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HIV-HBV coinfected patients have higher rates of liver-related morbidity, hospitalizations, and mortality compared to HBV or HIV mono-infected ones. Clinical studies have shown an accelerated progression of liver fibrosis and an increased incidence of HCC, resulting from the combined action of HBV replication, immune-mediated hepatocytolysis, and HIV-induced immunosuppression and immunosenescence. Antiviral therapy based on dually active antiretrovirals is highly efficient, but late initiation, global disparities in accessibility, suboptimal regimens, and adherence issues may limit its impact on the development of end-stage liver disease. In this paper, we review the mechanisms of liver injuries in HIV-HBV coinfected patients and the novel biomarkers that can be used for treatment monitoring in HIV-HBV coinfected persons: markers that assess viral suppression, markers for liver fibrosis evaluation, and predictors of oncogenesis. [ABSTRACT FROM AUTHOR]

The recommendation to start antiretroviral treatment independently of CD4 or viral load count is adopted as a strategy for reducing HIV/AIDS incidence rates in countries with a high prevalence rate, such as Lesotho. For example, the number of new HIV infections has lowered from 20,000 in 2010 to 11,000 in 2018 [UNAIDS Country Factsheets. (2019). ]. Lesotho introduced the 'test and treat' strategy in 2013 to address the HIV/AIDS pandemic, representing a shift from the provider-initiated HIV testing and counselling guidelines. The purpose of this paper was to understand pregnant women's concerns about starting antiretroviral treatment to limit risks of mother-to-child HIV-transmission during the implementation of 'test and treat' protocol in Lesotho. The study used a qualitative research approach and collected information from Lesotho public antenatal clinics. In-depth interviews were conducted with eighteen pregnant women living with HIV/AIDS and data were analysed manually following the constructivist grounded theory. Findings reveal the sadness experienced at the diagnosis stage, concerns about accessing treatment and maintaining adherence, and concerns about disclosure. It was concluded that these factors stemmed from fears about triggering enacted stigma in the illness experience of pregnant women, which could hamper the implementation of the 'test and treat' protocol in Lesotho. [ABSTRACT FROM AUTHOR]

Liver-related diseases are associated with the high levels of morbidity and mortality in people living with HIV. Between 13% and 18% of all-cause mortality in HIV-infected patients involves a liver-related damage, this being one of the main causes of death not related to acquired immunodeficiency syndrome (AIDS). People living with HIV, even when the disease is under control, are more likely to develop pathologies and complications of a liver-related origin than the general population, both due to common causes such as alcoholism, non-alcoholic fatty liver disease, hepatic viral infections and ageing, in addition to specific HIV-related processes such as antiretroviral treatment toxicity and liver damage inherent to HIV infection. On the other hand, some antiretroviral drugs may have a beneficial effect in reversing liver fibrosis in patients with HIV and chronic liver disease. This paper reviews the main risk factors associated with liver disease in people living with HIV and the role of antiretroviral therapy (ART) in this disease. [ABSTRACT FROM AUTHOR]

Introduction: retaining patients in antiretroviral treatment (ART) is essential for successful outcomes. Unfortunately, Cameroon continues to report suboptimal ART retention. This study focused on identifying determinants of ART retention in three HIV clinics in Cameroon within the HIV treat all context. Methods: a medical chart review of 423 subjects who initiated ART between July and September 2016 in the Limbe, Bamenda and Jamot Hospitals. Patients' sociodemographic and clinical characteristics and ART retention data were abstracted using structured paper forms. Chi square test was used to assess bivariate associations. Logistic regression was used to adjust for confounders. P-value was set at <0.05 at 95% confidence interval. Results: the mean age was 40±11 years, and 65.1% were females. Antiretroviral treatment retention after 24 months was 309/392 (78.83%) and 30/423 (7.1%) were transferred-out, 11/423 (2.6%) reported dead and 73/423 (17.3%) lost to follow-up. HIV status disclosure (AOR 0.16 95% CI: 0.05-0.51, p<0.01) and age group 31-50 years (AOR 3.63, 95% CI: 1.04- 12.59, P= 0.04) were associated with lower and higher ART retention respectively. Conclusion: about a quarter of the participants were not retained in ART after 24 months. Patient-level factors determined ART retention. These factors should be considered in designing strategies to improve ART retention. More research is needed to identify other determinants of ART retention under the HIV treat all strategy. [ABSTRACT FROM AUTHOR]

