The Moderating Role of HIV Stigma on the Relationship between Perceived Social Support and Antiretroviral Therapy Adherence Self-Efficacy among Adult PLHIV in South Africa.

BACKGROUND: People living with human immune deficiency virus (PLHIV) grapple with distinct challenges, including HIV stigma which affects their antiretroviral therapy (ART) adherence self-efficacy. This study investigates the interaction of HIV stigma and perceived social support on ART adherence self-efficacy among adult PLHIV in South Africa. METHODS: This study utilized a cross-sectional design that involved 201 participants selected using time location sampling at a tertiary health facility in Durban. RESULTS: HIV stigma was significantly and negatively associated with self-efficacy (ß = -7.860, t = -4.654, p = .001), with variations across different stigma levels (ß = -5.844, t = -4.003, p = .001). Social support was significantly and positively associated with self-efficacy at lower HIV stigma levels (ß = 7.440, t = 3.887, p = .001), in contrast to higher levels (ß = -2.825, t = 1.400, p = .163). CONCLUSION: Social support significantly influences ART adherence self-efficacy, particularly at lower levels of HIV stigma, but the effect of support weakens as stigma intensifies.

The relationship between perceived social support and antiretroviral therapy adherence self-efficacy among adult PLHIV in South Africa: The influence of HIV stigma.People living with HIV face unique challenges, such as HIV stigma, which impact their ability to adhere to antiretroviral therapy (ART). This study examined how HIV stigma and perceived social support affect the ART adherence self-efficacy of adults living with HIV in South Africa. This survey involved 201 participants who were selected by using time location sampling at a health facility in Durban, South Africa. The study found that HIV stigma had a significant and negative impact on self-efficacy (ß = −7.860, t = −4.654, p = .001), with variations depending on the level of stigma (ß = −5.844, t = −4.003, p = .001). On the other hand, social support had a significant and positive impact on self-efficacy at lower levels of HIV stigma (ß = 7.440, t = 3.887, p = .001), but this effect weakened at higher levels of stigma (ß = −2.825, t = 1.400, p = .163). Social support plays an important role in influencing self-efficacy, especially when HIV stigma is lower. However, the significant impact of social support diminishes as HIV stigma becomes more intense.

Comparison of Self and Caregiver Reports of Antiretroviral Treatment Adherence among Children and Adolescents Living with HIV in Western Kenya.

BACKGROUND: Youth living with HIV with perinatal infection spend a lifetime taking antiretroviral treatment (ART) to suppress the virus, and face significant challenges to successfully maintaining ART adherence. Tools to measure adherence include self-report, medication event monitoring system (MEMS) pill bottle caps, pill counts, and plasma or hair drug levels; however, the inter-rater agreement between child and caregiver self-report has not been validated in an African setting. This study aims to assess inter-rater agreement between child and caregiver self-reports, compared to reporting from MEMS pill bottle caps. METHODS: This was a secondary analysis of a cluster-randomized trial to evaluate an intervention for children living with HIV, conducted at the Academic Model Providing Access to Healthcare in western Kenya. We analyzed data from 285 child-caregiver dyads to compare adherence self-reported by children and their caregivers, and subsequently compared all self-reports to adherence reported by MEMS pill bottle caps to determine whether child or caregiver self-reports aligned more closely with adherence measured by MEMS. RESULTS: Children and their caregivers reported similar levels of adherence and numbers of missed doses in the past month, and both reports were similarly associated with adherence reported by MEMS pill bottle caps. Children with a caregiver that was not a biological parent were significantly more likely to report more missed doses than their caregiver. The correlation coefficient for the relationship between the child and caregiver self-reports was 0.71; for the relationship between child report and MEMS was 0.23; and for the relationship between caregiver report and MEMS was 0.20. Both children and caregivers under-reported non-adherence compared to MEMS data. CONCLUSION: Children and caregiver self-reports were generally similar in reporting adherence and were not highly correlated with MEMS reports of adherence, with children and caregivers reporting higher level of adherence than the MEMS data. This may indicate that children and caregiver reports are similarly inaccurate or biased; however, further research with larger sample sizes is required to further understand the differences in these reports.

