Proportion of HIV exposed infants aged 0-6 months that missed nevirapine prophylaxis in Mulago National Referral Hospital, Uganda: a cross-sectional study.

BACKGROUND: Nevirapine prophylaxis has been found to lower the risk of HIV transmission in breastfed infants. While about 95% of HIV positive pregnant and lactating mothers use Antiretroviral therapy in Uganda, a smaller percentage of HIV exposed infants (HEI) receive nevirapine (NVP) prophylaxis. This study aimed to determine the proportion of HEI who missed NVP prophylaxis and associated factors. METHODS: This was a cross-sectional study done using quantitative methods, conducted at Mulago National Referral Hospital (MNRH). A total of 228 mother-infant pairs were enrolled. The proportion of HEI who missed NVP, maternal, infant and health facility factors associated were determined using a pre-tested questionnaire. Bivariate analysis and binary logistic regression model were used to determine the proportion and factors associated with missing NVP prophylaxis. RESULTS: The proportion of HEI who missed NVP prophylaxis was 50/228 (21.9%). Factors significantly associated with HEI missing NVP prophylaxis included delivery from outside government health facilities (AOR = 8.41; P = 0.001), mothers not undergoing PMTCT counselling (AOR = 12.01; P = 0.001), not on ART (AOR = 8.47; P = 0.003) and not having disclosed their HIV status to their partners (AOR = 2.80; P = 0.001). The HEI that missed nevirapine and were HIV positive were 35 (70.0%). The HEI that were HIV infected despite receiving nevirapine prophylaxis were 5 out of 40(12.5%). CONCLUSION: One in five HEI missed NVP prophylaxis and nearly three quarters of those who missed NVP prophylaxis were HIV infected. Improving uptake of nevirapine by HEI will require interventions that can aid to strengthen PMTCT counselling.

HIV-1 subtype A1, D, and recombinant proviral genome landscapes during long-term suppressive therapy.

The primary obstacle to curing HIV-1 is a reservoir of CD4+ cells that contain stably integrated provirus. Previous studies characterizing the proviral landscape, which have been predominantly conducted in males in the United States and Europe living with HIV-1 subtype B, have revealed that most proviruses that persist during antiretroviral therapy (ART) are defective. In contrast, less is known about proviral landscapes in females with non-B subtypes, which represents the largest group of individuals living with HIV-1. Here, we analyze genomic DNA from resting CD4+ T-cells from 16 female and seven male Ugandans with HIV-1 receiving suppressive ART (n = 23). We perform near-full-length proviral sequencing at limiting dilution to examine the proviral genetic landscape, yielding 607 HIV-1 subtype A1, D, and recombinant proviral sequences (mean 26/person). We observe that intact genomes are relatively rare and clonal expansion occurs in both intact and defective genomes. Our modification of the primers and probes of the Intact Proviral DNA Assay (IPDA), developed for subtype B, rescues intact provirus detection in Ugandan samples for which the original IPDA fails. This work will facilitate research on HIV-1 persistence and cure strategies in Africa, where the burden of HIV-1 is heaviest.

Cytokines assets in PLWH in two-drug dolutergravir based or three-drug antiretroviral regimen.

