HIV disease metrics and COVID-19 infection severity and outcomes in people living with HIV in central and eastern Europe.

BACKGROUND: To date there remains much ambiguity in the literature regarding the immunological interplay between SARS-CoV-2 and HIV and the true risk posed to coinfected individuals. There has been little conclusive data regarding the use of CD4 cell count and HIV viral load stratification as predictors of COVID-19 severity in this cohort. METHODS: We performed a retrospective, observational cohort study on people living with HIV (PLWH) who contracted COVID-19 in central and eastern Europe. We enrolled 536 patients from 16 countries using an online survey. We evaluated patient demographics, HIV characteristics and COVID-19 presentation and outcomes. Statistical analysis was performed using SPSS 20.1. RESULTS: The majority of the study cohort were male (76.4%) and 152 (28.3%) had a significant medical comorbidity. Median CD4 cell count at COVID-19 diagnosis was 605 cells/µL [interquartile range (IQR) 409-824]. The majority of patients on antiretroviral therapy (ART) were virally suppressed (92%). In univariate analysis, CD4 cell count <350 cells/µL was associated with higher rates of hospitalization (p < 0.0001) and respiratory failure (p < 0.0001). Univariate and multivariate analyses found that an undetectable HIV VL was associated with a lower rate of hospitalization (p < 0.0001), respiratory failure (p < 0.0001), ICU admission or death (p < 0.0001), and with a higher chance of full recovery (p < 0.0001). CONCLUSION: We can conclude that detectable HIV viral load was an independent risk factor for severe COVID-19 illness and can be used as a prognostic indicator in this cohort.

The Effect of HIV Treatment Interruption on Subsequent Immunological Response.

Recovery of CD4-positive T lymphocyte count after initiation of antiretroviral therapy (ART) has been thoroughly examined among people with human immunodeficiency virus infection. However, immunological response after restart of ART following care interruption is less well studied. We compared CD4 cell-count trends before disengagement from care and after ART reinitiation. Data were obtained from the East Africa International Epidemiology Databases to Evaluate AIDS (IeDEA) Collaboration (2001-2011; n = 62,534). CD4 cell-count trends before disengagement, during disengagement, and after ART reinitiation were simultaneously estimated through a linear mixed model with 2 subject-specific knots placed at the times of disengagement and treatment reinitiation. We also estimated CD4 trends conditional on the baseline CD4 value. A total of 10,961 patients returned to care after disengagement from care, with the median gap in care being 2.7 (interquartile range, 2.1-5.4) months. Our model showed that CD4 cell-count increases after ART reinitiation were much slower than those before disengagement. Assuming that disengagement from care occurred 12 months after ART initiation and a 3-month treatment gap, CD4 counts measured at 3 years since ART initiation would be lower by 36.5 cells/µL than those obtained under no disengagement. Given that poorer CD4 restoration is associated with increased mortality/morbidity, specific interventions targeted at better retention in care are urgently required.

Immune response to ART initiation in advanced HIV infection.

OBJECTIVES: Our objective was to compare the immunological responses to commonly used antiretroviral therapy (ART) regimens among people with advanced HIV in the USA and to assess virological outcomes and regimen persistence. METHODS: This study included ART-naïve adults with advanced HIV infection (CD4 cell count <200 cells/µL) initiating ART with bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF), boosted darunavir (bDRV), dolutegravir (DTG), or elvitegravir (EVG/c)-containing regimens between 1 January 2018 and 31 December 2020 in the Observational Pharmaco-Epidemiology Research and Analysis (OPERA) cohort. Cox proportional hazards models and linear mixed models with random intercept were fit with inverse probability of treatment weighting. RESULTS: Overall, 1349 people with advanced HIV (816 B/F/TAF, 253 DTG, 146 EVG/c, 134 bDRV) were followed for a median of 22 months. Compared with B/F/TAF, a lower likelihood of achieving a CD4 cell count ≥200 cells/µL was observed with bDRV (hazard ratio [HR] 0.76; 95% confidence interval [CI] 0.60-0.96), DTG (HR 0.82; 95% CI 0.69-0.98), and EVG/c (HR 0.73; 95% CI 0.57-0.93). All groups had a similar pattern of CD4:CD8 ratio changes: a rapid increase in the first 6 months (ranging from +0.15 to +0.16 units), followed by a slower increase thereafter. Only 40 individuals (4%) achieved CD4:CD8 ratio normalization (≥1). B/F/TAF was associated with a faster time to virological suppression (viral load <200 copies/mL) and a slower time to discontinuation compared with other regimens. CONCLUSIONS: Among people with advanced HIV infection, B/F/TAF initiation was associated with faster CD4 cell count recovery and favourable virological outcomes compared with bDRV-, DTG-, and EVG/c-based regimens, although no difference was observed in CD4:CD8 ratio changes over time across regimens.

