Early Initiation Of Antiretroviral Therapy Research Articles

Autologous neutralizing antibody responses after antiretroviral therapy in acute and early HIV-1.

Early antiretroviral therapy initiation (ARTi) in HIV-1 restricts reservoir size and diversity while preserving immune function, potentially improving opportunities for immunotherapeutic cure strategies. For antibody-based cure approaches, the development of autologous neutralizing antibodies (anAb) after acute/early ARTi is relevant, but poorly understood. We characterize antibody responses in a cohort of 23 participants following ARTi in acute HIV (<60 days after infection) and early HIV (60-128 days after infection). Plasma virus sequences at the time of ARTi revealed evidence of escape from anAbs after early, but not acute, ARTi. HIV-1 Envs representing the transmitted/founder virus(es) (acute ARTi) or escape variants (early ARTi) were tested for sensitivity to longitudinal plasma IgG. After acute ARTi, no anAb responses developed over months to years of suppressive ART. In two of the three acute ARTi participants who experienced viremia after ARTi, however, anAbs arose shortly thereafter. After early ARTi, anAbs targeting those early variants developed between 12 and 42 weeks of ART and continued to increase in breadth and potency thereafter. Results indicate a threshold of virus replication (~60 days) required to induce anAbs, after which they continue to expand on suppressive ART to better target the range of reservoir variants. NCT02656511FUNDING. National Institutes of Health grants U01AI169767; R01AI162646; UM1AI164570; UM1AI164560; U19AI096109; K23GM112526; T32AI118684, P30-AI-045008, P30 AI027763, R24 AI067039. Gilead Sciences grant INUS2361354; Viiv healthcare grant A126326.

Adaptive NK Cells Rapidly Expand during Acute HIV Infection and Persist Despite Early Initiation of Antiretroviral Therapy.

HIV is associated with NK cell dysfunction and expansion of adaptive-like NK cells that persist despite antiretroviral therapy (ART). We investigated the timing of NK cell perturbations during acute HIV infection and the impact of early ART initiation. PBMCs and plasma were obtained from people with HIV (PWH; all men who have sex with men; median age, 26.0 y) diagnosed during Fiebig stages I, II, III, or IV/V. Participants initiated ART a median of 3 d after diagnosis, and immunophenotyping was performed at diagnosis and longitudinally after ART. Anti-CMV Abs were assessed by ELISA. Samples from matched HIV-uninfected males were also analyzed. Proportions of adaptive NK cells (A-NKs; defined as Fcε-Receptor-1γ-) were expanded at HIV diagnosis at all Fiebig stages (pooled median 66% versus 25% for controls; p < 0.001) and were not altered by early ART initiation. Abs to CMV immediate early protein were elevated in PWH diagnosed in Fiebig stages III and IV/V (p < 0.03 for both). Proportions of A-NKs defined as either Fcε-Receptor-1γ- or NKG2C+/CD57+ were significantly associated with HIV DNA levels at diagnosis (p = 0.046 and 0.029, respectively) and trended toward an association after 48 wk of ART. Proportions of activated HLA-DR+/CD38+ NK cells remained elevated in PWH despite early ART initiation. NK cell activation and A-NK expansion occur very early after HIV transmission, before T cell activation, and are not altered by ART initiation during acute infection. A-NKs may contribute to HIV control and thus be useful for HIV cure.

Predictors of liver disease progression in people living with HIV-HBV co-infection on antiretroviral therapy

