Long-Acting Injectable Cabotegravir/Rilpivirine as a Second-Line ART Regimen for Pregnant and Breastfeeding Women in Kenya: Modeling the Potential Impact on Vertical Transmission

Abstract

Background

Switching to injectable long-acting cabotegravir and rilpivirine (LA-CAB/RPV) may improve viral suppression among pregnant and breastfeeding women (PBFW) who have persistent viremia on first-line antiretroviral therapy (ART), resulting in the prevention of vertical transmission (PVT).

Methods

We used a microsimulation model of PBFW living with HIV in Kenya on dolutegravir-based first-line ART to evaluate the PVT potential of LA-CAB/RPV in 2 maternal populations—newly positive (NP) pregnant women who initiate ART during antenatal care, and known positive (KP) women who initiate ART prior to conception—during antenatal care through 18 months postpartum. For each population, we modeled a standard of care (SOC) without access to a second-line regimen, and a strategy with LA-CAB/RPV as a second-line regimen. Both strategies implement routine maternal viral load (VL) monitoring every 6 months and account for an imperfect cascade, including a 50% probability of regimen switching among eligible PBFW in the LA-CAB/RPV strategy.

Results

The average time from having unsuppressed VL to switching regimens was over 8 months, and 5.1% of NP and 8.2% of KP women ultimately switched. Compared to SOC, the LA-CAB/RPV strategy reduced vertical transmission by 1.2% for NP and 4.2% for KP women. These reductions increased to 4.0% and 11.5%, respectively, when assuming perfect adherence to more frequent VL monitoring (3-month intervals) and 100% regimen switching when eligible.

Conclusions

Supporting high switching rates and decreasing delays in switching will help optimize the PVT impact of second-line LA-CAB/RPV among PBFW who accept this regimen.

Antiretroviral therapy (ART) coverage expansion and improved viral suppression rates for pregnant and breastfeeding women (PBFW) have significantly decreased vertical (mother-to-child) transmission of HIV (VT) in high HIV burden settings over the last 2 decades. A recent milestone toward the elimination of VT was the introduction of dolutegravir (DTG)-based ART in resource-limited settings [1], due to its higher viral suppression efficacy and greater barrier to acquired drug resistance (ADR) than efavirenz-based ART [2, 3]. Modeling studies have projected that DTG-based first-line ART will substantially reduce VT by improving viral suppression among PBFW living with HIV and preventing HIV among PBFW via greater population-level viral suppression [4].

Since DTG-based ART became the preferred first-line regimen, World Health Organization guidelines have continued to recommend switching ART regimens for individuals with persistent viremia [5]. Prior to the availability of DTG, switching to protease inhibitor-based second-line ART was beneficial because a high proportion of individuals with persistent viremia on efavirenz-based ART had developed ADR [6]. However, the prevalence of ADR among individuals on DTG-based ART with viremia remains relatively low [7], particularly for those who were previously ART-naïve [8, 9]. This suggests that the majority of persistent viremia is likely caused by poor medication adherence and that switching to a protease inhibitor-based regimen may not be beneficial for many individuals [10].

Viral load (VL) monitoring can help some individuals with elevated VL successfully continue DTG-based ART by prompting adherence counseling to achieve (re-)suppression. In a prior modeling study of Kenyan PBFW on DTG-based ART, we projected that increasing the healthcare system's adherence to VL monitoring guidelines from 0% to 100% would reduce VT by 2.7% versus 14.3% among PBFW who initiated ART during antenatal care (Newly Positive [NP] women) versus among PBFW who were ART-experienced prior to antenatal care (known positive [KP] women), respectively [11]. In that analysis, women whose viremia persisted after adherence counseling did not switch to a second-line regimen.

