Human Immunodeficiency Virus Mortality Research Articles

Mortality and comorbidities in a Nationwide cohort of HIV-infected adults: comparison to a matched non-HIV adults' cohort, France, 2006-18.

Human immunodeficiency virus (HIV) remains a significant cause of morbidity and mortality worldwide. The aim of this study was to describe the mortality rate and associated comorbidities in a nationwide population-based cohort of persons living with HIV (PLWHIV) and to compare it with mortality in an age and gender-matched cohort of non-HIV individuals in France. Using data from the French national health data system, we identified and included 173712 PLWHIV (66.5% men) and 173712 non-HIV participants (66.5% men) matched for age and gender. PLHIV were identified based on ICD-10 HIV diagnoses, HIV-specific laboratory tests, and/or prescriptions for antiretroviral therapy specific to HIV. Hazard ratios (HRs) of mortality were assessed using multiple Cox regression models. During the 13 years of follow-up (2006-18), we observed 20018 deaths among PLWHIV compared with 6262 deaths among non-HIV participants (11.52% vs. 3.60%, P < 0.001). The over-mortality of PLWHIV was expressed by univariable HR = 2.135 (2.072-2.199), which remained significant after adjustment for region, Complementary Universal Health Insurance and AME, with multivariable HR = 2.182 (2.118-2.248). The results remained significant after adjusting for comorbidities, including infectious diseases [HR = 1.587 (1.538-1.638)]. Notably, PLWHIV were more importantly associated with mortality in women [HR = 2.966 (2.767-3.180)], compared in men [HR = 1.961 (1.898-2.027)]. Although the life expectancy of PLWHIV has globally increased, the causes of death should be prioritized in prevention policies and care management. Gender-specific policies should be highlighted, as we observed a higher impact of HIV mortality in women.

Loss to Follow-up and Death Among Individuals With Newly Diagnosed Human Immunodeficiency Virus Receiving Dolutegravir-Based First-Line Antiretroviral Treatment in Eastern Ethiopia: Implications for 95% United Nations Targets.

Loss to follow-up (LTFU) and death are unfavorable outcomes of human immunodeficiency virus (HIV) treatment. This study aimed to identify the predictors of LTFU and death among individuals with newly diagnosed HIV receiving dolutegravir (DTG)-based first-line antiretroviral treatment (ART) in eastern Ethiopia. A multisite prospective cohort study was carried out between October 2020 and July 2022. New case patients who started ART were enrolled consecutively and then followed up for the next 6 months. A structured questionnaire and checklists were used to collect data. HIV viral load was determined using the Abbott RealTime HIV-1 assay. Bivariable and multivariable logistic regression models were used to identify baseline factors associated with the outcomes. A total of 235 people with newly diagnosed HIV were enrolled; 16.6% (95% confidence interval, 12.3%-21.9%) were lost to follow-up, and 5.9% (3.5%-9.8%) died within 6 months of follow-up. Baseline World Health Organization clinical stage I (adjusted odds ratio, 3.93 [95% confidence interval, 1.34-11.57]), low viral load (3.67 [1.09-12.36]), and body weight (1.04 [1.01-1.07]) were predictors of LTFU, whereas nonfunctional status (10.02 [1.9-51.3]) was the only factor associated with death. LTFU and death rates among patients with DTG were relatively high, accounting for roughly a quarter of the attrition of people with newly diagnosed HIV from ART care and services. Thus, targeted interventions are required to reduce LTFU and death among individuals with HIV on ART. Further investigation is necessary to evaluate the long-term effects of DTG-based regimens on LTFU and its impact on HIV mortality rates, and qualitative research, specifically tracing LTFU, is recommended.

EPH242 Adherence and Factors Associated with Cotrimoxazole Preventive Therapy Among Adult Human Immunodeficiency Virus (HIV) Patients Attending Antiretroviral Clinics in Jigjiga Hospitals

Co-trimoxazole, a fixed-dose combination of two antimicrobial drugs offers a synergistic effect with a broad spectrum of antimicrobial action. Adherence to cotrimoxazole preventive therapy has been found to reduce the incidence of opportunistic infections and other AIDS-related illnesses. Cotrimoxazole preventive therapy is self-administered, and therefore, adherence cannot be ensured, and the adherence has been low and opportunistic infections continue to be the major cause of mortality and morbidity in HIV, accounting for 47% of AIDS-related deaths. This study aimed to assess adherence and factors associated with cotrimoxazole preventive therapy (CPT) among adult human immunodeficiency virus (HIV) patients attending antiretroviral clinics in Jijiga hospitals.

High Seroprevalence of Kaposi Sarcoma-Associated Herpesvirus in Men Who Have Sex With Men With HIV in the Southern United States.

