Late Antiretroviral Therapy Initiation Research Articles

Evaluation of rapid antiretroviral initiation strategy in a cohort of newly diagnosed people living with HIV in Panama, 2018–2019

ABSTRACT Antiretroviral therapy (ART) has been adopted as a form of HIV treatment and prevention. This study assesses rapid ART initiation using clinical outcomes such as viral load (VL) and CD4+ T lymphocytes count. Over the course of one year, the progress of newly diagnosed people living with HIV who started ART early in a hospital in Panama City was followed. The evaluation of early initiation of ART in achieving viral suppression (VL <200 copies/ml) was analyzed using descriptive statistics. Additionally, the cost difference between early (first 7 days) and late initiation of ART was evaluated from the perspective of the service provider. In total, 209 people were followed up during the study; 85% were male, 70% started ART on same day from hospital arrival, 80% had suppressed viral load at 6 months, and the median count of CD4 increased from 285 (IQR: 166–429) to 509 (IQR: 373–696) over 12 months. Starting ART early led to a 42% increase for the provider in terms of staffing costs; however, the clients had the opportunity to decrease absenteeism in daily activities. The results reveal that early initiation of ART generates clinical and economic benefits for the person in treatment.

Trends and the associated factors of optimal immunological response and virological response in late anti-retroviral therapy initiation HIV cases in Taiwan from 2009 to 2020

BackgroundLate cART initiation (CD4 count ≤200 cells/μL or AIDS-defining opportunistic illnesses [AOIs] at cART initiation) impedes CD4 count recovery and virologic suppression after cART initiation. However, studies to evaluate trends of and modifiable factors for optimal immunological response (IR) and virological response (VR) in people living with HIV (PLWH) with late cART initiation with the current HIV treatment strategies are limited. MethodsWe retrospectively identified 475 PLWH with late cART initiation in 2009–2020. Patients were grouped based on the presence of IR (CD4 count ≥200 cells/μL) or VR (plasma viral load [PVL] ≤ 50 copies/mL) within 18 months after cART initiation (403 [84.8%] IR(+) and 72 [15.2%] IR(−); 422 [88.8%] VR(+) and 53 [11.2%] VR(−)). We used Joinpoint regression to identify IR (+) and VR(+) proportion changes. ResultsFrom 2009 to 2020, the proportion of IR(+) patients remained unchanged (75% to 90%, P = 0.102), whereas that of VR(+) patients increased significantly (75% to 95%, P = 0.007). No join point was identified for either IR(+) or VR(+), and the annual percentage change was 0.56% (nonsignificant) and 1.35% (significant) for IR(+) and VR(+), respectively. Compared to IR(−) patients, IR(+) patients were more likely to have a higher pre-cART PVL, to start with a first-line INSTI-based regimen, or to start cART within 14 days of HIV diagnosis but were less likely to have chronic kidney disease, composite AOIs, or a lower pre-cART CD4 count. Compared to VR(−) patients, VR(+) patients were more likely to start a single-tablet regimen but were less likely to have a higher pre-cART PVL. ConclusionsOur study identified several modifiable factors for optimal IR (rapid cART initiation and INSTI-based regimen initiation) and for optimal VR (STR initiation) among late initiators, which may guide early treatment modifications to reduce their AIDS-defining event incidence and mortality.

Factors associated with late initiation of antiretroviral therapy in Iran’s HIV/AIDS surveillance data

Early initiation of Antiretroviral Treatment (ART) in HIV patients is essential for effectively suppressing the viral load and prognosis. This study utilized National HIV/AIDS Surveillance Data in Iran to identify factors associated factors with the duration to initiate ART. This hybrid cross-sectional historical cohort study was conducted on Iran’s National HIV/AIDS Surveillance Data from 2001 to 2019. Sociodemographic characteristics, route of transmission, HIV diagnosis date, and ART initiation date were collected. Multivariable linear and quantile regression models were employed to analyze the duration to initiate ART by considering predictor variables. This study included 17,062 patients (mean age 34.14 ± 10.77 years, 69.49% males). Multivariate quantile regression coefficients varied across different distributions of the dependent variable (i.e., duration to initiate ART) for several independent variables. Generally, male gender, injecting drug use (IDU), and having an HIV-positive spouse were significantly associated with an increased duration to initiate ART (p < 0.05). However, a significant decrease was observed in older patients, those with a university level education, men who had sex with men (MSM), and patients diagnosed after 2016 (p < 0.05). Despite improvements in the duration to initiate ART after implementing the WHO’s 2016 program in Iran, various sociodemographic groups were still vulnerable to delayed ART initiation in the region. Therefore, programs including early testing, early ART initiation, active care, educational and cultural interventions, and appropriate incentives are required for these groups.

