Antiretroviral Therapy Initiation Research Articles

Rapid initiation of antiretroviral therapy in Turkey: a modeling study.

To effectively control the HIV epidemic and meet global targets, policymakers recommend the rapid initiation of antiretroviral therapy (ART). Our study aims to investigate the effect of rapid ART programs on individuals diagnosed with HIV, considering varying coverage and initiation days after diagnosis, and compare it to standard-of-care ART treatment in Turkey. We used a dynamic compartmental model to simulate the dynamics of HIV infection in Turkey. Rapid treatment, defined as initiation of ART within 7 days of diagnosis, was contrasted with standard-of-care treatment, which starts within 30 days of diagnosis. This study considered three coverage levels (10%, 50%, and 90%) and two rapid periods (7 and 14 days after diagnosis), comparing them to standard-of-care treatment in evaluating the number of HIV infections between 2020 and 2030. Annual HIV incidence and prevalence for a 10-year period were obtained from model projections. In the absence of a rapid ART program, the model projected approximately 444,000 new HIV cases while the number of cases were reduced to 345,000 (22% reduction) with 90% of diagnosed cases included in the rapid ART program. Similarly, 10% and 50% rapid ART coverage has resulted in 3% and 13% reduction in HIV prevalence over a 10-year period. Rapid ART demonstrates the potential to mitigate the increasing HIV incidence in Turkey by reducing the number of infections. The benefit of the rapid ART program could be substantial when the coverage of the program reaches above a certain percentage of diagnosed population.

Bispecific antibodies promote natural killer cell-mediated elimination of HIV-1 reservoir cells

The persistence of CD4+ T cells carrying latent human immunodeficiency virus-1 (HIV-1) proviruses is the main barrier to a cure. New therapeutics to enhance HIV-1-specific immune responses and clear infected cells will probably be necessary to achieve reduction of the latent reservoir. In the present study, we report two single-chain diabodies (scDbs) that target the HIV-1 envelope protein (Env) and the human type III Fcγ receptor (CD16). We show that the scDbs promoted robust and HIV-1-specific natural killer (NK) cell activation and NK cell-mediated lysis of infected cells. Cocultures of CD4+ T cells from people with HIV-1 on antiretroviral therapy (ART) with autologous NK cells and the scDbs resulted in marked elimination of reservoir cells that was dependent on latency reversal. Treatment of human interleukin-15 transgenic NSG mice with one of the scDbs after ART initiation enhanced NK cell activity and reduced reservoir size. Thus, HIV-1-specific scDbs merit further evaluation as potential therapeutics for clearance of the latent reservoir.

Assessing index CD4 and associated outcomes at 1-year in a tertiary HIV clinic, KwaZulu-Natal.

Human immunodeficiency virus (HIV) management guidelines have evolved from initiating therapy at CD4 counts of ≤ 200 cells/m3to implementing universal test and treat (UTT). This study aimed to assess whether in clinical practice, patients are presenting with higher baseline CD4 counts, describe the incidence of opportunistic infections and the proportion that achieved viral suppression. A retrospective cohort design with convenience sampling was conducted. Cohort 1 included patients initiated on antiretroviral therapy (ART) between 01 January 2014 and 31 December 2014, when criteria were set at CD4 count ≤ 350 cells/mm3. Cohort 2 included patients initiated on ART between 01 January 2019 and 31 December 2019, during the UTT era. At ART initiation, the median CD4 cell was 170 cells/mm3(interquartile range [IQR]: 85.5-287) in Cohort 1 cells/mm3and 243 cells/mm3(IQR: 120-411) in Cohort 2. Tuberculosis was the predominant OI in the group with CD4 cell count ≤ 200 cells/m3in both Cohort 1 (26.8%) and Cohort 2 (27.9%),p= 0.039. At 1 year, virological suppression was achieved in only 77.7% and 84.7% of Cohorts 1 and 2 patients. A notable portion of patients at King Edward VIII Hospital's HIV clinic commenced ART with CD4 counts significantly below the recommended guideline thresholds.Contribution:The research revealed a delay in initiating ART. A comprehensive reevaluation is essential to pinpoint the factors contributing to this delay and to devise customised interventions.