Humoral immune response to inactivated COVID-19 vaccination at the 3rd month among people living with HIV.

BACKGROUND: Research on the immune response to inactivated COVID-19 vaccination among people living with HIV (PLWH) is limited, especially among those with low CD4+ T lymphocyte (CD4 cell) count. This prospective cohort study aimed to assess the humoral immune response to inactivated COVID-19 vaccination among PLWH compared to HIV negative controls (HNCs) and to determine the impact of CD4 cell count on vaccine response among PLWH. METHODS: The neutralizing antibodies (nAbs) and the specific IgM and IgG-binding antibody responses to the inactivated COVID-19 vaccine at the third month after the second dose of inactivated COVID-19 vaccination were measured among 138 PLWH and 35 HNCs. Multivariable logistic regression and multiple linear regression models were conducted to identify factors associated with the seroconversion rate of antibodies and the magnitude of anti-SARS-CoV-2 antibody titers, respectively. RESULTS: At the end of the third month after two doses of vaccination, the seroconversion rates of IgG were comparable between PLWH (44.9%; 95% CI 36.5-53.3%) and HNCs (60.0%; 95% CI 42.9-77.1%), respectively. The median titers and seroconversion rate of nAbs among PLWH were 0.57 (IQR: 0.30-1.11) log10 BAU/mL and 29.0% (95% CI 21.3-36.8%), respectively, both lower than those in HNCs (P < 0.05). After adjusting for age, sex, comorbidities, and CD4 cell count, the titers and seroconversion rate of nAbs were comparable between PLWH and HNCs (P > 0.05). Multivariable regression analyses showed that CD4 cell count < 200/µL was independently associated with lower titers and seroconversion rate of nAbs among PLWH (P < 0.05). A positive correlation was observed between the CD4 cell count and nAbs titers in PLWH (Spearman's ρ = 0.25, P = 0.0034). CONCLUSION: Our study concluded that the immune response to inactivated COVID-19 vaccination among PLWH was independently associated with CD4 cell count, PLWH with lower CD4 cell count showed a weaker humoral immune response, especially those with CD4 cell count < 200/µL. This finding suggests that expanding COVID-19 vaccination coverage among PLWH is impendency. In addition, aggressive ART should be carried out for PLWH, especially for those with low CD4 cell count, to improve the immune response to vaccines.

Predictors associated with CD4 cell count changes over time among HIV-infected children on anti-retroviral therapy follow-up in Mekelle General Hospital, Northern Ethiopia, 2019: a retrospective longitudinal study.

INTRODUCTION: AIDS continues to be a serious global public health issue. It targets CD4 cells and immunological cells, which are in charge of the body's resistance against pathogenic pathogens. In situations with limited resources, CD4 cell measurement is essential for assessing treatment responses and clinical judgments in HIV-infected children receiving Anti-Retroviral Therapy (ART). The volatility of CD4 cells during ART follow-up is still largely uncharacterized, and there are few new datasets on CD4 cell changes over time. Therefore, the purpose of this analysis was to identify the factors that were predictive of CD4 cell count changes over time in children who started ART at Mekelle General Hospital in northern Ethiopia. METHODS: A retrospective follow-up study was done. 437 patients in Mekelle general hospital, northern Ethiopia, from 2014-2016 were involved. All patients who have started anti-retrieval treatment (ART) and measured their CD4 cell count at least twice, including the baseline and those who initiated ART treatment, were included in the study population. An exploratory data analysis and linear mixed model analysis were used to explore the predictors of CD4 cell count change in patients and consider variability within and between patients. RESULTS: This study found the correlation variation explained in cells accounted for between patients was 61.3%, and the remaining 38.7% variation existed within. This indicates that there is a substantial change in random slope and intercept between and within patients. WHO clinical stage IV (ß = -1.30, 95% CI: -2.37, -0.23), co-infection HIV/TB (ß = -1.78, 95% CI: -2.58, -0.98), children aged 2-5 (ß = -0.43; 95% CI: -0.82, -0.04), and 6-14 years (ß = -1.02; 95% CI: -1.47, -0.56), non-opportunistic infection (ß = 1.33, 95% CI: 0.51, 2.14), and bedridden functional status (ß = -1.74, 95% CI: -2.81, -0.68) were predictors of cell changes over time. CONCLUSIONS: This study found that patients receiving ART experienced a significant change in CD4 cells over time. Because 61.3% of the variation in CD4 cells explained between patients and the remaining 38.7% within patients, such nested data structures are often strong correlation evidence. Co-infection of HIV/TB, functional status, age category of children, WHO clinical stage, and opportunistic infections are potential predictors of CD4 cells count change. Hence, special guidance and attention is also required, especially for those patients who have an opportunistic infections, higher WHO clinical stages, co-infections with HIV and TB, and bedridden functional status.