Adolescents living with HIV (ALHIV) face unique challenges resulting in persistent treatment gaps, particularly viral non-suppression. Country programs adopt policies, guidelines, and innovations, based on WHO recommendations and best practices from elsewhere. However, it is unclear to what extent these tools address the management of adolescents with viral non-suppression. We report on a review of guidelines for the provision of HIV services to ALHIV in Namibia. We conducted a systematic document review using Content Analysis and Thematic Analysis methodology, and the READ approach. We identified seven relevant policy documents, four of which somewhat addressed viral non-suppression (treatment gap) in ALHIV and outlined interventions to improve treatment outcomes in adolescents considering their lived experience and unique challenges. The persistent treatment gap may reflect policy implementation gaps in specifically addressing viral non-suppression. It may be worthwhile to leverage existing documents to develop specific operational guidance for ALHIV with unsuppressed viral loads. Plain Language Summary : Study analysing the potential gaps in the contents of policies and programme documents meant to address management of adolescents living with HIV with high viral load Viral load suppression is a huge challenge in adolescents living with HIV (ALHIV). Globally, adolescents lag when compared to children and adults in achieving viral suppression levels set for achieving HIV epidemic control. The WHO and global HIV program initiatives recommend evidence-based interventions to be included in policies and guidelines to address unique barriers adolescents face that prevent them from staying in HIV care and adhering to their medication. The extent to which country policies guide service providers in managing high viral load cases among adolescents is important in identifying and addressing the persistent gaps. We reviewed the contents of policies, guidelines and other programmatic documents that address HIV management in adolescents in Namibia to assess the extent to which the documents guide management of ALHIV who have high viral load. Seven documents addressing management of ALHIV in Namibia were identified. Four documents address viral suppression among adolescents and recommend some interventions to improve treatment outcomes in adolescents in general. The documents acknowledge the uniqueness of the adolescence, with unique experiences and challenges. However, the documents fall short in providing comprehensive and specific guidance in managing adolescents with high viral loads, for program implementers and direct service providers for ALHIV. The fragmented guidance on managing adolescents with unsuppressed viral loads may be leading to implementation gaps or uncertainties among service providers on how to manage unique cases. It would be essential to focus future efforts on consolidation or development of comprehensive guidance on management of adolescents with high viral load, and capacitating the healthcare providers and stakeholders engaged in addressing social determinants of health affecting these adolescents. A multisectoral approach may provide a pathway to improved viral suppression among ALHIV. [ABSTRACT FROM AUTHOR]

Person-centered care (PCC) aims to improve client's experiences in HIV care while advancing outcomes. This study team developed the PCC assessment tool (PCC-AT) to assess PCC service performance in HIV treatment settings in Ghana. Study objectives aimed to describe the range of PCC-AT scores within and across study facilities and examine the feasibility of PCC-AT implementation in diverse HIV treatment settings. The PCC-AT was piloted at five health facilities providing HIV services among 37 staff. Immediately following each pilot, focus group discussions (FGDs) were conducted to gather feasibility data. Thematic qualitative analysis was conducted on translated FGD transcripts. Across facilities, providers scored highest in the staffing domain, followed by service provision, and direct client support. Time required to implement the PCC-AT averaged 62 minutes. Providers described the tool as well-structured, user-friendly, relevant, reflective of the core PCC delivery elements, and useful in elucidating actions to improve PCC service delivery across domains. The PCC-AT holds potential to strengthen activities that support clients' broader clinical, mental and psychosocial wellbeing by offering friendly services that attend to each client's holistic needs while contributing progress towards epidemic control. [ABSTRACT FROM AUTHOR]

Introduction: Person-centered care (PCC) is considered a fundamental approach to address clients' needs. There is a dearth of data on specific actions that HIV treatment providers identify as priorities to strengthen PCC. Objective: This study team developed the Person-Centered Care Assessment Tool (PCC-AT), which measures PCC service delivery within HIV treatment settings. The PCC-AT, including subsequent group action planning, was implemented across 29 facilities in Zambia among 173 HIV treatment providers. Mixed-methods study objectives included: (1) identify types of PCC-strengthening activities prioritized based upon low and high PCC-AT scores; (2) identify common themes in PCC implementation challenges and action plan activities by low and high PCC-AT score; and (3) determine differences in priority actions by facility ART clinic volume or geographic type. Methods: The study team conducted thematic analysis of action plan data and cross-tabulation queries to observe patterns across themes, PCC-AT scores, and key study variables. Results: The qualitative analysis identified 39 themes across 29 action plans. A higher proportion of rural compared to urban facilities identified actions related to stigma and clients' rights training; accessibility of educational materials and gender-based violence training. A higher proportion of urban and peri-urban compared to rural facilities identified actions related to community-led monitoring. Discussion: Findings provide a basis to understand common PCC weaknesses and activities providers perceive as opportunities to strengthen experiences in care. Conclusion: To effectively support clients across the care continuum, systematic assessment of PCC services, action planning, continuous quality improvement interventions and re-measurements may be an important approach. [ABSTRACT FROM AUTHOR]