Latency to initiation of antiretroviral therapy in people living with HIV in Japan

Rapid initiation of antiretroviral therapy (ART) in HIV infection is recommended because it increases care retention rate and reduces the time to viral suppression. In Japan, although ART initiation is delayed, there is little information on the latency to ART initiation (time from HIV diagnosis to ART initiation). The present study was designed to obtain information on the latency to ART initiation in individuals with 1) acute or recent HIV infection (ARH), and with 2) advanced HIV diseases. Questionnaires were sent to 379 regional AIDS facilities requesting information on the people living with HIV (PLWH) who visited their facilities during 2020. Among 1098 new PLWH visitors, 706 were treatment-naïve patients, including 111 (15.7%) with ARH and 304 (43.1%) with advanced HIV diseases. Among those with ARH, only 8.2% received rapid ART initiation (latency to ART <2 weeks) and the time from diagnosis to virological suppression was longer than 14 weeks in 40.4%. Among those with advanced HIV diseases, 36.2% received late ART initiation (latency to ART ≧6 weeks). Our data showed that only a small proportion of PLWH with ARH in Japan received rapid ART. Furthermore, in PLWH with advanced HIV diseases in Japan, current latency to ART seems too long, though the timing of ART commencement should be tailored according to the presence/lack of opportunistic infections and accessibility to medical care. Further investigation is required to identify barriers to rapid ART initiation in Japan.

Factors Associated With Delayed and Late Initiation of Antiretroviral Therapy Among Patients With HIV in Beijing, China, 2010-2020.

Objectives: To determine factors associated with late and delayed antiretroviral therapy (ART) initiation in China and provide evidence for HIV prevention. Methods: Logistics regression model was used to determine factors associated with three outcomes: late (CD4 cell count <200cells/µL or clinical AIDS diagnosis prior to ART initiation), delayed (more than 1month between HIV diagnosis date and ART initiation) and either late or delayed ART initiation. Results: Multivariable analysis revealed that male, heterosexual, HIV diagnosis before 2014, HBV/HCV seropositive, and tuberculosis were associated with increased odds of all three outcomes. Conversely, married or cohabiting patients were less likely to have delayed ART initiation and either late or delayed ART initiation, while people who inject drugs were more likely to have these two outcomes. Additionally, older age was associated with an increased risk of having either late or delayed ART initiation, but a decreased risk of delayed ART initiation. Conclusion: The proportion of late and delayed ART initiation decreased significantly after the release of the 2016 guidelines in China. To further improve late diagnosis and early treatment, precise interventions for key populations are required.

Aspects of HIV-associated cardiovascular pathology against the background of antiretroviral therapy

BACKGROUND: The detection of cardiovascular pathology in patients at various stages of HIV infection is highly relevant. Given the data presented in the scientific medical literature on the negative impact of this infection on the cardiovascular system (CVS), a higher level of mortality in this group of patients from cardiovascular diseases has recently increased several times.&#x0D; AIM: to identify cardiovascular pathology in patients at different stages of HIV infection (3 and 4), to determine the relationship with antiretroviral therapy (ART) regimens to improve the quality of medical care and disease prognosis.&#x0D; MATERIALS AND METHODS: We examined 60 patients (outpatient and inpatient) with HIV infection at different stages of the disease from June 2020 to December 2021. Retrospectively, an analysis was performed of electronic medical records of persons registered and observed at the MHC AIDS DZM (supervisor MD, prof. A.I. Mazus) based on the State Budgetary Healthcare Institution ICB No. 2 DZM. The following were analyzed: age, gender, medical history (terms of the disease, comorbidities), results of an objective examination, routine laboratory blood tests, and ART regimens. Cardiovascular pathology was identified by performing special instrumental diagnostics ECG, Echo-KG, and Doppler ultrasound of the brachiocephalic arteries followed by a consultation with a cardiologist in case of abnormalities. Categorical data were described with indications of absolute values and extensive indicators. Quantitative indicators were assessed for compliance with the normal distribution using the Shapiro-Wilk test and the Kolmogorov-Smirnov test. Statistical processing was performed using Microsoft Excel and StatTech v. 1.2.0. Differences were considered statistically significant at p 0.05.&#x0D; RESULTS: Based on the data presented, it can be noted that the observed group of HIV-infected patients was of middle age (41.38.5 years), and men accounted for 78%. Cardiovascular pathology was detected in 38 (63%), and stage 4 HIV infection was 71%. Among the pathologies of the heart, infective endocarditis (IE) with damage to the tricuspid valve (58%) was most often diagnosed, and most of them (77%) had stage 4 HIV infection. An analysis of the intake of ART showed that in patients who did not receive it for the entire period of the disease, such pathology was detected in 68.4% of cases; among patients with late initiation of ART or lack of adherence in 58% of cases; in those who received ART in a timely and regular manner, cardiovascular pathology was diagnosed five times less often in 11.8%, which indicates an obstructive effect of ART on the development of cardiovascular pathology in HIV infection. The statistical significance of the development of IE in the group of patients with intravenous use of PAS was revealed, which suggests the influence of drug addiction on the occurrence of heart pathology.&#x0D; CONCLUSION: The data obtained from this study may have specific practical significance, suggesting criteria for examining patients with HIV infection to identify cardiovascular pathology, which will affect the quality of medical care and the prognosis of the disease.