Synergist effect of antiretroviral therapy adherence and viral load suppression on quality of life of people with HIV/AIDS.

AIMS: This study investigated the synergistic and independent effects of adherence to antiretroviral therapy (ART) and viral load on quality of life (QoL) among people with HIV/AIDS. METHODS: This was a cross-sectional study of 129 patients with HIV/AIDS. The WHOQOL-BREF and the Morisky Medication Adherence Scale were used to measure QoL and adherence respectively. Information on viral load and CD4 cell count was obtained from patients' records and verified by a physician. An additive interaction method was used to estimate the synergistic effect of the linear regression. FINDINGS: Patients who were adhering to ART and had an undetectable viral load had significantly higher scores on four domains of QoL - environment, physical health, social relationships and psychological - than those who were non-adherent. Moreover, ART adherence and undetectable viral load had a positive synergistic effect on QoL after controlling for covariate variables. CONCLUSION: Participants were more likely to have a good QoL if they had both undetectable viral loads and good ART adherence.

Etiologies of fever of unknown origin in HIV/AIDS patients, Hanoi, Vietnam.

BACKGROUND: Fever of unknown origin (FUO) is a challenge for clinicians treating patients with HIV/AIDS. CD4 counts can be helpful in the diagnosis and treatment. This study aimed to determine several common etiologies of FUO stratified by CD4 count levels in HIV/AIDS patients. METHODS: A cross-sectional retrospective and prospective study was conducted in 195 HIV/AIDS patients with FUO admitted to the National Hospital for Tropical Diseases from January 2016 to June 2019. Clinical parameters, immune status, and etiologies for each patient were recorded. Odds ratios were calculated to compare the distributions of common etiologies in groups with two different CD4 count levels: < 50 cells/mm3 and ≥ 50 cells/mm3. RESULTS: The proportions of opportunistic infections and noninfectious etiologies were 93.3% and 3.6%, respectively. Tuberculosis was the most common opportunistic infection (46.7%), followed by talaromycosis (29.2%) and Pneumocystis jiroveci (PCP) infection (20.5%). Tuberculosis was predominant in all CD4 level groups. Most patients with talaromycosis had CD4 counts below 50 cells/mm3. In total, 53.8% of the patients were infected by one pathogen. The risks of tuberculosis and talaromycosis in FUO-HIV patients were high when their CD4 counts were below 50 cells/mm3. CONCLUSIONS: Opportunistic infections, especially tuberculosis, are still the leading cause of FUO in HIV/AIDS patients. Tuberculosis and Talaromyces marneffei (TM) infection should be considered in patients with CD4 cell counts < 50 cells/mm3. This study implies that guidelines for appropriate testing to identify the etiology of FUO in HIV/AIDS patient based on the CD4 cell count should be developed, thereby reducing resource waste.

Determinants of therapy failure among adults on first-line antiretroviral therapy in Asmara, Eritrea: a multicenter retrospective matched case-control study.