In people living with HIV-HBV, liver fibrosis progression can occur even with suppressive antiretroviral therapy (ART). We investigated the relationship between liver fibrosis and biomarkers of inflammation, apoptosis, and microbial translocation. In this observational cohort study adults living with HIV-HBV already on effective ART were recruited in Australia and Thailand and followed for 3 years including 6 monthly clinical review and blood tests and annual transient elastography. Differences in clinical and laboratory predictors of liver fibrosis progression were tested followed by regression analysis adjusted for CD4+ T-cells at study entry. A linear mixed model was fitted to longitudinal data to explore changes over time. 67 participants (85% male, median age 49y) were followed for 175 person-years. Median duration of ART was 10 years (interquartile range (IQR) 8-16 years). We found 11/59 (19%) participants during 3-years follow-up (6/100 person-years) met the primary endpoint of liver disease progression, defined as increased Metavir stage from baseline to final scan. In regression analysis, progressors compared to non-progressors had higher levels of high mobility group box 1 protein (HGMB1), (median (IQR) 3.7 (2.6-5.0) and 2.4ng/mL (1.5-3.4) respectively, adjusted relative risk 1.47, 95% CI [1.00, 2.17]) and lower nadir CD4+ T-cell percentage (median 4% (IQR 2-8) and 11% (4-15) respectively (relative risk 0.93, 95% CI [0.88, 0.98]). Progression in liver fibrosis occurs in people with HIV-HBV on suppressive ART. Fibrosis progression was associated with higher HMGB1 and lower percentage nadir CD4+ T-cell count, highlighting the importance of early initiation of HBV-active ART. This work was supported by NHMRC project grant 1101836; NHMRC practitioner fellowship 1138581 and NHMRC program grant 1149990. The funder had no role in study design, data collection, data analysis, interpretation, writing of this manuscript or decision to submit for publication.

Impact of antiretroviral therapy during acute or early HIV infection on virologic and immunologic outcomes: results from a multinational clinical trial.

To assess how antiretroviral therapy (ART) initiation during acute or early HIV infection (AEHI) affects the viral reservoir and host immune responses. Single-arm trial of ART initiation during AEHI at 30 sites in the Americas, Africa, and Asia. HIV DNA was measured at week 48 of ART in 5 million CD4+ T cells by sensitive qPCR assays targeting HIV gag and pol. Peripheral blood mononuclear cells were stimulated with potential HIV T cell epitope peptide pools consisting of env, gag, nef, and pol peptides and stained for expression of CD3, CD4, CD8, and intracellular cytokines/chemokines. From 2017 to 2019, 188 participants initiated ART during Fiebig stages I (n = 6), II (n = 43), III (n = 56), IV (n = 23), and V (n = 60). Median age was 27 years (interquartile range 23-38), 27 (14%) participants were female, and 180 (97%) cisgender. Among 154 virally suppressed participants at week 48, 100% had detectable HIV gag or pol DNA. Participants treated during Fiebig I had the lowest HIV DNA levels (P < 0.001). Week 48 HIV DNA mostly did not correlate with concurrent CD4+ or CD8+ T cell HIV-specific immune responses (rho range -0.11 to +0.19, all P > 0.025). At week 48, the magnitude, but not polyfunctionality, of HIV-specific T cell responses was moderately reduced among participants who initiated ART earliest. Earlier ART initiation during AEHI reduced but did not eliminate the persistence of HIV-infected cells in blood. These findings explain the rapid viral rebound observed after ART cessation in early-treated individuals with undetectable HIV DNA by less sensitive methods.

Diagnostic tests of HIV infection and AIDS

Background: Human immunodeficiency virus (HIV) infection presents a major global health challenge. According to the World Health Organization, approximately 39.0 million people have HIV, as of 2022, with 1.3 million new infections annually. In Korea, the first HIV cases were reported in 1985, and the number of cases has increased continuously since 1988. In 2022, 1,066 cases were newly diagnosed, increasing the total number of cases to approximately 15,880.Current Concepts: Diagnostics play a crucial role in the management of HIV, for early diagnosis and initiation of antiretroviral therapy. Approval of the first HIV antibody test in 1985 by the US Food and Drug Administration marked a notable advance in the ability to diagnose HIV infection. The screening test for HIV infection typically consists of a two-step approach, in which a fourth-generation combination HIV-1/2 immunoassay is followed by a confirmatory Western blot. Despite its high accuracy for chronic infections, the window period and the early-stage of HIV infections are problematic, and populations with low HIV prevalence show a low positive predictive value. A false positive result can occur from blood transfusions, vaccinations, and autoantibodies. Novel diagnostic tools, such as nucleic acid testing for viral RNA/DNA and antigen testing for p24 antigen have reduced the window period, allowing for earlier detection and differentiation between HIV-1 and HIV-2. Pointof-care tests are beneficial in resource-limited settings although their lower sensitivity and specificity require additional confirmatory follow-up testing.Discussion and Conclusion: In this review, we provide a historical perspective on the evolution of HIV diagnostics (serological and molecular) and describe the roles of conventional and point-of-care testing within the laboratory diagnostic network.

Early Initiation of Antiretroviral Therapy is Protective Against Seizures in Children With HIV in Zambia: A Prospective Case-Control Study.