Disparities in mortality in human immunodeficiency virus (HIV)-associated Kaposi sarcoma have been described, particularly in Black men in the southern United States. It is unclear if there are racial/ethnic differences in the seroprevalence of Kaposi sarcoma-associated herpesvirus (KSHV) that may be contributing. This is a cross-sectional study of men who have sex with men (MSM) and transgender women with HIV. Participants were recruited from an outpatient HIV clinic in Dallas, Texas, for a 1-time study visit and were excluded from analysis if they had any history of KSHV disease. Plasma was tested for antibodies to KSHV K8.1 or ORF73 antigens, and KSHV DNA was measured in oral fluids and blood by polymerase chain reaction. KSHV seroprevalence and viral shedding in blood and oral fluids were calculated. Additionally, independent risk factors for KSHV seropositivity were assessed by multivariable logistic regression analysis. Two hundred five participants were included in our analysis. Overall, KSHV seroprevalence was high (68%) with no significant difference between racial/ethnic groups. Among seropositive participants, KSHV DNA was detected in 28.6% of oral fluids and 10.9% of peripheral blood specimens, respectively. The factors most strongly associated with KSHV seropositivity were oral-anal sex (odds ratio [OR], 3.02), oral-penile sex (OR, 4.63), and methamphetamine use (OR, 4.67). High local seroprevalence of KSHV is likely a key driver of the high burden of KSHV-associated diseases regionally, though it does not explain the observed disparities in KSHV-associated disease prevalence among racial/ethnic groups. Our findings support that KSHV is primarily transmitted via exchange of oral fluids.

Impact of the COVID-19 pandemic and the dynamic COVID-zero strategy on HIV incidence and mortality in China

BackgroundIn response to the coronavirus disease 2019 (COVID-19) pandemic, the Chinese government implemented the dynamic COVID-zero strategy. We hypothesized that pandemic mitigation measures might have reduced the incidence, mortality rates, and case fatality ratios (CFRs) of the human immunodeficiency virus (HIV) in 2020–2022.MethodWe collected HIV incidence and mortality data from the website of the National Health Commission of the People’s Republic of China from January 2015 to December 2022. We compared the observed and predicted HIV values in 2020–2022 with those in 2015–2019 using a two-ratio Z-test.ResultsFrom January 1, 2015, to December 31, 2022, a total of 480,747 HIV incident cases were reported in mainland China, of which 60,906 (per year) and 58,739 (per year) were reported in 2015–2019 (pre-COVID-19 stage) and 2020–2022 (post-COVID-19 stage), respectively. The average yearly HIV incidence decreased by 5.2450% (from 4.4143 to 4.1827 per 100,000 people, p < 0.001) in 2020–2022 compared with that in 2015–2019. However, the average yearly HIV mortality rates and CFRs increased by 14.1076 and 20.4238%, respectively (all p < 0.001), in 2020–2022 compared with those in 2015–2019. During the emergency phase in January 2020 to April 2020, the monthly incidence was significantly lower (23.7158%) than that during the corresponding period in 2015–2019, while the incidence during the routine stage in May 2020–December 2022 increased by 27.4334%, (all p < 0.001). The observed incidence and mortality rates for HIV decreased by 16.55 and 18.1052% in 2020, by 25.1274 and 20.2136% in 2021, and by 39.7921 and 31.7535% in 2022, respectively, compared with the predicted values, (all p < 0.001).ConclusionsThe findings suggest that China’s dynamic COVID-zero strategy may have partly disrupted HIV transmission and further slowed down its growth. Without China’s dynamic COVID-zero strategy, HIV incidence and deaths in the country would have likely remained high in 2020–2022. There is an urgent need to expand and improve HIV prevention, care, and treatment, as well as surveillance in the future.

Changes of human immunodeficiency virus (HIV) burden globally and in China over three decades: a secondary analysis of global HIV statistics.

A more comprehensive understanding of the trends of incidence, prevalence, and mortality in human immunodeficiency virus (HIV), and their complex interrelationships, may provide important evidence for decision-making related to HIV prevention and control. The variances in these indices between different population groups, genders, and ages are critical to decipher evolving patterns of the HIV epidemic in specific populations. A secondary analysis of relevant data was conducted using data extracted from the Global Burden of Disease study of 2019. HIV/acquired immune deficiency syndrome (AIDS) incidence, prevalence, AIDS-related mortality, and mortality-to-prevalence ratio (MPR) for annual percentage change, average annual percentage change (AAPC), and corresponding 95% confidence intervals (CIs) were calculated using joinpoint regression statistical analysis. The AAPC of HIV/AIDS incidence, prevalence, AIDS-related mortality rate, and MPR were -1.4 (95% CI: -1.6, -1.2), 4.1 (95% CI: 4.0, 4.3), 2.0 (95% CI: 1.7, 2.3), and -2.1 (95% CI: -2.3, -1.8) between 1990 and 2019 globally, and were 3.5 (95% CI: 2.2, 4.8), 6.9 (95% CI: 6.8, 7.0), 8.1 (95% CI: 7.1, 9.1), and 1.2 (95% CI: 0.1, 2.3) in China during the same period. In terms of differences in the preceding indicators by gender, we observed a similar pattern of trends for male and female genders both globally and in China during the entire study period. Each specific age group exhibits a distinct pattern in terms of incidence, prevalence, mortality rate, and MPR both globally and in China. Prevalence and mortality rates of HIV/AIDS have increased between 1990 and 2019 globally and in China. While the incidence rate and MPR have declined globally over the past three decades, these two indicators are observed to present an increasing trend in China. There is a high HIV burden among young and middle-aged adults globally; however, the elderly have a high HIV burden in China. HIV screening at older age should be scaled up, and patients with advanced HIV disease should be provided early with additional care and health resources.