Dolutegravir in late pregnancy: where to from here?

Strategies to eliminate the perinatal transmission of HIV include initiation of effective antiretroviral therapy (ART) as soon as possible before or during pregnancy and maintaining a suppressed viral load throughout pregnancy and postpartum. Late initiation of ART in pregnant women with HIV has been associated with increased risk of perinatal transmission and perinatal mortality in infants.1 In the DolPHIN-2 study,2 268 pregnant women with HIV (median gestational age 31 weeks) from Cape Town, South Africa and Kampala, Uganda, were enrolled and randomly assigned to receive either dolutegravir-based or efavirenz-based ART.

The contribution of late HIV diagnosis on the occurrence of HIV-associated tuberculosis.

To describe the timing of tuberculosis (TB) presentation in relation to diagnosis of HIV infection and antiretroviral therapy (ART) initiation and to evaluate whether the established impact from late presentation to care and late initiation of ART on the risk of TB is retained beyond the observation period of clinical trials. We used marginal structural models to emulate a clinical trial with up to 5 years of follow-up to evaluate the impact of late initiation on TB risk. People with HIV (PWH) were enrolled from 2007 to 2016 in observational cohorts from Uganda, Peru, Mexico and Italy. The risk of TB was compared in LP (accessing care with CD4 + cell count ≤350 cells/μl) vs. nonlate presentation using survival curves and a weighted Cox regression. We emulated two strategies: initiating ART with CD4 + cell count less than 350 cells/μl vs. CD4 + cell count at least 350 cells/μl (late initiation). We estimated TB attributable risk and population attributable fraction up to 5 years from the emulated date of randomization. Twenty thousand one hundred and twelve patients and 1936 TB cases were recorded. Over 50% of TB cases were diagnosed at presentation for HIV care. More than 50% of the incident cases of TB after ART initiation were attributable to late presentation; nearly 70% of TB cases during the first year of follow-up could be attributed to late presentation and more than 50%, 5 years after first attending HIV care. Late presentation accounted for a large share of TB cases. Delaying ART initiation was detrimental for incident TB rates, and the impact of late presentation persisted up to 5 years from HIV care entry.

Treatment Outcomes of HIV Infected Children After Initiation of Antiretroviral Therapy in Southwest China: An Observational Cohort Study.

BackgroundThe number of HIV infected children receiving antiviral treatment in Guangxi is increasing. Understanding factors and trends of mortality and attrition in HIV-infected children under antiretroviral therapy (ART) was an urgent need to improve treatment outcomes. This study aimed to estimate mortality and attrition rates and identify factors that were associated with mortality and attrition after ART initiation among children with HIV in Guangxi, China between 2004 and 2018.MethodsCohort study data were extracted from the National Free Antiretroviral Treatment Program (NFATP) database, which has standard guidelines for core treatment indicators and other data at all HIV/AIDS treatment facilities in Guangxi. A total of 901 HIV-infected children who have started ART were included in the study. The study collected the following data: age, gender, WHO clinic stages before ART, CD4 cell count before ART, Cotrimoxazole prophylaxis (CTX) use before ART, initial ART regimen, malnutrition before ART, abnormal liver function before ART, abnormal kidney function before ART, severe anemia before ART, and the time lag between an HIV diagnosis and ART initiation.ResultsHIV-infected children under ART had a mortality rate of 0.87 per 100 person-years [95% Confidence Interval (CI) 0.63–1.11], and an attrition rate of 3.02 per 100 person-years (95% CI 2.57–3.47). Mortality was lower among children with a CD4 count between 200 and 500 copies/ml [Adjusted Hazard Ratio (AHR) 0.22, 95% CI 0.09–0.55], and CD4 count ≥500 copies/ml (AHR 0.10, 95% CI 0.03–0.29); but higher among children with late ART initiation at 1–3 months (AHR 2.30, 95% CI 1.07–4.94), and at ≥3 months (AHR 2.22, 95% CI 1.04–4.74). Attrition was lower among children with a CD4 count ≥500 copies/ml (AHR 0.62, 95% CI 0.41–0.95), but higher among children with late ART initiation at 1–3 months (AHR 1.55, 95% CI 1.05–2.30).ConclusionSupportive programs are needed to educate children's families and parents on early ART, link HIV-infected children to care and retain them in care among other programs that treat and manage the medical conditions of HIV-infected children before ART initiation.