IRIS is a common complication in HIV-infected patients treated for tuberculosis (TB) and cART. Our aim was to evaluate NK cell reconstitution in HIV-infected patients with TB-IRIS compared to those without IRIS. 147 HIV-infected patients with TB from the CAMELIA trial were enrolled. HIV+TB+ patients were followed for 32 weeks. The NK cell repertoire was assessed in whole blood at different time points. As CAMELIA has two arms (early and late cART initiation), we analysed them separately. At enrolment, individuals had low CD4 cell counts (27 cells/mm3) and high plasma viral loads (5.76 and 5.50 log/mL for IRIS and non-IRIS individuals, respectively). Thirty-seven people developed IRIS (in the early and late arms). In the early and late arms, we observed similar proportions of total NK and NK cell subsets in TB-IRIS and non-IRIS individuals during follow-up, except for the CD56dimCD16pos (both arms) and CD56dimCD16neg (late arm only) subsets, which were higher in TB-IRIS and non-IRIS individuals, respectively, after cART. Regarding the repertoire and markers of NK cells, significant differences (lower expression of NKp30, NKG2A (CD159a), NKG2D (CD314) were observed in TB-IRIS compared to non-IRIS individuals after the start of cART. In the late arm, some changes (increased expression of CD69, NKG2C, CD158i) were observed in TB-IRIS compared to non-IRIS individuals, but only before cART initiation (during TB treatment). KIR expression by NK cells (CD158a and CD158i) was similar in both groups. CD69 expression by NK cells decreased in all groups. Expression of the NCR repertoire (NKp30, NKp44, NKp46) has similar kinetics in TB-IRIS subjects compared to non-IRIS subjects regardless of the arm analysed. NK cell reconstitution appeared to be better in TB-IRIS subjects. Although NK cell reconstitution is impaired in HIV infection after cART, as previously reported, it does not appear to be affected by the development of IRIS in HIV and TB-infected individuals. [ABSTRACT FROM AUTHOR]

Endothelial glycocalyx (EG) derangement has been associated with cardiovascular disease (CVD). Studies on EG integrity among people living with HIV (PLWH), are lacking. We conducted a prospective cohort study among treatment-naïve PLWH who received emtricitabine/tenofovir alafenamide, combined with either an integrase strand transfer inhibitor (INSTI, dolutegravir, raltegravir or elvitegravir/cobicistat), or a protease inhibitor (PI, darunavir/cobicistat). We assessed EG at baseline, 24 (±4) and 48 (±4) weeks, by measuring the perfused boundary region (PBR, inversely proportional to EG thickness), in sublingual microvessels. In total, 66 consecutive PLWH (60 (90.9%) males) with a median age (interquartile range, IQR) of 37 (12) years, were enrolled. In total, 40(60.6%) received INSTI-based regimens. The mean (standard deviation) PBR decreased significantly from 2.17 (0.29) μm at baseline to 2.04 (0.26) μm (p = 0.019), and then to 1.93 (0.3) μm (p < 0.0001) at 24 (±4) and 48 (±4) weeks, respectively. PBR did not differ among treatment groups. PLWH on INSTIs had a significant PBR reduction at 48 (±4) weeks. Smokers and PLWH with low levels of viremia experienced the greatest PBR reduction. This study is the first to report the benefit of antiretroviral treatment on EG improvement in treatment-naïve PLWH and depicts a potential bedside biomarker and therapeutic target for CVD in PLWH. [ABSTRACT FROM AUTHOR]