BACKGROUND: Information on treatment failure (TF) in People living with HIV in a data-poor setting is necessary to counter the epidemic of TF with first-line combined antiretroviral therapies (cART) in sub-Saharan Africa (SSA). In this study, we examined the risk factors associated with TF in Asmara, Eritrea from 2001 to 2020. METHODS: A multicenter, retrospective 1:2 matched (by age and gender) case-control study was conducted in four major hospitals in Asmara, Eritrea on adults aged ≥ 18 years who were on treatment for at least 6 months. Cases were patients who fulfills at least one of the WHO therapy failure criterion during the study period. Controls were randomly selected patients on first-line treatment and plasma viral load < 1000 copies/ml in their latest follow-up measurement. Multivariable logistic regression analysis was conducted to identify risk factors for TF. All P-values were 2-sided and the level of significance was set at P < 0.05 for all analyses. RESULTS: Of the 1068 participants (356 cases; 712 controls), 585 (54.7%) were females. The median age at treatment initiation was 46 years [interquartile range (IQR): 39-51]. Median time to combined antiretroviral therapy (cART) failure was 37 months (IQR = 24-47). In the multivariate analysis, factors associated with increased likelihood of TF included initial nucleoside reverse transcriptase inhibitors (NRTI) backbone (Zidovudine + Lamivudine (AZT + 3TC): adjusted odds ratio (aOR) = 2.70, 95% Confidence interval (CI): 1.65-4.41, P-value < 0.001), (Abacavir + lamivudine (ABC + 3TC): aOR = 4.73, 95%CI: 1.18-18.92, P-value = 0.028], and (Stavudine + Lamivudine (D4T + 3TC): aOR = 5.00; 95% CI: 3.03-8.20, P-value < 0.001) in comparison to Emtricitabine and Tenofovir diproxil fumarate (FTC + TDF). Additional associations included prior exposure to cART (aOR = 2.28, 95%CI: 1.35-3.86; P- value = 0.002), record of sub-optimal drug adherence (aOR = 3.08, 95%CI: 2.22-4.28; P < 0.001), ambulatory/bedridden at presentation (aOR = 1.61, 95%CI: 1.12-4.28; P-value = 0.010), presence of comorbidities (aOR = 2.37; 95%CI: 1.36-4.10, P-value = 0.002), duration of cART (< 5 years: aOR: 5.90; 95% CI: 3.95-8.73, P-value < 0.001), and use of SMX-TMP prophylaxis (aOR = 2.00, 95%CI, 1.44-2.78, P-value < 0.001). CONCLUSION: Our findings underscore the importance of optimizing cART adherence, diversification of cART regimens, and interventions directed at enhancing early HIV diagnosis, prompt initiations of treatment, and improved patient-focused monitoring of treatment response.

Immunodeficiency and Cancer in 3.5 Million People Living With Human Immunodeficiency Virus (HIV): The South African HIV Cancer Match Study.

BACKGROUND: We analyzed associations between immunodeficiency and cancer incidence in a nationwide cohort of people living with human immunodeficiency virus (HIV; PLWH) in South Africa. METHODS: We used data from the South African HIV Cancer Match Study built on HIV-related laboratory measurements from the National Health Laboratory Services and cancer records from the National Cancer Registry. We evaluated associations between time-updated CD4 cell count and cancer incidence rates using Cox proportional hazards models. We reported adjusted hazard ratios (aHRs) over a grid of CD4 values and estimated the aHR per 100 CD4 cells/µL decrease. RESULTS: Of 3 532 266 PLWH, 15 078 developed cancer. The most common cancers were cervical cancer (4150 cases), Kaposi sarcoma (2262 cases), and non-Hodgkin lymphoma (1060 cases). The association between lower CD4 cell count and higher cancer incidence rates was strongest for conjunctival cancer (aHR per 100 CD4 cells/µL decrease: 1.46; 95% confidence interval [CI], 1.38-1.54), Kaposi sarcoma (aHR, 1.23; 95% CI, 1.20-1.26), and non-Hodgkin lymphoma (aHR, 1.18; 95% CI, 1.14-1.22). Among infection-unrelated cancers, lower CD4 cell counts were associated with higher incidence rates of esophageal cancer (aHR, 1.06; 95% CI, 1.00-1.11) but not breast, lung, or prostate cancer. CONCLUSIONS: Lower CD4 cell counts were associated with an increased risk of developing various infection-related cancers among PLWH. Reducing HIV-induced immunodeficiency may be a potent cancer-prevention strategy among PLWH in sub-Saharan Africa, a region heavily burdened by cancers attributable to infections.

Predictors of in-hospital mortality among HIV-positive patients presenting with an acute illness to the emergency department.

OBJECTIVES: Despite better access to antiretroviral therapy (ART) over recent years, HIV remains a major global cause of mortality. The present study aimed to identify predictors of in-hospital mortality among HIV-positive patients presenting to an emergency department (ED). METHODS: In this cross-sectional study, HIV-positive patients presenting to the Charlotte Maxeke Johannesburg Academic Hospital adult ED between 07 July 2017 and 18 October 2018 were prospectively enrolled. Data were compared between participants who survived to hospital discharge and those who died. The data were further subjected to univariate and multivariate logistic regression analyses to determine variables that were associated with in-hospital mortality. RESULTS: Of a total of 1224 participants, the in-hospital mortality was 13.6% (n = 166). On multivariate analysis, respiratory rate > 20 breaths/min [odds ratio (OR) = 1.90, P = 0.012], creatinine > 120 µmol/L (OR = 1.97, P = 0.006), oxygen saturation < 90% (OR = 2.09, P = 0.011), white cell count < 4.0 × 109 /L (OR = 2.09, P = 0.008), ART non-adherence or not yet on ART (OR = 2.39, P = 0.012), Glasgow Coma Scale < 15 (OR = 2.53, P = 0.000), albumin < 35 g/L (OR = 2.61, P = 0.002), lactate > 2 mmol/L (OR = 4.83, P = 0.000) and cryptococcal meningitis (OR = 6.78, P = 0.000) were significantly associated with in-hospital mortality. CONCLUSIONS: Routine clinical and laboratory parameters are useful predictors of in-hospital mortality in HIV-positive patients presenting to the ED with an acute illness. These parameters may be of value in guiding clinical decision-making, directing the appropriate use of resources and influencing patient disposition, and may also be useful in developing an outcome prediction tool.