Factors Associated With Late Antiretroviral Therapy Initiation Among People Living With HIV in Southern Iran: A Historical Cohort Study.

ObjectivesLate initiation of antiretroviral therapy (ART) is associated with poor outcome among people living with HIV (PLHIV) and higher risk of transmission of infection. This study was conducted to identify the determinants of late ART initiation among PLHIV in Southern Iran.MethodsA historical cohort study was conducted on 1,326 PLHIV of ≥15 years of age who were registered with the behavioral diseases counseling center (BDCC) in southern Iran from August 1997 to March 2021. Late ART initiation was defined as a CD4 cell count <200 cells/mm3 or having a clinical AIDS diagnosis at the time of ART initiation. The required demographic and clinical data were collected from the patients' medical records. Multiple regression analysis was conducted to define late ART initiation associated factors.ResultsLate ART initiation was found among 81.9% of patients. Based on the results of the multivariate analysis, older age (odds ratio [OR] = 1.02, 95% CI = 1.00–1.04), being single (ORsingle/married = 1.80, 95% CI = 1.17–2.78), history of drug use (ORyes/no = 1.64, 95% CI = 1.02–2.62), year of ART initiation (OR2011−2013/2018−2021 = 3.65, 95% CI = 2.28–5.86), and possible route of transmission (ORdruginjection/sexual = 7.34, 95% CI = 1.16–46.21) were directly associated with the risk of late ART initiation.ConclusionsThe results show that the prevalence of late ART initiation was alarmingly high. For better infection control and better prognosis of infection, people at high risk need to be provided with timely services (e.g., diagnosis, treatment, training, and social support).

Factors Associated with Early and Late Initiation of Antiretroviral Therapy among People Living with Human Immunodeficiency Virus in Lahore, Pakistan

Background: Despite the availability of antiretroviral therapy (ART), HIV is still responsible for substantial illness and death, especially in developing countries. Early start of treatment (ART) is associated with better therapeutic outcome, reduced transmissibility of HIV, reduction in loss to follow-up, and remarkably reduced death rate. Objectives: To find out the factors associated with early and late Initiation of ART among patients affected by HIV in Lahore, Pakistan Methods: From November 2017 to April 2018, researchers conducted an analytical cross-sectional study on 156 HIV patients aged 18 and older that began antiretroviral therapy (ART) at Jinnah &amp; Mayo Hospital, Lahore's HIV clinics. Samples were selected by non-probability convenience sampling and Univariate and multivariate analyses were performed to assess factors related to early and late Initiation of ART. The p-value of less than

Growth and CD4 patterns of adolescents living with perinatally acquired HIV worldwide, a CIPHER cohort collaboration analysis.

IntroductionAdolescents living with HIV are subject to multiple co‐morbidities, including growth retardation and immunodeficiency. We describe growth and CD4 evolution during adolescence using data from the Collaborative Initiative for Paediatric HIV Education and Research (CIPHER) global project.MethodsData were collected between 1994 and 2015 from 11 CIPHER networks worldwide. Adolescents with perinatally acquired HIV infection (APH) who initiated antiretroviral therapy (ART) before age 10 years, with at least one height or CD4 count measurement while aged 10–17 years, were included. Growth was measured using height‐for‐age Z‐scores (HAZ, stunting if <‐2 SD, WHO growth charts). Linear mixed‐effects models were used to study the evolution of each outcome between ages 10 and 17. For growth, sex‐specific models with fractional polynomials were used to model non‐linear relationships for age at ART initiation, HAZ at age 10 and time, defined as current age from 10 to 17 years of age.ResultsA total of 20,939 and 19,557 APH were included for the growth and CD4 analyses, respectively. Half were females, two‐thirds lived in East and Southern Africa, and median age at ART initiation ranged from <3 years in North America and Europe to >7 years in sub‐Saharan African regions. At age 10, stunting ranged from 6% in North America and Europe to 39% in the Asia‐Pacific; 19% overall had CD4 counts <500 cells/mm3. Across adolescence, higher HAZ was observed in females and among those in high‐income countries. APH with stunting at age 10 and those with late ART initiation (after age 5) had the largest HAZ gains during adolescence, but these gains were insufficient to catch‐up with non‐stunted, early ART‐treated adolescents. From age 10 to 16 years, mean CD4 counts declined from 768 to 607 cells/mm3. This decline was observed across all regions, in males and females.ConclusionsGrowth patterns during adolescence differed substantially by sex and region, while CD4 patterns were similar, with an observed CD4 decline that needs further investigation. Early diagnosis and timely initiation of treatment in early childhood to prevent growth retardation and immunodeficiency are critical to improving APH growth and CD4 outcomes by the time they reach adulthood.

