Advanced HIV Infection in Treatment Naïve Individuals: Effectiveness and Persistence of Recommended Three-Drug Regimens

Background Approximately 20% of newly diagnosed people with HIV (PWH) in the U.S. have advanced HIV infection, yet literature on current antiretroviral therapy (ART) options is limited. Discontinuation/modification and effectiveness of common regimens were compared among ART-naïve people with advanced HIV infection (CD4 cell count <200 cells/μL). Methods ART-naïve adults with advanced HIV infection initiating bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) or a boosted darunavir (bDRV)-, dolutegravir (DTG)- or elvitegravir/cobicistat (EVG/c)-based three-drug regimen between 1JAN2018 and 31JUL2019 in the OPERA cohort were included. The association between regimen and discontinuation or viral suppression (<50 or <200 copies/mL) was assessed using Cox proportional hazards models with inverse probability of treatment weights. Results Overall, 961 PWH were included (416 B/F/TAF, 106 bDRV, 271 DTG, 168 EVG/c); 70% achieved a CD4 cell count ≥200 cells/μL over a 16 months median follow-up. All regimens were associated with a statistically higher likelihood of discontinuation than B/F/TAF (bDRV aHR: 2.65 [95% CI: 1.75, 4.02], DTG: 2.42 [1.75, 3.35], EVG/c: 3.52 [95% CI: 2.44, 5.07]). Compared to B/F/TAF, bDRV initiators were statistically less likely to suppress to <50 copies/mL (0.72 [0.52, 0.99]) and <200 copies/mL (0.55 [0.43, 0.70]); no statistically significant difference was detected with DTG or EVG/c. Conclusions Among people with advanced HIV infection, those initiating B/F/TAF were less likely to discontinue/modify their regimen than those on any other regimen, and more likely to achieve viral suppression compared to those on bDRV but not compared to those on other integrase inhibitors.

Risk Factors for COVID-19 Mortality Among People Living with HIV: A Scoping Review

People living with HIV (PLWH) are particularly vulnerable to worsened outcomes of COVID-19. Therefore, the purpose of this work was to provide a scoping review of the literature to assess the risk factors for COVID-19 mortality among PLWH. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR), searches were conducted in PubMed, Scopus, Global Health, and WHO Coronavirus Database. Articles were eligible for inclusion if they were in English, included PLWH who died after COVID-19 infection, and described risk factors for mortality. Results were descriptively synthesized and pooled thereafter. Study quality was assessed using the Joanna Brigg Institute’s critical appraisal tools. 20 studies were eligible for inclusion, with the pooled death rate being 11.7%. Age was a major risk factor, especially after 50 (23.2%) and after 70 (41.8%), and males had a death rate nearly double that of females. As total comorbidities increased, the death rate also greatly increased; among those with comorbidities, the highest fatality rates were those with cardiovascular disease (30.2%), chronic kidney disease (23.5%), obesity (22.4%), and diabetes (18.4%). Other risk factors for mortality among PLWH included having a Black racial background, being an injection drug user, being a smoker, and having a CD4 cell count below 200. There is a need to better study confounding factors, and to understand how vaccination influences mortality risk. Overall, the findings highlight a need to ensure that focus is placed on the varying demographics of PLWH amidst COVID-19 control efforts.

SPAG5 Expression Correlated With Prognostic Implication and Immune Infiltration in Lung Adenocarcinoma

Background Sperm-associate antigen 5 (SPAG5) is a critical oncogene in several cancers. But the role of SPAG5A in lung adenocarcinoma (LUAD) remains unclear. Thus, the aims of our study are to explore the function and underlying mechanism of SPAG5 in LUAD. Methods Expression of SPAG5 was determined using the Oncomine, TIMER, and GEPIA databases. Correlation of SPAG5 and survival was detected by GEPIA database, PrognoScan, Kaplan-Meier Plotter databases. And the association between SPAG5 and tumor malignant phenotypes were analyzed by the CancerSEA. Besides, the correlation between SPAG5 expression and tumor immune infiltration as well as immune checkpoints were analyzed by TIMER. the co-expression genes of SPAG5 were identified using STRING, and the mutation and biological function of SPAG5 and its co-expression genes were determined by cBioPortal and Metascape, respectively. Finally, the SPAG5 expression in LUAD samples was determined by tissues microarrays (TMA) and immunohistochemistry (IHC) analyses.Results We found that upregulated SPAG5 associated with poor survival of LUAD patients. Besides, SPAG5 expression associated to B cell, CD4+ cell, CD8+ cell, macrophage, DC cell as well as CD274, CTLA4, GZMB, LAG3, PDCD1, TIGIT in LUAD. SPAG5 expression also associated with cell proliferation, cell cycle, DNA damage and repair, epithelial-mesenchymal transition (EMT), invasion, and stemness, inflammation in LUAD. Conclusion Our finding indicated that SPAG5 acted as a crucial oncogene in LUAD, and correlated with unfavorable survival as well as tumor infiltration inflation.