Aim: DIAMANTE is a retrospective and prospective, non-interventional, cohort study to describe the effectiveness of darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) in real clinical practice in Italy. Patients & methods: The study enrolled 246 patients: group 1 included patients treated with a darunavir-based regimen (n = 81); group 2 included patients who received antiretroviral treatment not including darunavir before D/C/F/TAF (n = 43); and group 3 included naive patients (n = 122). Effectiveness was evaluated as the virological response at week 48. Results: The D/C/F/TAF virological response rate was 72.1–78.8% and was obtained despite longer follow-up intervals due to the coronavirus 2019 pandemic. The safety of D/C/F/TAF was good as was the overall patient satisfaction and quality of life. Conclusion: This study confirmed the effectiveness and tolerability of D/C/F/TAF in a real-life setting both in naive and pretreated patients, with and without darunavir. Clinical Trial Registration:NCT03577470 (ClinicalTrials.gov) Darunavir-based antiretroviral therapies have been shown to be effective in providing a long-lasting reduction of HIV-RNA level in the blood up over detection limit and to have a good safety profile in patients infected with HIV. This study shows the effectiveness and safety of the combination of darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) given to patients living with HIV. The study, which took place in Italy, included 246 patients infected with HIV. The groups were: Patients that had previously received a darunavir-based treatment; Patients that had received a different antiretroviral treatment (not including darunavir) and; Patients that had never been treated The results of the study confirm that D/C/F/TAF is safe and caused a strong virological response. Italian real-world study confirms efficacy and safety of darunavir-based therapy for HIV patients. Darunavir/cobicistat/emtricitabine/tenofovir alafenamide regimen induces a strong virological response, ensuring long-lasting results. Promising for HIV treatment. #HIVresearch #AntiretroviralTherapy. [ABSTRACT FROM AUTHOR]

In the last years, many antiretroviral drugs (ART) have been developed with increased efficacy. Nowadays, the main reasons for treatment switches are adverse events, proactive strategy or simplification. We conducted a retrospective cohort study to investigate the reason for treatment interruption in the last 20 years. We merged data of eight cohorts of the SCOLTA project: lopinavir/r (LPV), atazanavir/r (ATV), darunavir/r or /c (DRV), rilpivirine (RPV), raltegravir (RAL), elvitegravir/c (EVG), dolutegravir (DTG) and bictegravir (BIC). We included 4405 people with HIV (PWH). Overall, 664 (15.1%), 489 (11.1%), and 271 (6.2%) PWH interrupted the treatment in the first, second, and third years after starting a new ART. Looking at the interruption in the first year, the most frequent causes were adverse events (3.8%), loss to follow-up (3.7%), patients' decisions (2.6%), treatment failure (1.7%), and simplification (1.3%). In the multivariate analysis regarding experienced patients, treatment with LPV, ATV, RPV or EVG/c, having less than 250 CD4 cells/mL, history of intravenous drug use, and HCV positivity were associated with an increased risk of interruption. In naive people, only LPV/r was associated with an increased risk of interruption, while RPV was associated with a lower risk. In conclusion, our data on more than 4400 PWH show that adverse events have represented the most frequent cause of treatment interruptions in the first year of ART (3.84%). Treatment discontinuations were more frequent during the first year of follow-up and decreased thereafter. First-generation PI in both naïve and experienced PWH, and EVG/c, in experienced PWH, were associated with a higher risk of treatment interruptions. [ABSTRACT FROM AUTHOR]