The Impact of Timing of Antiretroviral Therapy Initiation on Retention in Care, Viral Load Suppression and Mortality in People Living with HIV: A Study in a University Hospital in Thailand.

Studies investigating same-day antiretroviral therapy (ART) initiation demonstrate different clinical outcomes depending on settings. We retrospectively reviewed adults with newly positive human immunodeficiency virus (HIV) antibody testing. The proportion of individuals who were retained in care at 12 months was compared between early (≤2 weeks) and late (>2 weeks) ART initiation groups. Of all, the median (IQR) time from HIV diagnosis to ART initiation was 18 (9-30) days. This duration was 7 (7-13) days in the early ART initiation group (n = 116) and 28 (21-46) days in the late ART initiation group (n = 154). In the multivariate logistic regression, having pneumocystis pneumonia [odds ratio (OR) 9.30, 95% CI 2.56-33.75], tuberculosis (OR 2.21, 95% CI 1.03-4.73), and weight loss (OR 12.98, 95% CI 1.00-167.68) were associated with late ART initiation. The early ART initiation group had a slightly higher proportion of individuals retained in care at 12 months than those in the late ART initiation group (88.8% vs 80.5%, P = .066) and had a higher significant proportion of HIV viral load suppression (81.0% vs 70.1%, P = .041). No significant differences were observed in the proportion of individuals who died at 12 months (2.6% vs 3.2%, P = 1.000) between the two groups. Early ART initiation trends to retain individuals in care and higher HIV viral load suppression was determined. Nevertheless, ART initiation timing might not be a solely important factor in improving HIV care and minimizing mortality among HIV-infected individuals in a university hospital setting.

Support for Establishing Best Practices for Breastfeeding in the Current HIV/ART Era.

In this issue of the Journal of the Pediatric Infectious Diseases Society, Yusuf et al describe an initiative to support women living with HIV (WLHIV) who chose to breastfeed at Johns Hopkins Hospital. The authors successfully developed and implemented a comprehensive harm reduction program in response to recent changes in Department of Health and Human Services (DHHS) perinatal HIV guidelines. Yusuf et al are the first to report outcome data in the United States of 10 infants born to WLHIV who started antiretroviral therapy (ART) preconception. None acquired HIV infection after breastfeeding for a median duration of 4.4 months. There is a growing body of evidence to suggest that postnatal HIV transmission during breastfeeding is exceedingly rare among mothers who maintain sustained viral suppression while on ART throughout pregnancy and breastfeeding. Among 4 studies of breastfeeding WLHIV on ART (N = 2392), overall infant HIV transmission at 6 months was 0.37% (95% CI 0.17%-0.71%), and all breastfeeding transmissions occurred in the context of either maternal detectable viremia (n = 5), reported ART adherence challenges (n = 2), or late initiation of ART (≤3 months prior to delivery) (n = 2) [1–4]. In light of these international data, the benefits of breastfeeding and the risks to the infant of not breastfeeding must be considered. Breastfeeding lowers risk for major drivers of infant mortality (sudden infant death syndrome [SIDS], necrotizing enterocolitis [NEC], and sepsis) and is associated with lower rates of childhood obesity, asthma, and diabetes [5]. Early immune development is shaped by breastmilk-associated gut microbiome, which can lower risk for autoimmunity later in life [6]. Many infants born to WLHIV in the United States already face disproportionate risk for adverse health outcomes linked with lower socioeconomic status. Breastfeeding restrictions may unintentionally increase the odds of poor health outcomes in this vulnerable population.

Size of HIV-1 reservoir is associated with telomere shortening and immunosenescence in early-treated European children with perinatally acquired HIV-1.