To minimize the toxicity and impact of combined antiretroviral therapy (cART) on the lifestyle of people living with Human Immunodeficiency Virus (PLWH), scientific community evaluated the efficacy, safety and sustained virologic response of two drugs antiretroviral regimens, in particular dolutegravir (DTG). The effects of deintensification therapy on inflammatory settings are currently unknown in PLWH. Thus, our study explored the inflammatory state in virologically suppressed HIV individuals between patients in treatment with a DTG-containing dual therapy (2DR) versus triple regimen therapies (3DR). We enrolled a total of 116 subjects in 2DRs or 3DRs regimens, and the plasma levels of pro- and anti-inflammatory cytokines (in particular IL-1ß, IL-10, IL-18, IL-33, IL-36 and IFN-γ) have been evaluated. CD4 + cell's median value was 729.0 cell/µL in the 3DR group and 771.5 cell/µL in 2DR group; the viral load was negative in all patients. Significant differences were found in levels of IL-18 (648.8 cell/µL in 3DR group vs. 475.0 cell/µL in 2DR group, p = 0.034) and IL-36 (281.7 cell/µL in 3DR group vs. 247.0 cell/µL in 2DR group, p = 0.050), and a correlation between IL-18 and IL-36 was found in 3DR group (rho = 0.266, p = 0.015). This single-center retrospective pharmacological study confirms the absence of significant differences in IL-1ß, IL-10, IL-33, and IFN-γ levels between patients on two-drug antiretroviral regimens compared to patients on 3DR antiretroviral regimens. Patients in 2DR show greater control over IL-18 and IL-36 serum levels, cytokines related to an increased cardiovascular risk and development of age-related chronic diseases. Based on our results, we suggest that DTG-based 2DR antiretroviral regimens could be associated with better control of the chronic inflammation that characterizes the population living with HIV in effective ART.

Attrition from care and its predictors among women exposed to dolutegravir- and efavirenz-based first-line antiretroviral therapy in Ethiopia: a before-and-after study.

Background: The effect of dolutegravir (DTG)-based regimens on reducing attrition from care among women enrolled in the prevention of mother-to-child transmission (PMTCT) care program is unknown. Therefore, this study aimed to compare the incidence of attrition among women exposed to DTG-based with those exposed to efavirenz (EFV)-based first-line antiretroviral therapy (ART) in Ethiopia. Methods: An uncontrolled before-and-after study was conducted involving 932 women (with 466 on EFV-based and 466 on DTG-based regimens) who were enrolled in the PMTCT care program from September 2015 to February 2023. The outcome variable was attrition (i.e., maternal death or loss to follow-up before their infants' final HIV status was determined). A Kaplan-Meier estimator was employed to estimate the probability of attrition. The Cox proportional hazards regression model was fitted to identify predictor variables. The adjusted hazard ratio (aHR) with the corresponding 95% confidence interval (CI) was calculated to examine the risk difference in the comparison groups. Results: The cumulative incidence of attrition among women was 5.2% (3.0% for those placed in the DTG-based regimen arm and 7.3% for those placed in the EFV-based regimen arm). Women on DTG-based regimens had a 57% (aHR: 0.43; 95% CI: 0.23-0.80) lower risk of attrition from care compared to those on EFV-based regimens. Women who delivered their infants at home (aHR: 2.35; 95% CI: 1.14-4.85), had poor/fair adherence (aHR: 3.23; 95% CI: 1.62-6.45), had unsuppressed/unknown viral load status (aHR: 2.61; 95% CI: 1.42-4.79), and did not disclose their status to partners (aHR: 2.56; 95% CI: 1.34-4.92) had a higher risk of attrition from PMTCT care compared to their counterparts. Conclusion: The cumulative incidence of attrition among women receiving PMTCT care is optimal. In addition, the risk of attrition among women receiving DTG-based regimens is lower than that among women receiving EFV-based regimens. Thus, DTG-based first-line ART regimen supplementation should be sustained to achieve a national retention target of 95% and above.

"I want to be healthy and move on": A qualitative study of barriers and facilitators to antiretroviral treatment adherence among young adult survivors with perinatal HIV in Thailand.