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.

Counseling Supporting HIV Self-Testing and Linkage to Care Among Men Who Have Sex With Men: Systematic Review and Meta-Analysis.

Counseling supporting HIV self-testing (HIVST) is helpful in facilitating linkage to care and promoting behavior changes among men who have sex with men (MSM). Different levels of counseling support for MSM HIVST users may lead to variance in the linkage to care. This study aims to synthesize evidence on counseling supporting MSM HIVST users and to conduct a meta-analysis to quantify the proportion of MSM HIVST users who were linked to care. A systematic search was conducted using predefined eligibility criteria and relevant keywords to retrieve studies from the MEDLINE, Global Health, Web of Science, Embase, APA PsycINFO, and Scopus databases. This search encompassed papers and preprints published between July 3, 2012, and June 30, 2022. Studies were eligible if they reported counseling supporting HIVST or quantitative outcomes for linkage to care among MSM and were published in English. The screening process and data extraction followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The quality of the included studies was assessed by the National Institutes of Health quality assessment tool. Data were extracted using random effects models to combine the proportion of HIVST users who were linked to care. Subgroup analyses and metaregression were conducted to assess whether linkage to care varied according to study characteristics. All analyses were performed with R (version 4.2.1; R Foundation for Statistical Computing) using the metafor package. A total of 55 studies published between 2014 and 2021, including 43 observational studies and 12 randomized controlled trials, were identified. Among these studies, 50 (91%) provided active counseling support and 5 (9%) provided passive counseling support. In studies providing active counseling support, most MSM HIVST users were linked to various forms of care, including reporting test results (97.2%, 95% CI 74.3%-99.8%), laboratory confirmation (92.6%, 95% CI 86.1%-96.2%), antiretroviral therapy initiation (90.8%, 95% CI 86.7%-93.7%), and referral to physicians (96.3%, 95% CI 85%-99.2%). In studies providing passive counseling support, fewer MSM HIVST users were linked to laboratory confirmation (78.7%, 95% CI 17.8%-98.4%), antiretroviral therapy initiation (79.1%, 95% CI 48.8%-93.7%), and referral to physicians (79.1%, 95% CI 0%-100%). Multivariate metaregression indicated that a higher number of essential counseling components, a smaller sample size (<300), and the use of mobile health technology to deliver counseling support were associated with better linkage to care. The quality of the studies varied from fair to good with a low to high risk of bias. Proactively providing counseling support for all users, involving a higher number of essential components in the counseling support, and using mobile health technology could increase the linkage to care among MSM HIVST users. PROSPERO CRD42022346247; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=346247.

The Cascade of Care for Early Infant Diagnosis in Zimbabwe: Point of Care HIV Testing at Birth and 6-8 Weeks.

Routine birth testing of HIV-exposed infants (HEI) using point of care (POC) nucleic acid testing may allow for earlier diagnosis and treatment of infants living with HIV, but more data are needed on retention in care for those diagnosed at birth and re-testing for those with a negative HIV birth test. POC birth testing (within 48 hours of birth) was offered to all HEI born at 10 public maternities in Zimbabwe from November 2018 to July 2019. Data were abstracted from routine registers, including information on re-testing at 6-8 weeks for infants testing HIV-negative at birth and 6-month retention in care among infants diagnosed with HIV at birth. Of 2854 eligible HEIs, 2806 (98.3%) received POC HIV birth testing. Thirty-nine infants with HIV were identified (1.4%), and 23 (59%) were started on antiretroviral therapy (ART). Twenty infants (51%) remained on ART at 6 months. Of the 2694 infants who tested negative at birth, 1229 (46.5%) had a documented retest at 6-8 weeks. 7 (0.6%) of those infants tested HIV-positive. The uptake of POC birth testing was high in study facilities, but low rates of ART initiation after a positive birth test, despite high retention on ART through 6 months, diminish the impact of POC birth testing and must be addressed. Among infants who tested negative at birth, rates of testing at 6-8 weeks of life (46%) were slightly lower than national rates of testing at the same age without a birth test (56%) during the study period. Improving infant HIV testing rates at 6-8 weeks, regardless of birth testing, should be a priority.