Comparison of self-reported ART adherence rates among children and adolescents living with HIV in western Kenya The study aims to compare adherence between children and caregivers of Youth Living with HIV (YLWH) with perinatal infection, comparing data from 285 child-caregiver dyads and MEMS pill bottle caps. Results showed similar levels of adherence and missed doses in the past month, with a correlation coefficient of 0.71. However, children and caregivers reported higher levels of adherence than MEMS data. The study highlights the importance of understanding the reliability between self-reports and MEMS data in promoting adherence among YLWH.

Key informant views on potential acceptability and feasibility of long-acting antiretroviral treatment for HIV in Kenya.

BACKGROUND: In 2020, 14% of diagnosed persons living with HIV (PLWH) in Kenya were not taking antiretroviral therapy (ART), and 19% of those on ART had unsuppressed viral loads. Long-acting antiretroviral therapy (LA-ART) may increase viral suppression by promoting ART uptake and adherence. We conducted key informant (KI) interviews with HIV experts in Kenya to identify product and delivery attributes related to the acceptability and feasibility of providing LA-ART to PLWH in Kenya. METHODS: Interviews were conducted via Zoom on potential LA-ART options including intra-muscular (IM) injections, subcutaneous (SC) injections, implants, and LA oral pills. KI were asked to discuss the products they were most and least excited about, as well as barriers and facilitators to LA-ART roll-out. In addition, they were asked about potential delivery locations for LA-ART products such as homes, pharmacies, and clinics. Interviews were recorded and transcribed, and data were analyzed using a combination of inductive and deductive coding. RESULTS: Twelve KI (5 women, 7 men) participated between December 2021 and February 2022. Overall, participants reported that LA-ART would be acceptable and preferable to PLWH because of fatigue with daily oral pills. They viewed IM injections and LA oral pills as the most exciting options to ease pill burden and improve adherence. KI felt that populations who could benefit most were adolescents in boarding schools and stigmatized populations such as sex workers. SC injections and implants were less favored, as they would require new training initiatives for patients or healthcare workers on administration. In addition, SC injections would require refrigeration and needle disposal after use. Some KI thought patients, especially men, might worry that IM injections and implants would impact fertility, given their role in family planning. Pharmacies were perceived by most KI as suboptimal delivery locations; however, given ongoing work in Kenya to include pharmacies in antiretroviral delivery, they recommended asking patients their views. CONCLUSION: There is interest and support for LA-ART in Kenya, especially IM injections and LA oral pills. Identifying patient preferences for modes and delivery locations and addressing misconceptions about specific products as they become available will be important before wide-scale implementation.

How Would You Manage HIV Pre-exposure Prophylaxis in This Patient With Medical Comorbidities? : Grand Rounds Discussion From Beth Israel Deaconess Medical Center.

Despite advances in treatment, HIV infection remains an important cause of morbidity and mortality, with more than 30 000 new cases diagnosed in the United States each year. There are several interventions traditionally used to prevent HIV transmission, but these vary in effectiveness and there are challenges to their implementation. In 2014, the Centers for Disease Control and Prevention published initial guidance on the use of antiretroviral pre-exposure prophylaxis (PrEP) to prevent transmission of HIV infection in persons at risk based on multiple studies that showed it to be highly efficacious in various populations. It was updated in 2021 to reflect new drug options. The U.S. Preventive Services Task Force also recently updated its recommendations for PrEP, which strongly support its use in persons at risk. Despite its well-established effectiveness, the implementation of PrEP in clinical practice has been variable, especially among populations underserved by the medical system and marginalized by society. Fewer than one third of persons in the United States who are eligible for PrEP currently receive it. Here, 2 physicians experienced in HIV PrEP debate how best to identify patients who might benefit from PrEP, how to decide what regimen to use, and how to monitor therapy.

Acceptability of a pilot motivational interviewing intervention at public health facilities to improve the HIV treatment cascade among people who inject drugs in Indonesia.

