Tenofovir disoproxil fumarate (TDF) and lithium are associated with renal tubular toxicity which could be additive. Furthermore, a pharmacokinetic interaction may occur between TDF and lithium at the level of renal transporters. People with HIV on lithium for cognitive impairment and concurrently treated with a TDF containing regimen had their renal function monitored in the framework of a 24-week randomized trial of lithium versus placebo. Overall, 23 participants were allocated to the lithium arm and 30 participants to the placebo arm. Baseline characteristics were not statistically different with a mean age of 37.7 and 40.8 years, a median time on ART of 33 and 40 months and an eGFR of 139.3 and 131 mL/min in the lithium and placebo arms, respectively. Participants using medications that may predispose to lithium toxicity, with an eGFR <60 ml/min or dehydrated with diarrhoea were excluded. Renal function was evaluated at weeks 4, 8, 12, 16, 20 and 24. No statistical difference was observed in the reduction of estimated glomerular filtration rate (eGFR) calculated using the modification of diet in renal disease (MDRD) formula or increase in potassium between participants in the lithium treatment group versus placebo group during the 24 weeks follow-up period. Thus, coadministration of lithium and TDF did not increase the risk of renal impairment in people with HIV. The study has several limitations: small study population, relatively short follow-up and urine markers of tubulopathy were not measured. Finally, participants with renal impairment and concomitant medication which may potentiate lithium toxicity were excluded. Thus, this study cannot rule out nephrotoxicity of long-term concomitant treatment of TDF and lithium thus studies looking at long-term follow-up of TDF treated HIV-infected patients with lithium-treated bipolar disorder are needed.