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.

The changes in health service utilisation in Malawi during the COVID-19 pandemic.

The COVID-19 pandemic and the restriction policies implemented by the Government of Malawi may have disrupted routine health service utilisation. We aimed to find evidence for such disruptions and quantify any changes by service type and level of health care. We extracted nationwide routine health service usage data for 2015-2021 from the electronic health information management systems in Malawi. Two datasets were prepared: unadjusted and adjusted; for the latter, unreported monthly data entries for a facility were filled in through systematic rules based on reported mean values of that facility or facility type and considering both reporting rates and comparability with published data. Using statistical descriptive methods, we first described the patterns of service utilisation in pre-pandemic years (2015-2019). We then tested for evidence of departures from this routine pattern, i.e., service volume delivered being below recent average by more than two standard deviations was viewed as a substantial reduction, and calculated the cumulative net differences of service volume during the pandemic period (2020-2021), in aggregate and within each specific facility. Evidence of disruptions were found: from April 2020 to December 2021, services delivered of several types were reduced across primary and secondary levels of care-including inpatient care (-20.03% less total interactions in that period compared to the recent average), immunisation (-17.61%), malnutrition treatment (-34.5%), accidents and emergency services (-16.03%), HIV (human immunodeficiency viruses) tests (-27.34%), antiretroviral therapy (ART) initiations for adults (-33.52%), and ART treatment for paediatrics (-41.32%). Reductions of service volume were greatest in the first wave of the pandemic during April-August 2020, and whereas some service types rebounded quickly (e.g., outpatient visits from -17.7% to +3.23%), many others persisted at lower level through 2021 (e.g., under-five malnutrition treatment from -15.24% to -42.23%). The total reduced service volume between April 2020 and December 2021 was 8 066 956 (-10.23%), equating to 444 units per 1000 persons. We have found substantial evidence for reductions in health service delivered in Malawi during the COVID-19 pandemic which may have potential health consequences, the effect of which should inform how decisions are taken in the future to maximise the resilience of healthcare system during similar events.

Rapid Initiation of Antiretroviral Therapy With Coformulated Bictegravir, Emtricitabine, and Tenofovir Alafenamide Versus Efavirenz, Lamivudine, and Tenofovir Disoproxil Fumarate in HIV-Positive Men Who Have Sex With Men in China: Week 48 Results of the Multicenter, Randomized Clinical Trial.

Most international treatment guidelines recommend rapid initiation of antiretroviral therapy (ART) for people newly diagnosed with human immunodeficiency virus (HIV)-1 infection, but experiences with rapid ART initiation remain limited in China. We aimed to evaluate the efficacy and safety of efavirenz (400 mg) plus lamivudine and tenofovir disoproxil fumarate (EFV + 3TC + TDF) versus coformulated bictegravir, emtricitabine, and tenofovir alafenamide (BIC/FTC/TAF) in rapid ART initiation among men who have sex with men (MSM) who have been diagnosed with HIV. This multicenter, open-label, randomized clinical trial enrolled MSM aged ≥18 years to start ART within 14 days of confirmed HIV diagnosis. The participants were randomly assigned in a 1:1 ratio to receive EFV (400 mg) + 3TC + TDF or BIC/FTC/TAF. The primary end point was viral suppression (<50 copies/mL) at 48 weeks per US Food and Drug Administration Snapshot analysis. Between March 2021 and July 2022, 300 participants were enrolled; 154 were assigned to receive EFV + 3TC + TDF (EFV group) and 146 BIC/FTC/TAF (BIC group). At week 48, 118 (79.2%) and 140 (95.9%) participants in the EFV and BIC group, respectively, were retained in care with viral suppression, and 24 (16.1%) and 1 (0.7%) participant in the EFV and BIC group (P < .001), respectively, discontinued treatment because of adverse effects, death, or lost to follow-up. The median increase of CD4 count was 181 and 223 cells/μL (P = .020), respectively, for the EFV and BIC group, at week 48. The overall incidence of adverse effects was significantly higher for the EFV group (65.8% vs 37.7%, P < .001). BIC/FTC/TAF was more efficacious and safer than EFV (400 mg) + 3TC + TDF for rapid ART initiation among HIV-positive MSM in China.