BACKGROUND: HIV-positive people who inject drugs (PWID) experience challenges in initiating and adhering to antiretroviral treatment (ART). Counselling using motivational interviewing (MI) techniques may help them formulate individualised strategies, and execute actions to address these challenges collaboratively with their providers. We evaluated the acceptability of MI from a pilot implementation at three public health facilities in Indonesia. METHODS: Adapting the acceptability constructs developed by Sekhon (2017) we assessed the acceptability to HIV-positive PWID clients (n = 12) and providers (n = 10) in four synthesised constructs: motivation (attributes that inspire engagement); cost consideration (sacrifices made to engage in MI); learned understanding (mechanism of action); and outcomes (ability to effect change with engagement). We included all providers and clients who completed ≥ 2 MI encounters. Qualitative analysis with an interpretive paradigm was used to extract and categorise themes by these constructs. RESULTS: In motivation, clients valued the open communication style of MI, while providers appreciated its novelty in offering coherent structure with clear boundaries. In cost consideration, both groups faced a challenge in meeting MI encounters due to access or engagement in other health care areas. In learned understanding, clients understood that MI worked to identify problematic areas of life amenable to change to support long-term ART, with reconciliation in family life being the most targeted change. By contrast, providers preferred targeting tangible health outcomes to such behavioural proxies. In outcomes, clients were confident in their ability to develop behaviours to sustain ART uptakes, whereas providers doubted the outcome of MI on younger PWID or those with severe dependence. CONCLUSIONS: There is broad acceptability of MI in motivating engagement for both actors. Relative to providers, clients were more acceptable in its mechanism and had greater confidence to perform behaviours conducive to ART engagement. Design innovations to improve the acceptability of MI for both actors are needed.

The association between HIV pretreatment drug resistance and virological outcomes in children and adults in sub-Saharan Africa: A systematic review and meta-analysis.

INTRODUCTION: Pretreatment drug resistance (PDR) could occur in antiretroviral treatment (ART) naïve individuals, those previously exposed to ART, or individuals re-initiating ARV after a long period of interruption. Few studies have shown its association with virological outcomes, although inconsistent. The objective of this review was to provide a synthesis of the association between PDR and virological outcomes (virological failure or suppression). METHODS: This report is presented following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The method was subdivided into three main phases: record identification, screening, and report inclusion. Record identification consisted of an initial search with search term "HIV pretreatment drug resistance". Another search was done using terms "Pretreatment drug resistance OR pre-treatment drug resistance OR Pretreatment drug resist* OR pre-treatment drug resist* OR pretreatment antiretroviral resistance OR pretreatment medic* OR pretreatment medic* resist*" and a list of all the countries in sub-Saharan Africa. After the electronic search, studies were screened from full list based on their title and abstract and then full articles retrieved and studies were assessed based on set criteria. Inclusion criteria involved observational studies that report the association between PDR and virological failure. Data from trials that reported the association were also included. Published articles like modelling studies and reviews, and studies with data that had been previously included in the review were excluded. The Mantel Haenszel method with odds ratios was used for synthesis (meta-analyses) with the weights of each study which depends on the number of events and totals. RESULTS: A total of 733 records(studies) were obtained from all database search of which 74 reported on PDR, virological outcomes in sub-Saharan Africa (SSA). Out of the 74 articles, 11 were excluded and 26 did not explicitly report data needed, and 5 did not meet the inclusion criteria. Of the remaining 32 studies, 19 studies that had complete data on the number of participants with PDR and no PDR according to virological failure (VF) were included in the metanalyses. The pooled results from eleven (13) of these studies showed those with PDR had higher odds of virological failure compared to those without PDR OR 3.64[95% CI 2.93, 4.52]. The result was similar when stratified in adults and in children. In six (6) studies that had Virological suppression (VS) as outcome, there was a reduction in the odds of VS in those with PDR compared to those without PDR, OR 0.42 (95% CI 0.30, 0.58). CONCLUSION: In conclusion, this systematic review indicates that PDR increases the risk of virological failure in sub-Saharan Africa. The risk could be reduced by PDR monitoring for NNRTIs and INSTIs.

Evaluation of the effects of Artemisia Annua L. and Moringa Oleifera Lam. on CD4 count and viral load among PLWH on ART at Mbarara Regional Referral Hospital: a double-blind randomized controlled clinical trial.

