Discontinuation Of Antiretroviral Therapy Research Articles

Managing Modern Antiretroviral Therapy in the Intensive Care Unit: Overcoming Challenges for Critically Ill People With Human Immunodeficiency Virus.

People with human immunodeficiency virus (HIV) have a 50% excess risk for intensive care unit (ICU) admission, often for non-HIV-related conditions. Despite this, clear guidance for managing antiretroviral therapy (ART) in this setting is lacking. Selecting appropriate ART in the ICU is complex due to drug interactions, absorption issues, and dosing adjustments. Continuing ART in the ICU can be challenging due to organ dysfunction, drug interactions, and formulary limitations. However, with careful consideration, continuation is often feasible through dose adjustments or alternative administration methods. Temporary discontinuation of ART may be beneficial depending on the clinical scenario. Clinicians should actively seek resources and support to mitigate adverse events and drug interactions in critically ill people with HIV. Navigating challenges in the ICU can optimize ART and improve care and outcomes for critically ill people with HIV. This review aims to identify strategies for addressing the challenges associated with the use of modern ART in the ICU.

[Artículo traducido] Análisis de la interrupción de la terapia antirretroviral en personas que viven con VIH/sida durante el periodo 2010–2021

ObjectiveIn the context of the advancement of antiretroviral therapy and, as the characteristics of people living with HIV progress toward an aging population, understanding the causes of treatment interruption becomes crucial. The aim of the study was to determine the change in reasons for antiretroviral treatment discontinuation for 12 years. Secondarily, compare annual antiretroviral regimen discontinuation rate and factors associated. MethodsWe conducted an analysis using data from people living with HIV who were receiving antiretroviral therapy and discontinued it for any reason. The study included people with HIV infection who visited an outpatient hospital pharmacy clinic from January 2010 to December 2021. Two periods were differentiated for the analysis: 2010–2015 and 2016–2021. The reasons for antiretroviral treatment discontinuation followed classification described by Swiss cohort. In the context of this study, it is pertinent to note that the term ‘interruption’ will be consistently used in this article to refer to the act of switching or stopping antiretroviral treatment. To examine factors associated with antiretroviral therapy discontinuation, we utilized Kaplan–Meier methods and Cox proportional models. ResultsWe included 789 people living with HIV, predominantly male (81,5%). The main reason for discontinuation was clinical decision (50.2%) followed by adverse effects (37.9%). Focusing on clinical decision, we observed a trend change that went from antiretroviral treatment simplification regimen (56.1%) in the first part of the period analyzed to the therapeutic optimization (53.6%) in the second half. Furthermore, factors that were statistically significantly associated with antiretroviral treatment discontinuation were people with HIV ≥50 years (HR 1.60; 95%CI 1.25–2.04), post-discontinuation single-tablet regimen (HR 1.49; 95%CI 1.06–2.11) and antiretroviral drug classes. ConclusionsOver the 12 years there has been a change in the main cause of antiretroviral treatment discontinuation, currently therapeutic optimization being the main reason. Integrase inhibitors-based regimens and singletablet regimen strategies were less likely to be discontinued than others antiretroviral drug classes, allowing for better clinical management due to the efficacy profile, especially in people living with HIV ≥50 years with comorbidities.

Induction of durable remission by dual immunotherapy in SHIV-infected ART-suppressed macaques.

The eradication of the viral reservoir represents the major obstacle to the development of a clinical cure for established HIV-1 infection. Here, we demonstrate that the administration of N-803 (brand name Anktiva) and broadly neutralizing antibodies (bNAbs) results in sustained viral control after discontinuation of antiretroviral therapy (ART) in simian-human AD8 (SHIV-AD8)-infected, ART-suppressed rhesus macaques. N-803+bNAbs treatment induced immune activation and transient viremia but only limited reductions in the SHIV reservoir. Upon ART discontinuation, viral rebound occurred in all animals, which was followed by durable control in approximately 70% of all N-803+bNAb-treated macaques. Viral control was correlated with the reprogramming of CD8+ T cells by N-803+bNAb synergy. Thus, complete eradication of the replication-competent viral reservoir is likely not a prerequisite for the induction of sustained remission after discontinuation of ART.