The replication-competent HIV reservoir is a genetically restricted, younger subset of the overall pool of HIV proviruses persisting during therapy, which is highly genetically stable over time.

Within-host HIV populations continually diversify during untreated infection, and this diversity persists within infected cell reservoirs during antiretroviral therapy (ART). Achieving a better understanding of on-ART proviral evolutionary dynamics, and a better appreciation of how the overall persisting pool of (largely genetically defective) proviruses differs from the much smaller replication-competent HIV reservoir, is critical to HIV cure efforts. We reconstructed within-host HIV evolutionary histories in blood from seven participants of the Women's Interagency HIV Study who experienced HIV seroconversion, and used these data to characterize the diversity, lineage origins, and ages of proviral env-gp120 sequences sampled longitudinally up to 12 years on ART. We also studied HIV sequences emerging from the reservoir in two participants. We observed that proviral clonality generally increased over time on ART, with clones frequently persisting long term. While on-ART proviral integration dates generally spanned the duration of untreated infection, HIV emerging in plasma was exclusively younger (i.e., dated to the years immediately pre-ART). The genetic and age distributions of distinct proviral sequences remained stable during ART in all but one participant, in whom there was evidence that younger proviruses had been preferentially eliminated after 12 years on ART. Analysis of the gag region in three participants corroborated our env-gp120-based observations, indicating that our observations are not influenced by the HIV region studied. Our results underscore the remarkable genetic stability of the distinct proviral sequences that persist in blood during ART. Our results also suggest that the replication-competent HIV reservoir is a genetically restricted, younger subset of this overall proviral pool.IMPORTANCECharacterizing the genetically diverse HIV sequences that persist in the reservoir despite antiretroviral therapy (ART) is critical to cure efforts. Our observations confirm that proviruses persisting in blood on ART, which are largely genetically defective, broadly reflect the extent of within-host HIV evolution pre-ART. Moreover, on-ART clonal expansion is not appreciably accompanied by the loss of distinct proviral lineages. In fact, on-ART proviral genetic composition remained stable in all but one participant, in whom, after 12 years on ART, proviruses dating to around near ART initiation had been preferentially eliminated. We also identified recombinant proviruses between parental sequence fragments of different ages. Though rare, such sequences suggest that reservoir cells can be superinfected with HIV from another infection era. Overall, our finding that the replication-competent reservoir in blood is a genetically restricted, younger subset of all persisting proviruses suggests that HIV cure strategies will need to eliminate a reservoir that differs in key respects from the overall proviral pool.

Impact of social determinants of health on time to antiretroviral therapy initiation and HIV viral undetectability for migrants enrolled in a multidisciplinary HIV clinic with rapid, free, and onsite B/F/TAF: 'The ASAP study'.

