People with HIV Have Higher Risk of COVID-19 Diagnosis but Similar Outcomes than the General Population

Background We investigated the effect of HIV on COVID-19 outcomes with attention to selection bias due to differential testing and to comorbidity burden. Methods Retrospective cohort analysis using four hierarchical outcomes: positive SARS-CoV-2 test, COVID-19 hospitalization, intensive care unit (ICU) admission, and hospital mortality. The effect of HIV status was assessed using traditional covariate-adjusted, inverse probability weighted (IPW) analysis based on covariate distributions for testing bias (testing IPWs), HIV infection status (HIV IPWs), and combined models. Among PWH, we evaluated whether CD4 count and HIV plasma viral load (pVL) discriminated between those who did or did not develop study outcomes using receiver operating characteristic analysis. Results Between March and November 2020, 63,319 people were receiving primary care services at UCSD, of whom 4,017 were people living with HIV (PWH). PWH had 2.1 times the odds of a positive SARS-CoV-2 test compared to those without HIV after weighting for potential testing bias, comorbidity burden, and HIV-IPW (95% CI 1.6-2.8). Relative to persons without HIV, PWH did not have an increased rate of COVID-19 hospitalization after controlling for comorbidities and testing bias [adjusted incidence rate ratio (aIRR): 0.5, 95% CI: 0.1-1.4]. PWH had neither a different rate of ICU admission (aIRR:1.08, 95% CI; 0.31-3.80) nor in-hospital death (aIRR:0.92, 95% CI; 0.08-10.94) in any examined model. Neither CD4 count nor pVL predicted any of the hierarchical outcomes among PWH. Conclusions PWH have a higher risk of COVID-19 diagnosis but similar outcomes compared to those without HIV.

Immune correlates of Mycobacterium Tuberculosis patients in Zambia stratified by HIV serostatus and level of immunity-a cross-sectional analytical laboratory based study

Background People living with HIV (PLHIV) co-infected with tuberculosis (TB) have a distinct clinical presentation and poorer treatment outcomes compared to HIV-seronegative TB patients. Excluding low CD4 count, innate immune factors associated with TB are not fully elucidated. We, therefore, characterised and compared the expression of IL-6, TNF-α, IFN-γ, and IL-10 in whole blood of treatment naïve TB patients stimulated with heat-killed Mycobacterium tuberculosis stratified by HIV status and the level of CD4 count. Results We recruited 39 HIV seropositive and 31 HIV seronegative TB patients. Median (IQR) age was 35(28–42) years and 31(25–36) years respectively, and a majority had pulmonary tuberculosis i.e. 38(95%) and 30(97%), respectively. The two groups were significantly different in the distribution of CD4 count, 563 [465–702.5 cells/mm3] vs 345 [157–483 cell/mm3] in HIV negative vs HIV positive respectively p = <0.001. Post stimulation, the expression of IL-6 in HIV negative TB patients was significantly higher than in the HIV positive 16,757366 [8,827–23,686 pg/ml] vs. 9,508 [5,514–15,008 pg/ml], respectively; p = 0.0360. TNF-α and IFN-γ were highly expressed in HIV negative TB patients compared to the HIV positive though not statistically significant. We only observed higher expression of IL-6 in HIV negative patients in comparison to the HIV positive when stratified by level of CD4 counts as < 500 and ≥ 500 cell/mm3 for both cohorts. 21,953 [8,990–24,206 pg/ml] vs 9,505 [5,400–15,313 pg/ml], p value = 0.0585 in patients with CD4 count < 500 cell/mm3 and 13,168 [7,087–22,584 pg/ml] vs 10,413 [7,397–14,806 pg/ml], p value = 0.3744 for patients with CD4 count of ≥ 500 cell/mm3 respectively. We found a positive pairwise correlation between TNF-α -alpha and IL-6 in both HIV positive and HIV negative patients, r = 0.61 (95% CI 0.36–0.72; p < 0.0001) and r = 0.48 (95% CI 0.15–0.68; p = 0.005) respectively. The IFNγ/IL-10 ratio was higher in HIV negative when compared to HIV positive individuals, 0.052 [0.0–0.28] vs 0.007 [0–0.32] respectively; p = 0.05759. IL-6 independently reduced the probability of TB/HIV, Adjusted odds ratio 0.99, p value 0.007. Conclusions This study suggests that HIV seronegative TB patients have a higher pro-inflammatory response to MTB than HIV seropositive TB patients. Further, it also shows that the level of CD4 influences immunomodulation. The findings suggest that the difference in cytokine expression may be responsible for the distinct patterns of TB presentation between HIV positive and HIV negative patient.