Seizures are relatively common among children with HIV in low- and middle-income countries and are associated with significant morbidity and mortality. Early treatment with antiretroviral therapy (ART) may reduce this risk by decreasing rates of central nervous system infections and HIV encephalopathy. We conducted a prospective, unmatched case-control study. We enrolled children with new-onset seizure from University Teaching Hospital in Lusaka, Zambia and 2 regional hospitals in rural Zambia. Controls were children with HIV and no history of seizures. Recruitment took place from 2016 to 2019. Early treatment was defined as initiation of ART before 12 months of age, at a CD4 percentage >15% in children aged 12-60 months or a CD4 count >350 cells/mm 3 for children aged 60 months or older. Logistic regression models were used to evaluate the association between potential risk factors and seizures. We identified 73 children with new-onset seizure and compared them with 254 control children with HIV but no seizures. Early treatment with ART was associated with a significant reduction in the odds of seizures [odds ratio (OR) 0.04, 95% confidence interval: 0.02 to 0.09; P < 0.001]. Having an undetectable viral load at the time of enrollment was strongly protective against seizures (OR 0.03, P < 0.001), whereas history of World Health Organization Stage 4 disease (OR 2.2, P = 0.05) or CD4 count <200 cells/mm 3 (OR 3.6, P < 0.001) increased risk of seizures. Early initiation of ART and successful viral suppression would likely reduce much of the excess seizure burden in children with HIV.

Early antiretroviral therapy and its impact on natural killer cell dynamics in HIV-1 infected men who have sex with men: a cross-sectional pilot study evaluating the impact of early ART initiation on NK cell perturbation in HIV infection.

Phenotypic changes and functional impairment of natural killer (NK) cells occur early in HIV-1 infection. Antiretroviral therapy (ART) effectively restores CD4+ T cell counts and suppresses HIV-1 to undetectable levels. The role and efficacy of immediate ART initiation in mitigating NK cell aberrations remain to be elucidated comprehensively. This study hypothesized that HIV-1 infection negatively influences NK cell evolution and that early ART initiation restores these perturbations. Blood samples were collected longitudinally from five acutely HIV-1 infected men who have sex with men in Nairobi, Kenya. Participants were immediately initiated on ART after HIV-1 diagnosis. Blood samples were drawn pre-infection and at sequential bi-weekly post-infection time points. Peripheral blood mononuclear cells were stained with panel NK cells surface markers to assess HIV-induced phenotypic changes by flow cytometry. Some cells were also stimulated overnight with K562 cell line, IL-2, and IL-15 and stained for flow cytometry functionality. HIV-1 infection was associated with significant reductions in the production of IFN-γ (P = 0.0264), expression of CD69 (P = 0.0110), and expression of NK cell inhibitory receptor Siglec7 (P = 0.0418). We observed an increased NK cell degranulation (P = 0.0100) and an upregulated expression of cell exhaustion marker PD-1 (P = 0.0513) at post-infection time points. These changes mainly were restored upon immediate initiation of ART, except for Siglec7 expression, whose reduced expression persisted despite ART. Some HIV-associated changes in NK cells may persist despite the immediate initiation of ART in acute HIV-1 infections. Our findings suggest that understanding NK cell dynamics and their restoration after ART can offer insights into optimizing HIV-1 treatment and potentially slowing disease progression.IMPORTANCENatural killer (NK) cells play a crucial role in controlling of HIV-1 replication and progression to disease. Perturbations of their functionality may therefore result in deleterious disease outcomes. Previous studies have demonstrated reduced NK cell functionality in chronic HIV-1 infection that positively correlated to HIV-1 viral load. This may suggest that control of HIV-1 viremia in acute HIV-1 infection may aid in enhancing NK cell response boosting the inate immunity hence effective control of viral spread and establishment of viral reservoir. Antiretroviral therapy (ART) effectively supresses HIV-1 viremia to undectable levels and restores CD4+ T cell counts. Our study highlights the significant role of early ART initiation in mitigating NK cell disruptions caused by acute HIV-1 infection. Our results suggest that early initiation of ART could have benefits beyond suppressing viral load and restoring CD4+ T cell counts. In addition, it could boost the innate immunity necessary to control disease progression.