The recent availability of injectable long-acting (LA) ART, however, offers a promising second-line regimen for such viremic individuals, given its significantly reduced dosing requirements [12–14]. Although additional safety and efficacy data among PBFW are still needed [15], LA-ART has the potential to be a key intervention for the prevention of vertical transmission (PVT) among mothers on ART with persistent viremia. To inform this potential use of LA-ART, we conducted a simulation modeling study to evaluate the PVT impact of implementing injectable cabotegravir and rilpivirine (CAB/RPV) as a second-line regimen in NP versus KP PBFW in Kenya, where 13% of infants who acquired HIV in 2024 had mothers who successfully initiated and continued ART [16].

METHODS

Overview

We used a previously described microsimulation model of HIV progression and PVT care for pregnant women living with HIV in Kenya to conduct our evaluation [11, 17]. The model updates age and key clinical characteristics such as CD4 cell count, VL, and ART regimen status in monthly time cycles. Pregnancy, modeled as 9 monthly time cycles (39 weeks gestation), is confirmed at the first antenatal clinic (ANC) visit at 5 months' gestation [18] and concludes in a full-term, singleton live birth. Table 1 shows key model parameters; a full description of the model is provided in the Supplementary Appendix.

Table 1.

Base Case Values for Key Model Parameters

Parameter	Base Case Values		References
	Known	Newly
	Positive	Positive
ART effectiveness: viral suppression (%)a,b
First-line DTG-based ART
Month 16	91.6		Kinuthia et al. [19], Dorward et al. [20]
Month 33	87.6
Second-line LA-CAB/RPV, Month 12	80.0		Barda et al. [13], Christopoulos et al. [12]
Viral load monitoring and switchingc
Adherence to viral load testing schedule (% attending each recommended test)	70		Adhiambo et al. [21]
Probability of re-suppression after a VL test (%)	50		Sokela et al. [22]
Switching, among those with virologic failure (%)	50		Bell-Gorrod et al. [23], Ekusai-Sebatta et al. [24]
Antenatal and HIV care
Months gestation at first antenatal clinic visitd	5		Aksunger et al. [18]
Months duration of breastfeeding	18		Glaubius et al. [25]
Interrupted ART (%, from first antenatal care visit to end of breastfeeding)b,e	8.5	23.5	Humphrey et al. [26], Chammartin et al. [27]
Peripartum vertical transmissionf
Probability in month of delivery (%), mother on ART			Mandelbrot et al. [28], Townsend et al. [29]
VL  <  50	0.0	0.5
50  <  VL  <  400	0.3	1.4
400  <  VL  <  10 000	2.2	2.4
VL >10 000	9.2	9.2
Probability in month of delivery (%), mother not on ART and HIV acquired preconception			Rollins et al. [30]
CD4  <  200	37
200  <  CD4  <  350	27
CD4  >  350	15
Postpartum (breastfeeding) vertical transmission			Dugdale et al. [31]
Monthly probability (%), mother on ART
VL  <  50	0.06
50  <  VL  <  1000	0.39
VL  >  1000	0.78
Monthly probability (%), mother not on ART	0.89

ART, antiretroviral therapy, VL, viral load.

^aSee Supplementary Appendix 1.5.3.

^bReported as a cumulative risk for ease of interpretation; modeled as a monthly probability during each month on ART following the month of initiation.

^cSee Supplementary Appendix 1.8.

^dGestational age is measured in months due to the monthly time cycle of the model. Corresponding ages in weeks are: month 5 = wks 17.4–21.7; month 3 = wks 8.8–13; month 8 = wks 30.4–34.7.

^eSee Supplementary Appendix 1.7. For known positive women, the corresponding monthly risk of ART interruption also applies to the time period between ART initiation and first antenatal clinic visit.

^fPeripartum vertical transmission parameters reflect combined in utero and intrapartum transmission.