Abstract Background Human immunodeficiency virus (HIV)/Acquired Immune Deficiency Syndrome (AIDS) is a public health issue of global importance. To our knowledge, no previous meta-analysis documenting the prevalence, socio-demographic, and service use determinants associated with HIV/AIDS disclosure to infected children has been conducted. The present study aimed to determine the prevalence, socio-demographics and service use determinants associated with the disclosure of HIV/AIDS status to infected children. Methods Studies in English published between 01 January 1985 and 01 November 2021, and available on PubMed, Scopus, Web of Science, and Cochrane electronic databases were searched. After reviewing for study duplicates, the full-text of selected articles were assessed for eligibility using Population, Intervention, Comparator, Outcomes (PICO) criteria. We used fixed and random-effects meta-analysis models to estimate the pooled prevalence, pooled odds ratio (OR), and 95% confidence intervals. Results After article duplicates were excluded, assessments of abstracts were completed, and full-text papers evaluated, 37 studies were included in this meta-analysis. The prevalence of the disclosure of HIV status to children was measured to be 41% in this research. The odds that a child of 10 years and older is informed that they are HIV-positive is 3.01 time the odds that younger children are informed. Those children who had primary or lower schooling level were 2.41 times more likely to be informed of their HIV-positive status than children with higher levels of schooling. Children who had a non-biological parents were 3.17 times more likely to have been disclose being HIV-positive; social support (OR = 8.29, 95%CI = 2.34, 29.42), children who had higher levels of social supports were 8.29 times more likely to disclose HIV-positive; the primary educational level of caregivers (OR = 2.03, 95%CI = 1.43, 2.89), respondents who had caregivers with primary education level were 2.03 times more likely to disclose HIV-positive; antiretroviral treatment (ART) adherence (OR = 2.59, 95%CI = 1.96, 3.42), participants who adhered to ART were 2.59 times more likely to disclose HIV-positive and hospital follow-up (OR = 2.82, 95%CI = 1.85, 4.29), those who had hospital follow-up were 2.82 times more likely to disclose HIV-positive; were all significantly associated with the disclosure of HIV/AIDS status to infected children. Conclusion Such data are of importance for healthcare pediatrics HIV care professionals. Facilitating HIV diagnosis and disclosure to the infected children and ensuring access to HIV treatment will likely prevent secondary HIV transmission. Healthcare professionals are expected to provide age-appropriate counseling services to this population.

Background: Four large community-randomized trials examining universal testing and treatment (UTT) to reduce HIV transmission were conducted between 2012–2018 in Botswana, Kenya, Uganda, Zambia and South Africa. In 2014, the UNAIDS 90–90-90 targets were adopted as a useful metric to monitor coverage. We systematically review the approaches used by the trials to measure intervention delivery, and estimate coverage against the 90–90-90 targets. We aim to provide in-depth understanding of the background contexts and complexities that affect estimation of population-level coverage related to the 90–90-90 targets. Methods: Estimates were based predominantly on "process" data obtained during delivery of the interventions which included a combination of home-based and community-based services. Cascade coverage data included routine electronic health records, self-reported data, survey data, and active ascertainment of HIV viral load measurements in the field. Results: The estimated total adult populations of trial intervention communities included in this study ranged from 4,290 (TasP) to 142,250 (Zambian PopART Arm-B). The estimated total numbers of PLHIV ranged from 1,283 (TasP) to 20,541 (Zambian PopART Arm-B). By the end of intervention delivery, the first-90 target (knowledge of HIV status among all PLHIV) was met by all the trials (89.2%-94.0%). Three of the four trials also achieved the second- and third-90 targets, and viral suppression in BCPP and SEARCH exceeded the UNAIDS target of 73%, while viral suppression in the Zambian PopART Arm-A and B communities was within a small margin (~ 3%) of the target. Conclusions: All four UTT trials aimed to implement wide-scale testing and treatment for HIV prevention at population level and showed substantial increases in testing and treatment for HIV in the intervention communities. This study has not uncovered any one estimation approach which is superior, rather that several approaches are available and researchers or policy makers seeking to measure coverage should reflect on background contexts and complexities that affect estimation of population-level coverage in their specific settings. All four trials surpassed UNAIDS targets for universal testing in their intervention communities ahead of the 2020 milestone. All but one of the trials also achieved the 90–90 targets for treatment and viral suppression. UTT is a realistic option to achieve 95–95-95 by 2030 and fast-track the end of the HIV epidemic. [ABSTRACT FROM AUTHOR]

Objectives: International lockdowns during the COVID‐19 pandemic impacted antiretroviral drug supplies in Indonesia. We assessed the impact of antiretroviral treatment (ART) provision and being lost to follow‐up (LTFU) on people living with HIV, attending a key population‐focused HIV clinic in Denpasar, Bali. Methods: This was a retrospective note review of anonymized data from adult Indonesian patients living with HIV. We collected demographic data and information on being LTFU, and assessed the numbers of patients impacted by ART switches from fixed‐dose combination (FDC) tenofovir/lamivudine/efavirenz to multi‐pill zidovudine‐based regimens, during the first international lockdown from March 2020. Results: Records of 260 Indonesian adult patients registered for HIV care and prescribed ART were reviewed; 240 (92.3%) were men, and 90% were men who have sex with men. Between 13 March and 28 May 2020, 214 (87%) out of 247 patients (previously diagnosed with HIV) had to switch to individual, multi‐pill zidovudine‐based regimens from their FDC. The switch lasted a mean of 35 days (range 10–85). Twenty‐five patients (10%) were LTFU; patients who switched were more likely to remain in care. Data on viral load status and toxicity are lacking as laboratory testing requires self‐payment. Conclusions: The majority of patients living with HIV had no choice but to switch to multi‐pill, zidovudine‐based regimens. Despite significant efforts to minimize the impact of lockdown on care, 10% of patients were LTFU. Patients switching ART required greater clinic attention and support, improving retention. Complete national data are needed to understand the impact of ART stockouts on virological suppression and drug resistance throughout Indonesia. [ABSTRACT FROM AUTHOR]