A Randomized Trial of Dolutegravir Plus Darunavir/Cobicistat as a Switch Strategy in HIV-1-Infected Patients With Resistance to at Least 2 Antiretroviral Classes.

Suppressed patients with drug-resistant HIV-1 require effective and simple antiretroviral therapy to maintain treatment adherence and viral suppression. This randomized, open-label, noninferiority, multicenter pilot study involved HIV-infected adults who met the following criteria: confirmed HIV-1 RNA <50 copies/mL for ≥6 months preceding the study randomization, treatment with at least 3 antiretroviral drugs, and a history of drug resistance mutations against at least 2 antiretroviral classes but remaining fully susceptible to darunavir (DRV) and integrase inhibitors. Participants were randomized 1:1 to switch to dolutegravir (DTG; 50 mg once per day) plus DRV boosted with cobicistat (DRV/c; 800/150 mg once per day; 2D group) or continue with their baseline regimen (standard-of-care [SOC] group). The primary endpoint was the proportion of patients with HIV-1 RNA <50 copies/mL at week 48 relative to time to loss of virologic response, with a noninferiority margin set at -12.5%. Virologic failure was defined as confirmed HIV-1 RNA ≥50 copies/mL or a single determination of HIV-1 RNA >50 copies/mL followed by antiretroviral therapy discontinuation. Forty-five participants were assigned to the 2D group and 44 to the SOC group. Time to loss of virologic response showed no difference in the proportion maintaining HIV-1 RNA <50 copies/mL at week 48: 39 of 45 (86.7%; 95% CI, 73.21%-94.95%) in the 2D group vs 42 of 44 (95.4%; 95% CI, 84.53%-99.44%) in the SOC group (log-rank P = .159) with an estimated difference of -8.7 (95% CI, -22.72 to 5.14). Only 2 (4.5%) in the SOC group experienced virologic failure, and 3 participants from the 2D group experienced adverse events leading to treatment discontinuation. In suppressed patients with at least 2 resistant antiretroviral classes, noninferiority could not be demonstrated by fully active DRV/c plus DTG. Nevertheless, there were no unexpected adverse events or virologic failure. DRV/c plus DTG may be considered a once-daily therapy option only for well-selected patients. Clinical Trials Registration. ClinicalTrials.gov (NCT03683524).

Antiretroviral Treatment Gaps and Adherence Among People with HIV in the U.S. Medicare Program.

Approximately one-quarter of people with HIV (PWH) in the U.S. receive coverage through the Medicare program; however, no prior real-world study has examined antiretroviral therapy (ART) gaps and adherence and associated factors in this population. This retrospective cohort analysis used 2013-2018 national Medicare fee-for-service claims data to identify all PWH initiated on a new ART regimen including protease inhibitors [PI], non-nucleoside reverse transcriptase inhibitors [NNRTIs], or integrase strand transfer inhibitors [INSTIs] between 1/1/2014 and 12/31/2017. Study outcomes included ART adherence (based on proportion of days covered [PDC]), continuous treatment gaps ranging from 1 to 6 days to ≥ 180 days, and discontinuation (continuous gap ≥90 days) in the 12-month follow-up period. Multivariable regressions were used to assess factors associated with ART adherence and discontinuation. The final sample included 48,627 PWH (mean age: 54.5 years, 74.4% male, 47.5% White, 89.8% disabled). Approximately53.0% of PWH had a PDC ≥ 0.95, 30.2% had a PDC between 0.70 and < 0.95, and 16.8% had PDC < 0.70. Treatment gaps of at least ≥ 7-days (55.2%) and ≥ 30-days (26.2%) were common and 10.1% PWH discontinued treatment. Younger age, female sex, Black race, higher comorbidity score, mental health conditions, and substance use disorder were associated with higher odds of lower adherence and discontinuation (all p-values < 0.05). In conclusion, suboptimal adherence and treatment gaps in ART use were commonly observed among PWH in Medicare. Interventions and policies to mitigate barriers to adherence are urgently needed in this population to both improve their survival and increase the potential for ending the HIV epidemic in the US.