Immunological Challenges in Infants Living with HIV: A Review

This paper explores the intricate immunological challenges encountered by infants living with Human Immunodeficiency Virus (HIV). The vulnerability of the developing immune system in early life, coupled with the unique characteristics of HIV, presents a complex scenario that impacts the health and well-being of these infants. Key areas of focus include the disruption of immune system development, viral persistence mechanisms, consequences of chronic immune activation, and the increased susceptibility to opportunistic infections. The paper also discusses current therapeutic interventions, emphasizing the significance of early antiretroviral therapy (ART) initiation and emerging strategies aimed at improving immunological outcomes. Insights into the maternal-fetal interface and preventive measures are explored, providing a holistic perspective on addressing the challenges faced by infants born with HIV. This comprehensive analysis aims to contribute to a deeper understanding of the immunological landscape in this vulnerable population and guide future research and interventions for enhanced patient care.

The changing landscape of HIV-associated kidney disease.

The HIV epidemic has devastated millions of people globally, with approximately 40 million deaths since its start. The availability of antiretroviral therapy (ART) has transformed the prognosis of millions of individuals infected with HIV such that a diagnosis of HIV infection no longer automatically confers death. However, morbidity and mortality remain substantial among people living with HIV. HIV can directly infect the kidney to cause HIV-associated nephropathy (HIVAN) - a disease characterized by podocyte and tubular damage and associated with an increased risk of kidney failure. The reports of HIVAN occurring primarily in those of African ancestry led to the discovery of its association with APOL1 risk alleles. The advent of ART has led to a substantial decrease in the prevalence of HIVAN; however, reports have emerged of an increase in the prevalence of other kidney pathology, such as focal segmental glomerulosclerosis and pathological conditions associated with co-morbidities of ageing, such as hypertension and diabetes mellitus. Early initiation of ART also results in a longer cumulative exposure to medications, increasing the likelihood of nephrotoxicity. A substantial body of literature supports the use of kidney transplantation in people living with HIV, demonstrating significant survival benefits compared with that of people undergoingchronic dialysis, and similar long-term allograft and patient survival compared with that of HIV-negative kidney transplant recipients.

Characterization of HIV-1 Reservoirs in Children and Adolescents: A Systematic Review and Meta-Analysis Toward Pediatric HIV Cure

ObjectiveTo conduct a comprehensive, systematic review of the profile of HIV-1 reservoirs in children and adolescents with perinatally-acquired HIV infection. Study designRandomized and non-randomized trials, cohort studies, and cross-sectional studies on HIV reservoirs in pediatric populations, published between 2002 and 2022, were included. Archived-drug resistance mutations (ADRM) and the size of reservoirs were evaluated. Subgroup analyses were performed to characterize further the data, and the meta-analysis was done through random effect models. ResultsOverall, 49 studies from 17 countries worldwide were included, encompassing 2356 perinatally infected participants (48.83% females). There are limited data on the quantitative characterization of viral reservoirs in sub-Saharan Africa (SSA), with sensitive methodologies such as ddPCR rarely employed. The overall prevalence of ADRMs was 37.80% [95%CI: 13.89–65.17], with 48.79% [95%CI: 0–100] in Africa, 42.08% [6.68-82.71] in America, 23.88% [95%CI: 14.34–34.90] in Asia, and 20.00% [95%CI: 10.72–31.17] in Europe, without any difference between infants and adolescents (p=0.656). Starting antiretroviral therapy (ART) before 2 months of age limited the levels of HIV-1 DNA (p=0.054). Participants with long suppressed viremia (>5 years) had lower levels of HIV-1 DNA (p=0.027). Ppre- and post-ART CD4 ≤29% and pre-ART viremia ≥5Log were all found associated with higher levels of HIV-1 DNA (p=0.038, p=0.047 and p=0.041, respectively). ConclusionThe pooled prevalence of ADRMs is high in perinatally infected pediatric population, with larger proviral reservoir size driven by delayed ART initiation, a shorter period of viral suppression, and immuno-virological failures. Thus, strategies for pediatric HIV functional cure should target children and adolescents with very early ART initiation, immunocompetence, and long-term viral suppression.