BACKGROUND: Initiation of ART among people living with HIV (PLWH) having a CD4 count ≤ 350cells/µl, produces poor immunological recovery, putting them at a high risk of opportunistic infections. To mitigate this, PLWH on ART in Uganda frequently use herbal remedies like Artemisia annua and Moringa oleifera, but their clinical benefits and potential antiretroviral (ARV) interactions remain unknown. This study examined the impact of A. annua and M. oleifera on CD4 count, viral load, and potential ARV interactions among PLWH on ART at an HIV clinic in Uganda. METHODS: 282 HIV-positive participants on antiretroviral therapy (ART) with a CD4 count ≤ 350cells/µl were randomized in a double-blind clinical trial to receive daily, in addition to their routine standard of care either; 1) A. annua leaf powder, 2) A. annua plus M. oleifera, and 3) routine standard of care only. Change in the CD4 count at 12 months was our primary outcome. Secondary outcomes included changes in viral load, complete blood count, and ARV plasma levels. Participants were followed up for a year and outcomes were measured at baseline, 6 and 12 months. RESULTS: At 12 months of patient follow-up, in addition to standard of care, administration of A. annua + M. oleifera resulted in an absolute mean CD4 increment of 105.06 cells/µl, (p < 0.001), while administration of A. annua plus routine standard of care registered an absolute mean CD4 increment of 60.84 cells/µl, (p = 0.001) compared to the control group. The A. annua plus M. oleifera treatment significantly reduced viral load (p = 0.022) and increased platelet count (p = 0.025) and white blood cell counts (p = 0.003) compared to standard care alone, with no significant difference in ARV plasma levels across the groups. CONCLUSION: A combination of A. annua and M. oleifera leaf powders taken once a day together with the routine standard of care produced a significant increase in CD4 count, WBCs, platelets, and viral load suppression among individuals on ART. A. annua and M. oleifera have potential to offer an affordable alternative remedy for managing HIV infection, particularly in low-resource communities lacking ART access. TRIAL REGISTRATION: ClinicalTrials.gov NCT03366922.

Early antiretroviral therapy in SIV-infected rhesus macaques reveals a multiphasic, saturable dynamic accumulation of the rebound competent viral reservoir.

The rebound competent viral reservoir (RCVR)-virus that persists during antiretroviral treatment (ART) and can reignite systemic infection when treatment is stopped-is the primary barrier to eradicating HIV. We used time to initiation of ART during primary infection of rhesus macaques (RMs) after intravenous challenge with barcoded SIVmac239 as a means to elucidate the dynamics of RCVR establishment in groups of RMs by creating a multi-log range of pre-ART viral loads and then assessed viral time-to-rebound and reactivation rates resulting from the discontinuation of ART after one year. RMs started on ART on days 3, 4, 5, 6, 7, 9 or 12 post-infection showed a nearly 10-fold difference in pre-ART viral measurements for successive ART-initiation timepoints. Only 1 of 8 RMs initiating ART on days 3 and 4 rebounded after ART interruption despite measurable pre-ART plasma viremia. Rebounding plasma from the 1 rebounding RM contained only a single barcode lineage detected at day 50 post-ART. All RMs starting ART on days 5 and 6 rebounded between 14- and 50-days post-ART with 1-2 rebounding variants each. RMs starting ART on days 7, 9, and 12 had similar time-to-measurable plasma rebound kinetics despite multiple log differences in pre-ART plasma viral load (pVL), with all RMs rebounding between 7- and 16-days post-ART with 3-28 rebounding lineages. Calculated reactivation rates per pre-ART pVL were highest for RMs starting ART on days 5, 6, and 7 after which the rate of accumulation of the RCVR markedly decreased for RMs treated on days 9 and 12, consistent with multiphasic establishment and near saturation of the RCVR within 2 weeks post infection. Taken together, these data highlight the heterogeneity of the RCVR between RMs, the stochastic establishment of the very early RCVR, and the saturability of the RCVR prior to peak viral infection.

Can routine antenatal data be used to assess HIV antiretroviral therapy coverage among pregnant women? Evaluating the validity of different data sources in the Western Cape, South Africa.

