Highlights d The susceptibility of CD4 + T cell subsets to HIV-1 matches their metabolic activity d HIV-1 selectively infects CD4 + T cells with enhanced glycolysis and OXPHOS d Inhibition of metabolic activities blocks HIV-1 replication d Suboptimal inhibition of glycolysis impairs amplification of HIV-1 reservoirs

Nature MetabolisM T cells ex vivo can be isolated from HICs but not from cART individuals 8,10,18 (Fig. 1a). In the present study, it was first investigated whether this capacity of HIC CD8 + T cells could be found among naive, central memory, transitional memory and effector memory CD8 + T cell subsets (see Supplementary Fig. 1). As expected, naive CD8 + T cells from HICs had no HIV-suppressive capacity. In contrast, all sorted memory CD8 + T cell subsets from HICs, but not from cART individuals, suppressed HIV infection as efficiently as bulk CD8 + T cells (Fig. 1b). Therefore, although effector memory cells probably had more immediate antiviral capacity 12 , HIVspecific CD8 + TCMs from HICs can efficiently react to counteract HIV-1 infection during co-culture. These results support the view that the strong antiviral potential of HICs is already embedded in the programme of their HIV-specific CD8 + TCMs. Distinct gene expression profile in HIV-specific CD8 + TCMs from HICs. A comparison was then made of the single-cell gene expression profiles (96 genes associated with CD8 + T cell function, differentiation, metabolism and survival (see Supplementary Fig. 2 and Supplementary Data 1) of HIV-specific CD8 + TCMs from five HICs whose CD8 + T cells had strong HIV-suppressive capacity and from five cART individuals (see Supplementary Table 1). Cells from cART individuals and HICs analysed in the present study shared not only the same differentiation status but also the same activation phenotype, as defined by flow cytometry (Fig. 1c and see Supplementary Table 2). Despite their similar phenotype, t-SNE (t-distributed stochastic neighbour-embedding algorithm)-based

Thirty years after the identification of HIV, a cure for HIV infection is still to be achieved. Advances of combined antiretroviral therapy (cART) in recent years have transformed HIV infection into a chronic disease when treatment is available. However, in spite of the favorable outcomes provided by the newer therapies, cART is not curative and patients are at risk of developing HIV-associated disorders. Moreover, universal access to antiretroviral treatment is restricted by financial obstacles. This review discusses the most recent strategies that have been developed in the search for an HIV cure and to improve life quality of people living with HIV.

The subtype C epidemic in the southern Brazilian region was initiated by the introduction of a single founder strain closely related to subtype C strains from Burundi. Our results suggest that this founder event probably took place around the early 1980s, roughly a decade before the previous estimates.

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