The impact of the M184V resistance mutation on treatment outcomes in patients with HIV infection: a systematic review and meta-analysis.

HIV is a global deliberating infectious disease. Of note, more than 36 million people living with HIV (PLHIV) with approximately newly diagnosed 1.5 million cases annually. M184V is a single base mutation in the highly conserved YMDD domain of reverse transcriptase (RT). It is one of the most encountered resistances associated with mutations to nucleoside RT inhibitors. There were continuous efforts to evaluate the impact of M184V mutation on the treatment outcomes in PLHIV. Therefore, the present systematic review was executed to reveal the virological failure, virological suppression, and resistance to antiretroviral therapy (ART) regimens in PLHIV with the M184V mutation. All clinical studies comparing the treatment outcomes among PLHIV harboring or not harboring M184V mutation were appropriate for systematic review and meta-analysis. The present systematic review included six articles, encompassing 4760 PLHIV. Of them, 1222 (25.67%) patients had M184V mutation, while 3538 (74.32%) PLHIV did not. The meta-analysis showed that patients with M184V mutation were 1.87 times more liable to virological failure (risk ratio [RR] 1.87; 95% 1.09, 3.20; p = 0.02). Furthermore, pooling the data from two studies revealed a significantly higher risk of viral blips (RR 2.26; 95% 1.47, 3.46; p = 0.0002). Concerning discontinuation of ART, there was no statistical difference between patients with and without M184V mutation (RR: 0.99; 95% 0.78, 1.25; p = 0.90). The present study revealed the negative impact of the M184V mutation on treatment outcomes in PLHIV. This included a higher risk of virological failure and viral blips, relative to patients without the mutation. Such patients may benefit from more aggressive and combined therapy for better disease management.

Impact and cost-effectiveness of short-course tuberculosis preventive treatment for household contacts and people with HIV in 29 high-incidence countries: a modelling analysis

Guidelines and implementation of tuberculosis preventive treatment (TPT) vary by age and HIV status. Specifically, TPT is strongly recommended for people living with HIV/AIDS (PLWHA) and household contacts younger than 5 years but only conditionally recommended for older contacts. Cost remains a major barrier to implementation. The aim of this study was to evaluate the cost-effectiveness of TPT for household contacts and PLWHA. We developed a state-transition model to simulate short-course TPT for household contacts and PLWHA in 29 high-incidence countries based on data from previous studies and public databases. Our primary outcome was the incremental cost-effectiveness ratio, expressed as incremental discounted costs (2020 US$, including contact investigation costs) per incremental discounted disability-adjusted life year (DALY) averted, compared with a scenario without any TPT or contact investigation. We propagated uncertainty in all model parameters using probabilistic sensitivity analysis and also evaluated the sensitivity of results to the screening algorithm used to rule out active disease, the choice of TPT regimen, the modelling time horizon, assumptions about TPT coverage, antiretroviral therapy discontinuation, and secondary transmission. Between 2023 and 2035, scaling up TPT prevented 0·9 (95% uncertainty interval 0·4-1·6) people from developing tuberculosis and 0·13 (0·05-0·27) tuberculosis deaths per 100 PLWHA, at an incremental cost of $15 (9-21) per PLWHA. For household contacts, TPT (with contact investigation) averted 1·1 (0·5-2·0) cases and 0·7 (0·4-1·0) deaths per 100 contacts, at a cost of $21 (17-25) per contact. Cost-effectiveness was most favourable for household contacts younger than 5 years ($22 per DALY averted) and contacts aged 5-14 years ($104 per DALY averted) but also fell within conservative cost-effectiveness thresholds in many countries for PLWHA ($722 per DALY averted) and adult contacts ($309 per DALY averted). Costs per DALY averted tended to be lower when compared with a scenario with contact investigation but no TPT. The cost-effectiveness of TPT was not substantially altered in sensitivity analyses, except that TPT was more favourable in analysis that considered a longer time horizon or included secondary transmission benefits. In many high-incidence countries, short-course TPT is likely to be cost-effective for PLWHA and household contacts of all ages, regardless of whether contact investigation is already in place. Failing to implement tuberculosis contact investigation and TPT will incur a large burden of avertable illness and mortality in the next decade. Unitaid.