BACKGROUND: Accurate measurement of antenatal antiretroviral treatment (ART) coverage in pregnancy is imperative in tracking progress towards elimination of vertical HIV transmission. In the Western Cape, South Africa, public-sector individual-level routine data are consolidated from multiple sources, enabling the description of temporal changes in population-wide antenatal antiretroviral coverage. We evaluated the validity of different methods for measuring ART coverage among pregnant women. METHODS: We compared self-reported ART data from a 2014 antenatal survey with laboratory assay data from a sub-sample within the survey population. Thereafter, we conducted a retrospective cohort analysis of all pregnancies consolidated in the Provincial Health Data Centre (PHDC) from January 2011 to December 2020. Evidence of antenatal and HIV care from electronic platforms were linked using a unique patient identifier. ART coverage estimates were triangulated with available antenatal survey estimates, aggregated programmatic data from registers recorded in the District Health Information System (DHIS) and Thembisa modelling estimates. RESULTS: Self-reported ART in the 2014 sentinel antenatal survey (n = 1434) had high sensitivity (83.5%), specificity (94.5%) and agreement (k = 0.8) with the gold standard of laboratory analysis of ART. Based on linked routine data, ART coverage by the time of delivery in mothers of live births increased from 67.4% in 2011 to 94.7% by 2019. This pattern of increasing antenatal ART coverage was also seen in the DHIS data, and estimated by the Thembisa model, but was less consistent in the antenatal survey data. CONCLUSION: This study is the first in a high-burden HIV setting to compare sentinel ART surveillance data with consolidated individuated administrative data. Although self-report in survey conditions showed high validity, more recent data sources based on self-report and medical records may be uncertain with increasing ART coverage over time. Linked individuated data may offer a promising option for ART coverage estimation with greater granularity and efficiency.

Human immunodeficiency virus and oral microbiota: mutual influence on the establishment of a viral gingival reservoir in individuals under antiretroviral therapy.

The role of the oral microbiota in the overall health and in systemic diseases has gained more importance in the recent years, mainly due to the systemic effects that are mediated by the chronic inflammation caused by oral diseases, such as periodontitis, through the microbial communities of the mouth. The chronic infection by the human immunodeficiency virus (HIV) interacts at the tissue level (e.g. gut, genital tract, brain) to create reservoirs; the modulation of the gut microbiota by HIV infection is a good example of these interactions. The purpose of the present review is to assess the state of knowledge on the oral microbiota (microbiome, mycobiome and virome) of HIV-infected patients in comparison to that of HIV-negative individuals and to discuss the reciprocal influence of HIV infection and oral microbiota in patients with periodontitis on the potential establishment of a viral gingival reservoir. The influence of different clinical and biological parameters are reviewed including age, immune and viral status, potent antiretroviral therapies, smoking, infection of the airway and viral coinfections, all factors that can modulate the oral microbiota during HIV infection. The analysis of the literature proposed in this review indicates that the comparisons of the available studies are difficult due to their great heterogeneity. However, some important findings emerge: (i) the oral microbiota is less influenced than that of the gut during HIV infection, although some recurrent changes in the microbiome are identified in many studies; (ii) severe immunosuppression is correlated with altered microbiota and potent antiretroviral therapies correct partially these modifications; (iii) periodontitis constitutes a major factor of dysbiosis, which is exacerbated in HIV-infected patients; its pathogenesis can be described as a reciprocal reinforcement of the two conditions, where the local dysbiosis present in the periodontal pocket leads to inflammation, bacterial translocation and destruction of the supporting tissues, which in turn enhances an inflammatory environment that perpetuates the periodontitis cycle. With the objective of curing viral reservoirs of HIV-infected patients in the future years, it appears important to develop further researches aimed at defining whether the inflamed gingiva can serve of viral reservoir in HIV-infected patients with periodontitis.

Tuberculosis Preventive Treatment Update - U.S. President's Emergency Plan for AIDS Relief, 36 Countries, 2016-2023.