Objective: The primary endpoint of the study was to determine the proportion of patients with HIV RNA < 50 copies/mL at 48 weeks. Design: Phase IV, multicentric, open-label, single-arm clinical trial of participants recruited in 2018–2019 to evaluate the efficacy and safety of tenofovir alafenamide/emtricitabine/elvitegravir-cobicistat (TAF/FTC/EVG-c) as first-line treatment in HIV-1 infected naïve participants with advanced disease. Methods: Adverse events were graded according to the Division of AIDS scale version 2.0. Quantitative variables were recorded as median and interquartile range, and qualitative variables as absolute number and percentage. T-Student or Wilcoxon tests were used to analyze intragroup differences of the continuous variables. Results: Fifty participants were recruited with a baseline median CD4 lymphocyte count of 116 cells/µL and a viral load of 218,938 copies/mL. The proportion of patients with viral load <50 copies/mL at week 48 was 94% in the per-protocol analysis, with a median time of 1.9 months to achieve it. Three adverse events attributed to the study drug caused trial discontinuation. Conclusions: the use of TAF/FTC/EVG-c in patients with advanced HIV disease in our study demonstrated efficacy comparable to data from pivotal clinical trials with a good safety profile. [ABSTRACT FROM AUTHOR]

Disparities in antiretroviral treatment (ART) access by race for men who have sex with men (MSM) with HIV persist. We assessed whether race-based medical mistrust and HIV stigma impact ART adherence among MSM with HIV. Longitudinal data were drawn from a RCT of a messaging intervention to promote sexual health among MSM. Regression models tested associations between baseline race-based medical mistrust, HIV stigma, and ART adherence at follow-up. In multivariable models with the overall sample of MSM with HIV (n = 383), baseline medical mistrust was negatively associated with ART adherence 3-months post-baseline. Among participants of color (i.e., Black/African American, Hispanic/Latino, or another race; n = 301), HIV stigma was negatively associated with optimal ART adherence 6-months post-baseline. Medical mistrust was longitudinally associated with reduced ART adherence among racially and ethnically diverse MSM with HIV. HIV-related services might prioritize patients reporting medical mistrust for additional supports. [ABSTRACT FROM AUTHOR]

This study is motivated by the challenges faced by clinics in sub‐Saharan Africa in allocating scarce and unreliable supply of antiretroviral drugs (ARVs) among a large pool of eligible patients. Existing discussion of ARV allocation is focused on qualitative rules for prioritizing certain socioeconomic and demographic patient segments over others at the national level. However, such prioritization rules are of limited utility in providing quantitative guidance on scaling up of treatment programs at individual clinics. In this study, we take the perspective of a clinic administrator whose objective is to maximize the quality‐adjusted survival of the entire patient population in its service area by allocating scarce and unreliable supply of drugs among two activities: initiating treatment for untreated patients and continuing treatment for previously treated patients. The key trade‐off underlying this allocation decision is between the marginal health benefit obtained by initiating an untreated patient on treatment and that obtained by avoiding treatment interruption of a treated patient. This trade‐off has not been explicitly studied in the clinical literature, which focuses either on the incremental value obtained from initiating treatment (over no treatment) or on the value of providing continuous treatment (over interrupted treatment) but not on the difference of the two. We cast the clinic's problem as a stochastic dynamic program and provide a partial characterization of the optimal policy, which consists of dynamic prioritization of patient segments and is characterized by state‐dependent thresholds. We use this structure of the optimal policy to design a simpler Two‐Period heuristic and show that it substantially outperforms the Safety‐Stock heuristic, which is commonly used in practice. In our numerical experiments based on realistic parameter values, the performance of the Two‐Period heuristic is within 4% of the optimal policy whereas that of the Safety‐Stock heuristic can be as much as 20% lower than that of the optimal policy. Our model can serve as a basis for developing a decision support tool for clinics to design their ARV treatment program scale‐up plans. [ABSTRACT FROM AUTHOR]