Highly active antiretroviral therapy discontinuation time is associated with therapeutic failure among human immunodeficiency virus (HIV)-infected immigrant adults: A cohort study from a Peruvian referral hospital during the Venezuelan exodus.

To evaluate the association between Highly Active Antiretroviral Therapy (HAART) discontinuation time and therapeutic failure (TF) in Venezuelan immigrants with HIV that restart HAART. We carried out a retrospective cohort study in a large hospital in Peru. We included Venezuelan immigrants who restarted HAART and were followed over at least 6 months. The primary outcome was TF. Secondary outcomes were immunologic (IF), virologic (VF) and clinical (CF) failures. The exposure variable was HAART discontinuation, categorised as no discontinuation, less than 6 months, and 6 months or more. We applied generalised linear models Poisson family with robust standard errors to calculate crude (cRR) and adjusted (aRR) relative risks by statistical and epidemiological criteria. We included 294 patients, 97.2% were males, and the median age was 32 years. Out of all the patients, 32.7% discontinued HAART for less than 6 months, 15.0% discontinued for more than 6 months and the remaining 52.3% did not discontinue. The cumulative incidence of TF was 27.9%, 24.5% in VF, 6.0% in IF and 6.0% in CF. Compared with non-discontinued HAART patients, the discontinuation for less than 6 months (aRR = 1.98 [95% CI: 1.27-3.09]) and from 6 months to more (aRR = 3.17 [95% CI: 2.02-4.95]) increased the risk of TF. Likewise, treatment discontinuation of up to 6 months (aRR = 2.32 [95% CI: 1.40-3.84]) and from 6 months to more (aRR = 3.93 [95% CI: 2.39-6.45]) increased the risk of VF. HAART discontinuation increases the probability of TF and VF in Venezuelan immigrants.

Peripheral blood biomarkers predict viral rebound following antiretroviral therapy discontinuation in SIV-infected, early ART-treated rhesus macaques

The discovery of biomarkers that predict viral rebound after discontinuation of antiretroviral therapy (ART) would significantly contribute to the HIV cure field. We previously initiated ART in 20 rhesus macaques on days 0, 1, 2, and 3 following SIVmac251 infection. After 6months, we discontinued ART and observed viral rebound in 9 of 20 animals, which provided an opportunity to define peripheral biomarkers on ART that predicted viral rebound following ART discontinuation. We show that interleukin-1 (IL-1), IL-6_JAK_STAT3, IL-10, transforming growth factor β (TGF-β), IL-22, and IL-23 signaling and activation of monocyte, macrophage, and antigen processing and presentation pathways during ART suppression correlated with viral rebound. These signatures were validated in a second cohort of macaques. Our data suggest that low levels of antigen and proinflammatory signaling during ART suppression correlate with the presence of a rebound-competent viral reservoir. Interventions that modulate these peripheral biomarkers may be promising candidates to evaluate as potential HIV-1 cure strategies.

Potential biomarkers: Predicting post-treatment viral rebound in rhesus macaques

In this issue of Cell Reports Medicine, Aid and colleagues define peripheral blood biomarkers, which predict viral rebound after antiretroviral therapy (ART) discontinuation in SIV-infected rhesus macaques treated early with ART, providing insights into potential HIV cure strategies.1.

