. 2025 Aug 15;22(1):44. doi: 10.1007/s11904-025-00751-2

Table 2.

Key studies on long-acting injectable antiretroviral agents for ART or PrEP including pregnant and breastfeeding women

Drug/Regimen	Efficacy Trials	Bridging Studies (including pregnancy/breastfeeding women)	Implementation Studies/Demonstration Projects
Cabotegravir (CAB-LA) HIV prevention regimen	HPTN 083 and 084 [6, 10] Studies showed that CAB-LA was superior to oral PrEP; 66–89% HIV risk reduction in MSM, TGW, and cis women.	HPTN 084 OLE Pregnancy Sub-study [33]: Ongoing study tracking pregnancy outcomes of women enrolled in HPTN 084. PALISADE [36]: This study provides long-term follow-up of participants from HPTN 083/084, evaluating CAB-LA for PrEP, including pregnancy outcomes in those who become pregnant. Tshireletso [37]: Ongoing trial on Safety, efficacy and feasibility of Cabotegravir-LA PrEP in a high-risk breastfeeding population. 500 postpartum women and infants will be followed for 24 months to assess PrEP adherence, safety, and outcomes, including a PK sub study with 30 pairs. PrIMO [34]: Ongoing study on PrEP Pregnancy Registry and observational cohort evaluating the pregnancy, infant and maternal health outcomes among PrEP-eligible pregnant women and their infants up to one year postpartum. (A total of 621 mother-infant pairs on either CAB LA or oral PrEP).	SEARCH (Uganda/Kenya) [38, 39]: The trial found that CAB-LA was highly acceptable and expanded HIV prevention options, though users noted concerns around injection pain, side effects, and access. Path To Scale(Malawi), [40, 41]: Ongoing study that is tracking pregnancy outcomes on women on PrEP using a Pregnancy Registry. (N = ~ 900) PrEPared to Choose [42] (South Africa): The study evaluates CAB-LA delivery within a real-world HIV prevention program offering multiple PrEP options, focusing on uptake, preferences, and feasibility. CATALYST [43] (South Africa, Zimbabwe, Lesotho, Uganda, Kenya)*: Study explores how to deliver and scale up client-centered HIV prevention, including CAB-LA and oral PrEP, across multiple African countries.
Lenacapavir (LEN) HIV prevention regimen	PURPOSE 1 and 2 [3, 19]:.PURPOSE 1: trial enrolled a total of 5,338 cisgender women, randomized as follows: 2,134 received LEN, 2,136 were assigned daily oral F/TAF, and 1,068 received daily oral F/TDF as the active comparator. 100% efficacy in the LEN group. PURPOSE 2 trial enrolled 3,265 MSM/TGW participants, HIV incidence was significantly lower in the LEN group (0.10 per 100 person-years) compared to both the F/TDF group (0.93 per 100 person-years) and the background population (2.37 per 100 person-years).	PURPOSE 1 Pregnancy Sub-study [3]: Study tracking the outcomes of pregnancies among women on LEN in PURPOSE 1. Breastmilk/infant PK is ongoing and initial data reassuring [35].	PURPOSE 3–5 [44]: Implementation trials in high-risk groups.
CAB + Rilpivirine (RPV-LA ) Long acting dual HIV Treatment regimen	ATLAS/FLAIR [4, 45]: Monthly injections of CAB+RPV-LA non-inferior to oral ART. ATLAS-2M [46]: 8weekly dosing (Q8W) non-inferior to 4 weekly dosing (Q4W) dosing. CARES [47]: CAB + RPV-LA had non-inferior efficacy compared with oral therapy with a good safety profile.IMPALA [48]: CAB/RPV-LA was non-inferior to oral ART in maintaining viral suppression at 48 weeks among individuals with previous adherence challenges, with 91% vs 89% achieving VL <50 copies/mL, respectively. While all cases of confirmed virologic failure occurred in the injectable group (1.9%), there were significantly fewer episodes of VL >1000 copies/mL, demonstrating some virologic superiority of injectable ART.	IMPAACT 2040 [49]: PK/safety of CAB/RPV-LA Q4W and Q8W in pregnancy. Up to 45 pregnant women (and their infants)—including 25 in the Q4W switch group and 10 in the Q8W continuation group	CUSTOMIZE (USA) [50]: Evaluated the implementation of CAB + RPV-LA across diverse healthcare settings in the United States. CARISEL (EU) [51]: Feasible clinic integration with high viral suppression and staff acceptability. Limited use in pregnancy pending safety data.