We know that HIV treatment outcome depends on antiretroviral treatment (ART) adherence. Young adults with perinatal HIV (YPHIV) who survived have endured various adherence challenges in their adolescent years. While some of them could maintain perfect adherence with sustainable virologic suppression, many experienced one or more episodes of virologic failure. We explored factors affecting ART adherence from real-life experiences of YPHIV. A qualitative study was conducted between June and November 2022. Twenty YPHIV aged 21-29 years with a history of virologic failure and resumed virologic suppression during adolescent years were invited to share their experiences through individual in-depth interviews. Audio records were transcribed verbatim and analyzed using deductive thematic analysis. We divided excerpts into two themes: barriers and facilitators to ART adherence. The socio-ecological model was used to frame subthemes at personal, societal, and healthcare system levels. Most barriers to adherence were concentrated at the personal level, including work/study-related conditions, personal entertainment, medication issues, mental health problems, thought, and belief. At the societal level, social activities and fear of HIV disclosure were frequently mentioned as barriers. Medical care cost was the only identified barrier at the healthcare system level. The facilitators to adherence at the personal level included perceiving health deterioration, being afraid of hospitalization and medical procedures, and wishing to be healthy and move on. At the same time, perceived family support and determination to complete family without HIV transmission were identified as facilitators at the societal level. Service behaviors of healthcare providers were mentioned as facilitators to adherence at the healthcare system level. From this study, most factors associated with non-adherence in adolescents were at the personal level, and the fear of HIV disclosure was critical at the societal level. The key facilitator to adherence was the determination to be healthy and have a promising future. Our findings reinforce the importance of establishing youth-friendly services in the existing HIV care setting. More time allocation for tailored individual counseling, using other novel approaches like mHealth, online media, and involvement of social support from different sectors might be beneficial to maximize adherence self-efficacy during the transitional period of YPHIV.

Health Outcomes around Pregnancy and Exposure to HIV/Antiretrovirals (HOPE) study protocol: a prospective observational cohort study of reproductive-aged women living with HIV.

INTRODUCTION: Over 265 000 women are living with HIV in the USA, but limited research has investigated the physical, mental and behavioural health outcomes among women living with HIV of reproductive age. Health status during the reproductive years before, during and after pregnancy affects pregnancy outcomes and long-term health. Understanding health outcomes among women living with HIV of reproductive age is of substantial public health importance, regardless of whether they experience pregnancy. The Health Outcomes around Pregnancy and Exposure to HIV/Antiretrovirals (HOPE) study is a prospective observational cohort study designed to investigate physical and mental health outcomes of young women living with HIV as they age, including HIV disease course, engagement in care, reproductive health and choices and cardiometabolic health. We describe the HOPE study design, and characteristics of the first 437 participants enrolled as of 1 January 2024. METHODS AND ANALYSIS: The HOPE study seeks to enrol and follow 1630 women living with HIV of reproductive age, including those with perinatally-acquired HIV, at 12 clinical sites across 9 US states and Puerto Rico. HOPE studies multilevel dynamic determinants influencing physical, mental and social well-being and behaviours of women living with HIV across the reproductive life course (preconception, pregnancy, post partum, not or never-pregnant), informed by the socioecological model. Key research areas include the clinical course of HIV, relationship of HIV and antiretroviral medications to reproductive health, pregnancy outcomes and comorbidities and the influence of racism and social determinants of health. HOPE began enrolling in April 2022. ETHICS AND DISSEMINATION: The HOPE study received approval from the Harvard Longwood Campus Institutional Review Board, the single institutional review board of record for all HOPE sites. Results will be disseminated through conference presentations, peer-reviewed journals and lay summaries.

Genotypic Analysis of Transmitted and Acquired HIV Drug Resistance in People Living with HIV/AIDS in Surabaya, Indonesia, from 2018 to 2019.

