Novel and Investigational HIV Therapies for Treatment and Prevention: Focus on Cabotegravir, Islatravir, and Lenacapavir

Inclusion of Transgender and Gender Diverse People in Phase III Trials: Examples from HIV Pharmacologic Prevention Studies

“…Cabotegravir (CAB) is an integrase strand transfer inhibitor with favorable physicochemical characteristics for a long-acting antiretroviral agent, including low aqueous solubility and a high melting point, as well as favorable pharmacologic characteristics, including high antiviral potency and a long half-life (5.6 to 11.5 weeks). 46,47 The drug was formulated as an extended-release injectable nanosuspension for intramuscular delivery. 46 HPTN 083, an ongoing phase IIb/III noninferiority trial, compared CAB-based regimens to daily oral F/TDF (Table 1).…”

“…46,47 The drug was formulated as an extended-release injectable nanosuspension for intramuscular delivery. 46 HPTN 083, an ongoing phase IIb/III noninferiority trial, compared CAB-based regimens to daily oral F/TDF (Table 1). Overall, HPTN 083 demonstrated superiority of CAB-LA in preventing HIV via sexual transmission.…”

“…46 Results of phase III trials of lenacapavir for HIV treatment are described elsewhere. 46 For HIV prevention, PURPOSE-1 and 2 trials are ongoing phase III RCTs that will compare a lenacapavir-based regimen (600 mg oral lenacapavir lead-in for 2 days plus subcutaneous 927 mg lenacapavir injections every 26 weeks) to either daily oral F/TAF or F/TDF (PURPOSE-1) or daily oral F/TDF only (PURPOSE-2; Table 1). Although PURPOSE-1 is recruiting cisgender women only, PURPOSE-2's priority populations are transgender women and cisgender men (all ages ≥16 years and at risk of HIV).…”

“…Islatravir, an investigational, oncemonthly oral nucleoside reverse transcriptase translocation inhibitor, was in phase III development for both HIV treatment and prevention. 46 Investigators planned to include transgender women in the phase III noninferiority trial between islatravir and F/TDF or F/TAF among 1,500 adults at high risk for HIV (IMPOWER 24). However, as of July 2022, the FDA paused islatravir-based clinical trials because of decreased lymphocyte and CD4+ T-cell counts.…”

“…In December 2021, the FDA approved long‐acting injectable cabotegravir (CAB‐LA) as the first long‐acting pharmacologic intervention to reduce the risk of sexually acquired HIV‐1 transmission. Cabotegravir (CAB) is an integrase strand transfer inhibitor with favorable physicochemical characteristics for a long‐acting antiretroviral agent, including low aqueous solubility and a high melting point, as well as favorable pharmacologic characteristics, including high antiviral potency and a long half‐life (5.6 to 11.5 weeks) 46,47 . The drug was formulated as an extended‐release injectable nanosuspension for intramuscular delivery 46 …”