Optimal Timing of Antiretroviral Therapy Initiation in Acquired Immunodeficiency Syndrome–Associated Toxoplasmic Encephalitis: A Prospective Observational Multicenter Study in China

Abstract Background Toxoplasmic encephalitis (TE) is the most frequent cause of expansive brain lesions among patients with acquired immunodeficiency syndrome (AIDS). However, the optimal timing of antiretroviral therapy (ART) initiation in these patients remains controversial. This study aims to investigate the differences in outcomes of ART initiation at different times, in order to help clarify the treatment timing of AIDS-associated TE. Methods This multicenter prospective observational study included 87 patients recruited from 11 research centers in China (from March 2019 to December 2022). Of the patients, 38 were assigned to the early ART group (initiating ART within 2 weeks after anti-Toxoplasma treatment initiation), and the remaining 49 patients received deferred ART (initiating ART at least 2 weeks after anti-Toxoplasma treatment initiation). The main outcomes included mortality and emergence of immune reconstitution inflammatory syndrome (IRIS). Human immunodeficiency virus (HIV)-1 viral load and CD4+ T-cell counts at weeks 24 and 48 were observed. Results The number of deaths (1 vs. 5, P = 0.225) and incidence of IRIS (2.6% vs. 0, P = 0.437) were not significantly different between the early and deferred ART groups at week 48. Early ART initiation did not contribute significantly to HIV-1 viral load control (&lt;50 copies/mL, n = 8 vs. n = 3 at week 24, P = 0.142; n = 7 vs. n = 7 at week 48, P = 1.000). The median CD4+ T-cell counts between the two groups were not significantly different, either at week 24 (155 vs. 91 cells/mm3, P = 0.837) or at week 48 (181 vs. 146 cells/mm3, P = 0.219). Conclusion In patients with AIDS-associated TE, early ART initiation was not significantly different from deferred ART initiation in terms of incidence of mortality, IRIS, and HIV virological and immunological outcomes. Trial registration: This study was registered (registration number: ChiCTR1900021195) as one of 12 clinical trials under the title of a general project at the Chinese Clinical Trial Registry (chictr.gov) on February 1, 2019. Enrollment for this study began in March 2019.

An exploratory qualitative study of the psychological effects of HIV diagnosis; the need for early involvement of mental health professionals to improve linkage to care

BackgroundDiagnosing a life-threatening disease like the human immunodeficiency virus (HIV) can be unbearable to the individual, which has implications for their subsequent care-seeking decision-making. However, an essential element of HIV testing is identifying infected individuals and linking them with adequate care services, thus contributing to the UNAIDS 95-95-95 targets. The attainment of these targets has been particularly challenging for lower and middle-income countries (LMIC). This study explored the psychological reactions to a positive HIV status in a hospital treatment centre to provide insight into mental health interventions’ role in improving HIV screening and early antiretroviral therapy (ART) initiation to enhance the quality of life.MethodsAn exploratory qualitative study was investigated among adults who were diagnosed as HIV positive. Participants were purposively recruited from an HIV Treatment Centre. Data were collected with semi-structured interviews that explored the interpretations and psychological reactions to their positive HIV status. Overall, 18 participants were interviewed to reach saturation. Data were transcribed verbatim and analysed thematically to produce findings that address the study’s objective.ResultsFollowing analysis of participants’ interpretations, understanding and implications of their HIV-positive diagnosis, two major themes emerged: (1) anxiety regarding the impact of the disease on self, family and society was overwhelming. Participants were anxious because of the stigma, fear, worry, shock, and shame they faced. (2) Participants expressed hopelessness and could not see meaning or purpose in life. Suicidal ideation, suicide plans and self-harm characterised hopelessness.ConclusionsThe initial reaction to the diagnosis of HIV in this LMIC context has the potential to impact linkage to care negatively and, thus, the attainment of the global 95-95-95 targets. It is, therefore, essential that mental health and psychological support services are integrated with testing services to manage the initial reactions and support individuals to improve early linkage to care and thus improve overall outcomes for the infected individual and society.

Chronic kidney disease and its predictors among highly active antiretroviral therapy naïve and experienced HIV-infected individuals at the selected hospitals, Southwest Ethiopia: a comparative cross-sectional study

ObjectiveThis study aimed to determine the prevalence of chronic kidney disease (CKD) and its predictors among highly active antiretroviral therapy (HAART) naïve and experienced HIV-infected individuals.Method and analysisHospital-based comparative cross-sectional...