We used this model to construct 2 cohorts of 25-year-old pregnant women living with recently acquired HIV who present for antenatal care: an NP Cohort who initiate DTG-based ART at the first ANC visit and a KP Cohort that has been on DTG-based ART for 6 months at their time of conception. HIV acquisition occurs 1 month prior to conception for all NP women and 1 year prior to conception for all KP women. Key maternal events are synchronized within each cohort, including conception, the first ANC visit, delivery, and the conclusion of breastfeeding at 18 months postpartum (Supplementary Appendix 1.2). To evaluate the PVT impact of LA-CAB/RPV, we modeled 2 HIV care strategies for each cohort: (1) a standard of care (SOC) without access to a second-line ART regimen and (2) a strategy in which PBFW with persistent viremia can switch to injectable LA-CAB/RPV. All simulations were programmed in Matlab R2021a and results were analyzed using R 4.4.3.

DTG-based First-Line ART Effectiveness

We define ART effectiveness as the probability that the regimen successfully reduces and maintains low VL at levels ranging from <50 copies/mL to low-level viremia <1000 copies/mL, consistent with observed outcomes (see Supplementary Appendix 1.4.2 and 1.5.2 for VL dynamics) [32]. Reflecting both the pharmacologic characteristics of the regimen and the individual's adherence, this estimate is informed by data from Kenya and South Africa (Supplementary Appendix 1.5.3) [19, 20]. Effective ART also (1) promotes CD4 cell count recovery, which in turn reduces the risk of acute clinical events and HIV-related death, and (2) decreases VT risk, particularly when initiated earlier in the maternal timeline (Table 1). We model a monthly risk that poor adherence renders ART ineffective—at which point VL rebounds to pretreatment levels [33], CD4 cell count decline resumes, and VT risk increases. These same changes occur when women experience ART interruption, modeled as a monthly risk that is higher for NP women, following empirical studies of NP versus KP women in Kenya (Table 1) [26, 34]. While KP women may experience ART interruption prior to entering antenatal care, we assume that these women resume ART at the first ANC visit.

Viral Load Monitoring and LA-CAB/RPV

Women in care are offered VL monitoring at intervals determined by age- and PBFW-based national guidelines (Supplementary Appendix 1.8.1). Due to their prior ART initiation, the KP Cohort receives a routine VL test at the first ANC visit, whereas the NP Cohort has their first VL test 3 months after ART initiation (Figure 1). Subsequent routine VL tests for both KP and NP women who have achieved viral suppression occur every 6 months. Given existing gaps in the VL testing cascade [35], each time a VL test is indicated, we assume there is only a 70% probability that the VL test occurs [21]. If a routine VL test detects VL ≥ 200 copies/mL, this prompts 3 months of adherence counseling prior to repeating a VL test, per Kenyan guidelines [36]. These individuals then have a 50% probability of reestablishing declines in VL that are consistent with effective ART (“re-suppression,” Table 1).

Figure 1.

Timeline of key events for the Newly and Known Positive Cohorts. The timeline depicts months since conception, through 18 months of postpartum breastfeeding. White arrows indicate routine viral load tests among those virally suppressed at the prior routine test, and red arrows indicate repeat tests for those with viral load ≥ 200 copies/mL at the prior routine test. Stars mark the potential month of switching for those whose repeat viral load remains ≥200 copies/mL under the LA-CAB/RPV strategy. See Supplementary Appendix 1.2 for additional details.

We assume the VL test is laboratory-based, the most widely implemented version of VL testing in HIV high-burden countries, rather than point-of-care [37]. Repeat VL testing for viremic women thus occurs 4 months after a routine VL test: 1 month for obtaining results and communicating them to the individual, plus 3 months of adherence counseling. If an individual's VL remains ≥ 200 copies/mL at the repeat test (virologic failure), they are eligible for LA-CAB/RPV, which is delivered in monthly injections, as this aligns with monthly ANC and postnatal visits. Given the suboptimal regimen switching rates observed in the efavirenz-era [23] and the possibility that some providers or individuals will not accept injectable LA-CAB/RPV due to limited safety and efficacy data among PBFW or fear of injections [15, 24], we assume that only 50% of eligible individuals switch. Regimen switching occurs 1 month after the repeat VL test to account for test turnaround time (Figure 1).