IntroductionPersistence of HIV‐1, causing chronic immune activation, is a key determinant of premature senescence. Early antiretroviral therapy (ART) has been associated with a reduced HIV‐1 reservoir in children with perinatally acquired HIV‐1 (PHIV), but its impact on the senescence process is an open question. We investigated the association between HIV‐1 reservoir and biological and immune ageing profile in PHIV enrolled in the multicentre cross‐sectional study CARMA (Child and Adolescent Reservoir Measurements on early suppressive ART) conducted within the EPIICAL (Early treated Perinatally HIV Infected individuals: Improving Children's Actual Life) consortium.MethodsBetween September 2017 and June 2018, CARMA enrolled 40 PHIV who started ART before 2 years of age and had undetectable viremia for at least 5 years before sampling date. Samples from 37 children with a median age of 13.8 years were available for this study. HIV‐1 DNA copies on CD4 cells, relative telomere length (marker of cellular senescence) and levels of T‐cell receptor rearrangement excision circle (TREC, marker of thymic output) on CD4 and CD8 cells were quantified by qPCR. Immunological profile was assessed by flow cytometry. Associations between molecular and phenotypic markers, HIV‐1 reservoir and age at ART initiation were explored using a multivariable Poisson regression.ResultsHigher HIV‐1 reservoir was associated (p<0.001) with telomere shortening (incidence rate ratio [IRR] = 0.15 [0.13–0.17]), immunosenescence (CD28–CD57+, IRR = 1.23 [1.21–1.26]) and immunoactivation (CD38+ HLADR+, IRR = 7.29 [6.58–8.09]) of CD4 cells. Late ART initiation (after 6 months of age) correlated with higher HIV‐1 reservoir levels (552 [303–1001] vs. 89 [56–365] copies/106 CD4 cells, p = 0.003) and percentage of CD4 senescent cells (2.89 [1.95–6.31] vs. 1.02 [0.45–2.69, p = 0.047). TREC levels in CD8 cells were inversely associated with HIV‐1 reservoir (IRR = 0.77 [0.76–0.79]) and were significantly lower in late treated PHIV (1128 [486–1671] vs. 2278 [1425–3314], p = 0.042).ConclusionsLater ART initiation is associated with higher HIV‐1 reservoir size, which correlates with increased telomere shortening and senescence of CD4 cells. Timing of ART initiation in infancy has long‐term consequences on the immune and biological ageing profile of children with perinatally acquired HIV‐1.

Changing Patterns of Lymphoma in the Antiretroviral Therapy Era in Johannesburg, South Africa.

South Africa has a high HIV prevalence, which associates with an increased risk of lymphoma. Antiretroviral therapy (ART) became accessible in 2004, but the program has substantially expanded. Changes in lymphoma patterns are documented in high-income countries after wide-scale ART including declining high-grade B-cell non-Hodgkin lymphomas (HG B-NHLs), particularly diffuse large B-cell lymphoma, and increased Hodgkin lymphoma (HL). There are limited data from Africa. This study aimed to compare HG B-NHL characteristics in the early (2007) and later (2017) ART era. All incident lymphomas at the National Health Laboratory Service, Johannesburg, were identified using the laboratory information system, and data were collected for each patient. The total number of lymphoma cases increased from 397 (2007) to 582 (2017). This was associated with improved lymphoma classification and patient referral for oncological care. HG B-NHL remained the most diagnosed lymphoma subtype in 2017 comprising 70% of HIV-associated lymphomas, followed by HL (24%). Diffuse large B-cell lymphoma comprised 65% of all HG B-NHLs and 45% of all lymphomas in people with HIV in 2017. Significantly more patients were on ART in 2017, with improvements in virological control documented. Despite this, 47.6% of patients were not virologically suppressed, and 37.5% of patients were ART-naive at time of diagnosis in 2017. Immunological reconstitution was suboptimal, which may reflect late initiation of ART. Public health initiatives to initiate ART as early as possible and to retain patients in ART programs may assist in decreasing the number of HIV-associated lymphomas in our setting.

Late initiation of antiretroviral therapy: inequalities by educational level despite universal access to care and treatment