Systematic review and meta-analysis of COVID-19 vaccines safety, tolerability, and efficacy among HIV-infected patients

Objective To conduct a comprehensive systematic review and meta-analysis of all recommended SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) vaccines in people living with HIV (PLWH), as well as an overview of the safety, tolerability, and efficacy of the vaccines in PLWH. Methods We searched six databases, Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Medline, Medrxiv, Global research on COVID-19 database, and Google Scholar for studies investigating the effects of SARS-CoV-2 vaccines on PLWH. Results of the association were summarised by SARS-CoV-2 IgG seroconversion and level, vaccines efficacy and tolerability. A meta-analysis was performed for studies, using random-effects model and a pooled RR with 95% CI was reported. Results Twenty-three of the 1052 studies screened met the inclusion criteria. The review included 28, 246 participants among whom 79.55% (22,469/28, 246) were PLWH with median CD4 >=200 cells/mm3. The pooled estimate of SARS-CoV-2 IgG seroconversion and positive neutralizing antibodies after the second vaccination dose between PLWH vs HIV negative were RR 0.95 (95%CI: 0.92 to 0.99, P = 0.006) and 0.88 (95%CI: 0.82 to 0.95, P = 0.0007), respectively. The mean difference of IgG antibodies level (BAU/ml) was found higher in mRNA vaccines MD -1444.97 (95%CI: -1871.39 to -1018.55). PLWH with CD4 less than 500 cells/mm3 had 15% risk reduction of neutralizing antibodies response compared to those with CD4>=500 cells/mm3 (P = 0.003). The SARS-CoV-2 vaccine effectiveness was 65% (95%CI: 56% to 72%, P <0.001) among vaccinated compared to unvaccinated PLWH. PLWH with CD4 count <350 cells/mm3 had lower vaccine effectiveness compared to CD4 count >=350 cells/mm3 with 59% vs 72%, respectively. Vaccine tolerability was the same between PLWH and HIV negatives. Conclusion According to our findings, PLWH with CD4>=200 cells/mm3 had lower immunogenicity and antigenicity in COVID-19 vaccines than HIV negatives. Additional doses of SARS-CoV-2 vaccination are needful in PLWH.

Causes of death and associated factors over a decade of follow-up in a cohort of people living with HIV in rural Tanzania

Background Nearly half of HIV-related deaths occur in East and Southern Africa, yet data on causes of death (COD) are scarce. We determined COD and associated factors among people living with HIV (PLHIV) in rural Tanzania. Methods PLHIV attending the Chronic Diseases Clinic of Ifakara, Morogoro are invited to enrol in the Kilombero and Ulanga Antiretroviral Cohort (KIULARCO). Among adults (≥ 15 years) enrolled in 2005–2018, with follow-up through April 2019, we classified COD in comprehensive classes and as HIV- or non-HIV-related. In the subset of participants enrolled in 2013–2018 (when data were more complete), we assessed cause-specific mortality using cumulative incidences, and associated factors using proportional hazards models. Results Among 9871 adults (65% female, 26% CD4 count < 100 cells/mm3), 926 (9%) died, among whom COD were available for 474 (51%), with missing COD mainly in earlier years. The most common COD were tuberculosis (N = 127, 27%), non-AIDS-related infections (N = 72, 15%), and other AIDS-related infections (N = 59, 12%). Cardiovascular and renal deaths emerged as important COD in later calendar years, with 27% of deaths in 2018 attributable to cardiovascular causes. Most deaths (51%) occurred within the first six months following enrolment. Among 3956 participants enrolled in 2013–2018 (N = 203 deaths, 200 with COD ascertained), tuberculosis persisted as the most common COD (25%), but substantial proportions of deaths from six months after enrolment onwards were attributable to renal (14%), non-AIDS-related infections (13%), other AIDS-related infections (10%) and cardiovascular (10%) causes. Factors associated with higher HIV-related mortality were sex, younger age, living in Ifakara town, HIV status disclosure, hospitalisation, not being underweight, lower CD4 count, advanced WHO stage, and gaps in care. Factors associated with higher non-HIV-related mortality included not having an HIV-positive partner, lower CD4 count, advanced WHO stage, and gaps in care. Conclusion Incidence of HIV-related mortality was higher than that of non-HIV-related mortality, even in more recent years, likely due to late presentation. Tuberculosis was the leading specific COD identified, particularly soon after enrolment, while in later calendar years cardiovascular and renal causes emerged as important, emphasising the need for improved screening and management.

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.