Multidisciplinary care with free, rapid, and on-site bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) dispensation may improve health outcomes among migrants living with HIV. However, models for rapid B/F/TAF initiation are not well studied among migrants living with HIV, and an understanding of how social determinants of health (SDH) may affect HIV-related health outcomes for migrants enrolled in such care models is limited. Within a 96-week pilot feasibility prospective cohort study at a multidisciplinary HIV clinic, participants received free B/F/TAF rapidly after care linkage. The effects of SDH (i.e., birth region, sexual orientation, living status, education, employment, French proficiency, health coverage, use of a public health facility outside our clinic for free blood tests, and time in Canada) and other covariates (i.e., age, sex) on median time to antiretroviral therapy (ART) initiation and HIV viral undetectability from care linkage were calculated via survival analyses. Thirty-five migrants were enrolled in this study. Median time to ART initiation and HIV undetectability was 5 days (range 0-50) and 57 days (range 5-365), respectively. Those who took significantly longer to initiate ART were aged <35 years, identified as heterosexual, had less than university-level education, or were unemployed. No factor was found to significantly affect time to undetectability. Despite the provision of free B/F/TAF, several SDH were linked to delays in ART initiation. However, once initiated and engaged, migrants living with HIV reached HIV undetectability efficiently. Findings provide preliminary support for adopting this care model with migrants living with HIV and suggest that SDH should be considered when designing clinical interventions for more equitable outcomes.

Barriers and facilitators to improving the cascade of HIV care in Ontario: a mixed method study

BackgroundEngagement in care is important for people living with HIV (PLH) to achieve optimal outcomes. Several strategies have been developed to improve client flow through the HIV care cascade, specifically targeting initiation of treatment, adherence to antiretroviral therapy (ART), retention in care, and engagement in care. We have previously identified effective care cascade strategies in a systematic review. Initiation of ART could be improved by mobile health interventions, and changes in healthcare delivery. Adherence to ART could be improved by mobile health interventions, incentives, counselling, and psychotherapy. Retention in care could be improved by mobile health interventions, incentives, education, and electronic interventions. The aim of this study was to investigate barriers and facilitators to implementing these effective interventions in HIV clinics in Ontario, Canada.MethodsWe conducted a sequential explanatory mixed methods study. In the quantitative strand, we administered a survey to health workers who provide care to PLH to identify barriers and facilitators. In the qualitative strand, we conducted in-depth interviews informed by the theoretical domains framework (TDF) with health workers and with PLH to explain our quantitative findings. Qualitative and quantitative data were merged to create meta-inferences.ResultsTwenty health workers from 8 clinics in 9 cities in Ontario took the survey. Nine PLH and 10 health workers participated in the qualitative interviews. Clinics in Ontario implemented all the effective interventions identified from the literature for initiation of treatment, adherence to ART, and retention in care despite concerns about resources. Barriers to physical and financial access to care, the workload for tailored care, and expertise were identified by both health workers and PLH. Key facilitators were virtual care and client preparedness through education and peer support.ConclusionClinics in Ontario appear to implement several evidence-based strategies to improve PLH engagement. There is a need for more health workers with skills to address unique PLH needs. Virtual care is beneficial to both health workers and PLH.

Stroke, HIV and the Immune Reconstitution Inflammatory Syndrome in the absence of opportunistic infections

IntroductionStroke in people living with HIV (PLWH) has been described to occur soon after the initiation of antiretroviral therapy (ART) possibly related to the Immune Reconstitution Inflammatory Syndrome (IRIS). We sought to investigate whether there was a temporal association between stroke and recent ART initiation in the absence of opportunistic infections (OIs), and to identify risk factors for this. MethodsThis cross-sectional study recruited PLWH with new-onset stroke at a hospital in Johannesburg, South Africa, from 2014 to 2017, excluding all patients with OIs. Patients were assessed for ART duration, CD4 count, HIV viral load, inflammatory markers and cardiovascular risk factors. Results77 PLWH were recruited, of which 35 were on ART at the time of stroke. Of the patients with confirmed ART duration (n = 28), 9 (32.1%) had a stroke within the first 6 months of starting ART (crude incidence rate of 0.73 cases per patient year). In the period beyond 6 months, 19 strokes occurred (crude incidence rate of 0.21 cases per patient year), translating to a 3.5 times greater risk in the first 6 months (p = 0.0002). There were no clearly identified risk factors when comparing those who had strokes in the first 6 months to those after 6 months and ART-naïve patients. ConclusionAlmost a third of strokes in PLWH may be related to IRIS, with a crude incidence rate 3.5 times higher in the first 6 months following ART-initiation compared to beyond 6 months. This appears to be independent of OIs. Risk factors are unclear.