BackgroundLate antiretroviral treatment initiation for HIV disease worsens health outcomes and contributes to ongoing transmission. We investigated whether socioeconomic inequalities exist in access to treatment in a setting with universal access to care and treatment.MethodsThis study investigated the association of educational level, used as a proxy for socioeconomic status, with late treatment initiation and treatment initiation with advanced disease. Study participants included adults (≥25 years) who started treatment from 2005 to 2018 at Instituto Nacional de Infectologia Evandro Chagas of Fundação Oswaldo Cruz (INI/FIOCRUZ), Rio de Janeiro, Brazil. Educational level was categorized following UNESCO’s International Standard Classification of Education: incomplete basic education, basic education, secondary level, and tertiary level. We defined late treatment initiation as those initiating treatment with a CD4 < 350 cells/mL or an AIDS-defining event, and treatment initiation with advanced disease as those initiating treatment with a CD4 < 200 cells/mL or an AIDS-defining event. A directed acyclic graph (DAG) was constructed to represent the theoretical-operational model and to understand the involvement of covariates. Logistic regression models were used to estimate the adjusted odds ratios (aOR) and 95% confidence intervals (95%CI). Multiple imputation using a chained equations approach was used to treat missing values and non-linear terms for continuous variables were tested.ResultsIn total, 3226 individuals composed the study population: 876 (27.4%) had incomplete basic education, 540 (16.9%) basic, 1251 (39.2%) secondary level, and 525 (16.4%) tertiary level. Late treatment initiation was observed for 2076 (64.4%) while treatment initiation with advanced disease was observed for 1423 (44.1%). Compared to tertiary level of education, incomplete basic, basic and secondary level increased the odds of late treatment initiation by 89% (aOR:1.89 95%CI:1.47–2.43), 61% (aOR:1.61 95%CI:1.23–2.10), and 35% (aOR:1.35 95%CI:1.09–1.67). Likewise, the odds of treatment initiation with advanced disease was 2.5-fold (aOR:2.53 95%CI:1.97–3.26), 2-fold (aOR:2.07 95%CI:1.59–2.71), 1.5-fold (aOR:1.51 95%CI:1.21–1.88) higher for those with incomplete basic, basic and secondary level education compared to tertiary level.ConclusionDespite universal access to HIV care and antiretroviral treatment, late treatment initiation and social inequalities persist. Lower educational level significantly increased the odds of both outcomes, reinforcing the existence of barriers to “universal” antiretroviral treatment.

Early Initiation of ARV Therapy Among TB–HIV Patients in Indonesia Prolongs Survival Rates!

BackgroundThe HIV epidemic remains a public health problem with rising tuberculosis (TB) numbers around the world. Antiretroviral (ARV) therapy (ART) is essential to increase the survival of patients with TB–HIV coinfection. The aim of this study is to investigate the effect of ARV treatment initiation within TB treatment duration for the survival of patients with TB–HIV coinfection.MethodsThis is a retrospective cohort study of patients with TB–HIV coinfection and who were ARV naive from Prof. Dr. Sulianti Saroso Infectious Disease Hospital between January 2011 and May 2014 (N = 275). The Kaplan–Meier method, bivariate with the log rank test, and multivariate with the Cox regression were applied in this study.ResultsCumulative survival probability of the patients with TB–HIV coinfection receiving ARV in a year was 81.5%. The death rate in patients with TB–HIV coinfection who received late ART initiation during TB treatment is higher by 2.4 times [adjusted hazard ratio (aHR) = 2.4, 95% confidence interval: 1.3–4.5, p = 0.006] compared with the patients who were in early ART initiation and were thereafter adjusted by the location of Mycobacterium tuberculosis infection.ConclusionThe effect of ART initiation is essential in the intensive phase (2–8 weeks) of anti-TB medication to increase the survival among TB–HIV coinfection group.

Infectious morbidity of breastfed, HIV-exposed uninfected infants under conditions of universal antiretroviral therapy in South Africa: a prospective cohort study

