Peer-led counselling with problem discussion therapy for adolescents living with HIV in Zimbabwe: A cluster-randomised trial

Background Adolescents living with HIV have poor virological suppression and high prevalence of common mental disorders (CMDs). In Zimbabwe, the Zvandiri adolescent peer support programme is effective at improving virological suppression. We assessed the effect of training Zvandiri peer counsellors known as Community Adolescent Treatment Supporters (CATS) in problem-solving therapy (PST) on virological suppression and mental health outcomes. Methods and findings Sixty clinics were randomised 1:1 to either normal Zvandiri peer counselling or a peer counsellor trained in PST. In January to March 2019, 842 adolescents aged 10 to 19 years and living with HIV who screened positive for CMDs were enrolled (375 (44.5%) male and 418 (49.6%) orphaned of at least one parent). The primary outcome was virological nonsuppression (viral load ≥1,000 copies/mL). Secondary outcomes were symptoms of CMDs measured with the Shona Symptom Questionnaire (SSQ ≥8) and depression measured with the Patient Health Questionnaire (PHQ-9 ≥10) and health utility score using the EQ-5D. The adjusted odds ratios (AORs) and 95% confidence intervals (CIs) were estimated using logistic regression adjusting for clinic-level clustering. Case reviews and focus group discussions were used to determine feasibility of intervention delivery. At baseline, 35.1% of participants had virological nonsuppression and 70.3% had SSQ≥8. After 48 weeks, follow-up was 89.5% for viral load data and 90.9% for other outcomes. Virological nonsuppression decreased in both arms, but there was no evidence of an intervention effect (prevalence of nonsuppression 14.7% in the Zvandiri-PST arm versus 11.9% in the Zvandiri arm; AOR = 1.29; 95% CI 0.68, 2.48; p = 0.44). There was strong evidence of an apparent effect on common mental health outcomes (SSQ ≥8: 2.4% versus 10.3% [AOR = 0.19; 95% CI 0.08, 0.46; p < 0.001]; PHQ-9 ≥10: 2.9% versus 8.8% [AOR = 0.32; 95% CI 0.14, 0.78; p = 0.01]). Prevalence of EQ-5D index score <1 was 27.6% versus 38.9% (AOR = 0.56; 95% CI 0.31, 1.03; p = 0.06). Qualitative analyses found that CATS-observed participants had limited autonomy or ability to solve problems. In response, the CATS adapted the intervention to focus on empathic problem discussion to fit adolescents’ age, capacity, and circumstances, which was beneficial. Limitations include that cost data were not available and that the mental health tools were validated in adult populations, not adolescents. Conclusions PST training for CATS did not add to the benefit of peer support in reducing virological nonsuppression but led to improved symptoms of CMD and depression compared to standard Zvandiri care among adolescents living with HIV in Zimbabwe. Active involvement of caregivers and strengthened referral structures could increase feasibility and effectiveness. Trial registration Pan African Clinical Trials Registry PACTR201810756862405.

Hepatocellular Carcinoma in Chronic Viral Hepatitis: Where Do We Stand?

Hepatocellular carcinoma (HCC) is one of the major causes of cancer-related death. Although the burden of alcohol- and NASH-related HCC is growing, chronic viral hepatitis (HBV and HCV) remains a major cause of HCC development worldwide. The pathophysiology of viral-related HCC includes liver inflammation, oxidative stress, and deregulation of cell signaling pathways. HBV is particularly oncogenic because, contrary to HCV, integrates in the cell DNA and persists despite virological suppression by nucleotide analogues. Surveillance by six-month ultrasound is recommended in patients with cirrhosis and in “high-risk” patients with chronic HBV infection. Antiviral therapy reduces the risks of development and recurrence of HCC; however, patients with advanced chronic liver disease remain at risk of HCC despite virological suppression/cure and should therefore continue surveillance. Multiple scores have been developed in patients with chronic hepatitis B to predict the risk of HCC development and may be used to stratify individual patient’s risk. In patients with HCV-related liver disease who achieve sustained virological response by direct acting antivirals, there is a strong need for markers/scores to predict long-term risk of HCC. In this review, we discuss the most recent advances regarding viral-related HCC.