Predictors of discontinuation of antiretroviral therapy among HIV-infected adults at Hospital Sungai Buloh: A 10-year retrospective cohort study

Predictors of discontinuation of antiretroviral therapy among HIV-infected adults at Hospital Sungai Buloh: A 10-year retrospective cohort study

Factors associated with post-treatment control of viral load in HIV-infected patients: a systematic review and meta-analysis

ObjectivesThis study aimed to investigate the factors associated with maintenance of viral suppression after antiretroviral therapy (ART) discontinuation. MethodsDatabases were searched for studies published between January 01, 2011, and July 01, 2022, that correlated the time of virus rebound with treatment interruption (TI). The corresponding data were extracted from these studies. A fixed-effects model was used to calculate pooled estimates. ResultsThirty-one studies were included in this analysis. Results showed that patients who started ART during acute or early infection had longer viral control than those who started ART during chronic infection. It has been reported that some broadly neutralizing HIV-1-specific antibodies can significantly prolong viral inhibition. The study also found that approximately 7.2% of patients achieved post-treatment control (PTC) approximately a year after TI. ConclusionART initiation in the acute or early phases can delay viral rebound after TI. Cell-associated HIV RNA and HIV DNA have been difficult to prove as able to predict viral rebound time. Many vaccines and antibodies have also been shown to be effective in prolonging viral control in people without PTC, and more research is needed to develop alternative ART therapies that can effectively inhibit or even eliminate HIV.

Progressive transformation of the HIV-1 reservoir cell profile over two decades of antiviral therapy

HIV-1 establishes a life-long reservoir of virally infected cells which cannot be eliminated by antiretroviral therapy (ART). Here, we demonstrate a markedly altered viral reservoir profile of long-term ART-treated individuals, characterized by large clones of intact proviruses preferentially integrated in heterochromatin locations, most prominently in centromeric satellite/micro-satellite DNA. Longitudinal evaluations suggested that this specific reservoir configuration results from selection processes that promote the persistence of intact proviruses in repressive chromatin positions, while proviruses in permissive chromosomal locations are more likely to be eliminated. A bias toward chromosomal integration sites in heterochromatin locations was also observed for intact proviruses in study participants who maintained viral control after discontinuation of antiretroviral therapy. Together, these results raise the possibility that antiviral selection mechanisms during long-term ART may induce an HIV-1 reservoir structure with features of deep latency and, possibly, more limited abilities to drive rebound viremia upon treatment interruptions.

Isolated exercise-induced pulmonary hypertension is associated with clinical worsening and poor immunological control in HIV patients

Exercise-induced pulmonary hypertension (Ex-PH), due to impaired pulmonary vascular and right ventricular (RV) contractile reserve on effort, may represent the earliest sign of pulmonary arterial hypertension (PAH), which may develop in Human immunodeficiency virus (HIV) patients with poor disease control. We investigated its association with clinical determinants of immunological status, virological control, and response to antiviral therapy in HIV patients at risk for PAH. In 31 consecutive HIV patients with either low ( n = 29) or intermediate probability ( n = 3) of PH at rest, we evaluated the association of isolated ExPH with: time to HIV diagnosis, CD4+ T cell count, clinical progression to AIDS, development of resistance to antiretroviral therapy (ART), HIV RNA levels (copies/mL), time to onset of ART, current use of protease inhibitors, combination of ART with boosters (ritonavir e cobicistat), virological response to ART, ART discontinuation. Isolated ExPH at stress echocardiography (ESE) was defined as absence of PH at rest and systolic pulmonary arterial pressure (sPAP) >45 mmHg or a raise of >20 mmHg during low-intensity exercise (while not exceeding a cardiac output of 10 l/min). 20% of the enrolled population developed ExPH. ExPH was inversely associated with CD4+ T cell count ( p = 0.047), time to HIV diagnosis ( p = 0.014) and time to onset of ART ( p = 0.041) compared to patients without ExPH. Patients with ExPH had greater worsening of functional class than patients without ExPH ( p < 0.001). ExPH and AIDS showed a non-statistically significant trend of direct association ( p = 0.093). However, AIDS patients had an increase in pulmonary vascular reserve index (PVRI) compared to patients without ExPH (p = 0.020) at rest echocardiography. We also observed an inverse correlation between the time to onset of ART with right atrium area ( r = − 0.411, p = 0.022) and indexed right atrial volume ( r = − 0.102, p = 0.009). Isolated ExPH associates with clinical worsening and poorer immunological control in HIV patients. The assessment of ExPH by ESE may help identify subgroups of HIV patients with a propensity to develop subclinical impairment of pulmonary circulation following poor control of HIV infection.