Tuberculosis (TB) is the leading cause of death among persons with HIV. In 2022, an estimated 167,000 TB-related deaths occurred globally among persons with HIV. TB preventive treatment (TPT) helps prevent TB disease and is recommended for persons at high risk for developing TB, including those with HIV. TPT, when taken with antiretroviral treatment (ART), can reduce TB-attributable deaths among persons with HIV. In 2018, the U.S. President's Emergency Plan for AIDS Relief (PEPFAR) program committed to offer one course of TPT to all eligible clients receiving ART. This analysis describes trends in TPT initiation and completion among PEPFAR-supported programs in 36 countries in Africa, Central and South America, and Asia during fiscal years (FYs) 2017-2023. Overall, TPT initiation rates peaked in FY19, a possible sign of programmatic saturation. TPT initiation among clients who had been on ART <6 months reached 59%, and overall completion rates up to 87% were reported. Approximately 13 million persons with HIV have completed TPT since FY17, but widespread adoption of shorter regimens, patient-centered approaches, and electronic medical record systems might be needed to ensure full TPT coverage. Through PEPFAR's partnership with national HIV programs, TPT has become the standard of care for persons with HIV.

Linkage Case Management and Posthospitalization Outcomes in People With HIV: The Daraja Randomized Clinical Trial.

Importance: Despite the widespread availability of antiretroviral therapy (ART), people with HIV still experience high mortality after hospital admission. Objective: To determine whether a linkage case management intervention (named "Daraja" ["bridge" in Kiswahili]) that was designed to address barriers to HIV care engagement could improve posthospital outcomes. Design, Setting, and Participants: Single-blind, individually randomized clinical trial to evaluate the effectiveness of the Daraja intervention. The study was conducted in 20 hospitals in Northwestern Tanzania. Five hundred people with HIV who were either not treated (ART-naive) or had discontinued ART and were hospitalized for any reason were enrolled between March 2019 and February 2022. Participants were randomly assigned 1:1 to receive either the Daraja intervention or enhanced standard care and were followed up for 12 months through March 2023. Intervention: The Daraja intervention group (n = 250) received up to 5 sessions conducted by a social worker at the hospital, in the home, and in the HIV clinic over a 3-month period. The enhanced standard care group (n = 250) received predischarge HIV counseling and assistance in scheduling an HIV clinic appointment. Main Outcomes and Measures: The primary outcome was all-cause mortality at 12 months after enrollment. Secondary outcomes related to HIV clinic attendance, ART use, and viral load suppression were extracted from HIV medical records. Antiretroviral therapy adherence was self-reported and pharmacy records confirmed perfect adherence. Results: The mean age was 37 (SD, 12) years, 76.8% were female, 35.0% had CD4 cell counts of less than 100/µL, and 80.4% were ART-naive. Intervention fidelity and uptake were high. A total of 85 participants (17.0%) died (43 in the intervention group; 42 in the enhanced standard care group); mortality did not differ by trial group (17.2% with intervention vs 16.8% with standard care; hazard ratio [HR], 1.01; 95% CI, 0.66-1.55; P = .96). The intervention, compared with enhanced standard care, reduced time to HIV clinic linkage (HR, 1.50; 95% CI, 1.24-1.82; P < .001) and ART initiation (HR, 1.56; 95% CI, 1.28-1.89; P < .001). Intervention participants also achieved higher rates of HIV clinic retention (87.4% vs 76.3%; P = .005), ART adherence (81.1% vs 67.6%; P = .002), and HIV viral load suppression (78.6% vs 67.1%; P = .01) at 12 months. The mean cost of the Daraja intervention was about US $22 per participant including startup costs. Conclusions and Relevance: Among hospitalized people with HIV, a linkage case management intervention did not reduce 12-month mortality outcomes. These findings may help inform decisions about the potential role of linkage case management among hospitalized people with HIV. Trial Registration: ClinicalTrials.gov Identifier: NCT03858998.

Uncovering HIV and malaria interactions: the latest evidence and knowledge gaps.

The geographical distribution of malaria and HIV infections widely overlap in sub-Saharan Africa, constituting a complex global health challenge. The interplay between both infections raises concerns about potential immunological, clinical, and therapeutic interactions. Both diseases have been reported to exacerbate the transmission of the other, including the possible vertical transmission of HIV in pregnant individuals with malaria. Co-infection also increases the risk of adverse outcomes such as severe malaria and death. In addition, interactions between antiretroviral and antimalarial drugs have been reported, potentially reducing the efficacy of these drugs. We review the current knowledge of the epidemiological, clinical, immunological, and therapeutic interactions of both infections. We focus on the latest available data and identify key knowledge gaps that should be addressed to guide policy makers in providing optimal HIV and malaria prevention, care, and treatment in vulnerable populations.