Optimised electronic patient records to improve clinical monitoring of HIV-positive patients in rural South Africa (MONART trial): study protocol for a cluster-randomised trial

Background There is poor viral load monitoring (VLM) and inadequate management of virological failure in HIV-positive individuals on antiretroviral therapy in rural KwaZulu-Natal, South Africa. This could be contributing to increasing HIV drug resistance in the setting. This study aims to investigate the clinical and process impediments in VLM within the health system and to evaluate a quality improvement package (QIP) to address the identified gaps. The QIP comprises (i) a designated viral load champion responsible for administrative management and triaging of viral load results (ii) technological enhancement of the routine clinic-based Three Interlinked Electronic Register (TIER.Net) to facilitate daily automatic import of viral load results from the National Health Service Laboratory to TIER.Net (iii) development of a dashboard system to support VLM. Methods/design The study will evaluate the effectiveness of the QIP compared to current care for improving VLM and virological suppression using an effectiveness implementation hybrid type 3 design. This will use a cluster-randomised design with the primary healthcare clinics as the unit of randomisation with ten clinics randomised in a 1:1 ratio to either the intervention or control arm. We will enrol 150 HIV-positive individuals who had been on ART for ≥ 12 months from each of the ten clinics (750 in 5 intervention clinics vs. 750 in 5 control clinics) and follow them up for a period of 12 months. The primary outcome is the proportion of all patients who have a viral load (VL) measurement and are virally suppressed (composite outcome) after 12 months of follow up. Secondary outcomes during follow up include proportion of all patients with at least one documented VL in TIER.Net, proportion with VL ≥ 50 copies/mL, proportion with VL ≥ 1000 copies/mL (virological failure) and subsequent switch to second-line ART. Discussion We aim to provide evidence that a staff-centred quality improvement package, designated viral load monitoring champion, and augmentation of TIER.Net with a dashboard system will improve viral load monitoring and lead to improved virological suppression. Trial registration: This trial is registered on ClinicalTrials.gov on 8 Oct 2021. Identifier: NCT05071573; https://clinicaltrials.gov/ct2/show/NCT05071573?term=NCT05071573&draw=2&rank=1

Determinants of precocious B-cell aging in European adolescences living with perinatally acquired HIV-1 after over 10 years of suppressive therapy

HIV infection results in a state of chronic immune activation leading to premature immune aging, B-cells dysfunction, that persists despite prolonged virological suppression. In this scenario, adolescence living with perinatally acquired HIV (PHIV), deserve a peculiar attention since potentially exposed for their entire life to chronic immune activation. Here we identified determinants of precocious aging B cells in 40 PHIV undergoing suppressive antiretroviral therapy (ART) for median 13.5 years. All individuals started ART by 2 nd year of life and achieved virus suppression within the 1 st year of ART, with majority of patient maintaining suppression until analysis and 5/40 experiencing viral Spike (transient elevation of HIV-1 VL, 50-999 copies/ml). We employed a multi-omics approach including deep immunological B and T cell phenotype in PBMC, with aging B cells defined by the expression of T-bet and CD11c; plasma proteomics analysis by mass spectrometry and serum level of anti-measles antibodies as correlates of humoral response. We found that individuals with expansion of aging B cell, defined by the expression of T-bet+CD11c+, were those starting treatment later, presenting detectable levels of cell-associated HIV-1 RNA, history of Spikes, and a higher frequency of exhausted T-cells, including those expressing PD-1, LAG3, TIGIT. Accordingly, the proteomic analysis revealed that subjects with expansion of aging B cells and exhausted T cells had enrichment of proteins involved in immune inflammation and complement activation pathways, such as CLU and APCS which are also involved in tumor progression. Signs of precocious aging were associated with a reduced capacity to maintain virological memory against measles vaccination. To our knowledge, this is the first study focusing on precocious B-cell aging and dysfunctionality in PHIV with long-term virological suppression. Our experimental strategy enabled identification of clinical, viral, cellular and plasma soluble markers associated with B-cells aging. Our results pave the way to further define risk of disease progression or lymphoproliferative disorders in PHIV.

EXPERIENCE WITH DOLUTEGRAVIR IN HIV PATIENTS AT A PUBLIC SECTOR HOSPITAL IN KARACHI, PAKISTAN

Objective: To study the tolerability and efficacy of dolutegravir in naïve and experienced patients, their management and outcome. Study Design: Cross sectional study. Place and Duration of Study: Ruth KM Pfau Civil Hospital, Karachi Pakistan, from Apr 2018 to Apr 2020. Methodology: In this study all treatment-naïve and experienced HIV infected patients were included and started on integrase strand-transfer inhibitor dolutegravir (DTG) containing fixed dose combination at Sindh AIDS Control Program (SACP) was conducted. We documented virological suppression, defined as a viral load of <1000 copies/ml, immunological and clinical outcomes. Results: Eighty-two patients, of whom 53 (64.6%) were ARV naïve and 29 (35.4%) experienced, were started on DTG. Fifty six (68.3%) were males. The median age was 31.6 ± 9. Of 82, 61 returned for their first follow-up visit for assessment and viral load determination. Of 61, adverse effects to DTG were reported in 12 (19.6%), including 9 with pruritis. Of 35 naive patients, 30 achieved virological suppression by 3.3 ± 0.7 months and 1 at 8 months. All 26 experienced patients achieved virological suppression by 4.5 ± 0.9 months. Overall, of 61 patients, 57 (93.4%) achieved virological suppression, of whom 1 had immunelogical failure and none had clinical failure after 6 months of DTG. Three (3.6%) patients died within the first two months ofinitiating DTG. Conclusion: Dolutegravir has good tolerability, with virological suppression achieved in the majority, including in highly ARV experienced patients.