Without breastfeeding and maternal antiretroviral therapy (ART), HIV-exposed uninfected (HEU) infants have greater infectious morbidity than HIV-unexposed (HU) infants. We hypothesised that with the introduction of universal maternal ART, breastfed HEU and HU infants would have similar morbidity. We prospectively studied a cohort of HIV-infected pregnant women initiating ART, and a parallel group of HIV-uninfected pregnant women, starting from their first antenatal care visit at the Gugulethu Midwife Obstetrics Unit in Cape Town, South Africa. All pregnant women attending their first antenatal care visit were eligible for enrolment if aged 18 years or older and planning to deliver in Cape Town, without gestational age restrictions. HIV-infected women were participants of the Maternal Child Health ART (MCH-ART) study, and HIV-uninfected women were participants of the HIV-Unexposed Uninfected (HU2) study. All enrolled women were followed up during pregnancy and through delivery. At the early neonatal visit (scheduled for the first week after birth), mother-infant pairs who practiced any breastfeeding in the first 7 days of life were eligible for further postnatal follow-up for at least 12 months post partum. HIV infection was excluded among HEU infants at ages 6 weeks and 12 months by PCR. We evaluated the effect of HIV exposure on two primary outcomes: hospitalisation (all-cause and infection-related admission to hospital) and longitudinal prevalence of child infectious illness (diarrhoea and presumed lower respiratory tract infection [LRTI]). Hospitalisation data were abstracted from routine health records. Crude and adjusted incidence rate ratios (aIRRs; with adjustment for maternal HIV disease severity, timing of ART initiation, breastfeeding, timely vaccination, and birth outcomes [gestational size and age]) for infection-related hospitalisations were calculated from Poisson regression models (with variance corrected for clustering). Prevalence of infant infectious illness was based on maternal self-report for the preceding 2 weeks of each visit, with questions based on Demographic and Health Survey (DHS) questionnaires. Infants who acquired HIV infection during follow-up were excluded from this analysis. MCH-ART is registered on ClinicalTrials.gov, NCT01933477. Pregnant women were recruited between March 20, 2013, and Aug 19, 2015. Mother-infant pairs (HEU, n=459; HU, n=410) were followed up for a median of 12 months until March 24, 2017. Compared with HU infants, HEU infants had more infection-related hospitalisations between the age of 8 days and 3 months (HEU, 34·2 admissions per 100 child-years [24·4-47·9] vs 9·8 per 100 child-years [95% CI 5·1-18·8]; IRR 3·50 [95% CI 1·68-7·30]), but rates were similar at other ages. In infants aged 8 days to 3 months, infection-related hospitalisations for HEU infants with healthier mothers (n=84; ART initiation at <24 weeks' gestation, CD4 count >350 cells per μL, HIV viral load <4·0 log10 copies per mL: 15·88 admissions per 100 child-years [5·12-49·23]) approximated those of HU infants (9·77 per 100 child-years [5·08-18·78]; aIRR 1·28 [0·27-6·05]). HEU infants of mothers with late ART initiation (at ≥24 weeks' gestation) and advanced disease (CD4 count ≤350 cells per μL and HIV viral load ≥4·0 log10 copies per mL; n=44) had the highest admission rate (40·44 per 100 child-years [15·18-107·74]; aIRR 5·01 [1·50-16·71]). In this age group, reduced admissions were seen in HEU infants with optimal breastfeeding (initiated within 1 h of birth and exclusive through age 3 months) and timely vaccination (required doses received within 2 weeks of indicated age; n=90; 9·63 admissions per 100 child-years [2·41-38·49]). Between birth and age 6 months, HEU infants had an almost five times greater prevalence of LRTIs than HU infants (aPR 4·69 [2·40-9·17]), and a three-times greater prevalence of diarrhoeal illness (aPR 2·93 [1·70-5·07]). After age 6 months, these associations were ameliorated. Despite ART in pregnancy, breastfed HEU infants versus breastfed HU infants had transiently increased infectious morbidity risks in early infancy. However, differences were driven by factors potentially amenable to intervention, including delayed diagnosis and ART initiation in HIV-positive mothers, and suboptimal breastfeeding and vaccination of their infants. US National Institute of Child Health and Human Development, Elizabeth Glaser Pediatric AIDS Foundation, South African Medical Research Council, Fogarty Foundation and the Office of AIDS Research.

Early mortality after late initiation of antiretroviral therapy in the TREAT Asia HIV Observational Database (TAHOD) of the International Epidemiologic Databases to Evaluate AIDS (IeDEA) Asia-Pacific.

Early mortality among those still initiating antiretroviral therapy (ART) with advanced stages of HIV infection in resource-limited settings remains high despite recommendations for universal HIV treatment. We investigated risk factors associated with early mortality in people living with HIV (PLHIV) starting ART at low CD4 levels in the Asia-Pacific. PLHIV enrolled in the Therapeutics, Research, Education and AIDS Training in Asia (TREAT Asia) HIV Observational Database (TAHOD) who initiated ART with a CD4 count<100cells/μL between 2003 and 2018 were included in the study. Early mortality was defined as death within 1 year of ART initiation. PLHIV in follow-up for > 1 year were censored at 12months. Competing risk regression was used to analyse risk factors with loss to follow-up as a competing risk. A total of 1813 PLHIV were included in the study, of whom 74% were male. With 73 (4%) deaths, the overall first-year mortality rate was 4.27 per 100 person-years (PY). Thirty-eight deaths (52%) were AIDS-related, 10 (14%) were immune reconstituted inflammatory syndrome (IRIS)-related, 13 (18%) were non-AIDS-related and 12 (16%) had an unknown cause. Risk factors included having a body mass index (BMI)<18.5 [sub-hazard ratio (SHR) 2.91; 95% confidence interval (CI) 1.60-5.32] compared to BMI 18.5-24.9, and alanine aminotransferase (ALT)≥5 times its upper limit of normal (ULN) (SHR 6.14; 95% CI 1.62-23.20) compared to ALT<5 times its ULN. A higher CD4 count (51-100cells/μL: SHR 0.28; 95% CI 0.14-0.55; and >100cells/μL: SHR 0.12; 95% CI 0.05-0.26) was associated with reduced hazard for mortality compared to CD4 count≤25cells/μL. Fifty-two per cent of early deaths were AIDS-related. Efforts to initiate ART at CD4 counts > 50cell/μL are associated with improved short-term survival rates, even in those with late stages of HIV disease.