Dolutegravir plus lamivudine versus efavirenz plus tenofovir disoproxil fumarate and lamivudine in antiretroviral-naive adults with HIV-1 infection

Background Concerns regarding potential toxicity and drug-drug interactions during long-term treatment with three-drug active antiretroviral therapy (ART) regimens have been attracting increasing attention. We aimed to evaluate the efficacy and safety of dolutegravir (DTG) plus lamivudine (3TC) in ART-naive adults in China. Methods This prospective observational cohort study enrolled HIV-naive inpatients treated with DTG + 3TC (2DR arm) or efavirenz (EFV) plus tenofovir disoproxil fumarate (TDF) and 3TC (3DR arm). There were no limits on baseline viral load. Inflammatory biomarkers were also investigated in the 2DR arm. Results Between September 2019 and January 2020, 27 patients treated with DTG + 3TC and 28 patients treated with EFV + TDF + 3TC were enrolled in the study. At week 12, the proportion of patients with viral loads < 50 copies/mL in the 2DR arm was 81.5% (22/27) compared with 53.6% (15/28) in the 3DR arm (p < 0.01). At week 24, the proportion of patients with viral loads < 50 copies/mL in the 2DR arm was 100% (26/26) compared with 83.3% (20/24) in the 3DR arm (p < 0.05). Mean changes in CD4 cell counts from baseline at week 12 were 125.46 cells/µL in the 2DR arm and 41.20 cells/µL in the 3DR arm (p < 0.05). Mean changes in CD4 cell counts from baseline at week 24 were 209.68 cells/µL in the 2DR arm and 73.28 cells/µL in the 3DR arm (p < 0.05). Conclusions DTG + 3TC achieved virologic suppression more rapidly than EFV + TDF + 3TC after 12 and 24 weeks. DTG + 3TC could represent an optimal regimen for advanced patients. Clinical Trial Registration ChiCTR1900027640 (22/November/2019).

Modelling trends of CD4 counts for patients on antiretroviral therapy (ART): a comprehensive health care clinic in Nairobi, Kenya

Background In resource-limited settings, changes in CD4 counts constitute an important component in patient monitoring and evaluation of treatment response as these patients do not have access to routine viral load testing. In this study, we quantified trends on CD4 counts in patients on highly active antiretroviral therapy (HAART) in a comprehensive health care clinic in Kenya between 2011 and 2017. We evaluated the rate of change in CD4 cell count in response to antiretroviral treatment. We further assessed factors that influenced time to treatment change focusing on baseline characteristics of the patients and different initial drug regimens used. This was a retrospective study involving 432 naïve HIV patients that had at least two CD4 count measurements for the period. The relationship between CD4 cell count and time was modeled using a semi parametric mixed effects model while the Cox proportional hazards model was used to assess factors associated with the first regimen change. Results Majority of the patients were females and the average CD4 count at start of treatment was 362.1 $$cell/mm^3$$ c e l l / m m 3 . The CD4 count measurements increased nonlinearly over time and these trends were similar regardless of the treatment regimen administered to the patients. The change of logarithm CD4 cell count rises fast for in the first 450 days of antiretroviral initiation. The average time to first regimen change was 2142 days. Tenoforvir (TDF) based regimens had a lower drug substitution(aHR 0.2682, 95% CI:0.08263- 0.8706) compared to Zidovudine(AZT). Conclusion The backbone used was found to be associated with regimen changes among the patients with fewer switches being observed, with the use of TDF when compared to AZT. There was however no significant difference between TDF and AZT in terms of the rate of change in logarithm CD4 count over time.