Longitudinal patterns of inflammatory mediators after acute HIV infection correlate to intact and total reservoir.

Despite the beneficial effects of antiretroviral therapy (ART) initiation during acute HIV infection (AHI), residual immune activation remains a hallmark of treated HIV infection. Plasma concentrations of 40 mediators were measured longitudinally in 39 early treated participants of a Belgian AHI cohort (HIV+) and in 21 HIV-negative controls (HIV-). We investigated the association of the inflammatory profile with clinical presentation, plasma viral load, immunological parameters, and in-depth characterization of the HIV reservoir. While levels of most soluble mediators normalized with suppressive ART, we demonstrated the persistence of a pro-inflammatory signature in early treated HIV+ participants in comparison to HIV- controls. Examination of these mediators demonstrated a correlation with their levels during AHI, which seemed to be viremia-driven, and suggested involvement of an activated myeloid compartment, IFN-γ-signaling, and inflammasome-related pathways. Interestingly, some of these pro-inflammatory mediators correlated with a larger reservoir size and slower reservoir decay. In contrast, we also identified soluble mediators which were associated with favorable effects on immunovirological outcomes and reservoir, both during and after AHI. These data highlight how the persistent pro-inflammatory profile observed in early ART treated individuals is shaped during AHI and is intertwined with viral dynamics.

Caregivers’ experiences of accessing HIV Early Infant Diagnosis (EID) services and its barriers and facilitators, India

BackgroundIndia has rolled out Early Infant Diagnosis (EID) program for HIV infection in all states. EID program consists of testing of Infants exposed to HIV periodically over 18 months of age which is a multi-step complex testing cascade. Caregivers represent the primary beneficiary of EID program i.e., infants exposed to HIV and face multiple challenges to access EID services. As part of national EID program outcome assessment study, this study narrates caregivers’ perspectives on barriers and facilitators to access and utilize EID services.MethodsThe study was conducted in 31 integrated counselling and testing centres (ICTCs) located in 11 high burden HIV states. A total of 66 in-depth interviews were conducted with caregivers’ of infants enrolled in EID program. Thematic analysis was carried out to help identify themes underlying barriers and facilitators to access EID services and utilization from caregivers’ perspectives.ResultsThe stigma and discrimination prevalent in society about HIV remains a key demand side (caregiver-level) barrier. Non-disclosure or selective disclosure of HIV status led to missed or delayed EID tests and delayed HIV diagnosis and initiation of Anti-Retroviral Therapy (ART) for infants exposed to HIV. On supply side (health system-level), accessibility of healthcare facility with EID services was reported as a key barrier. The distance, time and cost were key concerns. Many caregivers faced difficulties to remember the details of complex EID test schedule and relied on a phone call from ICTC counsellor for next due EID test. Delayed EID test results and lack of communication of test results to caregiver were reported as primary barriers for completing the EID test cascade.DiscussionThe study reports caregiver-level and health system-level barriers and facilitators for access to EID services from the caregivers’ perspectives. While, decentralisation and single window approaches can improve the access, timely communication of test results to the caregiver also need to be built in with appropriate use of technology. A holistic intervention including PLHIV support networks and the peer-led support mechanisms would be useful to address societal factors.ConclusionThe study findings have high significance for developing program implementation strategies to improve access and to build right-based and patient-centred EID services.

Discontinuation of tenofovir disoproxil fumarate from initial ART regimens because of renal adverse events: An analysis of data from four multi-country clinical trials.

