A sub-group evaluation of the multi-month dispensing strategy for differentiated HIV care: is personalization of care guidelines warranted in Haiti?

Background Differentiated care strategies are rapidly becoming the norm for HIV care delivery globally. Building upon an interest in tailoring antiretroviral therapy (ART) delivery for client-centered needs, the Ministry of Health and Population in Haiti formally endorsed multiple-month dispenses (MMD) in the 2016 national ART guidelines This study explores heterogeneity in retention in care with MMD for specific Haitian populations living with HIV and evaluates if a targeted algorithm for optimal ART prescription intervals is warranted in Haiti. Methods This study included ART-naïve individuals who started ART on or after January 1st, 2017 in Haiti. To identify subgroups in which to explore heterogeneity of retention, we implemented a double-lasso regression method to determine which individual characteristics would define the subgroups. Characteristics evaluated for potential subgroup definition included: sex, age category, WHO clinical stage, and body mass index category. We employed instrumental variable models to estimate the causal effect of increasing ART dispensing length on ART retention, by client subgroup. The outcome of interest was retention in care after one year in treatment. We then estimated the marginal effect of a 30-day increase to ART dispensing length to retention in care for each of these subgroups. Results There was evidence for heterogeneity in the effect of extending ART dispensing intervals on retention by WHO clinical stage. We observed significant improvements to retention in care at one year with a 30-day increase in ART dispense length for all subgroups defined by WHO clinical stages 1-4. The effects ranged from a 14.7% increase (95% CI: 12.4-17.0) to the likelihood of retention for people with HIV in WHO stage 1 to a 21.6% increase (95% CI: 18.7-24.5) to the likelihood of retention for those in WHO stage 3. Conclusions All the subgroups defined by WHO clinical stage experienced a benefit of extending ART intervals to retention in care at one year. Though the effect did differ slightly by WHO stage, the effects went in the same direction and were of similar magnitude. Therefore, a standardized recommendation for MMD among those living with HIV and new on ART is appropriate for Haiti treatment guidelines.

Time to develop severe acute malnutrition and its predictors among children living with HIV in the era of test and treat strategies at South Gondar hospitals, northwest, Ethiopia, 2021: a multicentre retrospective cohort study

Background Although severe acute malnutrition is a major public issue among HIV infected children, there is no prior evidence in Ethiopia. Hence, this study aims to assess the time to develop severe acute malnutrition and its predictors among children living with human immunodeficiency virus in Ethiopia, 2012. Methods An institution based retrospective cohort study was conducted in South Gondar hospitals among 363 HIV infected children from February 10, 2014, to January 7, 2021. Epi-data version 3.1 was used to enter data, which was then exported to STATA version 14 for analysis. Besides, WHO (World Health Organization) Anthro Plus software was used to assess the nutritional status of the children. A standardized data extraction tool was used to collect the data. The Kaplan Meier survival curve was used to estimate the median survival time. The Cox-proportional hazard model assumption was checked via the Schoenfeld residual ph test and a stph plot. Bivariable and multivariable Cox proportional hazard models were employed at 95% confidence intervals (CI). A variable having a p-value < 0.05 was considered a statistically significant predictor of severe acute malnutrition. Results A total of 363 children living with HIV, 97 (26.72%) developed severe acute malnutrition during the follow-up period. The overall incidence rate was 5.4 (95% CI: 4.7–5.9) person per year with a total of 21, 492 months or 1791 years of observation. Moreover, the median survival time was 126 months. Treatment failure [AHR =3.4 (95% CI: 2.05–5.75)], CD4 count below threshold [AHR =2.5 (95% CI: 1.64–3.95)], and WHO stage III & IV [AHR =2.9 (95% CI: 1.74–4.73)] were all significant predictors of severe acute malnutrition. Conclusion The time to develop severe acute malnutrition was found to be very low. Treatment failure, CD4 count below threshold, and WHO stage III were all significant predictors of severe acute malnutrition. Hence, emphasizing those predictor variables is essential for preventing and controlling the occurrence of severe acute malnutrition among HIV infected children.

Valganciclovir as Add-On Therapy Modifies the Frequency of NK and NKT Cell Subpopulations in Disseminated Kaposi Sarcoma Patients

Human herpesvirus-8 infection (HHV-8) is the causative agent of Kaposi sarcoma (KS) and is highly prevalent among people living with HIV (KS/HIV). It has been reported that valganciclovir (VGC) reduces HHV-8 replication in KS/HIV patients. However, currently it is unclear if VGC modifies the frequency and induces changes in markers of immune regulation of immune cells necessary to eliminate HHV8-infected cells, such as Natural Killer (NK) and NK T cells (NKT). This study evaluated the effect of VGC used as antiviral HHV8 therapy in KS patients on the frequency of NK and NKT subpopulations based on the CD27 and CD57 expression, and the immunosenescence markers, PD-1 and KLRG1. Twenty KS/HIV patients were followed-up at baseline (W0), 4 (W4), and 12 weeks (W12) of the study protocol. Among them, 10 patients received a conventional treatment scheme (CT), solely antiretroviral therapy (ART), and 10 patients received a modified treatment regime (MT), including VGC plus ART. In both groups, bleomycin/vincristine was administrated according to the treating physician’s decision. The soluble levels of IL-15, PD-L1, PD-L2, and E-cadherin were quantified across the follow-up. Our results showed that the higher IL-15 levels and lower NK frequencies cells in KS/HIV patients reach almost normal values with both treatments regimes at W12. CD27+ NK and NKT cell frequencies increased since W4 on KS/HIV patients with MT. Furthermore, PD-1 expression decreased while KLRG1 increased on NK and NKT subpopulations at W12, and it is accompanied by increased PD-L1 plasma level since W4. Our study highlights the disruption of NK and NKT subpopulations in patients with KS/HIV and explores VGC treatment’s contribution to immune reconstitution during the first weeks of treatment.