BACKGROUND: Despite the availability of various effective antiretroviral (ARV) drugs, human immunodeficiency virus (HIV) infection has come with HIV drug resistance (HIVDR), which compromises its effectiveness in reducing HIV-related morbidity, mortality, and transmission. The emergence of transmitted (TDR) and acquired HIVDR (ADR) among antiretroviral therapy (ART)-naïve and experienced individuals have been reported in several Indonesian regions. Therefore, continuous HIVDR surveillance is needed in Indonesia, especially in Surabaya, which is identified as having the highest prevalence of HIV infection in East Java; thus, this study aimed to identify the emergence of TDR and ADR among people living with HIV/acquired immune deficiency syndrome (AIDS) (PLWHA). METHODS: Fifty-eight PLWHA infected with HIV type 1 (HIV-1), comprising 21 and 37 ART-naïve and experienced individuals were enrolled in this study, respectively. Blood samples collected from study participants were subjected to genotypic analysis, mainly towards the pol gene encoding protease (PR gene) and reverse transcriptase (RT gene) of HIV-1. RESULTS: Seventeen PR and 21 RT genes were successfully amplified and sequenced from 29 samples. HIV-1 subtyping revealed CRF01_AE as the most dominant subtype (24/29; 82.76%), followed by subtype B (3/29; 10.34%). Uncommon subtypes, including subtype D and a recombinant containing subtypes B and G genomic fragments, were also identified. TDR for PR inhibitors was not detected; however, TDR and ADR for RT inhibitors were identified in 11.11% and 41.67% of samples, respectively. Two amino acid insertions at position 69 of the RT gene (69ins), a previously never-reported mutation in Indonesia, were identified in this study. CONCLUSION: Both TDR and ADR have emerged among PLWHA residing in Surabaya, East Java, Indonesia. Uncommon drug-resistance mutations and subtypes were identified in this study. These situations might hamper ART efficacy and treatment success. Continuous surveillance of HIVDR is necessary to monitor both TDR and ADR in Indonesia.

Consensus recommendations for use of long-acting antiretroviral medications in the treatment and prevention of HIV-1: Endorsed by the American Academy of HIV Medicine, American College of Clinical Pharmacy, Canadian HIV and Viral Hepatitis Pharmacists Network, European AIDS Clinical Society, and Society of Infectious Diseases Pharmacists: An executive summary.

Five long-acting (LA) antiretrovirals (ARVs) are currently available in a limited number of countries worldwide for HIV-1 prevention or treatment - cabotegravir, rilpivirine, lenacapavir, ibalizumab, and dapivirine. Implementing use of LA ARVs in routine clinical practice requires significant changes to the current framework of HIV-1 prevention, treatment, and service provision. Given the novelty, complexity, and interdisciplinary requirements of safe and optimal use of LA ARVs, consensus recommendations on the use of LA ARVs will assist clinicians in optimizing use of these agents. The purpose of these recommendations is to provide guidance for the clinical use of LA ARVs for HIV-1 treatment and prevention. In addition, future areas of research are identified and discussed.

Consensus recommendations for use of long-acting antiretroviral medications in the treatment and prevention of HIV-1: Endorsed by the American Academy of HIV Medicine, American College of Clinical Pharmacy, Canadian HIV and Viral Hepatitis Pharmacists Network, European AIDS Clinical Society, and Society of Infectious Diseases Pharmacists.

Five long-acting (LA) antiretrovirals (ARVs) are currently available in a limited number of countries worldwide for HIV-1 prevention or treatment-cabotegravir, rilpivirine, lenacapavir, ibalizumab, and dapivirine. Implementing use of LA ARVs into routine clinical practice requires significant changes to the current framework of HIV-1 prevention, treatment, and service provision. Given the novelty, complexity, and interdisciplinary requirements needed to safely and optimally utilize LA ARVs, consensus recommendations on the use of LA ARVs will assist clinicians in optimizing use of these agents. The purpose of these recommendations is to provide guidance for the clinical use of LA ARVs for HIV-1 treatment and prevention. In addition, future areas of research are also identified and discussed.

Impact of HIV pre-exposure prophylaxis (PREP) on health-related quality of life (QOL) of patients followed up at a reference center in São Paulo, Brazil.