Stroke among highly active antiretroviral therapy-naive people living with the human immunodeficiency virus in China: a retrospective study of the characteristics, risk factors, and prognosis

Background We aimed to clarify the characteristics, risk factors, and prognosis of stroke among HAART-naive people living with HIV (PLWH) in China. Methods We selected HAART-naive PLWH admitted to Beijing Ditan Hospital, Capital Medical University, from 1 January 2009 to 31 December 2019. Demographic and clinical data were obtained by searching an anonymous electronic case system. Descriptive analysis and logistic regression and Cox proportional hazard models were used to determine the characteristics and predictors of stroke among all HAART-naive PLWH and evaluate the risk factors of mortality in HAART-naive PLWH with stroke. Results Stroke was diagnosed in 105 cases (3.7%) of 2867 HAART-naive PLWH. Multivariate logistic regression indicated that age of 30–55 years (OR 1.903, 95% CI 1.005–3.603, p = 0.048), age of ≥ 55 years (OR 4.104, 95% CI 1.928–8.737, p < 0.001), and CD4 count of < 200 cells/µL (OR 2.005, 95% CI 1.008–3.985, p = 0.047) were associated with increased odds of stroke. Diabetes (OR 3.268, 95% CI 1.744–6.125, p < 0.001), hypertension (OR 2.301, 95% CI 1.425–3.717, p = 0.001), syphilis (OR 2.003, 95% CI 1.300–3.089, p = 0.002), and complicated AIDS-defining CNS diseases (OR 7.719, 95% CI 4.348–13.703, p < 0.001) were risk factors for stroke. Of the 105 stroke patients, 12 (11.4%) died during hospitalisation, and the risk factors for mortality among patients with stroke were age of > 65 years (AHR: 8.783, 95% CI 1.522–50.668, p = 0.015), complicated severe pneumonia (AHR: 3.940, 95% CI 1.106–14.029, p = 0.034), and AIDS-defining CNS diseases (AHR: 19.766, 95% CI 3.586–108.961, p = 0.001). Conclusions For HAART-naive people living with HIV (PLWH), stroke occurred in various age groups, and early screening for stroke, timely intervention for risk factors among patients in various age groups, and controlling the CD4 count are extremely important in reducing the burden of stroke.

Incidence and predictors of reoccurrence of opportunistic infection among adult HIV/AIDS patients attending ART clinic at public health facilities in Arba Minch town, southern Ethiopia: A retrospective cohort study

Background Human immunodeficiency virus (HIV) infected individuals are prone to opportunistic infections (OIs) due to HIV mediated immune suppression. When opportunistic infections occur in the form of relapse or reinfection, it is said to be reoccurrence. This study was aimed to assess Incidence and predictors of reoccurrence of opportunistic infections among adult people living with HIV (PLHIV) attending ART clinics in Arba Minch Town, Southern Ethiopia Methods This retrospective cohort study was conducted on 450 HIV/AIDS patients attending anti-retro viral therapy (ART) clinics in Arba Minch town, southern Ethiopia. Simple random sampling technique was used. Kaplan-Meier graph and log rank test were used for group wise comparison. Bivariate and multivariable Cox Proportional Hazard Regression model were used to identify independent predictors of reoccurrence of opportunistic infection. Result One hundred nineteen HIV/AIDS patient had reoccurrence of opportunistic infection. The incidence rate was 11.5 per 1000 person months. The mean time of reoccurrence was 56 months. One of the most reoccurred OIs was pulmonary tuberculosis (PTB). Predictors that were associated significantly were recent cell differentiation 4 (CD4) count, recent body mass index (BMI), recent functional status, and duration on anti-retroviral therapy (ART). Conclusion Though the incidence rate of OIs decreased from previous findings, attention should be given to HIV patients with low CD4 count, low BMI and for those bedridden patients.

HIV Myelopathy- A cross-sectional study of constellation of bone marrow findings in HIV/AIDS

Introduction and Aim: Haematological manifestations in HIV disease is common and can happen at any phase during the disease course. Anemia and thrombocytopenia are the most frequent hematologic abnormalities and are associated with high morbidity and mortality. The objective of current study was to observe and analyse various spectrum of bone marrow changes and haematological abnormalities in HIV/AIDS and to correlate findings with CD4 count. Material and Methods: A total of 44 patients over a period of 5 years were included. Clinical findings, hematological profile, bone-marrow aspirate, biopsy findings and CD4 count of these patients were documented. The association between absolute lymphocyte count (ALC) and CD4 count were further established. Results: The most common clinical indication for bone-marrow aspiration and trephine biopsy was pancytopenia (47.3%), pyrexia of unknown origin (15.1%), and unresolving hepatosplenomegaly (13.6%). Anemia (72.7%) was commonest haematological abnormality. Bone marrow aspirate was normocellular in majority of patients. Marrow findings were correlated with CD4 count and were found to be statistically significant. Tri-lineage dysplasia was observed in 9.1% of patients, and megakaryocytic dysplasia being the commonest(61.4%). Histiocytic aggregates (27.3%) were noted among which 6.8% showed acid fast bacilli in Ziehl-Neelsen stain. Fungal stains revealed histoplasmosis in 4.5% patients. Conclusion: There was a strong negative association between presence of anemia and dysplasia and CD4 count. When CD4 was <200/µL and ALC<1000/mm3, presence of anemia and dysplasia affecting various cell lines were commonly observed; therefore, can be used as indicators to assess the severity of the disease.