Mortality in relation to hepatitis B virus (HBV) infection status among HIV-HBV co-infected patients in sub-Saharan Africa after immediate initiation of antiretroviral therapy.

It is unknown how past and active hepatitis B virus (HBV) infection affect immunorecovery and mortality in people with HIV who initiate tenofovir-based antiretroviral therapy (ART). Using data collected between 2008 and 2015, we studied people with HIV in sub-Saharan Africa initiating immediate ART in the Temprano randomized control trial. We classified participants into HBV groups at ART initiation: hepatitis B surface antigen (HBsAg)-positive with HBV DNA ≥ 2,000 IU/ml; HBsAg-positive with HBV DNA < 2,000 IU/ml; isolated HBcAb-positive; resolved infection (HBsAb-positive/HBcAb-positive); and HBV non-immune/vaccinated (HBcAb-negative). We compared square-root CD4-cell count increases using mixed-effect, non-linear regression adjusted for age, sex, baseline CD4 cell count, and HIV RNA. We compared all-cause mortality using Bayesian parametric survival regression. Among 879 participants, 24 (2.7%) had HBsAg with high HBV DNA, 76 (8.6%) HBsAg with low HBV DNA, 325 (37.0%) isolated anti-HBcAb, 226 (25.7%) resolved HBV infection and 228 (25.9%) HBV non-immune/vaccinated. We found no significant difference in CD4 cell increases between HBV-infection groups after adjustment (p = 0.16). Participants with HBsAg and high HBV DNA had the highest incidence of all-cause mortality (1.9/100 person-years, 95% Credibile Interval [CrI] = 1.0-3.4). By comparison, incidence rates of mortality were reduced by 57% (95%CrI = -79%, -13%), 60% (95%CrI = -82%, -12%) and 66% (95%CrI = -84%, -23%) in those who had isolated anti-HBcAb-positive, resolved HBV infection and HBV non-immune/vaccinated, respectively. In conclusion, individuals with HIV and past HBV infection or isolated anti-HBcAb-positive serology, much like HBV non-immune/vaccinated, experience lower mortality than those with HBsAg and high HBV DNA. Additional HBV-related management would not be necessary for these individuals.

Determinants of change in CD4 count and relationship with survival among children with HIV in Ethiopia.

We identify the determinants of the change in CD4 cell count and survival time of children living with HIV taking antiretroviral therapy. In a retrospective study, a cohort of 201 children living with HIV/AIDS aged less than 15 years were followed from October 2013 to March 2017. Separate linear effect models were done for the longitudinal outcome of CD4 cell count. The Cox PH model was conducted for the time-to-event outcome. Joint modeling was performed both for the longitudinal and survival outcomes, results were compared with the separate analysis. However, with the specific interest in identifying the determinants and characterizing the relationship between longitudinal CD4 cell count and time-to-event outcomes, the study focused on joint modeling. The finding from the joint model indicated that the estimated association parameter was -0.10, this shows lower values of CD4 cells associated with higher death. Seemingly; observation time, age, WHO clinical stages, history of Tuberculosis (assuming that Tuberculosis is active), and functional status were determinants for the mean change in the square root of CD4 cell count. Furthermore, WHO clinical stages, functional status, history of TB, and Body Mass Index have a significant negative impact on the survival probabilities of children living with HIV.

Association between Veterans Aging Cohort Study (VACS) index and neurocognitive function among people living with HIV-a cross sectional study in coastal South India.