BACKGROUND: HIV Pre-Exposure Pophylaxis (PrEP) is provided free of charge by the Brazilian national health system. Though effective in preventing HIV infection, little is known about its impact on the health-related Quality of Life (QoL) of users. OBJECTIVE: The present study aimed at assessing the impact of PrEP on the QoL of its users. METHODS: Prospective cohort study with 114 HIV-negative participants aged 18 years or older. Participants' QoL was assessed before starting PrEP and after 7 months of use, using the self-responsive WHOQOL-bref questionnaire. Sociodemographic and behavioral aspects were described and the Wilcoxon signed-rank test with p ≤ 0.05 was considered statistically significant. RESULTS: Improvement was seen in QoL scores for the environment domain (p = 0.02), which addresses feeling of physical safety, access to information and health services, and participation in leisure activities. Furthermore, participants reported improved satisfaction with their sex life, when questioned about the social relationships domain. There was no statistically significant change in the global QoL score, in the global health score, in the physical and psychological domains, nor in the total score for the social relationships domain. As for their socio-demographic profile, most participants were white and highly educated young cisgender men who have sex with men. 76.3% had unprotected sex in the 3 months before starting PrEP. 60.5% had reported substance use: marijuana (42.1%), club drugs (35.1%), and poppers (20.2%). CONCLUSIONS: This study unveiled that PrEP benefited our cohort beyond its effectiveness in preventing HIV infection, having improved environmental aspects of QoL and self-satisfaction with sex life.

Prepare Romania: study protocol for a randomized controlled trial of an intervention to promote pre-exposure prophylaxis adherence and persistence among gay, bisexual, and other men who have sex with men.

BACKGROUND: Gay, bisexual, and other men who have sex with men (GBMSM) represent a high-risk group for HIV transmission in Romania, yet they possess few resources for prevention. Despite having no formal access to pre-exposure prophylaxis (PrEP) through the health system, GBMSM in Romania demonstrate a high need for and interest in this medication. In anticipation of a national rollout of PrEP, this study tests the efficacy of a novel strategy, Prepare Romania, that combines two evidence-based PrEP promotion interventions for GBMSM living in Romania. METHODS: This study uses a randomized controlled trial design to examine whether GBMSM living in Romania receiving Prepare Romania, a culturally adapted counseling and mobile health intervention (expected n = 60), demonstrate greater PrEP adherence and persistence than those assigned to a PrEP education control arm (expected n = 60). Participants from two main cities in Romania are prescribed PrEP and followed-up at 3 and 6 months post-randomization. PrEP adherence data are obtained through weekly self-report surveys and dried blood spot testing at follow-up visits. Potential mediators (e.g., PrEP use motivation) of intervention efficacy are also assessed. Furthermore, Prepare Romania's implementation (e.g., proportion of enrolled participants attending medical visits, intervention experience) will be examined through interviews with participants, study implementers, and healthcare officials. DISCUSSION: The knowledge gained from this study will be utilized for further refinement and scale-up of Prepare Romania for a future multi-city effectiveness trial. By studying the efficacy of tools to support PrEP adherence and persistence, this research has the potential to lay the groundwork for PrEP rollout in Romania and similar contexts. Trial registration This study was registered on ClinicalTrials.gov, identifier NCT05323123 , on March 25, 2022.

Real world community-based HIV Rapid Start Antiretroviral with B/F/TAF versus prior models of antiretroviral therapy start - the RoCHaCHa study, a pilot study.

BACKGROUND: The rapid start of antiretroviral therapy (RSA) model initiates antiretroviral therapy (ART) as soon as possible after a new or preliminary diagnosis of HIV, in advance of HIV-1 RNA and other baseline laboratory testing. This observational study aims to determine if RSA with a single tablet regimen of bictegravir, emtricitabine, and tenofovir alafenamide (B/F/TAF) is an effective regimen for achieving viral suppression and accepted by patients at the time of diagnosis. METHODS: Adults newly or preliminarily diagnosed with HIV were enrolled from October 2018 through September 2021. Real world advantage, measured in days between clinical milestones and time to virologic suppression, associated with B/F/TAF RSA was compared to historical controls. RESULTS: All Study RSA participants (n = 45) accepted treatment at their first visit and 43(95.6%) achieved virologic suppression by week 48. Study RSA participants had a significantly shorter time (median 32 days) from diagnosis to ART initiation and virologic suppression, in comparison to historical controls (median 181 days) (n = 42). Qualitative feedback from study RSA participants showed high acceptance positive response to RSA. CONCLUSIONS: RSA is feasible and well accepted by patients in a real-world community-based clinic setting. Promoting RSA in community-based clinics is an important tool in ending the HIV epidemic.