A hybrid of long short-term memory neural network and autoregressive integrated moving average model in forecasting HIV incidence and morality of post-neonatal population in East Asia: global burden of diseases 2000–2019

BackgroundTo forecast the human immunodeficiency virus (HIV) incidence and mortality of post-neonatal population in East Asia including North Korea, South Korea, Mongolia, Japan and China Mainland and Taiwan province.MethodsThe data on the incidence and mortality of HIV in post-neonatal population from East Asia were obtained from the Global Burden of Diseases (GBD). The morbidity and mortality of post-neonatal HIV population from GBD 2000 to GBD 2013 were applied as the training set and the morbidity and mortality from GBD 2014 to GBD 2019 were used as the testing set. The hybrid of ARIMA and LSTM model was used to construct the model for assessing the morbidity and mortality in the countries and territories of East Asia, and predicting the morbidity and mortality in the next 5 years.ResultsIn North Korea, the incidence and mortality of HIV showed a rapid increase during 2000–2010 and a gradual decrease during 2010–2019. The incidence of HIV was predicted to be increased and the mortality was decreased. In South Korea, the incidence was increased during 2000–2010 and decreased during 2010–2019, while the mortality showed fluctuant trend. As predicted, the incidence of HIV in South Korea might be increased and the mortality might be decreased during 2020–2025. In Mongolia, the incidence and mortality were slowly decreased during 2000–2005, increased during 2005–2015, and rapidly decreased till 2019. The predicted incidence and mortality of HIV showed a decreased trend. As for Japan, the incidence of HIV was rapidly increased till 2010 and then decreased till 2015. The predicted incidence of HIV in Japan was gradually increased. The mortality of HIV in Japan was fluctuant during 2000–2019 and was slowly decreased as predicted. The incidence and mortality of HIV in Taiwan during 2000–2019 was increased on the whole. The predicted incidence of HIV during was stationary and the mortality was decreased. In terms of China Mainland, the incidence and mortality of HIV was fluctuant during 2000–2019. The predicted incidence of HIV in China Mainland was stationary while the mortality was rapidly decreased.ConclusionOn the whole, the incidence of HIV combined with other diseases in post-neonatal population was increased before 2010 and then decreased during 2010–2019 while the mortality of those patients was decreased in East Asia.

The effects of traditional healing on HIV and AIDS management: An ethnographic study.

BackgroundThis article presents the effects of traditional healing on the management of human immunodeficiency virus (HIV) and acquired immune deficiency syndrome (AIDS) in the Vhembe district, South Africa. The Vhembe district is one of the rural districts in Limpopo Province, South Africa, in which traditional healers are used as the first point of consultation for most ailments, regardless of their causes.MethodsThis ethnographic study was based on Leininger’s theory of culture care diversity and universality. It was carried out in selected villages in the Vhembe district. Observation and interviews with 15 purposively selected key informants, who are traditional healers, were used to collect data. Interviews were tape-recorded and field notes were also taken. The data were analysed using the ethnographic content analysis method.ResultsThe results suggest that traditional healing has both negative and positive effects on HIV and AIDS management. The positive effects are the effective treatment of some opportunistic infections, such as diarrhoea, skin lesions and childhood diseases. Negative effects, however, include incisions to let the ‘dirty blood flow out’ and inducing of vomiting and diarrhoea, which may lead to anaemia, dehydration and electrolyte imbalances. Some traditional healers are of the view that HIV does not exist and that people either have an ancestral calling or are bewitched. Even though their claims have not been scientifically proven, some traditional healers stated that they can heal HIV and AIDS.ConclusionThe research brings insight as to whether Vhavenda traditional healing has a favourable or unfavourable impact on HIV and AIDS management. Using Leininger’s steps for adaptation for culture care diversity and universality will help with re-Africanisation of HIV management. The researcher recommend the modification of practices with a high risk of HIV infection to reduce this risk, whilst also supporting the continuation of beneficial practices that reduce HIV mortality, such as diarrhoea management.

Prevalence of Clinical Cardiovascular Disease Risk Factors Among HIV Infected Patients on Anti-Retroviral Treatment in a Tertiary Hospital in Ethiopia.

