There have been eight previously reported cases of lung transplantation in HIV seropositive patients globally [2–4]. Of the 5 patients who received transplantation more than 3 years ago, 4 have achieved 3-year survival, which is a comparable outcome to non-HIV seropositive patients [4, 10]. There are also numerous reports of HIV seropositive patients who have received heart transplants, the majority of which have had good outcomes since the introduction of HAART [11]. Observational data from renal and liver transplant populations have generally suggested that HIV seropositive patients have similar survival compared to seronegative patients if maintained on HAART [12–15]. Conversely, the largest cohort study of HIV seropositive liver and kidney recipients to date reported an increased risk of graft failure in recipients from both subpopulations [16], and a higher risk of mortality in liver recipients. Multiple other studies have also suggested a higher than expected risk of acute rejection in HIV seropositive kidney recipients [13, 15, 17, 18].

Until recently, induction immunosuppression was thought to increase the risks of adverse outcomes in HIV seropositive patients [19]. Modern immunosuppression regimens for induction and acute rejection in solid-organ transplant recipients rely on the inhibition of lymphocyte proliferation and activity, and occasionally the more widespread reduction of lymphocyte populations. This latter approach presents unique challenges in HIV seropositive transplant recipients given CD4⁺ cell populations and CD4⁺:CD8⁺ ratios are important prognostic factors in the management of HIV progression and treatment response [20–22]. This applies to both medications frequently used in the induction and maintenance phases of post-lung transplantation immunosuppression.

Induction therapies for lung transplant typically include anti-thymocyte globulin (ATG) and basiliximab. ATG is a polyclonal antibody that actively depletes T-lymphocytes. ATG reduces CD4⁺ cell counts immediately after treatment, and also causes prolonged suppression of CD4⁺:CD8⁺ ratios [23–25]. When used as induction immunosuppression in lung transplantation, ATG may increase overall survival by reducing graft loss despite also increasing the risk of infection [26]. In the largest cohort of HIV seropositive liver and kidney transplant recipients to date, ATG use in the first week post-kidney transplantation was associated with increased mortality and graft loss [13, 16]. Other studies in HIV seropositive renal transplant recipients have instead suggested that induction immunosuppression with ATG does not increase the risk of infection compared to HIV seronegative controls, and furthermore decreases the risk of graft loss and increases survival [19, 27]. Basiliximab is an IL-2 receptor antagonist that inhibits proliferation and differentiation of T-cells. IL-2 receptor antagonists continue to be the most frequently used induction agents in HIV seronegative lung transplant recipients [28]. Basiliximab use in induction for HIV seropositive renal transplant recipients has been associated with a lower incidence of delayed graft function, reduced graft loss, and a trend towards longer survival compared to no induction [19]. These findings therefore support the use of basiliximab in the induction phase for HIV seropositive lung and renal transplant recipients. Basiliximab may be a preferable induction agent for HIV seropositive patients given ATG’s adverse effects on CD4⁺ cell populations and its association with increased mortality and graft loss in HIV seropositive renal transplant populations. Our patient tolerated the use of basiliximab as induction therapy well, and had no major adverse events and long-term sequelae attributed to its use.

Maintenance immunosuppressive therapies post-lung transplantation in most centers typically include tacrolimus, MMF, and prednisone, which all exert cytostatic effects on T-cell populations via several mechanisms [29–35]. MMF also exerts apoptotic effects on CD4⁺ cells in vitro [36]. Despite these findings, neither HIV seropositive or seronegative patients treated with these medications exhibit sustained decreases in their absolute CD4⁺ cell counts or declines in their CD4⁺:CD8⁺ ratios [13, 18, 25, 36–40]. Cobicistat and the protease inhibitor medications increase plasma calcineurin inhibitor levels via cytochrome P450 3A and P-glycoprotein inhibition [5–8], necessitating close monitoring of drug levels when these medications are co-administered with tacrolimus. These interactions were avoided in our patient with alterations to his HAART. Based on this information, HIV seropositive lung transplant recipients can safely be managed with MMF and tacrolimus. Our patient received these medications, as well as prednisone, and had no long-term complications with respect to graft rejection or control of HIV over a 2-year period, which further suggests that HIV seropositive patients can tolerate this immunosuppressant regimen if their HAART is carefully tailored.

In summary, this is the first HIV seropositive lung transplant recipient in Canada to our knowledge, and one of only several patients reported globally. Our immunosuppression selection included basiliximab, corticosteroids, tacrolimus and MMF; a regimen that is supported by evidence drawn from kidney and liver transplant populations. This case report adds to the growing body of literature that these medications are safe in HIV seropositive patients undergoing lung transplantation, and that these patients can achieve long-term outcomes that are comparable to HIV seronegative patients. There is, however, a need for large-scale studies of this specific population given the lack of evidence in optimal immunosuppression for these patients, as well as their long-term prognosis. This is especially the case with future trends towards increasing acceptance of solid-organ transplantation in selected HIV seropositive patients.