Barriers and facilitators for adherence to antiretroviral therapy, and strategies to address the barriers in key populations, Mumbai-A qualitative study.

BACKGROUND: Even though quantitative studies have described barriers to anti-retroviral therapy (ART), a more exploratory approach will provide in-depth information on these issues, and potential suggestions to address these issues at individual as well as structural level. We designed this qualitative study to examine the barriers and facilitators for antiretroviral therapy adherence in key population (KP) in Mumbai, India. We also wanted to understand the strategies adopted by these groups and get suggestions to improve adherence to ART. METHODS: This is a qualitative analysis of seven focus group discussions (FGDs) conducted with four KP subgroups in Mumbai. We conducted two FGDs each with female sex workers (FSW), men who have sex with men (MSM), male-to-female transgendered people/Hijras (TGH) each, and one FGD with people who inject drugs (IDU). We transcribed the audio-recorded electronic records of these FGDs. We also added the notes of the observers on the group dynamics to the transcribed data. We used the Framework Approach to analyse these data. RESULTS: Some experiences-such as side effects to ART medicines-were common across groups. However, incarceration as a reason for stopping ART was reported by FSWs but not by other KPs. Friends and family (including Guru) are important support systems for HIV infected individuals and adherence to ART. Stigma and discrimination by community members and general community prevent regular access of ART centres and other health care facilities. Additional factors which led to missed doses were mental health issues, alcohol use, and misplacing the ART tablets during police raids or during robbery attempts at the cruising sites. Since a common source of discrimination among peers and the community was the presence of 'Green book' (or their treatment book); the key population wanted the AIDS program to change it to digital cards so that labelling one as 'HIV positive' for being seen with the book can be avoided. CONCLUSIONS: The qualitative study helped us explore the barriers to ART among key population and the community provided specific suggestions to address them. In addition to Key Population centric enhanced adherence counselling, some administrative guidelines and procedures may need to be altered to improve adherence to ART in these populations.

SPECIFICS OF PRESCRIBING ANTIRETROVIRAL DRUGS IN THE TREATMENT OF HIV INFECTION.

HIV infection is one of the most acute problems of our time, characterized by slow development, prolonged course, and numerous clinical manifestations. Currently, there is a large number of drugs acting on different processes of human immunodeficiency virus replication, which constitute the group of highly active antiretroviral therapy (HAART). This article shows a theoretical review of modern HAART and analyzes the prescribed treatment regimens for patients with HIV infection. The study revealed two most common combinations: nucleoside reverse transcriptase inhibitors + protease inhibitors; nucleoside + non-nucleoside reverse transcriptase inhibitors.

Programme science in action: lessons from an observational study of HIV prevention programming for key populations in Lusaka, Zambia.