Features of application of raltegravir in HIV-infected patients with different somatic pathologies

Purpose of the study. Evaluation of the efficacy, safety and tolerability of raltegravir regimens in HIV-infected patients with concomitant pathology in real clinical practice.Materials and methods. A retrospective analysis was carried out of 277 outpatient records of HIV-infected patients who received raltegravir (RAL) as a third component both in patients without previous experience of antiretroviral therapy (ART) and in patients with experience of treatment with various somatic pathologies. The main criterion for the effectiveness of the scheme was the proportion of patients with undetectable viral load at the start of the analysis. Additional criteria for evaluating the efficacy and safety of the regimen were the dynamics of the number of CD4-lymphocytes, the frequency and nature of undesirable side reactions.Results. On average, patients with no experience of treatment and with experience of treatment received regimens with raltegravir for about 5 years. At the time of the study in 2020, 69.8% of patients on ART for the first time continued to take a regimen containing raltegravir. In this group, the proportion of patients with virological suppression (PCR of HIV RNA less than 50 kopecks / ml) was 97.7%. 75.2% of patients in the second group in 2020 continued to take the RAL regimen. The proportion of patients with virological suppression (VL less than 50 kopecks / ml) in this group was 97.5%. During the treatment, there was no discontinuation of the regimen in both groups due to undesirable side reactions to raltegravir.Conclusion. The results of this study confirm that RAL-based regimens provide a high level of efficacy with a good tolerance and safety profile in routine clinical practice for both naive and experienced patients with various somatic pathologies.

Factors Associated With Virological Suppression of HIV Viral Load in Patients on Antiretroviral Therapy in Conakry, Guinea

BackgroundThe viral load has become an indispensable tool in evaluating antiretroviral therapy (ART) in people living with HIV / AIDS. This study aimed to assess virological suppression among in people living with HIV / AIDS on antiretroviral therapy in Guinea.MethodsThis was a descriptive cross-sectional study of more than three years that involved adult HIV-positive patients treated in different sites in Conakry. A total of 9815 viral load data were collected. The viral load was quantified by the Generic Biocentric technique and the detection threshold set at 350 copies/ml. Statistical analyses were performed by R software version R4.0.3..ResultsA total of 9815 viral load data collected at the national public health laboratory were analysed. The sample was dominated by women (72%), with an average age of 29 [29, 39]. Of these, 6,706 (68%) of HIV-positive people on ART had viral load suppression. The univaried analysis showed that women were 22% more likely to have VL suppression (p-value <0.001) moreover, the chance for all HIV-positive people on treatment to achieve viral load suppression was related to the length of treatment.Conclusionthe results of this study show viral load suppression greater than 68%. The length of antiretroviral therapy, female gender, and advancing age of PLHIV were all favourable to VL suppression.

Evaluation of a community-based HIV test and start program in a conflict affected rural area of Yambio County, South Sudan

Background Antiretroviral therapy (ART) coverage in South Sudan is around 10%. Access to HIV care in settings with low ART coverage or conflict affected is still low; innovative strategies are needed to increase access and ensure continuation of ART during instability. A pilot HIV test and start project was implemented in a conflict-affected area of South Sudan. In a retrospective analysis, we determined the feasibility and outcomes of this intervention. Methods Programme data from July 2015 to June 2018 was analysed. The project involved five mobile teams offering HIV counselling and testing (HCT) and same day ART initiation at community level. Baseline and follow-up information on clinical, immunological and viral load (VL) was routinely recorded, as well as treatment outcomes. A semi-qualitative study was conducted to assess acceptability of the program among beneficiaries and community members. Results By June 2018, 14824 people received counselling and testing for HIV and 498 (3.4%) tested positive. Out of those 395 (79.3%) started ART. A total of 72 ART patients were organized in 26 Community ART Groups (CAGs) and contingency plan was activated 9 times for 101 patients. Kaplan-Meier estimated retention in care (RIC) at 12 and 18 months was 80.6% [95% CI: 75.9–84.5%] and 69.9% [95% CI: 64.4–74.8%] respectively. RIC was significantly higher at 18 months in patients under community ART groups (CAGs) (90.9% versus 63.4% p<0.001) when compared to patients on regular follow up. VL suppression at 12 months was 90.3% and overall virological suppression reached 91.2%. A total of 279 persons were interviewed about the MSF program perception and acceptance: 98% had heard about the programme and 84% found it beneficial for the community, 98% accepted to be tested and only 4% found disadvantages to the programme. Conclusions Our study shows that HCT and early ART initiation in conflict affected populations can be provided with good program outcomes. RIC and virological suppression are comparable with facility-based HIV programs and to those in stable contexts. This model could be extrapolated to other similar contexts with low access to ART and where security situation is a concern.