ABSTRACT
Introduction: Antiretroviral therapy for people living with HIV-1 must be taken lifelong due to the persistence of latent virus in long-lived and proliferating CD4+ T cells. Vitamin D3 is a steroidal gene transcription regulator which exerts diverse effects on immune and epithelial cells including reductions in CD4+ T cell proliferation and improvement in gut barrier integrity. We hypothesised that a high dose of vitamin D3 would reduce the size of the HIV-1 reservoir by reducing CD4+ T cell proliferation. Methods: We performed a randomised placebo-controlled trial evaluating the effect of 24 weeks of vitamin D3 (10,000 international units per day) on the HIV-1 reservoir and immunologic parameters in 30 adults on antiretroviral therapy; participants were followed for 12 weeks post-treatment. The primary endpoint was the effect on total HIV-1 DNA at week 24. Parameters were assessed using mixed-effects models. Results: We found no effect of vitamin D3 on the change in total HIV-1 DNA from week 0 to week 24 relative to placebo. There were also no changes in integrated HIV-1 DNA, 2-long-terminal repeat (2-LTR) circles or cell-associated HIV-1 RNA. Vitamin D3 induced a significant increase in the proportion of central memory CD4+ and CD8+ T cells, a reduction in the proportion of senescent CD8+ T cells and a reduction in the natural killer cell frequency at all time points including week 36, 12 weeks after the study drug cessation. At week 36, there was a significant reduction in total HIV-1 DNA relative to placebo and persistently elevated 25-hydroxyvitamin D levels. No significant safety issues were identified. Conclusions: Vitamin D3 administration had a significant impact on the T cell differentiation but overall effects on the HIV-1 reservoir were limited and a reduction in HIV-1 DNA was only seen following cessation of the study drug. Additional studies are required to determine whether the dose and duration of vitamin D3 can be optimised to promote a continued depletion of the HIV-1 reservoir over time. Trial registration: ClinicalTrials.gov NCT03426592.
ABSTRACT
Background The aim of this study is to estimate the reduction in new HIV infections and resultant cost outcomes of providing antiretroviral treatment (ART) through Australia's 'universal access' health scheme to all temporary residents with HIV infection living legally in Australia, but currently deemed ineligible to access subsidised ART via this scheme. METHODS: A mathematical model to estimate the number of new HIV infections averted and the associated lifetime costs over 5 years if all HIV-positive temporary residents in Australia had access to ART and subsidised medical care was developed. Input data came from a cohort of 180 HIV-positive temporary residents living in Australia who are receiving free ART donated by pharmaceutical companies for up to 4 years. RESULTS: Expanding ART access to an estimated total 450 HIV+ temporary residents in Australia for 5 years could avert 80 new infections. The model estimated the total median discounted (5%) cost for ART and associated care to be A$36million, while the total savings in lifetime-discounted costs for the new infections averted was A$22million. CONCLUSIONS: It is estimated that expanded access to ART for all HIV-positive temporary residents in Australia will substantially reduce HIV transmission to their sexual partners at little additional cost. In the context of Australia's National HIV strategy and Australia's endorsement of global goals to provide universal access to ART for all people with HIV, this is an important measure to remove inequities in the provision of HIV-related treatment and care.