Effect of dolutegravir on folate, vitamin B12 and mean corpuscular volume levels among children and adolescents with HIV: a sub-study of the ODYSSEY randomized controlled trial.

INTRODUCTION: Dolutegravir-based antiretroviral therapy (ART) is the preferred antiretroviral treatment for children and adolescents living with HIV. A large surveillance study in Botswana previously raised concerns about an association between pre-conception dolutegravir and neural tube defects. Before these concerns were subsequently resolved, we set up a sub-study to look at the effect of dolutegravir on levels of folate and vitamin B12 in children and adolescents within the randomized ODYSSEY trial, as folate and vitamin B12 are known to play a crucial role in neural tube development. METHODS: We conducted the sub-study among Ugandan ODYSSEY participants and compared folate and vitamin B12 between children randomized to dolutegravir-based ART (DTG) and non-dolutegravir-based standard-of-care treatment (SOC). Plasma folate was measured at enrolment and week 4 on stored samples; in addition, plasma and red blood cell (RBC) folate and vitamin B12 were assayed at week ≥96 in prospectively collected samples. RBC mean corpuscular volume (MCV) was measured 24-weekly in all ODYSSEY participants. Samples analysed in the sub-study were collected between September 2016 and October 2020. RESULTS: A total of 229 children aged ≥6 years were included in the sub-study with median age at trial enrolment of 12.3 (interquartile range [IQR] 9.0, 14.7) years, and CD4 count of 501 (IQR 228, 695); 112 (49%) children were male. Most participants (225/229, 98%) had plasma folate results at enrolment and 214 (93%) children had results available for RBC folate, vitamin B12 and plasma folate at week ≥96. MCV results were analysed on 679 children aged ≥6 years enrolled in ODYSSEY. At week 4, mean plasma folate was significantly higher in the dolutegravir arm than in SOC (difference [DTG-SOC] 1.6 ng/ml, 95% CI 0.8, 2.3; p<0.001), and this difference persisted to week ≥96 (2.7 ng/ml, 95% CI 1.7, 3.7; p<0.001). Mean RBC folate at ≥96 weeks was also higher in the DTG arm (difference 73 ng/ml, 95% CI 3, 143; p = 0.041). There was no difference in the treatment arms for vitamin B12 levels at ≥96 weeks or change in MCV through trial follow-up. CONCLUSIONS: Plasma and RBC folate levels were higher in children and adolescents receiving dolutegravir-based ART than on other ART regimens. Further studies are needed to clarify the mechanisms of these interactions and the clinical implications of increased blood folate levels.

Viral load suppression after intensive adherence counselling among adult people living with HIV at Kiswa health centre, Kampala: a retrospective cohort study. Secondary data analysis.

BACKGROUND: The Joint United Nations Programme on HIV/AIDS through the 95-95-95 target requires 95% of people living with HIV (PLHIV) on antiretroviral treatment (ART) to be virally suppressed. Viral Load (VL) non-suppression has been found to be associated with suboptimal ART adherence, and Intensive Adherence Counselling (IAC) has been shown to lead to VL re-suppression by over 70% in PLHIV on ART. Currently, there is data paucity on VL suppression after IAC in adult PLHIV in Uganda. This study aimed to evaluate the proportion of VL suppression after IAC and associated factors among adult PLHIV on ART at Kiswa Health Centre in Kampala, Uganda. METHODS: Study was a retrospective cohort design and employed secondary data analysis to review routine program data. Medical records of adult PLHIV on ART for at least six months with VL non-suppression from January 2018 to June 2020 at Kiswa HIV clinic were examined in May 2021. Descriptive statistics were applied to determine sample characteristics and study outcome proportions. Multivariable modified Poisson regression analysis was employed to assess predictors of VL suppression after IAC. RESULTS: Analysis included 323 study participants of whom 204 (63.2%) were female, 137 (42.4%) were between the age of 30 and 39 years; and median age was 35 years (interquartile range [IQR] 29-42). Participant linkage to IAC was 100%. Participants who received the first IAC session within 30 days or less after unsuppressed VL result were 48.6% (157/323). Participants who received recommended three or more IAC sessions and achieved VL suppression were 66.4% (202/304). The percentage of participants who completed three IAC sessions in recommended 12 weeks was 34%. Receipt of three IAC sessions (ARR = 1.33, 95%CI: 1.15-1.53, p < 0.001), having baseline VL of 1,000-4,999 copies/ml (ARR = 1.47, 95%CI: 1.25-1.73, p < 0.001) and taking Dolutegravir containing ART regimen were factors significantly associated with VL suppression after IAC. CONCLUSION: VL suppression proportion of 66.4% after IAC in this population was comparable to 70%, the percentage over which adherence interventions have been shown to cause VL re-suppression. However, timely IAC intervention is needed from receipt of unsuppressed VL results to IAC process completion.