BACKGROUND: HIV is an infectious disease affecting 36.7 million people worldwide. In recent times, Antiretroviral Therapy (ART) has become accessible to the majority of People Living with HIV (PLHIV) and this has transformed the course of infection to one that is chronic, characterized by fewer diseases pathognomonic of AIDS. In view of this, there is a pressing need for better markers, apart from the routine HIV indicators, to detect comorbidities such as Neurocognitive Impairment (NCI). The aim of this study was to find out the association between Veterans Aging Cohort Study (VACS) index and Neurocognitive function in HIV positive patients. METHODS: In our study, we included 97 HIV positive patients and their Neurocognitive function was assessed using a combination of Montreal Cognitive Assessment and Grooved Pegboard Test, while VACS index was calculated using the most recent laboratory values. Binomial Logistics Regression analyses, adjusting for potential confounding variables, was performed to determine the association between VACS score and Neurocognitive Impairment. RESULTS: We found that a higher VACS Index was associated with global and domain-wise Neurocognitive impairment (p < 0.01), specifically in the domains of attention (p < 0.01) and fine motor skills (p = 0.01). Our study also showed that among all the VACS components, older age (p = 0.02) and lower hemoglobin (p < 0.01) values were associated with global NCI. After plotting an ROC curve, a VACS cut-off score of 11.00 was identified as it had good sensitivity (87.0%) and specificity (71.4%) in identifying Global NCI. CONCLUSION: Our findings extend prior research on the use of VACS Index to predict global and domain-wise NCI in HIV-positive patients. However, further research with more comprehensive neurocognitive testing is required in our setting before VACS Index can be used as a tool to screen for neurocognitive dysfunction among PLHIV.

Patterns of Antiretroviral Therapy Use and Immunologic Profiles at Enrollment in the REPRIEVE Trial.

BACKGROUND: Patterns of antiretroviral therapy (ART) use and immunologic correlates vary globally, and contemporary trends are not well described. METHODS: The REPRIEVE trial (Randomized Trial to Prevent Vascular Events in HIV) enrolled persons with human immunodeficiency virus (HIV) who were aged 40-75 years, receiving ART, and had low-to-moderate cardiovascular disease risk. ART use was summarized within Global Burden of Disease (GBD) super-regions, with adjusted linear and logistic regression analyses examining associations with immune parameters and key demographics. RESULTS: A total of 7770 participants were enrolled, with a median age of 50 years (interquartile range, 45-55 years); 31% were female, 43% were black or African American, 15% were Asian, 56% had a body mass index >25 (calculated as weight in kilograms divided by height in meters squared), and 49% were current or former smokers. The median CD4 T-cell count was 620/µL (interquartile range, 447-826/ µ L), and the median duration of prior ART use, 9.5 years (5.3-14.8) years. The most common ART regimens were nucleoside/nucleotide reverse-transcriptase inhibitor (NRTI) plus nonnucleoside reverse-transcriptase inhibitor (43%), NRTI plus integrase strand transfer inhibitor (25%), and NRTI plus protease inhibitor (19%). Entry ART varied by GBD region, with shifts during the trial enrollment period. In adjusted analyses, entry CD4 cell count and CD4/CD8 ratio were associated with GBD region, sex, entry regimen, duration of ART, and nadir CD4 cell count; CD4 and CD8 cell counts were also associated with body mass index and smoking status. CONCLUSIONS: There were substantial variations in ART use by geographic region and over time, likely reflecting the local availability of specific medications, changes in treatment guidelines and provider/patient preferences. The analyses of CD4 cell counts and CD4/CD8 ratios may provide valuable insights regarding immune correlates and outcomes in people living with HIV. CLINICAL TRIALS REGISTRATION: NCT02344290.

Better Virological Outcomes Among People Living With Human Immunodeficiency Virus (HIV) Initiating Early Antiretroviral Treatment (CD4 Counts ≥500 Cells/µL) in the HIV Prevention Trials Network 071 (PopART) Trial in South Africa.

BACKGROUND: There have been concerns about reduced adherence and human immunodeficiency virus (HIV) virological suppression (VS) among clinically well people initiating antiretroviral therapy (ART) with high pre-ART CD4 cell counts. We compared virological outcomes by pre-ART CD4 count, where universal ART initiation was provided in the HIV Prevention Trials Network 071 (PopART) trial in South Africa prior to routine national and international implementation. METHODS: This prospective cohort study included adults initiating ART at facilities providing universal ART since January 2014. VS (<400 copies/mL), confirmed virological failure (VF) (2 consecutive viral loads >1000 copies/mL), and viral rebound were compared between participants in strata of baseline CD4 cell count. RESULTS: The sample included 1901 participants. VS was ≥94% among participants with baseline CD4 count ≥500 cells/µL at all 6-month intervals to 30 months. The risk of an elevated viral load (≥400 copies/mL) was independently lower among participants with baseline CD4 count ≥500 cells/µL (3.3%) compared to those with CD4 count 200-499 cells/µL (9.2%) between months 18 and 30 (adjusted relative risk, 0.30 [95% confidence interval, .12-.74]; P = .010). The incidence rate of VF was 7.0, 2.0, and 0.5 per 100 person-years among participants with baseline CD4 count <200, 200-499, and ≥500 cells/µL, respectively (P < .0001). VF was independently lower among participants with baseline CD4 count ≥500 cells/µL (adjusted hazard ratio [aHR], 0.23; P = .045) and 3-fold higher among those with baseline CD4 count <200 cells/µL (aHR, 3.49; P < .0001). CONCLUSIONS: Despite previous concerns, participants initiating ART with CD4 counts ≥500 cells/µL had very good virological outcomes, being better than those with CD4 counts 200-499 cells/µL. CLINICAL TRIALS REGISTRATION: NCT01900977.