In spite of the efficacy of combinational antiretroviral treatment (cART), HIV-1 persists in the host and infection is associated with chronic inflammation, leading to an increased risk of comorbidities, such as cardiovascular diseases, neurocognitive disorders, and cancer. Myeloid cells, mainly monocytes and macrophages, have been shown to be involved in the immune activation observed in HIV-1 infection. However, less attention has been paid to neutrophils, the most abundant circulating myeloid cell, even though neutrophils are strongly involved in tissue damage and inflammation in several chronic diseases, in particular, autoimmune diseases. Herein, we performed a longitudinal characterization of neutrophil phenotype and we evaluated the interplay between neutrophils and T cells in the model of pathogenic SIVmac251 experimental infection of cynomolgus macaques. We report that circulating granulocytes consists mainly of immature CD10- neutrophils exhibiting a prime phenotype during primary and chronic infection. We found that neutrophil priming correlates with CD8+ T cell activation. Moreover, we provide the evidence that neutrophils are capable of modulating CD4+ and CD8+ T-cell proliferation and IFN-γ production in different ways depending on the time of infection. Thus, our study emphasizes the role of primed immature neutrophils in the modulation of T-cell responses in SIV infection. [ABSTRACT FROM AUTHOR]

Objective: As HIV shifts from "death sentence" to "chronic condition," disclosure of HIV status to intimate partners and family is a significant component of both prevention and treatment adherence. While disclosure is closely considered in many studies, few examine middle-aged and older persons' (age 40+) perspectives or practices. We trace older rural South Africans' views on HIV disclosure to their partners and family members in a high prevalence community over a period of extensive antiretroviral treatment (ART) rollout. Methods: Community focus group discussions (FGD) conducted in 2013 and 2018 show shifts in older persons' thinking about HIV disclosure. Findings: Our FGD participants saw fewer negative consequences of disclosure in 2018 than in 2013, and highlighted positive outcomes including building trust (partners) as well as greater support for medication collection and adherence (family). Discussion: Particularly as the epidemic ages in South Africa and globally, tracing changes in older persons' views on disclosure is an important step in developing messaging that could enhance treatment as prevention and ART adherence. [ABSTRACT FROM AUTHOR]

With the advent of HIV, most countries embarked on antiretroviral (ARV) treatment with the stated aim of reducing transmission, suppressing viral load, improving quality of life of patients and prolonging life expectancy. South Africa has been the epicentre of HIV infections, with 3.4 million people receiving antiretroviral treatment. This article evaluates the outcomes of the antiretroviral treatment in the rural setting of Mankweng Area, at the Phela-O-Phedise ARV Clinic, Limpopo Province. The article seeks to establish the proportion of adults with viral load suppression among people on antiretroviral treatment for a period of 12 months as well as the factors associated with failure to achieve viral load suppression among such patients. The article administered a questionnaire by mining medical records of 415 patients at the medical facility, which introduced a limitation in that the data does not capture the daily life conditions of the participants under investigation. It uses the binomial logistic regression model to identify factors associated with failure to suppress viral load; and it explores the health belief model, theory of planned behaviour and theory of gender and health to interpret results, as well as the theory of change and the results chain to assess performance of the intervention. The article concludes that antiretroviral treatment was effectively and efficiently implemented, and that it has achieved its main objective of suppressing the viral load. Almost 78% of patients on ARV treatment achieved viral load suppression, whereas 22% failed to do so. It is apparent that failure to suppress viral load is due to poor adherence to treatment; and the article recommends that HIV testing and diagnosis need to be conducted at early stages and that adherence counselling be up scaled. [ABSTRACT FROM AUTHOR]