BackgroundAnti-retroviral treatment has improved mortality of human immunodeficiency virus (HIV) infected patients, which is offset by an increasing burden of cardiovascular diseases (CVD). Data regarding prevalence of cardiovascular disease risk factors in HIV infected patients in Ethiopia are very scarce. The aim of this study was to determine the prevalence of CVD risks and associated factors in patients with HIV.MethodsA cross-sectional study was conducted on 333 patients with HIV infection, using a modified World Health Organization’s stepwise approach to surveillance questionnaire. Anthropometric and blood pressure measurement was done along with biochemical studies. Cardiovascular risk was estimated using Framingham risk score. Multivariate logistic regression was used to examine the association between cardiovascular risks and associated factors, with a p-value of <0.05 considered statistically significant.ResultsThe mean age of the participants was 45 years, and 69.2% were females. Most (80.9%) of the participants had viral load below 50 copies/mL and the mean CD4 count was 579 cells/mm3. Dyslipidemia was the most common risk factor identified in 69.4%, followed by abnormal fasting blood glucose (≥100 mg/dL) in 36.8%. Hypertension was diagnosed in 23.8%, while 22.8% and 11.1% had metabolic syndrome and obesity, respectively. Framingham risk score was low in 95.9%. Male gender, increasing age, high body mass index and previous ART regimen being tenofovir disoproxil fumarate, lamivudine and nevirapine increased CVD risk factors.ConclusionTraditional cardiovascular risk factors were high in the population studied. There is a need to raise awareness about the risk factors, and patients should have timely follow-up and care.

Medical Care for Tuberculosis-HIV-Coinfected Patients in Russia with Respect to a Changeable Patients' Structure.

To date, tuberculosis (TB) remains the primary cause of mortality in human immunodeficiency virus (HIV) patients in Russia. Since the beginning of 2000, a sharp change in the HIV patients’ structure, to the main known risk factors for HIV infection has taken place in Russia. The transmission of HIV through injectable drug use has begun to decline significantly, giving way to the prevalence of sexual HIV transmission today. These changes may require adjustments to organizational approaches to anti-TB care and the treatment of HIV-positive patients. Our study is aimed at identifying changes in TB-HIV coinfection patients’ structures in 2019 compared to 2000. Based on the results obtained, our goal was to point out the parameters that need to be taken into account when developing approaches to improve the organization of TB control care for people with HIV infection. We have carried out a cross-sectional, retrospective, epidemiological study using government TB registry data from four regions in two federal districts of Russia in 2019. The case histories of 2265 patients from two regions with high HIV prevalence, which are part of the Siberian Federal District of Russia, and 89 patient histories from two regions of low HIV prevalence, which are part of the Central Federal District of Russia, were analyzed. We found that parenteral transmission (69.4%) remains the primary route of HIV transmission among the TB-HIV coinfected. The unemployed of working age without disability account for 80.2% of all coinfected people, while the formerly incarcerated account for 53.7% and the homeless account for 4.1%. Those with primary multidrug-resistant TB (MDR-TB) comprise 56.2% of HIV-TB patients. When comparing the incidence of coinfection with HIV among TB patients, statistically significant differences were obtained. Thus, the chances of coinfection increased by 4.33 times among people with active TB (95% CI: 2.31; 8.12), by 2.97 times among people with MDR-TB (95% CI: 1.66; 5.32), by 5.2 times in people with advanced processes in the lungs, including destruction, (95% CI: 2.78; 9.7), as well as by 10.3 times in the case of death within the first year after the TB diagnosis (95% CI: 2.99; 35.5). The absence of data for the presence of TB during preventive examination was accompanied by a decrease in the chances of detecting coinfection (OR 0.36; 95% CI: 0.2; 0.64). We have identified the probable causes of the high incidence of TB among HIV-infected: HIV-patient social maladaptation usually results in delayed medical care, leading to TB treatment regimen violations. Furthermore, self-administration of drugs triggers MDR-TB within this group. Healthcare providers should clearly explain to patients the critical importance of immediately seeking medical care when initial TB symptoms appear.

Long-term effect of chronic hepatitis B on mortality in HIV-infected persons in a differential HBV transmission setting

BackgroundThere remain gaps in quantifying mortality risk among individuals co-infected with chronic hepatitis B (HBV) and human immunodeficiency virus (HIV) in sub-Saharan African contexts. Among a cohort of HIV-positive individuals in Rwanda, we estimate the difference in time-to mortality between HBV-positive (HIV/HBV co-infected) and HBV-negative (HIV mono-infected) individuals.MethodsUsing a dataset of HIV-infected adults screened for hepatitis B surface antigen (HBsAg) from January to June 2016 in Rwanda, we performed time-to-event analysis from the date of HBsAg results until death or end of study (31 December 2019). We used the Kaplan–Meier method to estimate probability of survival over time and Cox proportional hazard models to adjust for other factors associated with mortality.ResultsOf 21,105 available entries, 18,459 (87.5%) met the inclusion criteria. Mean age was 42.3 years (SD = 11.4) and 394 (2.1%) died during follow-up (mortality rate = 45.7 per 100,000 person-months, 95% confidence interval (CI) 41.4–50.4) Mortality rate ratio for co-infection was 1.7, 95% CI 1.1–2.6, however, Cox regression analysis did not show any association with mortality between compared groups. The adjusted analysis of covariates stratified by co-infection status showed that males, residing outside of the capital Kigali, drinking alcohol, WHO-HIV-clinical stage 3 and 4 were associated with increased mortality in this HIV cohort.ConclusionsHBV infection does not significantly influence mortality among HIV-infected individuals in Rwanda. The current cohort is likely to have survived a period of high-risk exposure to HBV and HIV mortality and limited health care until their diagnosis.