Antiretroviral Therapy and Detection of High-grade Cervical Intraepithelial Neoplasia (CIN2+) at Post-CIN Management Follow-up Among Women Living With Human Immunodeficiency Virus: A Systematic Review and Meta-Analysis.

BACKGROUND: We evaluated the association of antiretroviral therapy (ART), CD4+ count and human immunodeficiency virus (HIV) plasma viral load (PVL) on high-grade cervical intraepithelial neoplasia (CIN2+) detection at follow-up after CIN management among women living with HIV (WLHIV). METHODS: Medline, Embase, Global Health, and PubMed were searched from 1 January 1996 to 15 January 2020. Eligible studies investigated the association of ART, CD4+ count, or HIV PVL on histology-confirmed CIN2+ detection at follow-up. Summary estimates were obtained using random-effects meta-analyses; heterogeneity was examined using I2 statistic. PROSPERO registration: CRD42018115631. RESULTS: Eight studies representing 9 populations were identified, including 1452 WLHIV followed between 6 and 33 months post-CIN management. Pooled data from 8 populations (n = 1408) suggested weak evidence of a decreased risk of CIN2+ detection at follow-up among ART users compared to ART-naive women (crude odds ratio [cOR] = 0.70, 95% confidence interval [CI]: .36-1.36; I2 = 64.5%, P = .006; adjusted risk ratio [aRR] from 3 studies = 0.66, 95% CI: .20-2.24; I2 = 78.7%, P = .009). A significant association was observed in high-income countries (cOR = 0.24, 95% CI: .13-.45; I2 = 0.0%, P = .77) but not in low and middle-income countries (cOR = 1.13, 95% CI: .67-1.92; I2 = 18.8%, P = .30).In 3 populations, ART users with HIV PVL <50 copies/ml were less likely to have CIN2+ detection at follow-up (vs ≥50 copies/mL: cOR = 0.55, 95% CI: .32-.94; I2 = 0.0%, P = .23).There was weak evidence of decreased CIN2+ detection at follow-up among WLHIV with higher contemporary CD4+ cell counts (≥200 cells/µL vs <200 cells/µL [cOR = 0.36, 95% CI: .04-3.13; I2 = 81.3%, P = .021]) and significant evidence among women with a higher nadir CD4+ count (≥350 cells/µl vs <200 cells/µl [adjusted hazard ratio [aHR] = 0.35, 95% CI: .15-.84; I2 = 0%, P = .64]). CONCLUSION: ART may reduce the risk of CIN2+ detection at follow-up; this effect is most likely enhanced by a combination of adequate HIV control and excisional CIN treatment. Our findings support recommendations of early ART and the integration of CIN2+ screening and management into HIV care.

Patterns of presentation and survival of HIV-infected patients admitted to a tertiary-level intensive care unit.

OBJECTIVES: Compared to other countires internationally, South Africa has the largest number of people living with HIV. There are limited data in developing countries on the outcomes of HIV-infected patients in the intensive care unit (ICU). The objectives of this study were to describe the pattern of presentation of these patients and to determine factors that may influence survival to ICU discharge. METHODS: The medical charts of 204 consecutive HIV-infected individuals who were admitted to the Charlotte Maxeke Johannesburg Academic Hospital adult general ICU during the calendar year 2017 were retrospectively reviewed. Relevant data were subjected to univariate and multivariate analysis. RESULTS: Two-hundred and four (22.6%) out of a total of 903 patients who were admitted to the ICU were HIV positive. Sepsis-related illnesses were the most common reason for ICU admission (n = 95; 46.6%), followed by post-operative care (n = 69; 33.8%) and non-sepsis-related illnesses (n = 40; 19.6%). The median length of stay in the ICU was 5 (interquartile range 2-9) days. ICU mortality was 33.3% (n = 68). On univariate analysis, age (P = 0.039), length of stay in the ICU (P = 0.040), primary diagnostic category (P < 0.05), sepsis acquired during the ICU stay (P = 0.012), inotrope/vasopressor administration (P < 0.001), mechanical ventilation (P < 0.001), haemodialysis (P = 0.001), CD4 cell count (P = 0.011), Acute Physiology and Chronic Health Assessment (APACHE) II score (P < 0.001) and Sequential Organ Failure Assessment (SOFA) score (P < 0.001) were significantly associated with mortality. CONCLUSIONS: Age, diagnostic category, sepsis acquired during the ICU stay, inotrope/vasopressor administration, mechanical ventilation, haemodialysis, CD4 cell count, APACHE II score, SOFA score and length of ICU stay were associated with ICU mortality in HIV-infected patients.