INTRODUCTION: Optimizing uptake of pre-exposure prophylaxis (PrEP) for individuals at risk of HIV acquisition has been challenging despite clear scientific evidence and normative guidelines, particularly for key populations (KPs) such as men who have sex with men (MSM), female sex workers (FSWs), transgender (TG) people and persons who inject drugs (PWID). Applying an iterative Programme Science cycle, building on the effective programme coverage framework, we describe the approach used by the Centre for Infectious Disease Research in Zambia (CIDRZ) to scale up PrEP delivery and address inequities in PrEP access for KP in Lusaka, Zambia. METHODS: In 2019, CIDRZ partnered with 10 local KP civil society organizations (CSOs) and the Ministry of Health (MOH) to offer HIV services within KP-designated community safe spaces. KP CSO partners led KP mobilization, managed safe spaces and delivered peer support; MOH organized clinicians and clinical commodities; and CIDRZ provided technical oversight. In December 2021, we introduced a community-based intervention focused on PrEP delivery in venues where KP socialize. We collected routine programme data from September 2019 to June 2023 using programme-specific tools and the national electronic health record. We estimated the before-after effects of our intervention on PrEP uptake, continuation and equity for KP using descriptive statistics and interrupted time series regression, and used mixed-effects regression to estimate marginal probabilities of PrEP continuity. RESULTS: Most (25,658) of the 38,307 (67.0%) Key Population Investment Fund beneficiaries were reached with HIV prevention services at community-based venues. In total, 23,527 (61.4%) received HIV testing services, with 15,508 (65.9%) testing HIV negative and found PrEP eligible, and 15,241 (98.3%) initiating PrEP. Across all programme quarters and KP types, PrEP uptake was >90%. After introducing venue-based PrEP delivery, PrEP uptake (98.7% after vs. 96.5% before, p < 0.001) and the number of initiations (p = 0.014) increased significantly. The proportion of KP with ≥1 PrEP continuation visit within 6 months of initiation was unchanged post-intervention (46.7%, 95% confidence interval [CI]: 45.7%, 47.6%) versus pre-intervention (47.2%, 95% CI: 45.4%, 49.1%). CONCLUSIONS: Applying Programme Science principles, we demonstrate how decentralizing HIV prevention services to KP venues and safe spaces in partnership with KP CSOs enabled successful community-based PrEP delivery beyond the reach of traditional facility-based services.

Safety and Effectiveness From the Cabotegravir and Rilpivirine Implementation Study in European Locations Study: Phase 3b Hybrid Type III Implementation Study Integrating Cabotegravir + Rilpivirine Long-Acting Into European Clinical Settings.

BACKGROUND: Cabotegravir + rilpivirine long-acting (CAB + RPV LA) dosed every 2 months (Q2M) is a complete regimen for the maintenance of HIV-1 virologic suppression. In this study, we report month 12 clinical outcomes in patient study participants (PSPs) in the CAB and RPV Implementation Study in European Locations (CARISEL) study. SETTING: CARISEL is a phase 3b implementation-effectiveness study. METHODS: CARISEL was designed as a 2-arm, unblinded study with centers randomized to either enhanced or standard implementation arms. For PSPs, this study is single arm, unblinded, and interventional; all PSPs switched from daily oral therapy to CAB + RPV LA dosed Q2M. The primary objective was to evaluate the perceived acceptability, appropriateness, and feasibility of CAB + RPV LA implementation for staff participants (presented separately). Clinical secondary endpoints assessed through month 12 included the proportion of PSPs with plasma HIV-1 RNA ≥50 and <50 copies/mL (Snapshot algorithm), incidence of confirmed virologic failure (CVF; 2 consecutive plasma HIV-1 RNA levels ≥200 copies/mL), adherence to injection visit windows, and safety and tolerability. RESULTS: Four hundred thirty PSPs were enrolled and treated; the mean age was 44 years (30% ≥50 years), 25% were women (sex at birth), and 22% were persons of color. At month 12, 87% (n = 373/430) of PSPs maintained HIV-1 RNA <50 copies/mL, with 0.7% (n = 3/430) having HIV-1 RNA ≥50 copies/mL. One PSP had CVF. The safety profile was consistent with previous findings. Overall, the results were similar between implementation arms. CONCLUSION: CAB + RPV LA Q2M was well tolerated and highly effective in maintaining virologic suppression with a low rate of virologic failure.

Enhanced immune reconstitution with albuvirtide in HIV-infected immunological non-responders.