Has modern human immunodeficiency virus therapy decreased complications following total knee arthroplasty?

BackgroundAnti-retroviral therapy (ART) remains the cornerstone of decreasing morbidity and mortality in human immunodeficiency virus (HIV) patients. However, a large study comparing HIV patients taking ART prior to total knee arthroplasty (TKA) is lacking. We sought to examine: (1) readmissions; (2) post-operative complications; and (3) revisions in ART-treated or untreated HIV patients compared with a non-HIV population. MethodsWe queried a national, all-payer database to identify TKA patients from 2010-2020 (n = 1,393,357). The presence or absence of ART was identified and matched with non-HIV patients based on age, sex, diabetes, obesity, and tobacco status resulting in 889 patients in each cohort. Readmissions, post-operative complications, and revisions were assessed. ResultsReadmissions were higher among all HIV patients and even higher in those not taking ART, as compared to the matching cohort (4.8 versus 1.6%, p < 0.01). Prosthetic joint infections (PJIs) at 1-year were higher among HIV patients who were either taking ART (4.0%; OR, 1.41 [0.82–2.45]) or not taking ART (5.1%; OR, 2.44 [1.42–4.21]) as compared to non-HIV patients (2.1%, all p < 0.03). Revision rates at 1-year trended higher in HIV patients who were taking ART (2.6%; Odds Ratio (OR), 1.94 [0.96–3.93]) and who did not take ART (3.1%; OR, 2.38 [1.20–4.70]), compared to non-HIV patients (1.3%, all p < 0.09). ConclusionsART-treated HIV patients are associated with lower readmissions, post-operative complications, and revisions when compared to HIV patients not taking ART. The findings of this study underscore the utility of ART and patient optimization to reduce risk in HIV patients.

Coagulation Parameters in Human Immunodeficiency Virus Infected Patients: A Systematic Review and Meta-Analysis

Background Coagulation abnormalities are common complications of human immunodeficiency virus (HIV) infection. Highly active antiretroviral treatment (HAART) decreased the mortality of HIV but increased coagulopathies. HIV-related thrombocytopenia, prolonged prothrombin time (PT), activated partial thromboplastin time (APTT), and high D-dimer level commonly manifested in patients with HIV. Thus, this study is aimed to compare coagulation parameters of HAART-treated and HAART-naïve HIV-infected patients with HIV-seronegative controls. Methods A systematic literature search was conducted using the databases PubMed/MEDLINE, Embase, Web of Science, and Google Scholar of studies published until July 2021. The primary outcome of interest was determining the pooled mean difference of coagulation parameters between HIV-infected patients and seronegative controls. The Joana Briggs Institute (JBI) critical appraisal tool was used for quality appraisal. Statistical analyses were performed using Stata11.0 software. The statistical results were expressed as the effect measured by standardized mean difference (SMD) with their related 95% confidence interval (CI). Results A total of 7,498 participants (1,144 HAART-naïve patients and 2,270 HAART-treated HIV-infected patients and 3,584 HIV-seronegative controls) from 18 studies were included. HIV-infected patients (both on HAART and HAART-naive) exhibited significantly higher levels of PT than HIV-seronegative controls (SMD = 0.66; 95% CI: 0.53–0.80 and SMD = 1.13; 95% CI: 0.60–2.0, respectively). The value of APTT was significantly higher in patients with HIV on HAART than in seronegative controls. However, the values of PLT count, APTT, and fibrinogen level were significantly higher in seronegative controls. Besides, the level of fibrinogen was significantly higher in HAART-treated than treatment-naïve patients (SMD = 0.32; 95%CI: 0.08, 0.57). Moreover, the level of APTT and PT had no statistical difference between HAART and HAART-naïve HIV-infected patients. Conclusions This study identified that HIV-infected patients are more likely to develop coagulation abnormalities than HIV-seronegative controls. Therefore, coagulation parameters should be assessed regularly to prevent and monitor coagulation disorders in HIV-infected patients.

Mortality in HIV and tuberculosis patients following implementation of integrated HIV-TB treatment: Results from an open-label cluster-randomized trial.