Our estimate of the effectiveness of LA-CAB/RPV as an ART regimen is informed by a synthesis of data from adults in high-income countries who switched to injectable LA-CAB/RPV after persistent viremia on a first-line oral regimen (Table 1) [12, 13]. LA-CAB/RPV viral suppression rates in this population are lower than those observed among those who switched to LA-CAB/RPV after achieving viral suppression on an oral ART regimen [38], a finding that is consistent with the first-line adherence challenges experienced by this population. We assume ART interruption rates on LA-CAB/RPV are the same as on DTG-based ART, given the lack of engagement data specific to injectable LA-CAB/RPV.

Health Outcomes and Sensitivity Analyses

For each strategy, we projected numbers of women on each regimen, maternal viral suppression below 200 copies/mL, live births, maternal deaths, and peripartum versus postpartum infant infections. We quantified the PVT impact of the LA-CAB/RPV strategy as the relative (percent) reduction in infant infections per 10 000 live births compared to SOC. We performed 1-way sensitivity analyses for key model parameters, and to explore the maximum potential impact of second-line LA-CAB/RPV, we also conducted a series of scenario analyses with optimistic assumptions for several influential parameters, as well as a scenario with point-of-care VL testing that eliminates the 1 month of turnaround time for each VL test, a scenario with LA-CAB/RPV injections every other month that reduces potential for ART interruption, and 3 scenarios in which routine VL testing occurs every 3 months (see Supplementary Appendix 1.8.4 and 1.3).

Ethics

Data used to inform model parameters in this manuscript were publicly available aggregate data, for which consent is not required.

RESULTS

Maternal Outcomes

Due to the timing of routine and repeat VL tests, the first time point when regimen switching occurred under the LA-CAB/RPV strategy was at 4 months postpartum for NP women and 1 month postpartum for KP women (Figure 1). By 18 months postpartum, 10.3% of NP versus 15.4% of KP women presenting to antenatal care had experienced virologic failure on DTG-based ART and become eligible to switch regimens, and 5.1% of NP versus 8.2% of KP women ultimately switched to LA-CAB/RPV. These women who switched cumulatively experienced 5870 NP person-months and 10 121 KP person-months on the second-line regimen, per 10 000 women presenting to antenatal care (Supplementary Table 1). These person-months on LA-CAB/RPV translated into the LA-CAB/RPV strategy having a higher proportion of women in both cohorts with VL < 200 copies/mL compared to the SOC, with larger differences between the strategies for KP women than for NP women (Supplementary Figure 1). However, these differences were small, given the small total proportion of PBFW who switched to injectable LA-CAB/RPV. While some of the women who switched regimens experienced ART interruption by the end of breastfeeding while on LA-CAB/RPV (0.7% of the NP Cohort and 0.4% of the KP Cohort), most of the ART interruption occurred while women were on DTG-based ART (21.4% of the NP Cohort and 7.8% of the KP Cohort), preventing them from ever becoming eligible for a second-line regimen. Among those who did switch to injectable LA-CAB/RPV by 18 months postpartum, the average time between experiencing unsuppressed VL due to ineffective DTG-based ART and switching was 8.5 months in the NP Cohort and 9.8 months in the KP Cohort (Supplementary Table 1).

Vertical Transmission

Under both strategies, the NP Cohort had more peripartum and postpartum VT per 10 000 live births than the KP Cohort (Figure 2A). Compared to the SOC strategy, the LA-CAB/RPV strategy resulted in a 1.2% reduction in total VT for the NP Cohort and a 4.2% reduction in total VT for the KP Cohort (Figure 2B). Because the first opportunity for switching to LA-CAB/RPV was not until the postpartum period in both cohorts (Figure 1), the LA-CAB/RPV strategy did not prevent any peripartum transmission, which accounted for 29% and 20% of all VT occurring under that strategy in the NP and KP Cohorts, respectively (Supplementary Table 1). Percent reductions in VT were slightly greater when analyzed among postpartum transmissions only (Figure 2B).