1583. Optimal timing of antiretroviral therapy initiation in AIDS-associated Toxoplasma encephalitis: a prospective observational multicenter study in China

Abstract Background Toxoplasma encephalitis (TE) is the most frequent cause of expansive brain lesions among acquired immunodeficiency syndrome (AIDS) patients; however, the optimal timing of antiretroviral therapy (ART) initiation in these patients remains controversial. Methods This was a multicenter prospective observational study, and eligible patients were recruited from eleven treatment centers in China. Results In total, 87 patients were included, and 38 of them were assigned to the Early ART group (initiating ART within 2 weeks after anti-Toxoplasma treatment initiation), while the remaining 49 patients were allocated to receive deferred ART (initiating ART at least 2 weeks after anti-Toxoplasma treatment initiation). Our results indicated that the incidence of immune reconstitution inflammatory syndrome (IRIS) (2.6% vs. 0, p=0.437) and the number of death events (1 vs. 5, p=0.225) were not significantly different between the two groups at Week 48. The timing of ART initiation was also found to not significantly contribute to human immunodeficiency virus (HIV) viral load control. The difference in the number of patients who maintained an undetectable HIV viral load of &amp;lt;50 copies/mL in each of the two groups of patients was calculated to not be statistically significant at Week 24 (8 vs. 3, p=0.142) and Week 48 (7 vs. 7, p=1.000). Meanwhile, median CD4+ T-cell counts were also observed not to reach statistical significance between the two groups, both at Week 24 (155 vs. 91, p=0.837) and Week 48 (181 vs. 96, p=0.219). Conclusion In our study, early ART initiation was observed to not confer statistically significant differences in the incidence of IRIS, mortality, and HIV virological and immunological outcomes, when compared to deferred ART initiation. Disclosures All Authors: No reported disclosures

Viral Load Pattern of HIV Positive Children and Adolescents Attending a Paediatric Infectious Diseases Clinic in Owerri, Nigeria

Background: The Viral load (VL) test measures the number of copies of HIV RNA in one milliliter of blood and is the preferred antiretroviral therapy (ART) monitoring strategy. Viral suppression is defined as patients having ≤ 1000 copies of viral RNA/ml of blood.&#x0D; Methods/Materials: This study involved the retrospective review of viral load test result of patients aged 2-19years living with HIV/AIDS and enrolled in the treatment programme of the Paediatric infectious diseases clinic of the Federal University Teaching hospital Owerri.&#x0D; Results: 117 patients met the inclusion criteria and 103 were virally suppressed giving a suppression rate of 88%. Majority of those virally suppressed were in the 15-19 age group. A logistic regression analysis to ascertain the impact of age, gender, drug regimen, and duration on ARTs on the likelihood of viral suppression showed that age, gender, and drug regimen were not significant predictors of viral suppression (p &gt; 0.05). However, duration on ARTs was a significant predictor (p &lt; 0.01), with patients who had been on ARTs for greater than 24 months having higher odds of viral suppression (OR = 5.42, 95% CI = 1.84-15.93) compared to those who had been on ARTs for 0-6 months.&#x0D; Conclusion: Our study provides important insights into the viral load pattern of children and adolescents living with HIV/AIDS in Owerri. It highlights the importance of early initiation of ART, adherence to ART regimen, and routine viral load monitoring to achieve and maintain viral suppression.

Prevalence of delayed antiretroviral therapy initiation among people living with HIV: A systematic review and meta-analysis.

HIV continues to be a global challenge. Key recommendations for HIV prevention and treatment are presented on rapid antiretroviral therapy (ART) initiation. However, several studies showed a high prevalence of delayed ART initiation. The aim of this systematic review and meta-analysis was to assess the prevalence of delayed ART initiation among HIV-infected patients globally. This review summarised eligible studies conducted between January 2015 and August 2022 on the prevalence of delayed ART initiation in HIV-infected adults (age ≥ 15). Relevant studies were systematic searched through PubMed/Medline, EMBASE, Web of Science, China National Knowledge Infrastructure, Wanfang, and Chongqing VIP databases. Random-effects models were used to calculate pooled prevalence estimates. The heterogeneity was evaluated using Cochran's Q test and I2 statistics. Moreover, potential sources of heterogeneity were explored using univariate subgroup analysis. Data on the prevalence of delayed ART initiation was pooled across 29 studies involving 34,937 participants from 15 countries. The overall pooled prevalence of delayed ART initiation was 36.1% [95% confidence interval (CI), 29.7-42.5%]. In subgroup analysis, the estimated pooled prevalence decreased with age. By sex, the prevalence was higher among male patients (39.3%, 95% CI: 32.2-46.4%) than female (36.5%, 95% CI: 26.9-50.7%). Patients with high CD4 cell count were more likely to delay ART initiation than those with low CD4 cell count (>500cells/mm3: 40.3%; 201-500cells/mm3: 33.4%; and ≤200cells/mm3: 25.3%). Our systematic review and meta-analysis identified a high prevalence of delayed ART initiation. The prolonged time interval between diagnosis and treatment is a prevalent and unaddressed problem that should spur initiatives from countries globally. Further research is urgently needed to identify effective strategies for promoting the early ART initiation.