SummaryBackgroundHIV-TB treatment integration reduces mortality. Operational implementation of integrated services is challenging. This study assessed the impact of quality improvement (QI) for HIV-TB integration on mortality within primary healthcare (PHC) clinics in South Africa.MethodsAn open-label cluster randomized controlled study was conducted between 2016 and 2018 in 40 rural clinics in South Africa. The study statistician randomized PHC nurse-supervisors 1:1 into 16 clusters (eight nurse-supervisors supporting 20 clinics per arm) to receive QI, supported HIV-TB integration intervention or standard of care (control). Nurse supervisors and clinics under their supervision, based in the study health districts were eligible for inclusion in this study. Nurse supervisors were excluded if their clinics were managed by municipal health (different resource allocation), did not offer co-located antiretroviral therapy (ART) and TB services, services were performed by a single nurse, did not receive non-governmental organisation (NGO) support, patient data was not available for > 50% of attendees. The analysis population consists of all patients newly diagnosed with (i) both TB and HIV (ii) HIV only (among patients previously treated for TB or those who never had TB before) and (iii) TB only (among patients already diagnosed with HIV or those who were never diagnosed with HIV) after QI implementation in the intervention arm, or enrolment in the control arm. Mortality rates was assessed 12 months post enrolment, using unpaired t-tests and cox-proportional hazards model. (Clinicaltrials.gov, NCT02654613, registered 01 June 2015, trial closed).FindingsOverall, 21 379 participants were enrolled between December 2016 and December 2018 in intervention and control arm clinics: 1329 and 841 HIV-TB co-infected (10·2%); 10 799 and 6 611 people living with Human Immunodeficiency Virus (HIV)/ acquired immunodeficiency syndrome (AIDS) (PLWHA) only (81·4%); 1 131 and 668 patients with TB only (8·4%), respectively. Average cluster sizes were 1657 (range 170–5782) and 1015 (range 33–2027) in intervention and control arms. By 12 months, 6529 (68·7%) and 4074 (70·4%) were alive and in care, 568 (6·0%) and 321 (5·6%) had completed TB treatment, 1078 (11·3%) and 694 (12·0%) were lost to follow-up, with 245 and 156 deaths occurring in intervention and control arms, respectively. Mortality rates overall [95% confidence interval (CI)] was 4·5 (3·4–5·9) in intervention arm, and 3·8 (2·6–5·4) per 100 person-years in control arm clusters [mortality rate ratio (MRR): 1·19 (95% CI 0·79–1·80)]. Mortality rates among HIV-TB co-infected patients was 10·1 (6·7–15·3) and 9·8 (5·0–18·9) per 100 person-years, [MRR: 1·04 (95% CI 0·51–2·10)], in intervention and control arm clusters, respectively.InterpretationHIV-TB integration supported by a QI intervention did not reduce mortality in HIV-TB co-infected patients. Demonstrating mortality benefit from health systems process improvements in real-world operational settings remains challenging. Despite the study being potentially underpowered to demonstrate the effect size, integration interventions were implemented using existing facility staff and infrastructure reflecting the real-world context where most patients in similar settings access care, thereby improving generalizability and scalability of study findings.FundingResearch reported in this publication was supported by South African Medical Research Council (SAMRC), and UK Government's Newton Fund through United Kingdom Medical Research Council (UKMRC).

T-Cell Immune Dysregulation and Mortality in Women With Human Immunodeficiency Virus.

In women with HIV, higher activation and exhaustion of CD4+ T cells were associated with risk of non-HIV-related mortality during a median of 13.3 years of follow-up, independent of baseline demographic, behavioral, HIV-related, and cardiometabolic factors and longitudinal HIV disease progression. Dysregulation of adaptive immunity is a hallmark of human immunodeficiency virus (HIV) infection that persists on antiretroviral therapy (ART). Few long-term prospective studies have related adaptive immunity impairments to mortality in HIV, particularly in women. Among 606 women with HIV in the Women's Interagency HIV Study, peripheral blood mononuclear cells collected from 2002 to 2005 underwent multiparameter flow cytometry. Underlying cause of death was ascertained from the National Death Index up to 2018. We examined associations of CD4+ and CD8+ T-cell activation (%CD38+HLA-DR+), senescence (%CD57+CD28-), exhaustion (%PD-1+), and nonactivation/normal function (%CD57-CD28+) with natural-cause, HIV-related, and non-HIV-related mortality. At baseline, median participant age was 41, and 67% were on ART. Among 100 deaths during a median of 13.3 years follow-up, 90 were natural-cause (53 non-HIV-related, 37 HIV-related). Higher activation and exhaustion of CD4+ T cells were associated with risk of natural-cause and non-HIV-related mortality, adjusting for age, demographic, behavioral, HIV-related, and cardiometabolic factors at baseline. Additional adjustment for time-varying viral load and CD4+ T-cell count did not attenuate these associations. CD8+ T-cell markers were not associated with any outcomes adjusting for baseline factors. Persistent CD4+ T-cell activation and exhaustion may contribute to excess long-term mortality risk in women with HIV, independent of HIV disease progression.

Effect of Viral Replication and Liver Fibrosis on All-Cause Mortality in Human Immunodeficiency Virus-Hepatitis B Virus-Coinfected Individuals: A Retrospective Analysis of a 15-Year Longitudinal Cohort.