Figure 2.

Vertical transmission in the 2 maternal cohorts. A, Absolute numbers of peripartum and postpartum infections per 10 000 live births under each strategy, by cohort. B, Percent reductions in total and postpartum vertical transmission due to the LA-CAB/RPV strategy, by cohort.

Figure 3A provides a breakdown of postpartum VT by mother's ART status at the time of transmission. For both strategies, the proportion of postpartum VT that occurred among women experiencing interruption from DTG-based ART was more than double in the NP Cohort than in the KP Cohort. Under the SOC, when postpartum VT occurred among women on DTG-based ART, similar proportions occurred among women with a VL below versus above 200 copies/mL in both cohorts, due to most women maintaining viral suppression (Supplementary Figure 1) but there still being a non-negligible monthly postpartum VT risk when maternal VL is between 50 and 1000 copies/mL (Table 1). Under the LA-CAB/RPV strategy, less VT occurred among mothers on DTG-based ART with VL above 200 copies/mL than under SOC, as women had the opportunity to switch to and become virally suppressed with LA-CAB/RPV. While a small proportion of postpartum VT occurred after mothers switched to LA-CAB/RPV (Figure 3A), more than 90% of mothers who switched regimens did not experience VT (Supplementary Table 1). Among women who switched to LA-CAB/RPV and did experience VT, most of the transmission occurred after switching regimens, but for 25.9% of NP and 45.5% of KP women in this group, the transmission had already occurred prior to switching regimens (Figure 3B). For the VT occurring after switching, the majority occurred when the mother experienced a loss of viral suppression while on the new regimen, with some VT also occurring while suppressed on LA-CAB/RPV or during interrupted LA-CAB/RPV (Supplementary Figure 2).

Figure 3.

Vertical transmission per 10 000 live births, by cohort and mother's ART status. A, For postpartum vertical transmission (VT) under the Standard of Care (SOC) versus LA-CAB/RPV strategies, distribution of mother's ART status at the time of VT. For dolutegravir (DTG)-based ART, status is subdivided into viral load (VL) ≥ 200 copies/mL, VL < 200 copies/mL, or interrupted. The LA-CAB/RPV category includes VT that occurred after ART was interrupted. B, Distribution of the timing of total VT among those who switched to LA-CAB/RPV under that strategy. The red “VT After Switching” bars in panel B represent the same VT labeled “LA-CAB/RPV: On ART or Interrupted” in panel A. NP = Newly Positive; KP = Known Positive; PBFW = pregnant and breastfeeding women.

Sensitivity and Scenario Analyses

The scenario analyses with optimistic conditions for LA-CAB/RPV primarily conveyed the importance of high switching rates: raising the switching probability to 100% roughly doubled the relative reduction in total VT due to LA-CAB/RPV (Figure 4, Scenario J), and pairing 100% switching with 100% adherence to VL monitoring guidelines with routine VL testing every 3 months increased NP versus KP relative reductions to 4.0% versus 11.5%, respectively (Scenario M). These respective reductions were 2.0% versus 7.1% when routine VL testing frequency alone was increased (Scenario I). Scenarios that did not increase switching or testing but improved the VL monitoring cascade, such as 100% VL monitoring with 50% switching (Scenario G) and point-of-care VL testing (Scenario F), had more minor influences, as did the scenarios that decreased ART interruption (Scenarios B and E) and/or increased LA-CAB/RPV effectiveness to 100% (Scenarios D and H). All one-way sensitivity analyses other than switching probability also resulted in only modest changes to the relative reduction in total VT due to LA-CAB/RPV, with ranges of 0.3%–1.5% versus 3.0%–5.1% for the NP versus KP Cohorts, respectively (Supplementary Figures 3–5 and Table 2).