Hepatitis B–Related Hepatic Flare During Immune Reconstitution Syndrome After Antiretroviral Treatment Initiation in an HBV Surface Antigen–Positive Patient With HIV: Viroimmunological and Histological Characterization

HIV and hepatitis B virus (HBV) coinfection is relatively common. Initiation of antiretroviral therapy (ART) in people with HIV (PWH) causes a progressive restoration of cell-mediated immune functions. In the presence of overt or occult coinfections, immune restoration might lead to immune reconstitution inflammatory syndrome (IRIS). Here, we describe the clinical, immunological, virological, and histological characterization of a case of HBV-related IRIS hepatitis in a PWH after ART initiation. A liver biopsy was performed during HBV-related IRIS hepatic flare, and liver samples were analyzed through immunohistochemistry and molecular techniques, with the assessment of intrahepatic HBV-DNA, covalently closed circular DNA, and HBV pregenomic RNA through a droplet digital polymerase chain reaction system. Immune activation and senescence were also longitudinally assessed. In this clinical case, the hepatic flare occurred 6 weeks after ART initiation with a therapeutic regimen including tenofovir alafenamide (TAF) and emtricitabine (FTC). The episode was self-limiting, characterized by hyperactivation of peripheral blood CD4+ and CD8+ T-lymphocytes, and resolved without ART discontinuation, leading to the achievement of HBsAg seroconversion (HBsAg-/HBsAb+) and HBV-DNA plasma undetectability. Notably, hyperactivation of the immune system plays a pivotal role in promoting the control of HBV replication, thus triggering the achievement of HBsAg seroconversion during treatment with TAF/FTC.

Therapeutic efficacy of combined active and passive immunization in ART-suppressed, SHIV-infected rhesus macaques

The latent viral reservoir is the critical barrier for developing an HIV-1 cure. Previous studies have shown that therapeutic vaccination or broadly neutralizing antibody (bNAb) administration, together with a Toll-like receptor 7 (TLR7) agonist, enhanced virologic control or delayed viral rebound, respectively, following discontinuation of antiretroviral therapy (ART) in SIV- or SHIV-infected rhesus macaques. Here we show that the combination of active and passive immunization with vesatolimod may lead to higher rates of post-ART virologic control compared to either approach alone. Therapeutic Ad26/MVA vaccination and PGT121 administration together with TLR7 stimulation with vesatolimod resulted in 70% post-ART virologic control in SHIV-SF162P3-infected rhesus macaques. These data suggest the potential of combining active and passive immunization targeting different immunologic mechanisms as an HIV-1 cure strategy.

Therapeutic effect of (5R)-5-hydroxytriptolide (LLDT-8) in SIV infected rhesus monkeys