In individuals living with human immunodeficiency virus (HIV) and hepatitis B virus (HBV), widespread tenofovir (TDF)-containing antiretroviral therapy (ART) has led to substantial decreases in HBV-DNA and HIV-RNA detection. However, the links between viral replication, liver fibrosis, and mortality remain unclear. A total of 300 individuals living with HIV-HBV and undergoing ART were prospectively followed. Virological and clinical data were obtained at baseline and every 6-12 months. We quantified the associations between HBV-DNA, HIV-RNA, and liver fibrosis with risk of all-cause mortality using a joint longitudinal survival model. Viral detection, viral loads, and time-averaged cumulative viral loads of HIV and HBV were modeled as 3 separate exposures. During a median of 10.5 years (interquartile range, 4.0-14.6), the proportion undergoing TDF-containing ART (baseline = 18.7%, end of follow-up = 79.1%) and with undetectable HBV-DNA (baseline = 36.7%, end of follow-up = 94.8%) substantially increased. 42 participants died (incidence rate = 1.30/100 person-years, 95% confidence interval [CI] = .96-1.76). The leading causes of death were non-AIDS/non-liver-related malignancies (28.6%), followed by liver-related (16.7%), AIDS-related (16.7%), and other (16.7%). All-cause mortality was associated with HBV-DNA viral load (adjusted hazards ratio [aHR] per log10 IU/mL = 1.41, 95% CI = 1.04-1.93, P = .03) or time-averaged cumulative HBV-DNA (aHR per log10 copy-years = 1.37, 95% CI = 1.03-1.83, P = .03), but not undetectable HBV-DNA. Advanced liver fibrosis at baseline was also associated with increased mortality rates (aHR = 2.35, 95% CI = 1.16-4.76, P = .02). No significant association between HIV-RNA replication and mortality was observed. Concurrent and historical HBV replication and liver fibrosis are important drivers of all-cause mortality in largely TDF-treated individuals living with HIV-HBV, despite one-fifth of deaths being liver-related. HBV-DNA and liver fibrosis remain important prognostic indicators for this patient population.

The associations of population mobility in HIV disease severity and mortality rate in China.

BackgroundHuman immunodeficiency virus (HIV) infection has become a chronic disease and attracted public attention globally. Population migration was considered hindering the control and management of HIV infection, but limited studies have explored how population mobility could influence the development of HIV-related complications and overall prognosis.MethodsWe enrolled hospitalized HIV patients in this cross-sectional study between January 1, 2006, and December 31, 2016. We extracted demographic, hospitalization, and patient diagnosis data. Patients were divided into three groups according to the population type: (I) resident of Guangzhou City (local resident); (II) migrant outside of Guangzhou City but within Guangdong Province (migrant within the province); and (III) migrant outside of Guangdong Province (migrant outside the province). To represent the prognosis of HIV, in-hospital death was defined as the worst outcome, whereas vision-related events were considered moderate-to-severe complications. Logistic regression models were used to analyze factors influencing the prognosis of HIV.ResultsEight thousand and six hundred thirty-one inpatients (14,954 cases) were enrolled. The overall mortality was 7.9%, decreasing from 21.5% in 2006 to 3.8% in 2016. The prevalence of vision-related events was 14.4% between 2015 and 2016. Compared to local patients, migrant patients (within and outside the province) were younger, had significantly less access to health insurance, fewer hospitalization admissions, longer hospital stays, and a higher proportion of physical work (P<0.01). Furthermore, they had a higher prevalence of vision-related events (16.2% and 17.4% in migrant patients within the province and outside the province, respectively vs. 9.5%) and infectious diseases, but lower in-hospital mortality (5.9% and 7.0% vs. 12.3%) than local patients. Migrants correlated negatively with in-hospital death [odds ratio (OR) 95% CI, 0.37 (0.29–0.48) and 0.52 (0.40–0.68)] but correlated positively with vision-related events [OR (95% CI), 2.08 (1.54–2.80) and 2.03 (1.47–2.80)].ConclusionsMigrant patients have significantly poorer access to health insurance, with an increased risk of developing moderate-to-severe HIV infection but a decreased risk of in-hospital death, indicating a trend toward withdrawing treatment in migrant patients when they have advanced diseases. Managements such as optimizing access to health insurance and improving follow-up visits for HIV infection should be considered in the context of the population mobility of HIV patients.

Study the prevalence of Pulmonary Tuberculosis and HIV co-infection in all Pulmonary Tuberculosis patients at tertiary health care centre

Background: Co-infection of Human Immunodeficiency Virus (HIV) and tuberculosis(TB) is considered to be one of the emerging medical conditions responsible for huge social and economic burden globally. Tuberculosis is leading cause of mortality among people living with HIV/AIDS. Methodology: The present cross-sectional study was carried out in a tertiary care centre of a city in Maharashtra between the periods of 1st August 2019 to July 2020. Study population were IPD patients from department of pulmonary medicine of tertiary health care centre. Sampling technique: Every fifth PTB diagnosed patient admitted in ward of pulmonary medicine department was included in the study till the sample size was achieved. The data was entered to excel sheet and analyzed by Windows 10 excel software. Result: study subjects were from age group 16-30 years of age, in this age group 2 (0.75%) patient was co-infected with PTB and HIV. 86(32.33%) study subjects were from age group 31 – 45 years of age from this age group 8 (3.00%) patients were HIV PTB co-infected. 2(0.75%) patient was there in age group 13-15 years of age. Symptoms of study subjects in PTB with HIV patients most common symptoms were weight loss(100%), Loss of appetite(100%) and evening rise of fever (85.71%).While in PTB without HIV patients loss of appetite evening rise of fever and weight loss was most common symptoms. In patients of PTB and HIV co-infection, sputum smear positive rate was lower, 6 out of 14 patients (42.86%) as compared to patients without PTB and HIV co-infection, 148 out of 252(i.e., 58.73%). Conclusion: It can be concluded from our study that there is difference n demography of HIV co-infection with Tuberculosis also it differed in clinical and radiological features also we have noted that the mortality of HIV –TB co-infection was having higher mortality i.e. 14.28% as compared to without co-infection i.e. 3.96%, hence prompt treatment by antiviral drugs and timely screening for TB and timely treatment is mandatory.

