Factors associated with subclinical atherosclerosis in HIV infected patients from northeast of Brazil

Introduction: AIDS has changed its morbidity curve, rising cardiovascular diseases. HIV-infected patients have increased cardiovascular event rates but data on the prevalence of subclinical atherosclerosis are not uniform. Methods: HIV-infected patients underwent to coronary tomography for CACs assessement. We performed a comparison between 97 HIV-infected patients and 129 seronegative healthy controls. The univariable analysis matched the association of HIV infection, cardiovascular risk profile, and HIV-related factors with subclinical atherosclerosis. Results: HIV-infected patients with CACs above zero were older (54.8±7.0 vs. 43.3.5±11.0 years; p<0.001) and more likely to have hypertension (36.7% vs. 12.5%; p=0.07) than HIV(-) CACs zero ones. Factors associated with altered CACs in unadjusted hazard ratio were age (HR=1.13; 95%CI=1.07-1.20; p<0.0001) and hypertension (HR=4.05; 95%CI=1.42-11.60; p=0.0009). When adjusted hazard ratio was constructed age, male gender and protease inhibitors (PI) use appeared as factors associated with coronary calcification. HIV-infected patients were less likely to have hypertension (20.2% vs 50.4%; p<0.001) and diabetes (5.3% vs 23.3%; p<0.001) than HIV uninfected ones. Conversely, both groups have same CACs level. Among HIV-infected patients altered CACs was 30.9%, vs 42.3% among control. Most of HIV-infected patients showed undetectable viremia and high CD4+ count, in parallel with lipid profile disturbances. Conclusion: Increased CAC incidence was associated with age, male gender and PI use among HIV-infected patients. Despite younger, fewer traditional risk factors and with controlled disease, the PLHIV had similar CAC scores compared with controls. Besides viruses itself, antiretroviral drugs play a role, mainly because control viruses at expense of worsening in lipid profile.

Factors Associated With Peripartum Virologic Suppression in Eastern Cape Province, South Africa: A Retrospective Cross-Sectional Analysis

Background This study describes the characteristics of pregnant women on antiretroviral therapy (ART) and the rate of peripartum virologic suppression in a large prevention of mother-to-child transmission cohort who delivered in some selected maternity centers in Eastern Cape Province, South Africa. In addition, the study examines the factors associated with virologic suppression in the cohort. Methods This multicenter, retrospective cross-sectional analysis included medical data of 1709 women with human immunodeficiency virus between September 2015 and May 2016 in Eastern Cape Province. The main outcome measure was the rate of peripartum virologic suppression, defined as viral load (VL) &lt;1000 copies/mL and undetectable viremia (VL &lt;20 copies/mL). Correlates of peripartum virologic suppression and undetectable viremia were examined by fitting logistic regression model analysis. Results Of 1463 women with available VL results, the overall rate of peripartum suppression was 82%, and undetectable viremia was 56.9%. Being aged 24 years or younger (adjusted odds ratio [AOR], 0.68 [95% confidence interval {CI}, .48–.94]), smoking during pregnancy (AOR, 0.50 [95% CI, .28–.90]), and starting ART in the first trimester were associated with lower odds of viral suppression (&lt;1000 copies/mL). Women who had never defaulted ART had an increased odds of having an undetectable VL (AOR, 3.09 [95% CI, 2.12–4.49]) and virologic suppression (AOR, 3.88 [95% CI, 2.62–5.74]) compared to those who defaulted. Conclusions More than half of the women achieved undetectable VL, and 4 in 5 women achieved viral suppression at delivery in the region. Early antenatal booking, combined with enhanced adherence support for pregnant women on ART, would be crucial toward achieving the goal of elimination of mother-to-child transmission in the region.

Residual Proviral Reservoirs: A High Risk for HIV Persistence and Driving Forces for Viral Rebound after Analytical Treatment Interruption

Antiretroviral therapy (ART) has dramatically suppressed human immunodeficiency virus (HIV) replication and become undetectable viremia. However, a small number of residual replication-competent HIV proviruses can still persist in a latent state even with lifelong ART, fueling viral rebound in HIV-infected patient subjects after treatment interruption. Therefore, the proviral reservoirs distributed in tissues in the body represent a major obstacle to a cure for HIV infection. Given unavailable HIV vaccine and a failure to eradicate HIV proviral reservoirs by current treatment, it is crucial to develop new therapeutic strategies to eliminate proviral reservoirs for ART-free HIV remission (functional cure), including a sterilizing cure (eradication of HIV reservoirs). This review highlights recent advances in the establishment and persistence of HIV proviral reservoirs, their detection, and potential eradication strategies.

The Promise of Improved Adherence With Long-Acting Antiretroviral Therapy: What Are the Data?

As with other chronic conditions, adherence to daily medications remains a challenge for many individuals living with HIV due to structural, behavioral, and social barriers. Unfortunately, high levels of adherence to antiretroviral therapy are required to maintain virologic suppression. Alternative approaches are being explored to decrease the burden of daily pill administration, including long-acting injectable, oral, and implantable products. Phase 3 data support the efficacy of nanoformulated injectable cabotegravir and rilpivirine for HIV treatment in patients with undetectable viremia, but we have yet to learn how this strategy may benefit those with medication adherence challenges. Despite this, the affected community and HIV providers are very interested in exploring the role of long-acting therapies to address some types of barriers to medication adherence. This review summarizes available information about the potential for long-acting therapy to improve adherence for some patients and outlines associated opportunities and challenges with the implementation of long-acting therapy for the treatment and prevention of HIV.

