission studies by administering PICLC with or before rectal SIVmac239 (SIVwt) or SIVmac239ΔNef (SIVΔNef) challenge. Like PIC, PICLC activated DCs and T cells, increased expression of α4β7 and CD169, and induced type I IFN responses in vitro. The type of dsRNA and timing of dsRNA exposure differentially impacted in vitro DC-driven HIV infection. Rectal PICLC treatment similarly induced DC and T cell activation and pro- and anti-HIV factors locally and systemically. Importantly, this did not enhance SIV transmission in vivo. Instead, SIV acquisition was marginally reduced after a single high dose challenge. Interestingly, in the PICLC-treated, SIVΔNef-infected animals, SIVΔNef viremia was higher, in line with the importance of DC and T cell activation in SIVΔNef replication. In the right combination anti-HIV strategy, PICLC has the potential to limit HIV infection and boost HIV immunity.