Obeticholic acid attenuates human immunodeficiency virus/alcohol metabolism-induced pro-fibrotic activation in liver cells

BACKGROUNDThe morbidity and mortality of human immunodeficiency virus (HIV)-infection is often associated with liver disease, which progresses slowly into severe liver dysfunction. There are multiple insults which exacerbate HIV-related liver injury, including HIV-associated dysregulation of lipid metabolism and fat turnover, co-infections with hepatotropic viruses and alcohol abuse. As we reported before, exposure of hepatocytes to HIV and alcohol metabolites causes high oxidative stress, impairs proteasomal and lysosomal functions leading to accumulation of HIV in these cells, which end-ups with apoptotic cell death and finally promotes development of liver fibrosis.AIMTo study whether obeticholic acid (OCA) prevents HIV/ethanol metabolism-induced hepatotoxicity and subsequent activation of hepatic stellate cells (HSC) by HIV+ apoptotic hepatocyte engulfment. METHODSHuh7.5-CYP (RLW) cells were exposed to HIV and acetaldehyde-generating system (AGS) in the presence or absence of OCA. In the cells, we measured the expression of HIV-related markers: HIVgagRNA-by real-time polymerase chain reaction (PCR), p24- by western blot, HIV DNA-by semi-nested PCR, integrated HIV DNA-by ddPCR. Lysosomal and proteasomal activities were measured using fluorometrically-labeled substrates. For hepatocyte apoptosis, cleaved caspase 3 and cleaved PARP were visualized by western blot and cytokeratin 18- by M30 ELISA-in supernatants. Apoptotic bodies were generated from untreated and HIV-treated RLW cells exposed to UV light. Pro-fibrotic activation of HSC was characterized by Col1A1 and transforming growth factor-β mRNAs, while inflammasome activation- by NLRP3, caspase 1, interleukin (IL)-6, IL-1β mRNA levels.RESULTSIn RLW cells, OCA treatment attenuated HIV-AGS-induced accumulation of HIVgagRNA, HIV DNA and p24. OCA suppressed reactive oxygen species production and restored chymotrypsin-like proteasome activity as well as cathepsin B lysosome activity. OCA also decreased HIV-AGS-triggered apoptosis in RLW cells. Exposure of HIV-containing apoptotic hepatocytes to HSC prevented activation of inflammasome and induced pro-fibrotic activation in these cells. CONCLUSIONWe conclude that by suppressing oxidative stress and restoring proteasomal and lysosomal functions impaired by HIV and ethanol metabolism, OCA decreases accumulation of HIV in hepatocytes, leading to down-regulation of apoptosis in these cells. In addition, OCA reverses pro-fibrotic and inflammasome-related activation of HSC triggered by engulfment of HIV-containing apoptotic hepatocytes, potentially contributing to suppression of liver fibrosis development.

Inhibition of apoptosis signal-regulating kinase 1 mitigates the pathogenesis of human immunodeficiency virus-associated nephropathy.

Chronic kidney disease (CKD) is a common cause of morbidity and mortality in human immunodeficiency virus (HIV)-positive individuals. Among the HIV-related kidney diseases, HIV-associated nephropathy (HIVAN) is a rapidly progressive renal disease characterized by collapsing focal glomerulosclerosis (GS), microcystic tubular dilation, interstitial inflammation and fibrosis. Although the incidence of end-stage renal disease due to HIVAN has dramatically decreased with the widespread use of antiretroviral therapy, the prevalence of CKD continues to increase in HIV-positive individuals. Recent studies have highlighted the role of apoptosis signal-regulating kinase 1 (ASK1) in driving kidney disease progression through the activation of p38 mitogen-activated protein kinase and c-Jun N-terminal kinase and selective ASK-1 inhibitor GS-444217 was recently shown to reduce kidney injury and disease progression in various experimental models. Therefore we examined the efficacy of ASK1 antagonism by GS-444217 in the attenuation of HIVAN in Tg26 mice. GS-444217-supplemented rodent chow was administered in Tg26 mice at 4 weeks of age when mild GS and proteinuria were already established. After 6 weeks of treatment, the kidney function assessment and histological analyses were performed and compared between age- and gender-matched control Tg26 and GS-444217-treated Tg26 mice. GS-444217 attenuated the development of GS, podocyte loss, tubular injury, interstitial inflammation and renal fibrosis in Tg26 mice. These improvements were accompanied by a marked reduction in albuminuria and improved renal function. Taken together, GS-4442217 attenuated the full spectrum of HIVAN pathology in Tg26 mice. ASK1 signaling cascade is central to the development of HIVAN in Tg26 mice. Our results suggest that the select inhibition of ASK1 could be a potential adjunctive therapy for the treatment of HIVAN.