Deletion of CD2-Like (CD2v) and C-Type Lectin-Like (EP153R) Genes from African Swine Fever Virus Georgia-∆9GL Abrogates Its Effectiveness as an Experimental Vaccine

African swine fever virus (ASFV) is currently the most dreaded infectious disease affecting the global swine production industry. There is no commercial vaccine available, making the culling of infected animals the current solution to control outbreaks. Effective experimental vaccines have been developed by deleting virus genes associated with virulence. Deletion of the ASFV 9GL gene (∆9GL) has resulted in the attenuation of different ASFV strains, although the degree of attenuation varies across isolates. Here, we investigated the possibility of the increased safety of the experimental vaccine strain ASFV-G-Δ9GL by deleting two additional virus genes involved in pathogenesis, CD2v, a CD2 like viral encoded gene from the EP402R open reading frame (ORF), and C-type lectin-like viral gene, encoded from the EP153R ORF. Two new recombinant viruses were developed, ASFV-G-Δ9GL/ΔCD2v and ASFV-G-Δ9GL/ΔCD2v/ΔEP153R, harboring two and three gene deletions, respectively. ASFV-G-Δ9GL/ΔCD2v/ΔEP153R, but not ASFV-G-Δ9GL/ΔCD2v, had a decreased ability to replicate in vitro in swine macrophage cultures when compared with parental ASFV-G-Δ9GL. Importantly, ASFV-G-Δ9GL/ΔCD2v and ASFV-G-Δ9GL/ΔCD2v/ΔEP153R induced almost undetectable viremia levels when inoculated into domestic pigs and failed to protect them against challenge with parental virulent ASFV-Georgia, while ASFV-G-Δ9GL offered robust protection during challenge. Therefore, the deletion of CD2-like and C-type lectin-like genes significantly decreased the protective potential of ASFV-G-Δ9GL as a vaccine candidate. This study constitutes an example of the unpredictability of genetic manipulation involving the simultaneous deletion of multiple genes from the ASFV genome.

Maintenance of Viral Suppression in Human Immunodeficiency Virus Controllers Despite Waning T-Cell Responses During Antiretroviral Therapy

AIDS Clinical Trials Group study A5308 found reduced T-cell activation and exhaustion in human immunodeficiency virus (HIV) controllers start antiretroviral therapy (ART). We further assessed HIV-specific T-cell responses and post-ART viral loads. Before ART, the 31% of participants with persistently undetectable viremia had more robust HIV-specific T-cell responses. During ART, significant decreases were observed in a broad range of T-cell responses. Eight controllers in A5308 and the Study of the Consequences of the Protease Inhibitor Era (SCOPE) cohort showed no viremia above the level of quantification in the first 12 weeks after ART discontinuation. ART significantly reduced HIV-specific T-cell responses in HIV controllers but did not adversely affect controller status after ART discontinuation.

The Vogt-Koyanagi-Harada and SAPHO Syndrome: An Unusual Association

Vogt-Koyanagi-Harada syndrome(VKH) is a multisystemic disorder characterized by granulomatous panuveitis and cutaneous, otorhynolaryngologic and neurologic involvement, due to an autoimmune reaction against melanocytic antigens. Autoinflammatory associations of VKH, including inflammatory bowel disease and psoriasis, were rarely described. SAPHO syndrome (an acronym for synovitis, acne, hyperostosis, pustulosis and osteitis) is a rare autoinflammatorymusculo-scheletal disease. This paper reports on a male patient presenting for long-lasting bone and joint pain, dysphagia,having a ten-year history of bilateral optic neuritiswhich required high-dose corticosteroids. Fundoscopy revealed diffuse chorioretinalnonpigmented atrophic lesions. Vitiligo, acne scars, clavicular deformity, recurrent chest pain and sacroiliitis pointed to a long-standing SAPHO syndrome and late-phase VKH. Blood tests found inflammation and anti-hepatitis C antibodies with repeatedly undetectable viremia. Bone scintigraphy with the characteristic bull�s head upper chest uptake and the radiographs confirmed SAPHO syndrome. The patient was treated with sulphasalazine and cyclosporin A, with alleviation of the articular and bony disease. In conclusion, SAPHO syndrome may add to the list of the diseases associated with VKH. Although VKH and SAPHO syndrome may have appeared coincidentally, a common pathogenesis involving an infectious trigger and IL-17 could be considered.

Persistent Viral Reservoirs in Lymphoid Tissues in SIV-Infected Rhesus Macaques of Chinese-Origin on Suppressive Antiretroviral Therapy

Understanding HIV latent reservoirs in tissues is essential for the development of new strategies targeting these sites for eradication. Here, we assessed the size of latent reservoirs and the source of residual viruses in multiple lymphoid tissues of SIV-infected and fully suppressed rhesus macaques of Chinese-origin (cRMs). Eight cRMs were infected with SIVmac251 and treated with tenofovir and emtricitabine daily for 24 weeks initiated 4 weeks post-infection. Four of the eight animals reached sustained full viral suppression with undetectable viremia. The levels of cell-associated SIV DNA varied in peripheral blood mononuclear cells (PBMCs) and multiple lymphoid tissues, but with higher levels in the mesenteric lymph nodes (MesLNs). The levels of cell-associated SIV RNA also varied in different tissues. The higher frequency of viral RNA detection in the MesLNs was also observed by in situ hybridization. Consistently, the infection unit per million cells (IUPM) in the MesLNs was higher than in PBMCs and other tested lymphoid tissues by quantitative viral outgrowth assay (QVOA). Furthermore, env gp120 from tissue SIV RNA was amplified by single genome amplification. Phylogenetic analysis revealed diverse variants from tissues parallel to the viral inoculum in all viral suppressed animals. These results demonstrate that the latency and viral reservoirs in the lymphoid tissues still exist in aviremic macaques under full suppressive therapy. Moreover, the size of viral latent reservoirs differs in various lymphoid tissues with a relatively larger size in the MesLNs.