Drug/Regimen

Efficacy Trials

Bridging Studies (including pregnancy/breastfeeding women)

Implementation Studies/Demonstration Projects

Cabotegravir (CAB-LA)

HIV prevention regimen

HPTN 083 and 084 [6, 10] Studies showed that CAB-LA was superior to oral PrEP; 66–89% HIV risk reduction in MSM, TGW, and cis women.

HPTN 084 OLE Pregnancy Sub-study [33]: Ongoing study tracking pregnancy outcomes of women enrolled in HPTN 084.

PALISADE [36]: This study provides long-term follow-up of participants from HPTN 083/084, evaluating CAB-LA for PrEP, including pregnancy outcomes in those who become pregnant.

Tshireletso [37]: Ongoing trial on Safety, efficacy and feasibility of Cabotegravir-LA PrEP in a high-risk breastfeeding population. 500 postpartum women and infants will be followed for 24 months to assess PrEP adherence, safety, and outcomes, including a PK sub study with 30 pairs.

PrIMO [34]: Ongoing study on PrEP Pregnancy Registry and observational cohort evaluating the pregnancy, infant and maternal health outcomes among PrEP-eligible pregnant women and their infants up to one year postpartum. (A total of 621 mother-infant pairs on either CAB LA or oral PrEP).

SEARCH (Uganda/Kenya) [38, 39]: The trial found that CAB-LA was highly acceptable and expanded HIV prevention options, though users noted concerns around injection pain, side effects, and access.

Path To Scale(Malawi), [40, 41]: Ongoing study that is tracking pregnancy outcomes on women on PrEP using a Pregnancy Registry. (N = ~ 900)

PrEPared to Choose [42] (South Africa): The study evaluates CAB-LA delivery within a real-world HIV prevention program offering multiple PrEP options, focusing on uptake, preferences, and feasibility.

*CATALYST [43] (South Africa, Zimbabwe, Lesotho, Uganda, Kenya): Study explores how to deliver and scale up client-centered HIV prevention, including CAB-LA and oral PrEP, across multiple African countries.

Lenacapavir (LEN)

HIV prevention regimen

PURPOSE 1 and 2 [3, 19]:.PURPOSE 1: trial enrolled a total of 5,338 cisgender women, randomized as follows: 2,134 received LEN, 2,136 were assigned daily oral F/TAF, and 1,068 received daily oral F/TDF as the active comparator. 100% efficacy in the LEN group. PURPOSE 2 trial enrolled 3,265 MSM/TGW participants, HIV incidence was significantly lower in the LEN group (0.10 per 100 person-years) compared to both the F/TDF group (0.93 per 100 person-years) and the background population (2.37 per 100 person-years).

PURPOSE 1 Pregnancy Sub-study [3]: Study tracking the outcomes of pregnancies among women on LEN in PURPOSE 1. Breastmilk/infant PK is ongoing and initial data reassuring [35].

PURPOSE 3–5 [44]: Implementation trials in high-risk groups.

CAB + Rilpivirine (RPV-LA ) Long acting dual HIV Treatment regimen

ATLAS/FLAIR [4, 45]: Monthly injections of CAB+RPV-LA non-inferior to oral ART.

ATLAS-2M [46]: 8weekly dosing (Q8W) non-inferior to 4 weekly dosing (Q4W) dosing. CARES [47]: CAB + RPV-LA had non-inferior efficacy compared with oral therapy with a good safety profile.IMPALA [48]: CAB/RPV-LA was non-inferior to oral ART in maintaining viral suppression at 48 weeks among individuals with previous adherence challenges, with 91% vs 89% achieving VL <50 copies/mL, respectively. While all cases of confirmed virologic failure occurred in the injectable group (1.9%), there were significantly fewer episodes of VL >1000 copies/mL, demonstrating some virologic superiority of injectable ART.

IMPAACT 2040 [49]: PK/safety of CAB/RPV-LA Q4W and Q8W in pregnancy. Up to 45 pregnant women (and their infants)—including 25 in the Q4W switch group and 10 in the Q8W continuation group

CUSTOMIZE (USA) [50]: Evaluated the implementation of CAB + RPV-LA across diverse healthcare settings in the United States.

CARISEL (EU) [51]: Feasible clinic integration with high viral suppression and staff acceptability. Limited use in pregnancy pending safety data.

*Studies closed prematurely