BackgroundsHuman immunodeficiency virus (HIV) infections induce robust, generalized inflammatory responses and lead to pathological systemic immune activation. This abnormal immune status persists despite successful antiretroviral therapy (ART). Immune modulating strategies in conjunction with ART were tried to reduce abnormal immune activation. Previously, we demonstrated that Tripterygium Wilfordii Hook F has been shown immunosuppressive activity in HIV patients. (5R)-5-hydroxytriptolide (LLDT-8), a new analog of triptolide, and the most active ingredient of Tripterygium Wilfordii Hook F, has been shown to have lower cytotoxicity. However, the role of LLDT-8 in HIV or simian immunodeficiency virus (SIV) needs to be explored. MethodsSix male adult Chinese rhesus monkeys were enrolled in our study. All of them were healthy and negative for SIV, and chronically SIVmac239 infected macaques were treated with LLDT-8 combined with ART (n = 4) or ART only (n = 2) after 14 weeks of infection. ART was determined at week 33, and LLDT-8 was continued until week 48. T cell immune activation and inflammation were compared during the period, and viral rebound time and reservoir were supervised after stopping ART. ResultsThe RNA level of the two groups continued to decline after initiating ART, RNA of 4 rhesus monkeys declined to the lower limit of detection at week 20. LLDT-8 administration combined with ART did not affect T cell activation and plasma levels of IL-6 and CRP. The viral load of all the macaques in both groups was rebounded 2 weeks after ART discontinuation. Furthermore, no significant decrease of SIV DNA was observed in the LLDT-8 treatment group. ConclusionsLLDT-8 administration during chronic SIV infection had no effect on T cell activation and plasma levels; Furthermore, LLDT-8 may not contribute to suppression of viral rebound and reservoir. These results suggest that LLDT-8 is unlikely to reduce immune activation and viral persistence without additional interventions.

Therapeutic efficacy of an Ad26/MVA vaccine with SIV gp140 protein and vesatolimod in ART-suppressed rhesus macaques

Developing an intervention that results in virologic control following discontinuation of antiretroviral therapy (ART) is a major objective of HIV-1 cure research. In this study, we investigated the therapeutic efficacy of a vaccine consisting of adenovirus serotype 26 (Ad26) and modified vaccinia Ankara (MVA) with or without an SIV Envelope (Env) gp140 protein with alum adjuvant in combination with the TLR7 agonist vesatolimod (GS-9620) in 36 ART-suppressed, SIVmac251-infected rhesus macaques. Ad26/MVA therapeutic vaccination led to robust humoral and cellular immune responses, and the Env protein boost increased antibody responses. Following discontinuation of ART, virologic control was observed in 5/12 animals in each vaccine group, compared with 0/12 animals in the sham control group. These data demonstrate therapeutic efficacy of Ad26/MVA vaccination with vesatolimod but no clear additional benefit of adding an Env protein boost. SIV-specific cellular immune responses correlated with virologic control. Our findings show partial efficacy of therapeutic vaccination following ART discontinuation in SIV-infected rhesus macaques.

HIV envelope antibodies and TLR7 agonist partially prevent viral rebound in chronically SHIV-infected monkeys.

A key challenge for the development of a cure to HIV-1 infection is the persistent viral reservoir established during early infection. Previous studies using Toll-like receptor 7 (TLR7) agonists and broadly neutralizing antibodies (bNAbs) have shown delay or prevention of viral rebound following antiretroviral therapy (ART) discontinuation in simian-human immunodeficiency virus (SHIV)-infected rhesus macaques. In these prior studies, ART was initiated early during acute infection, which limited the size and diversity of the viral reservoir. Here we evaluated in SHIV-infected rhesus macaques that did not initiate ART until 1 year into chronic infection whether the TLR7 agonist vesatolimod in combination with the bNAb PGT121, formatted either as a human IgG1, an effector enhanced IgG1, or an anti-CD3 bispecific antibody, would delay or prevent viral rebound following ART discontinuation. We found that all 3 antibody formats in combination with vesatolimod were able to prevent viral rebound following ART discontinuation in a subset of animals. These data indicate that a TLR7 agonist combined with antibodies may be a promising strategy to achieve long-term ART-free HIV remission in humans.

Influence of paired pandemic of COVID-19 and HIV infection on pregnant women and children: A challenging issue.

COVID-19 infection started in China in December 2019 and was declared a global pandemic of international concern by the WHO in March 2020. With rapid spread of infection worldwide, health systems and health care programs came to a standstill, leaving essential services such as antenatal care and human immunodeficiency virus (HIV) comprehensive care for children and pregnant women completely devastated. Furthermore, due to lockdowns, children and pregnant women living with HIV were forced to stay at home with no access to health facilities, loss of follow-up, and discontinuation of antiretroviral drugs therapy. The present review briefs concerning the impact of COVID-19 and HIV/AIDS pandemics on children and pregnant women worldwide.