Progress towards the UNAIDS 95-95-95 targets in the Fifth Botswana AIDS Impact Survey (BAIS V 2021): a nationally representative survey.

BACKGROUND: In 2014, UNAIDS set a goal to end the AIDS epidemic by achieving targets for the percentage of people living with HIV who were aware of their status, on antiretroviral therapy (ART), and virally suppressed. In 2020, these targets were revised to 95% for each measure (known as 95-95-95), to be reached among people living with HIV by 2025. We used data from the Fifth Botswana AIDS Impact Survey (BAIS V) to measure progress towards these testing and treatment targets in Botswana. METHODS: BAIS V used a two-stage cluster design to obtain a nationally representative sample of people aged 15-64 years in Botswana. During March-August, 2021, 14 763 consenting participants were interviewed and tested for HIV in their households by survey teams. HIV-positive specimens were tested for viral load, presence of antiretroviral drugs, and recency of infection using the HIV-1 limiting antigen avidity enzyme immunoassay. Estimates of HIV-positive status and use of ART were based on self-report and the analysis of blood specimens for antiretroviral drugs. Viral load suppression was defined as an HIV RNA concentration of less than 1000 copies per mL. HIV incidence was calculated using the recent infection testing algorithm. Data were weighted to account for the complex survey design. FINDINGS: The national HIV prevalence in Botswana among people aged 15-64 years was 20·8% and the annual incidence of HIV infection was 0·2%. 95·1% (men 93·0%, women 96·4%) of people living with HIV aged 15-64 years were aware of their status, 98·0% (men 97·2%, women 98·4%) of those aware were on ART, and 97·9% (men 96·6%, women 98·6%) of those on ART had viral load suppression. Among young people (aged 15-24 years) living with HIV, 84·5% were aware of their status, 98·5% of those aware were on ART, and 91·6% of those on ART had viral load suppression. The prevalance of viral load suppression among all people living with HIV was 91·8%, and varied by district-ranging from 85·3% in Gaborone to 100·0% in Selibe Phikwe. INTERPRETATION: BAIS V is the first population-based survey worldwide to report the achievement of the UNAIDS 95-95-95 goals, both overall and among women. Strategies to reach undiagnosed men and young people, including young women, are needed. FUNDING: US President's Emergency Plan for AIDS Relief.

Predictors of antiretroviral treatment failure to the first line therapy: a cross-sectional study among Iranian HIV-positive adults.

BACKGROUND: HIV virological failure is one of the main problems in HIV-infected patients, and identifying the main predictors of such treatment failure may help in combating HIV/AIDS. METHODOLOGY: This cross-sectional study included 1800 HIV-infected patients with either virological failure or treatment response. HIV viral load, CD4 count, and other tests were performed. Statistical analysis was used to determine the predictors of virological failure. RESULTS: Clinical stage, treatment with reverse transcriptase inhibitors (RTIs), under therapy for three years or more, suboptimal adherence to antiretroviral treatment (ART), age > 40 years, CD4 count < 200 cells/mm3, unemployment, being infected through sex, and the presence of symptoms were the predominant risk factors for virological failure. In addition, 55% of patients who experienced virological failure failed to experience immunological and/or clinical failure. CONCLUSION: As the first study in southern Iran and the second in Iran, Iranian policymakers should focus on intensive counseling and adherence support and emphasize more effective treatment regimens such as protease and integrase inhibitors (PIs and INTIs), to increase the chance of a treatment response to ART. The accuracy of identifying clinical and immunological criteria in resource-limited settings is not promising. The present findings can be used to determine effective measures to control HIV treatment failure and design efficient strategies for the ambitious 95-95-95 plan.

Persistent poor clinical outcomes of people living with HIV presenting with AIDS and late HIV diagnosis - results from the ICONA cohort in Italy, 2009-2022.