Tenofovir disoproxil fumarate (TDF), a potent and commonly used antiretroviral drug, is associated with renal tubular dysfunction and renal adverse events. We evaluated the frequency of, time to, and baseline risk factors for discontinuing TDF from initial antiretroviral therapy (ART) regimens because of renal adverse events from presumed tenofovir renal toxicity. We conducted an observational cohort study as a secondary analysis of data from four clinical trials conducted mainly in low- and middle-income countries. We included ART naïve participants living with HIV who started TDF-containing ART regimens in the trials. Participants had to have estimated creatinine clearance (eCrCl) equal to or greater than 60ml/min before starting ART. The primary outcome was the first instance of discontinuing TDF because of renal adverse events attributed to tenofovir renal toxicity during the first 48 weeks after starting ART. We evaluated the cumulative incidence of discontinuing TDF and associated risk factors using Fine and Gray competing risk regression models with a backward elimination variable selection strategy. There were 2802 ART-naïve participants who started TDF-containing ART from the four clinical trials were included in the analysis. Fifty-eight percent were female, the median age was 34 years, and 87% had CD4 cell counts less than 200 cells/μl. Sixty-four participants (2.4%, 95% CI 1.7%-2.8%) discontinued TDF due to renal adverse events. Among the 64 participants, the median time to discontinue TDF was 9.4 weeks (IQR: 3.4-20.7 weeks). From multivariable Fine and Gray regression models, risk factors for discontinuing TDF were older age, CD4 cell count <200 cells/μl, presence and severity of anemia, and eCrCl <90 ml/min. The risk of discontinuing TDF because of renal adverse events was low in participants initiating TDF-containing ART with advanced HIV and normal renal function, attesting to the tolerability of TDF in ART in low- and middle-income countries.

Qualitative Evaluation of Treatment Partners for People With HIV in Botswana: Current Healthcare Provider Practices and Recommendations for Improvement.

Botswana has an adult HIV prevalence of 20.8% and annual incidence of 0.2%. We aimed to evaluate current practices and advance recommendations for treatment partners (informal adherence supporters) for people with HIV in Botswana. In January-February 2020, we conducted seven focus groups with 36 healthcare providers at seven HIV clinics in Gaborone, Botswana. Providers perceived treatment partners to be critical for quality patient care. They shared that in the new era of universal antiretroviral therapy (ART) initiation immediately after diagnosis ("test-and-treat"), providers no longer require patients to select treatment partners at ART initiation. Providers suggested a renewed emphasis on treatment partners. They believed that standard guidance for providers around treatment partner selection would ensure that providers cover similar topics across patients and endorsed implementation of workshops to educate treatment partners on how to support patients. However, streamlined ART initiation policies require innovative strategies, including eHealth interventions, to engage treatment partners.

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.

The role of an artificial intelligence model in antiretroviral therapy counselling and advice for people living with HIV.

People living with HIV may find personalized access to accurate information on antiretroviral therapy (ART) challenging given the stigma and costs potentially associated with attending physical consultations. Artificial intelligence (AI) chatbots such as ChatGPT may help to lower barriers to accessing information addressing concerns around ART initiation. However, the safety and accuracy of the information provided remains to be studied. We instructed ChatGPT to answer questions that people living with HIV frequently ask about ART, covering i) knowledge of and access to ART; ii) ART initiation, side effects, and adherence, and iii) general sexual health practices while receiving ART. We checked the accuracy of the advice against international HIV clinical practice guidelines. ChatGPT answered all questions accurately and comprehensively. It recognized potentially life-threatening scenarios such as abacavir hypersensitivity reaction and gave appropriate advice. However, in certain contexts, such as specific geographic locations or for pregnant individuals, the advice lacked specificity to an individual's unique circumstances and may be inadequate. Nevertheless, ChatGPT consistently re-directed the individual to seek help from a healthcare professional to obtain targeted advice. ChatGPT may act as a useful adjunct in the process of ART counselling for people living with HIV. Improving access to information on and knowledge about ART may improve access and adherence to ART and outcomes for people living with HIV overall.

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.