Increasing trends of overweight and obesity in treatment-naive people living with HIV in Shenzhen from 2014 to 2020: an emerging health concern.

With the early initiation of antiretroviral therapy (ART) in China, the demographics of treatment-naïve people living with HIV (PLWH) are moving closer to those of the general population, which is characterized by a gradual increase in metabolic indicators. However, the epidemic trends of overweight and obesity over the past decade in treatment-naïve PLWH ready to initiate ART have not yet been investigated. A cross-sectional study was conducted, including 12,135 consecutive treatment-naïve PLWH ready to initiate ART in Shenzhen, using data retrieved from the China National Free Antiretroviral Treatment Program database from 2014 to 2020. The chi-square test was used to examine the trends of overweight and obesity between age groups, and multivariate logistic regression was used to identify the association of overweight and obesity with hyperglycemia and dyslipidemia. During the 7-year study period, 12,135 treatment-naïve PLWH ready to initiate ART were included, among whom 1,837 (15.1%) were overweight and 388 (3.2%) were obese. The prevalence of overweight rose from 11.4 to 17.3% (Z = -4.58, P for trend <0.01) and that of obesity from 2.0% to 4.2% (Z = -6.45, P for trend <0.01) from 2014 to 2020. The annual prevalence of overweight was the highest in the age group of participants >35 years compared to prevalence in other age groups during the period 2014-2020. Compared with those who were not overweight or obese, PLWH who were overweight or obese were more likely to have hyperglycemia (aOR 1.84, 95% CI: 1.37-2.49 for overweight; aOR 2.68, 95% CI: 1.62-4.44 for obesity), higher ALT level (aOR 2.70, 95% CI: 2.33-3.13 for overweight; aOR 3.85, 95% CI: 2.93-5.05 for obesity), higher TG levels (aOR 1.89, 95% CI 1.63-2.19 for overweight; aOR 2.56, 95% CI 1.97-3.32 for obesity), and lower HDL levels (aOR 1.67, 95% CI 1.44-1.95 for overweight; aOR 2.06, 95% CI 1.54-2.77 for obesity). The prevalence of overweight and obesity in treatment-naive PLWH increased steadily from 2014 to 2020 in Shenzhen. Overweight and obese in treatment-naive PLWH ready to initiate ART were associated with dyslipidemia and hyperglycemia. Public health authorities should take proactive steps to address these issues by implementing targeted screening, intervention programs including lifestyle modifications, and integrated healthcare services.

Early Initiation of Antiretroviral Therapy Preserves the Metabolic Function of CD4+ T Cells in Subtype C Human Immunodeficiency Virus 1 Infection.

Immune dysfunction often persists in people living with human immunodeficiency virus (HIV) who are on antiretroviral therapy (ART), clinically manifesting as HIV-1-associated comorbid conditions. Early ART initiation may reduce incidence of HIV-1-associated immune dysfunction and comorbid conditions. Immunometabolism is a critical determinant of functional immunity. We investigated the effect of HIV-1 infection and timing of ART initiation on CD4+ T cell metabolism and function. Longitudinal blood samples from people living with HIV who initiated ART during hyperacute HIV-1 infection (HHI; before peak viremia) or chronic HIV-1 infection (CHI) were assessed for the metabolic and immune functions of CD4+ T cells. Metabolite uptake and mitochondrial mass were measured using fluorescent analogues and MitoTracker Green accumulation, respectively, and were correlated with CD4+ T cell effector functions. Initiation of ART during HHI prevented dysregulation of glucose uptake by CD4+ T cells, but glucose uptake was reduced before and after ART initiation in CHI. Glucose uptake positively correlated with interleukin-2 and tumor necrosis factor-α production by CD4+ T cells. CHI was associated with elevated mitochondrial mass in effector memory CD4+ T cells that persisted after ART and correlated with PD-1 expression. ART initiation in HHI largely prevented metabolic impairment of CD4+ T cells. ART initiation in CHI was associated with persistently dysregulated immunometabolism of CD4+ T cells, which was associated with impaired cellular functions and exhaustion.