Figure 4.

Percent reductions in total vertical transmission under optimistic scenarios for the LA-CAB/RPV strategy. Including the base case, results are ordered from top to bottom by lowest to greatest impact on the Newly Positive Cohort. “Low” ART interruption refers to 9.4% versus 3.4% cumulative interruption for newly positive versus known positive women, between first antenatal care visit and end of breastfeeding (see Supplementary Appendix 1.7 for details). *Strategies that increase routine VL monitoring frequency to every 3 months.

DISCUSSION

We used a simulation-based model to evaluate the potential PVT impact of providing injectable LA-CAB/RPV as a second-line regimen for Kenyan PBFW living with HIV. Under our base-case parameter settings, we found that, among NP and KP women who initiate DTG-based first-line ART, this intervention can reduce VT by 1.2% and 4.2%, respectively. Although the availability of an effective second-line regimen meets the specific needs of PBFW with persistent viremia, these modest VT reductions are consistent with its downstream position within the cascade of care, and the greater reduction for KP women is consistent with this group having a higher proportion of women who experienced virologic failure and more person-months on LA-CAB/RPV. This greater impact for KP women also parallels a prior analysis in which the PVT impact of VL monitoring in the absence of a second-line regimen was also greater among KP women [11]. For both NP and KP women, we also found that more frequent VL testing and a stronger VL monitoring cascade substantially improved VT reductions due to LA-CAB/RPV. Given that an estimated 8% of infants who acquired HIV globally were born to mothers who initiated ART and did not have subsequent ART interruption during pregnancy or breastfeeding [16], second-line ART has an important role to play in moving countries toward the elimination of VT.

Understanding the pathways through which LA-CAB/RPV impacts VT will be key to designing effective implementation strategies, and our analysis highlights several important considerations. First, the PVT potential of second-line ART depends on the size of the target population (PBFW with persistent viremia on first-line ART), as well as their access to and uptake of the intervention. Because these PBFW must stay on first-line ART and remain in care long enough to receive the VL tests that indicate persistent viremia, ART interruption prevents some PBFW from meeting switching criteria. In addition, PBFW remaining in care must also have persistently unsuppressed VL while on first-line ART to warrant a second-line regimen. Given the high potency of DTG-based ART, only a small subset of PBFW have persistent viremia. Finally, gaps in the VL monitoring cascade, including inconsistent VL testing and suboptimal regimen switching rates, may prevent in-care PBFW with persistent viremia from receiving LA-CAB/RPV. For example, when we assumed 100% adherence to VL monitoring guidelines and 100% regimen switching among PBFW eligible for LA-CAB/RPV, VT reductions increased to 3.3% versus 9.9% in NP versus KP women. These reductions further increased to 4.0% versus 11.5%, respectively, when the improved cascade also included more frequent routine VL testing.

Even when eligible PBFW did switch to LA-CAB/RPV in our model, the average time from having unsuppressed VL to switching was around 9 months, reflecting the wait time between routine VL tests, turnaround time for the results, 3 months of adherence counseling, and turnaround time for repeat VL test results and regimen switching. Among women who switched to LA-CAB/RPV and experienced VT, a significant proportion occurred prior to switching regimens. The modest VT reductions observed in this study thus do not reflect limitations intrinsic to injectable LA-ART, but rather the delays associated with the downstream nature of a second-line regimen. While the possibility of LA-ART as a first-line regimen for PBFW should be considered, our scenarios with routine VL monitoring every 3 months show how increasing opportunities for regimen switching can improve the PVT impact of LA-CAB/RPV as a second-line regimen.