The Difference Of PT, aPTT, Fibrinogen, D-Dimer Activities In HIV Patients With CD4 Count Of 200 uL

ABSTRACT Introduction: HIV is a developing disease that has been a global problem. The progress of HIV infection is characterized by decreased CD4 count. Hemostasis disorder is often found in patients with HIV, where the formed virus-antibody complex can activate the coagulation system, beginning from the activation of the Hageman factor (Factor XII) into the active form (Factor XIIa). This factor will activate the fibrinolysis process. Fibrin polymer is broken down into fragments X and Y. Fragment Y is further broken down into Fragment D and E, which is known as D-dimer. Objective: To determine the difference of PT, aPTT, Fibrinogen, and D-Dimer in HIV patients with a CD4 lymphocyte count of < 200/µL and > 200/µL in H. Adam Malik General Hospital Medan. Hypothesis: There is a difference of PT and aPTT activities in HIV patients with a CD4 count of < 200 cells/µL and ≥ 200 cells/µL and a difference of D-dimer and fibrinogen levels in HIV patients with a CD4 count of < 200/µL and > 200/µL in H. Adam Malik General Hospital Medan. Methods: This study was conducted in the Clinical Pathology Laboratory, Department of Internal Medicine, H. Adam Malik General Hospital. Samples were collected with a consecutive sampling method which included patients diagnosed with HIV in H. Adam Malik General Hospital Medan from September 2019 to July 2020 who fulfilled the inclusion and exclusion criteria. Thirty-eight patients were divided into two groups, i.e., HIV patients with a CD4 count of < 200/µL and HIV patients with a CD4 lymphocyte count of > 200/ µL. Results: Mann-Whitney test was used to assess the comparison of PT and aPTT values between HIV patients with a CD4 count of < 200 cells/µL and ≥ 200 cells/µL. The result was significant with a p-value = 0.002, which means that there is a significant difference in PT and aPTT values between HIV patients with a CD4 count of < 200 cells/µL and ≥ 200 cells/µL. An Independent T-test was used to assess the difference in fibrinogen level between HIV patients with a CD4 count of < 200/µL and > 200/µL, which resulted in p-value = 0.032. This means that there is a significant difference in fibrinogen levels between HIV patients with a CD4 count of < 200/µL and > 200/µL. Mann-Whitney test was used to determine the comparison in D-dimer level between HIV patients with a CD4 count of < 200/µL and > 200/µL, which showed a p-value = 0.002. This indicated a significant difference in D-dimer level between HIV patients with a CD4 count of < 200/µL and > 200/µL. Conclusion: The lower the CD4 lymphocyte count, the higher the activities of PT, aPTT, fibrinogen, and D-dimer in HIV patients. Keywords: HIV, PT, aPTT, D-Dimer, Fibrinogen, Hemostasis

A Real-World Evidence-Based Management of HIV by Differential Duration HAART Treatment and its Association with Incidence of Oral Lesions

Background: The efficacy of highly active antiretroviral therapy (HAART) therapy can be estimated by immunological response and the incidence of opportunistic infections. Objective: To evaluate the effectiveness of different durations of HAART in terms of immunological response markers (CD4 count and CD4/CD8 ratio) along with disease progression markers (incidence of oral lesions) in Chinese patients with HIV. Methods: This single-center, retrospective, real-world study included patients with HIV, grouped into treatment group and treatment-naïve group of which the former was further divided into (6, 12, and 18 months) based on the treatment duration. The CD4 and CD8 cell counts were analyzed by the FACSCalibur flow cytometry. Kruskal-Wallis test was applied to determine the outcome of different duration of HAART. Oral examination was carried out according to the WHO type IV examination Results: In 246 patients with HIV, CD4 counts increased significantly post-HAART compared with pre-HAART in all three treatment groups (P<.001), while CD8 count decreased significantly (P<.05) in all three treated group. A significant association of HAART with CD4/CD8 ratio was observed (P<.001). A significant increase in CD4 count was observed between 12-month and 18-month treatment group (P<.05). The occurrence of oral lesions reduced significantly in the treatment group. Conclusion: We observed a better response of HAART regimen with 18 months of duration than 12-months and 6-months therapies and reduction in oral lesions.