Oral environment and taste function of Japanese HIV-infected patients treated with antiretroviral therapy.

The aim of the study was to evaluate the oral environment and the taste function of Japanese HIV-infected patients treated with antiretroviral therapy. Their median age of 73 patients taking anti-HIV drugs was 46 years. The median period of taking anti-HIV drugs was 30 months. The oral condition was evaluated by measurement of oral moisture, amount of saliva secretion, the number of oral bacteria, presence of oral candida, a taste test, and the number of missing teeth. The levels of oral moisture and secreted saliva were significantly lower in the HIV-infected group than in the healthy volunteer (control) group. The HIV-infected group showed a more robust decrease in taste sensation than the control group. The number of missing teeth was significantly higher in the HIV-infected group than in the control group. Furthermore, all of the evaluated oral conditions were worse in the HIV-infected patients whose CD4+ T lymphocyte counts were less than 500/mm3 than in the control group. It became clear that the patients taking anti-HIV drugs, especially the CD4+ count < 500/mm3 group, had a deteriorated oral environment and dysgeusia, suggesting that the management of oral hygiene is necessary to maintain oral health, which leads to systemic health.

Effects of age, HIV, and HIV-associated clinical factors on neuropsychological functioning and brain regional volume in HIV+ patients on effective treatment.

It is yet unclear if people infected with human immunodeficiency virus (HIV+) on stable, combined antiretroviral therapies (cARTs) decline with age at the same or greater rate than healthy people. In this study, we examined independent and interactive effects of HIV, age, and HIV-related clinical parameters on neuropsychological functioning and brain regional volume in a sizable group of Polish HIV+ men receiving cART. We also estimated the impact of nadir CD4 cell count, CD4 cell count during participation in the study, duration of HIV infection, or duration of cART along with age. Ninety-one HIV+ and 95 control (HIV-) volunteers ages 23-75 completed a battery of neuropsychological tests, and 54 HIV+ and 62 HIV- of these volunteers participated in a brain imaging assessment. Regional brain volume in the cortical and subcortical regions was measured using voxel-based morphometry. We have found that HIV and older age were independently related to lower attention, working memory, nonverbal fluency, and visuomotor dexterity. Older age but not HIV was associated with less volume in several cortical and subcortical brain regions. In the oldest HIV+ participants, age had a moderating effect on the relationship between the duration of cART and visuomotor performance, such as that older age decreased speed of visuomotor performance along with every year on cART. Such results may reflect the efficacy of cART in preventing HIV-associated brain damage. They also highlight the importance of monitoring neuropsychological functioning and brain structure in HIV+ patients. This is particularly important in older patients with long adherence to cART.

A superiority of viral load over CD4 cell count when predicting mortality in HIV patients on therapy.

BACKGROUND: CD4 cell count has been identified to be an essential component in monitoring HIV treatment outcome. However, CD4 cell count monitoring sometimes fails to predict virological failure resulting in unnecessary switch of treatment lines which causes drug resistance and limitations of treatment options. This study assesses the use of both viral load (HIV RNA) and CD4 cell count in the monitoring of HIV/AIDS progression. METHODS: Time-homogeneous Markov models were fitted, one on CD4 cell count monitoring and the other on HIV RNA monitoring. Effects of covariates; gender, age, CD4 baseline, HIV RNA baseline and adherence to treatment were assessed for each of the fitted models. Assessment of the fitted models was done using prevalence plots and the likelihood ratio tests. The analysis was done using the "msm" package in R. RESULTS: Results from the analysis show that viral load monitoring predicts deaths of HIV/AIDS patients better than CD4 cell count monitoring. Assessment of the fitted models shows that viral load monitoring is a better predictor of HIV/AIDS progression than CD4 cell count. CONCLUSION: From this study one can conclude that although patients take more time to achieve a normal CD4 cell count and less time to achieve an undetectable viral load, once the CD4 cell count is normal, mortality risks are reduced. Therefore, both viral load monitoring and CD4 count monitoring can be used to provide useful information which can be used to improve life expectance of patients living with HIV. However, viral load monitoring is a better predictor of HIV/AIDS progression than CD4 cell count and hence viral load is deemed superior.