OBJECTIVES: Limited data are available on the long-term outcomes in recent years for late HIV diagnosis (LD). METHODS: All subjects with HIV enrolled in the ICONA cohort in 2009-2022 who started antiretroviral treatment (ART) within 4 months from diagnosis were included and divided into: (i) pre-ART CD4 count ≥350/mm3 without AIDS (non-LD), (ii) pre-ART CD4 count <350/mm3 without AIDS (LD asymptomatic), and (iii) with AIDS events pre-ART (LD-AIDS). The estimated probability and independent risk for mortality (all-cause and cause-specific) and treatment failure were evaluated. RESULTS: Of 6813 participants (2448 non-LD, 3198 LD asymptomatic, and 1167 LD-AIDS), 161 (2.4%) died after ART initiation. At survival analysis, a higher probability of all-cause mortality has been identified for LD than non-LD (P <0.001) and within the former, for LD-AIDS over LD asymptomatic (P <0.001). After adjusting for confounders, LD showed a higher risk of all-cause mortality (vs non-LD adjusted hazard ratio (aHR) 5.51, P <0.001) and, in particular, being an AIDS presenter predicted a greater risk of all-cause (aHR = 4.42, P <0.001), AIDS-related (adjusted subhazard ratio [aSHR] = 16.86, P <0.001), and non-AIDS-related mortality (aSHR = 1.74, P = 0.022) than the rest of the late presenters. Among the short-term survivors in the LD-AIDS group, the long-term mortality was mediated by the lack of immune recovery at 2 years. Finally, LD compared with non-LD and, particularly, among the former, LD-AIDS over LD asymptomatic showed a greater risk of treatment failure. CONCLUSIONS: In recent years, LD subjects, particularly, AIDS presenters, remained at a higher risk of poorer outcomes. Public health strategies for early HIV diagnosis are urgently needed to constrain the mortality gap.

Acceptability and tolerability of long-acting injectable cabotegravir or rilpivirine in the first cohort of virologically suppressed adolescents living with HIV (IMPAACT 2017/MOCHA): a secondary analysis of a phase 1/2, multicentre, open-label, non-comparative dose-finding study.

BACKGROUND: Long-acting injectable cabotegravir and rilpivirine have demonstrated safety, acceptability, and efficacy in adults living with HIV-1. The IMPAACT 2017 study (MOCHA study) was the first to use these injectable formulations in adolescents (aged 12-17 years) living with HIV-1. Herein, we report acceptability and tolerability outcomes in cohort 1 of the study. METHODS: In this a secondary analysis of a phase 1/2, multicentre, open-label, non-comparative dose-finding study, with continuation of pre-study oral combination antiretroviral treatment (ART), 55 adolescents living with HIV-1 were enrolled to receive sequential doses of either long-acting cabotegravir or rilpivirine and 52 received at least two injections. Participants had a body weight greater than 35 kg and BMI less than 31·5 kg/m2 and had been on stable ART for at least 90 consecutive days with an HIV-1 viral load of less than 50 copies per mL at a participating IMPAACT study site. Participants had to be willing to continue their pre-study ART during cohort 1. The primary objectives of the study were to confirm doses for oral and injectable cabotegravir and for injectable rilpivirine in adolescents living with HIV. This analysis of participant-reported outcomes included a face scale assessment of pain at each injection and a Pediatric Quality of Life Inventory (PedsQL) at baseline and week 16 for participants in the USA, South Africa, Botswana, and Thailand. A subset of 11 adolescents and 11 parents or caregivers in the USA underwent in-depth interviews after receipt of one or two injections. This trial is registered at ClinicalTrials.gov, NCT03497676. FINDINGS: Between March 19, 2019, and Nov 25, 2021, 55 participants were enrolled into cohort 1. Using the six-point face scale, 43 (83%) of participants at week 4 and 38 (73%) at week 8 reported that the injection caused "no hurt" or "hurts little bit", while only a single (2%) participant for each week rated the pain as one of the two highest pain levels. Quality of life was not diminished by the addition of one injectable antiretroviral. In-depth interviews revealed that parents and caregivers in the USA frequently had more hesitancy than adolescents about use of long-acting formulations, but parental acceptance was higher after their children received injections. INTERPRETATION: High acceptability and tolerability of long-acting cabotegravir or rilpivirine injections suggests that these are likely to be favoured treatment options for some adolescents living with HIV. FUNDING: National Institutes of Health and ViiV Healthcare.