Our analysis complements the 2 other modeling studies that have explored the VT impact of LA-ART implementation in Africa. First, Tewari et al. evaluated switching breastfeeding mothers with adherence challenges to LA-CAB/RPV immediately after delivery [39]. Among those not virally suppressed at delivery, switching decreased the 7.49% total VT under the SOC of continuing DTG-based ART to 6.58%, a 12% reduction. This 100% switching strategy early in postpartum, evaluated among the high-risk subgroup of unsuppressed women, naturally exceeds our projected VT reductions under 50% switching among all PBFW. Second, Phillips et al. used a population-level model that included horizontal transmission to evaluate the use of injectable lenacapavir/CAB as a second-line regimen for all adults on ART, with the option to use it as a first-line regimen for adults initiating ART [40]. While their projected 18% reduction in VT captures the PVT impact of primary prevention of HIV among women through population-level improvements in viral suppression over a 50-year time horizon, we modeled only second-line LA-CAB/RPV among PBFW living with HIV on ART through 18 months postpartum. Considering the differences in strategies, populations, time frames, and model structures, our findings are consistent with these studies and add insight into how benefit may vary for NP versus KP women.

Our analysis had several limitations arising from the limited amount of LA-CAB/RPV implementation data available, the impact of which we examined in our sensitivity analyses. In the absence of any contemporary data, we patterned switching rates after those observed in the pre-DTG era, but our sensitivity analyses indicate that higher switching rates would significantly increase the PVT impact of LA-CAB/RPV. We similarly addressed the lack of data regarding ART interruption on LA-CAB/RPV by using DTG-based ART interruption estimates, and our sensitivity analyses suggest that lower or higher rates would modestly influence the PVT impact of LA-CAB/RPV. Likewise, we found that reducing the potential for LA-CAB/RPV ART interruption via injections every other month rather than monthly would also only modestly improve PVT. In addition, given the lack of African data on viral suppression rates on second-line LA-CAB/RPV, we sourced studies done in high-income countries, many of which were conducted in academic medical centers. While we used these data to select a conservative LA-CAB/RPV effectiveness estimate, future research may indicate higher effectiveness for this regimen or alternatives such as CAB with lenacapavir [41]. On the other hand, given the cross-resistance between dolutegravir and CAB, ADR to dolutegravir would presumably decrease LA-CAB/RPV effectiveness. Although we did not explicitly model drug resistance to dolutegravir, the prevalence of ADR remains low in populations like our 2 maternal cohorts who have no ART experience prior to DTG-based ART (Supplementary Appendix 1.8.7). Our sensitivity analyses illustrate the potential PVT impact of net higher or lower ART effectiveness, and ongoing studies of the effectiveness of various LA-ART regimens as well as drug resistance surveillance will be critical for all populations, including PBFW. However, despite our sensitivity analyses, our results may not be directly applicable to PBFW who have ART-experience prior to switching to DTG-based ART, as they have a higher risk of ADR. Finally, while there are no current safety concerns regarding the use of CAB/RPV during pregnancy and breastfeeding, more clinical data is still needed [15]. Of the 2 agents, there is greater experience with CAB, but largely from pre-exposure prophylaxis studies. Data on the injectable formulation of RPV is limited, but studies of oral ART containing RPV indicate it is safe and effective during pregnancy [42]. While more research is needed to support its use in both pregnancy and breastfeeding, LA-CAB/RPV in our analysis was implemented only during breastfeeding.

CONCLUSION

Our analysis provides estimates of the potential PVT impact of injectable LA-CAB/RPV as second-line treatment for women with HIV in Kenya and offers insights to other countries with similar VL monitoring guidelines. As LA-ART is considered for rollout in African countries, our findings provide actionable evidence for policy leaders and other stakeholders that strengthening health systems' adherence to regimen switching and optimized VL monitoring guidelines will be essential to maximizing the real-world impact of this new intervention.

Supplementary Data

Supplementary materials are available at Open Forum Infectious Diseases online. Consisting of data provided by the authors to benefit the reader, the posted materials are not copyedited and are the sole responsibility of the authors, so questions or comments should be addressed to the corresponding author.