Background: Incomplete immune recovery in people living with HIV/AIDS (PLWHA) remains an important clinical challenge with the lack of an effective strategy currently available to restore their T-cell immune response. This study aimed to evaluate the effect of Albuvirtide (ABT) on immune recovery in immunological non-responders (INRs) and attempted to explore potential mechanisms of ABT on the functionality of immune cells. Methods: In this prospective, open-label, controlled clinical study, participants with incomplete immune reconstitution (continuous ART over 5 years and CD4+T lymphocyte absolute count of <500 cells/µl or ART for 2-5 years and CD4+T cell count of <200 cells/µl with undetectable viral load) were received intensive treatment with ABT or maintained on the original ART regimen at a ratio of 1:1. Immune response and safety were examined within 24 weeks. In the cytological study, T subsets, cell apoptosis and cell autophagy were analyzed using immunofluorescence staining and flow cytometry from 25 blood specimens. Results: Both groups (n=25 each) were comparable in age, gender, and ART duration. At week 12, CD4+T cell count increased significantly in the intensive ABT group compared with control group (the change from baseline in CD4+T cell count: 45 vs. -5 cells/µL, p<0.001). After ABT discontinuation, CD4+T cell counts remained significantly higher in the intensive ABT group at week 24 (55 vs. -5 cells/µL, p=0.012). In laboratory analysis, naïve CD4+ T cell amounts were lowest among participants with unsatisfactory immune response (uIR) to ABT (p=0.001). The proportion of caspase 3+CD45RA+CD31+CD4+ T cells was significantly lower in participants with satisfactory immune response (sIR) to ABT (p<0.05). Conclusion: Significant CD4+T cell count increase suggests ABT enhances immune function in INRs which may be attributed to its antiviral properties as well as its ability to increase thymic cell output and decrease cell apoptosis.

[Long-acting injection therapies: New opportunities and challenges]. / Lang wirksame Injektionstherapien: Chance und Herausforderung.

Since the development of an effective antiretroviral therapy (ART) in 1996, substantial progress has been made in terms of efficacy, safety and ease of use. While at the beginning of the ART era the foremost goal necessarily was patient survival, over time it has become increasingly possible to shift the focus towards aspects of patient's quality of life. The latest developments are the long-acting injection therapies (LAI), foregoing for the first time the necessity to take pills. The only available injection therapy so far comprises 2 intramuscular injections every 2 months, with 3 ml of Cabotegravir 600 mg and 3 ml of Rilpivirine 900 mg being injected, respectively. Through this, patient's needs that were hitherto precluded from consideration could be addressed. These needs are inextricably linked to the stigmata people living with HIV (PLWH) are still confronted with on a daily basis. LAI have the potential to relieve PLWH of some of the heavy psychological burdens associated with the continued stigmatization. However, as a new therapy, new challenges need to be considered the use of LAI.

The Effect of Real-Time Medication Monitoring-Based Digital Adherence Tools on Adherence to Antiretroviral Therapy and Viral Suppression in People Living With HIV: A Systematic Literature Review and Meta-Analysis.

BACKGROUND: Universal antiretroviral therapy (ART) has led to improved treatment outcomes in persons living with HIV. Adherence to ART is required to achieve viral suppression. Real-time medication monitoring (RTMM)-based digital adherence tools (DATs) could be effective in improving ART adherence and viral suppression in persons living with HIV. OBJECTIVES: The primary and secondary objectives of this review were to assess the effect of RTMM-based DATs on improving ART adherence and viral load suppression. METHODS: We searched MEDLINE, Embase, and Global Health for publications published through October 11, 2022. Narrative synthesis and random effects meta-analyses were conducted to synthesize the results. RESULTS: Of 638 papers identified, 8 were included. Six studies were randomized controlled trials (RCTs), and 2 were cohort studies. Two studies, an RCT in China (mean adherence: 96.2% vs 89.1%) and a crossover cohort study in Uganda (mean adherence: 84% vs 93%), demonstrated improved ART adherence. No studies demonstrated improved viral suppression. In the meta-analyses, we estimated that RTMM-based digital adherence tools had a statistically insignificant small positive effect on ART adherence and viral suppression with a standardized mean difference of 0.1922 [95% CI: -0.0268 to 0.4112, P-value: 0.0854] and viral suppression with an odds ratio of 1.3148 [95% CI: 0.9199 to 1.8791, P-value: 0.1331]. CONCLUSIONS: Our meta-analyses found that RTMM-based DATs did not have a significant effect on ART adherence and viral suppression. However, due to few published studies available, heterogeneity of target populations, intervention designs, and adherence measurement instruments, more data are required to provide conclusive evidence.