Chronic Kidney Disease in a Large National Human Immunodeficiency Virus Treatment Program

Introduction: Tenofovir disoproxil fumarate (TDF) is associated with a risk of chronic kidney disease (CKD), especially when used with protease inhibitors or in Asian populations. Data from the Thai national health insurance system were used to assess the incidence of CKD in patients receiving antiretroviral therapy (ART) in real-world practice. Materials and methods We analyzed data from patients who initiated one of the following first-line ART regimens: (i) zidovudine+lamivudine+nevirapine (AZT+3TC+NVP); (ii) zidovudine+lamivudine+efavirenz (AZT+3TC+EFV); (iii) tenofovir+lamivudine+nevirapine (TDF+3TC+NVP); (iv) tenofovir+lamivudine/emtricitabine+efavirenz (TDF+3TC/FTC+EFV); and (v) tenofovir+lamivudine+lopinavir/ritonavir (TDF+3TC+LPV/r). CKD was defined as glomerular filtration rate <60 mL/min/1.73 m2 for >3 months, or a confirmed 2010 WHO diagnosis (ICD-10 code N183, N184, or N185). Death competing risks survival regression models were used for the analysis. Results Among 27,313 participants, median age 36.8 years, body mass index 20.4 kg/m2, and absolute CD4 cell count 146 cells/mm3, followed for a median 2.3 years, 245 patients (0.9%) were diagnosed CKD (incidence 3.2 per 1,000 patient-years of follow-up; 95% confidence interval [CI] 2.8-3.6). Compared with patients receiving AZT+3TC+NVP, the risk of CKD measured by adjusted sub-distribution hazard ratio (aSHR) was higher in patients on TDF+3TC+LPV/r (6.5, 95% CI 3.9-11.1), on TDF+3TC+NVP (3.8, 95% CI 2.3-6.0) and on TDF+3TC/FTC+EFV (1.6, 95% CI 1.2-2.3). Among patients receiving TDF, compared with those receiving TDF+3TC/FTC+EFV, the risk was higher on TDF+3TC+LPV/r (4.0, 95%CI 2.3-6.8) on TDF+3TC+NVP (2.3, 95%CI 1.4-3.6) . Conclusions This real-world study suggest that the role of TDF in increasing the risk of CKD, especially when combined with LPV/r or NVP.

A double-blind, randomized controlled trial to examine the effect of Moringa oleifera leaf powder supplementation on the immune status and anthropometric parameters of adult HIV patients on antiretroviral therapy in a resource-limited setting

Background People living with HIV (PLHIV) in resource-limited settings are vulnerable to malnutrition. Nutritional interventions aimed at improving food insecurity and malnutrition, together with antiretroviral therapy (ART), could improve treatment outcomes. In Nigeria, there is a high awareness of the nutraceutical benefits of Moringa oleifera. Thus, this study aimed to evaluate the effects of Moringa oleifera leaf supplementation on the CD4 counts, viral load and anthropometric of HIV-positive adults on ART. Methods This was a double-blind, randomized study. Two hundred HIV-positive patients were randomly allocated to either the Moringa Oleifera group (MOG) given Moringa oleifera leaf powder or the control group (COG) given a placebo. Changes in anthropometric parameters [weight; body mass index (BMI)] and CD4 cell counts were measured monthly for six months, while HIV-1 viral loads were measured at baseline and the end of the study for both groups. Results Over the study period, the treatment by time interaction shows a significant difference in CD4 counts by treatment group (p<0.0001). A further estimate of fixed effects showed that the CD4 counts among MOG were 10.33 folds greater than COG over the study period. However, the viral load (p = 0.9558) and all the anthropometric parameters (weight; p = 0.5556 and BMI; p = 0.5145) between the two groups were not significantly different over time. All tests were conducted at 95CI. Conclusion This study revealed that Moringa oleifera leaf supplementation was associated with increased CD4 cell counts of PLHIV on ART in a resource-limited setting. Programs in low-resource settings, such as Nigeria, should consider nutritional supplementation as part of a comprehensive approach to ensure optimal treatment outcomes in PLHIV.

