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.

Construction and validation of a prognostic nomogram for predicting the survival of HIV/AIDS adults who received antiretroviral therapy: a cohort between 2003 and 2019 in Nanjing

Background Great achievements have been achieved by free antiretroviral therapy (ART). A rapid and accurate prediction of survival in people living with HIV/AIDS (PLHIV) is needed for effective management. We aimed to establish an effective prognostic model to forecast the survival of PLHIV after ART. Methods The participants were enrolled from a follow-up cohort over 2003-2019 in Nanjing AIDS Prevention and Control Information System. A nested case-control study was employed with HIV-related death, and a propensity-score matching (PSM) approach was applied in a ratio of 1:4 to allocate the patients. Univariable and multivariable Cox proportional hazards analyses were performed based on the training set to determine the risk factors. The discrimination was qualified using the area under the curve (AUC) and concordance index (C-Index). The nomogram was calibrated using the calibration curve. The clinical benefit of prognostic nomogram was assessed by decision curve analysis (DCA). Results Predictive factors including CD4 cell count (CD4), body mass index (BMI) and hemoglobin (HB) were determined and incorporated into the nomogram. In the training set, AUC and C-index (95% CI) were 0.831 and 0.798 (0.758, 0.839), respectively. The validation set revealed a good discrimination with an AUC of 0.802 and a C-index (95% CI) of 0.786 (0.681, 0.892). The calibration curve also exhibited a high consistency in the predictive power (especially in the first 3 years after ART initiation) of the nomogram. Moreover, DCA demonstrated that the nomogram was clinically beneficial. Conclusion The nomogram is effective and accurate in forecasting the survival of PLHIV, and beneficial for medical workers in health administration.

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.

The Relationship of Ghrelin Level with Levels of Cluster of Differentiation 4 (CD4) in Human Immunodeficiency Virus (HIV) Patients Receiving Antiretroviral (ARV) Therapy

Background: Ghrelin is primarily involved in the secretion of growth hormone (GH), glucose and lipid metabolism. HIV infection is thought to affect ghrelin levels in HIV patients, especially in patients with lipodystrophy. However, this effect is still unclear because many studies have obtained different results about low or high levels of ghrelin in people with HIV. Suppression of HIV replication with ART rapidly increases CD4 cell count. However, data on the effect of antiretroviral therapy on ghrelin levels is still scant. Aim: To examine the relationship between ghrelin levels and CD4 levels in HIV patients receiving ARV therapy. Method: This research is an observational analysis study, with cross-sectional design, implemented start from April 2020 in Tropical Diseases & Infection Polyclinic, H. Adam Malik Hospital. Blood samples were taken and examined at the Clinical Pathology Laboratory. Primary and secondary data collection from interviews and direct observation. Data will be analyzed with Pearson correlation test if normally distributed or Spearman's test if the data is not normally distributed using SPSS software. Results: A total of 43 the sample consists of 38 patient who received the AFC, 3 patients received Duviral + Efafirens, 1 patient received Tenofovir + Hiviral + Aluvia dan 1 patient received Tenofovir + Hiviral + Neviral. Demographic characteristics based on th highest ages group are 21-30 years and 31-40 years, each of which is 17 people. The correlation of ghrelin level with levels of CD4 on the HIV patient taking ARV shows a significance value of 0.943, it can be concluded that there was no significant relationship between Ghrelin levels and CD4. Conclusion: There was no correlation between ghrelin levels with CD4 levels on HIV patient receiving ARV therapy. Keywords: Ghrelin, HIV, CD4, Antiretrovirals.

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.

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.

High seroconversion rate and SARS-CoV-2 Delta neutralization in PLWHIV vaccinated with BNT162b2

ObjectivesTo assess the humoral and cellular responses against SARS-CoV-2 Delta variant after BNT162b2 vaccination in PLWHIV.DesignMulticenter cohort study of PLWHIV, with a CD4 cell count <500/mm3 and a viral load <50 copies/ml on stable antiretroviral therapy for at least 3 months.MethodsAnti-SARS-CoV-2 Receptor Binding Domain IgG antibodies (anti-RBD IgG) were quantified and their neutralization capacity was evaluated using an ELISA (GenScript) and a virus neutralization test (VNT), against historical strain, Beta and Delta variants before vaccination (day 0) and one month after a complete vaccination schedule (M1).Results97 patients were enrolled in the study: 85 received 2 vaccine doses (11 previous COVID-19 and 1 premature exit). The seroconversion rate in anti-RBD IgG was 97% CI95[90%; 100%] at M1. Median (IQR) anti-RBD IgG titer was 0.97 (0.97-5.3) BAU/ml at D0 and 1219 (602-1929) at M1. Neutralizing antibodies (NAbs) capacity improved between D0 (15% CI95[8%; 23%]) and M1 (94% CI95[87%; 98%]) with the GenScript assay (p<0.0001). At M1, NAbs against historical strain, Beta and Delta variants were present in 82%, 77% and 84% patients respectively. The seroconversion rate and median anti-RBD IgG were 91% and 852 BAU/ml in patients with CD4<250/mm3 (n=13) and 98% and 1270 BAU/ml in patients with CD4>250/mm3 (n=64) (p=0.3994). 73% of patients with CD4<250 had NAbs and 97% of those with CD4>250 (p=0.0130). The NAbs against Beta variant was elicited in 50% in CD4<250 and in 81% in CD4>250 (p=0.0292). No change in CD4+ or CD8+ T cells count was observed while a decrease of CD19+ B cells count was observed (208 ±124 cells/mm3 at D0 vs 188 ±112 cells/mm3 at M1, p<0.01). No notable adverse effects or COVID-19 were reported.ConclusionsThese results show a high seroconversion rate with a Delta neutralization in PLWHIV patients after a complete BNT162b2 vaccination schedule.

Prevalence and Distribution of HPV Genotypes in Immunosuppressed Patients in Lorraine Region

Background: The primary objective of this work was to assess the prevalence and distribution of HPV genotypes in immunosuppressed patients, and to compare them with the French Monsonego cohort. Secondary objectives were to evaluate whether the risk of HPV infection was correlated with HIV viral load, CD4 cell count in HIV-infected patients and the type, number of immunosuppressive therapies or type of pathology (transplant vs. autoimmune diseases) in patients undergoing long-term immunosuppressive therapy. Methods: An observational, monocentric and historical study was conducted including all immunosuppressed patients having received an HPV testing, in the Laboratory of Virology, Nancy Regional Teaching Hospital Center, between 2014 and 2020. Immunosuppressed patients were either HIV-infected or received long-term immunosuppressive therapy. Results: In our cohort, the prevalence of HPV infection (75.6% vs. 16.1% p < 0.05), the proportion of patients with high-risk HPV infection (48.9% vs. 15.1% p < 0.05) and with multiple HPV infection (41.1% vs. 5.7% p < 0.05) were significantly higher than in the Monsonego cohort. HPV 52 (13%), 53 (13%) and 16 (10%) were the most common in the immunosuppressed population, while it was HPV 16, 42 and 51 in the Monsonego cohort. Conclusions: This study supports that a particular attention must be given to all the immunosuppressed patients for the screening and care of HPV-related diseases because of major modifications of HPV epidemiology compared with the overall population.