Assessing the Impact of Universal Test and Treat Implementation Strategy on Retention to Antiretroviral Therapy in HIV Care: A Retrospective Cohort Review

Namibia has an adult HIV prevalence of 12.6% according to the Namibia population-based HIV impact assessment survey of 2017 making it one of the highest in the world. Early initiation of antiretroviral therapy (ART) has excellent outcomes for both morbidity and mortality. The National Strategic Framework for HIV and the Namibia Ministry of Health and Social Services (MoHSS) rolled out the WHO 2015 UTTS guidelines making Namibia one of the first African countries to implement UTTS. With UTTS guidelines, rolled out in October 2016, clients who test HIV positive are initiated on ART immediately preferably the same day or within seven days regardless of their HIV clinical stage or CD4 count. Retention in care is required for optimal clinical outcomes in patients with HIV infection. However, after two years of adopting the strategy, it is not well understood whether UTTS affects the retention to care. We therefore sought to establish any emerging differences in retention of ART care after the implementation of UTTS. We used a retrospective cohort review study design that employed both quantitative and qualitative methods. 879 client records were reviewed, 678 clients were initiated on treatment two years prior to the UTTS and 201 were initiated after January 2017 when the UTTS was fully rolled out and had been on treatment for at least 12 months. Data analysis was done using Excel and Statistical Package for Social Sciences (SPSS) version 23.0 software. The overall retention after 12 months of follow-up was (822/879) 93.5% (95% CI: 91.3% to 95.7%). The retention rate at 12 months among clients in the UTTS cohort was 95.5% (95% CI: 93.5% to 97.5%) and somewhat higher than that in the pre-UTTS cohort 92.9% (95% CI: 90.6% to 95.2%). At the end of the review period, attrition was higher in the pre-UTTS cohort 251/678 (37.0%; 95% CI 34.8 to 39.2) versus 42/201 (21.0%; 95% CI 19.0 to 23) during UTTS. Retention on ART was nearly 5% higher after UTTS implementation but young adults and men between 31 and 40 years of age had higher chances of attrition at the time of ART initiation. We recommend that all facilities in Namibia and other parts of sub-Saharan Africa should embrace the UTTS strategy to benefit their clients. Keywords: Antiretroviral therapy, Retention, Retrospective cohort review, Universal test &amp; treat.

Experiences of stigma and HIV care engagement in the context of Treat All in Rwanda: a qualitative study

Background‘Treat All’ policies recommending immediate antiretroviral therapy (ART) soon after HIV diagnosis for all people living with HIV (PLHIV) are now ubiquitous in sub-Saharan Africa. While early ART initiation and retention is effective at curtailing disease progression and transmission, evidence suggests that stigma may act as a barrier to engagement in care. This study sought to understand the relationships between HIV stigma and engagement in care for PLHIV in Rwanda in the context of Treat All.MethodsBetween September 2018 and March 2019, we conducted semi-structured, qualitative interviews with adult PLHIV receiving care at two health centers in Kigali, Rwanda. We used a grounded theory approach to data analysis to develop conceptual framework describing how stigma influences HIV care engagement in the context of early Treat All policy implementation in Rwanda.ResultsAmong 37 participants, 27 (73%) were women and the median age was 31 years. Participants described how care engagement under Treat All, including taking medications and attending appointments, increased their visibility as PLHIV. This served to normalize HIV and use of ART but also led to high levels of anticipated stigma in the health center and community at early stages of treatment. Enacted stigma from family and community members and resultant internalized stigma acted as additional barriers to care engagement. Nonetheless, participants described how psychosocial support from care providers and family members helped them cope with stigma and promoted continued engagement in care.ConclusionsTreat All policy in Rwanda has heightened the visibility of HIV at the individual and social levels, which has influenced HIV stigma, normalization, psychosocial support and care engagement in complex ways. Leveraging the individual and community support described by PLHIV to deliver evidence-based, peer or provider-delivered stigma reduction interventions may aid in attaining Treat All goals.