Single-Dose 13-Valent Conjugate Pneumococcal Vaccine in People Living With HIV – Immunological Response and Protection

BackgroundPatients living with HIV (PLHIV) are prone to invasive pneumococcal disease. The 13-valent conjugated pneumococcal vaccine (PCV13) is currently recommended for all PLHIV, followed in most guidelines by a 23-valent polysaccharide pneumococcal vaccine. Data are scarce concerning the immunological efficacy of PCV13 among PLHIV.ObjectiveTo assess the immunological response at one month, and the immunological protection at 1-, 6-, and 12 months in PLHIV with a CD4 cell count above 200 cells/µl after a single dose of PCV13, as measured by both ELISA and opsonophagocytic assay (OPA).MethodsPLHIV with CD4 cell count &gt;200 cells/µl were included. Specific IgG serum concentrations for eight serotypes by ELISA and seven serotypes by OPA were measured at baseline, 1-, 6-, and 12 months after the PCV13 vaccination. Global response was defined as a two-fold increase from baseline of specific IgG antibody levels (μg/ml) assayed by ELISA or as a four-fold increase in OPA titer from baseline, for at least five serotypes targeted by PCV13. Global protection was defined as an IgG-concentration ≥1 µg/ml by ELISA or as an opsonization titer ≥LLOQ by OPA for at least five tested serotypes targeted by PCV13. Factors associated with global response and global protection were assessed using logistic regression.ResultsOf the 38 PLHIV included, 57.9% and 63.2% were global responders, 92.1% and 78.9% were globally protected at one month, and 64.7% and 55.9% were still protected at 12 months, by ELISA and OPA respectively. A CD4/CD8 ratio of &gt;0.8 was significantly associated with a better global response by OPA (OR=6.11, p=0.02), and a CD4 nadir &lt;200 was significantly associated with a poorer global response by ELISA (OR=0.22, p=0.04). A CD4 cell count nadir &lt;200 and age over 50 years were associated with poorer global protection by OPA at M1 (OR=0.18, p=0.04) and M12 (OR= 0.15, p=0.02), respectively. Plasma HIV RNA viral load &lt;40 copies/ml was significantly associated with a better global protection at M1 by ELISA and OPA (OR=21.33, p=0.025 and OR=8.40, p=0.04)ConclusionVaccination with PCV13 in these patients induced immunological response and protection at one month. At one year, more than half of patients were still immunologically protected.

Mucosal and systemic responses to SARS-CoV-2 vaccination in infection naive and experienced individuals

With much of the world infected with or vaccinated against SARS-CoV-2, understanding the immune responses to the SARS-CoV-2 spike (S) protein in different situations is crucial to controlling the pandemic. We studied the clinical, systemic, mucosal, and cellular responses to two doses of SARS-CoV-2 mRNA vaccines in 62 individuals with and without prior SARS-CoV-2 exposure that were divided into three groups based on serostatus and/or degree of symptoms: Antibody negative, Asymptomatic, and Symptomatic. In the previously SARS-CoV-2-infected (SARS2-infected) Asymptomatic and Symptomatic groups, symptoms related to a recall response were elicited after the first vaccination. Anti-S trimer IgA and IgG levels peaked after 1st vaccination in the SARS2-infected groups, and were higher that the in the SARS2-naive group in the plasma and nasal samples at all time points. Neutralizing antibodies titers were also higher against the WA-1 and B.1.617.2 (Delta) variants of SARS-CoV-2 in the SARS2-infected compared to SARS2-naive vaccinees. After the first vaccination, differences in cellular immunity were not evident between groups, but the AIM+ CD4+ cell response correlated with durability of humoral immunity against the SARS-CoV-2 S protein. In those SARS2-infected, the number of vaccinations needed for protection, the durability, and need for boosters are unknown. However, the lingering differences between the SARS2-infected and SARS2-naive up to 10 months post-vaccination could explain the decreased reinfection rates in the SARS2-infected vaccinees recently reported and suggests that additional strategies (such as boosting of the SARS2-naive vaccinees) are needed to narrow the differences observed between these groups.

An Overview of HIV on World AIDS Day: A Short Commentary

Acquired immunodeficiency syndrome (AIDS) is caused by Human immunodeficiency virus (HIV). HIV infections cause a gradual decrease in CD4+ cells and these cells are an indicator of the immune system including the body’s natural defense system against pathogens and illness.1 AIDS is defined as the advanced stage of HIV infection with CD4 cell count less than 200/mm3. AIDS is characterized by immunosuppression which can result in several opportunistic infections, tumors, and cancers.