Background: Introduction of tenofovir (TDF) plus lamivudine (3TC) and dolutegravir (DTG) in first- and second-line HIV treatment regimens in South Africa warrants characterization of acquired HIV-1 drug resistance (ADR) mutations that could impact DTG-based antiretroviral therapy (ART). In this study, we sought to determine prevalence of ADR mutations and their potential impact on susceptibility to drugs used in combination with DTG among HIV-positive adults (≥ 18 years) accessing routine care at a selected ART facility in KwaZulu-Natal, South Africa. Methods: We enrolled adult participants in a cross-sectional study between May and September 2019. Eligible participants had a most recent documented viral load (VL) ≥ 1000 copies/mL after at least 6 months on ART. We genotyped HIV-1 reverse transcriptase and protease genes by Sanger sequencing and assessed ADR. We characterized the effect of ADR mutations on the predicted susceptibility to drugs used in combination with DTG. Results: From 143 participants enrolled, we obtained sequence data for 115 (80%), and 92.2% (95% CI 85.7–96.4) had ADR. The proportion with ADR was similar for participants on first-line ART (65/70, 92.9%, 95% CI 84.1–97.6) and those on second-line ART (40/44, 90.9%, 95% CI 78.3–97.5), and was present for the single participant on third-line ART. Approximately 89% (62/70) of those on first-line ART had dual class NRTI and NNRTI resistance and only six (13.6%) of those on second-line ART had major PI mutations. Most participants (82%) with first-line viraemia maintained susceptibility to Zidovudine (AZT), and the majority of them had lost susceptibility to TDF (71%) and 3TC (84%). Approximately two in every five TDF-treated individuals had thymidine analogue mutations (TAMs). Conclusions: Susceptibility to AZT among most participants with first-line viraemia suggests that a new second-line regimen of AZT + 3TC + DTG could be effective. However, atypical occurrence of TAMs in TDF-treated individuals suggests a less effective AZT + 3TC + DTG regimen in a subpopulation of patients. As most patients with first-line viraemia had at least low-level resistance to TDF and 3TC, identifying viraemia before switch to TDF + 3TC + DTG is important to avoid DTG functional monotherapy. These findings highlight a need for close monitoring of outcomes on new standardized treatment regimens. [ABSTRACT FROM AUTHOR]

Introduction: Differentiated service delivery (DSD) models for HIV treatment decrease health facility visit frequency and limit healthcare facility‐based exposure to severe acute respiratory syndrome coronavirus 2. However, two important evidence gaps include understanding DSD effectiveness amongst clients commencing DSD within 12 months of antiretroviral treatment (ART) initiation and amongst clients receiving only single annual clinical consultations. To investigate these, we pooled data from two cluster‐randomized trials investigating community‐based DSD in Zimbabwe and Lesotho. Methods: Individual‐level participant data of newly stable adults enrolled between 6 and 12 months after ART initiation were pooled. Both trials (conducted between August 2017 and July 2019) had three arms: Standard‐of‐care three‐monthly ART provision at healthcare facilities (SoC, control); ART provided three‐monthly in community ART groups (CAGs) (3MC) and ART provided six‐monthly in either CAGs or at community‐distribution points (6MC). Clinical visits were three‐monthly in SoC and annually in intervention arms. The primary outcome was retention in care and secondary outcomes were viral suppression (VS) and number of unscheduled facility visits 12 months after enrolment. Individual‐level regression analyses were conducted by intention‐to‐treat specifying for clustering and adjusted for country. Results and Discussion: A total of 599 participants were included; 212 (35.4%), 128 (21.4%) and 259 (43.2%) in SoC, 3MC and 6MC, respectively. Few participants aged <25 years were included (n = 32). After 12 months, 198 (93.4%), 123 (96.1%) and 248 (95.8%) were retained in SoC, 3MC and 6MC, respectively. Retention in 3MC was superior versus SoC, adjusted risk difference (aRD) = 4.6% (95% CI: 0.7%−8.5%). Retention in 6MC was non‐inferior versus SoC, aRD = 1.7% (95% CI: −2.5%−5.9%) (prespecified non‐inferiority aRD margin −3.25%). VS was similar between arms, 99.3, 98.6 and 98.1% in SoC, 3MC and 6MC, respectively. Adjusted risk ratio's for VS were 0.98 (95% CI: 0.92−1.03) for 3MC versus SoC, and 0.98 (CI: 0.95−1.00) for 6MC versus SoC. Unscheduled clinic visits were not increased in intervention arms: incidence rate ratio = 0.53 (CI: 0.16−1.80) for 3MC versus SoC; and 0.82 (CI: 0.25−2.79) for 6MC versus SoC. Conclusions: Community‐based DSD incorporating three‐ and six‐monthly ART refills and single annual clinical visits were at least non‐inferior to standard facility‐based care amongst newly stable ART clients aged ≥25 years. ClinicalTrials.gov: NCT03238846 & NCT03438370 [ABSTRACT FROM AUTHOR]