Case series of two persons living with HIV with detectable viral loads initiated then suppressed on cabotegravir/rilpivirine with lenacapavir

Introduction

Daily oral antiretroviral therapy (ART) is the backbone of human immunodeficiency virus (HIV) treatment but may not be realistic for all persons living with HIV (PLWH). ¹ Pill dysphagia, inability to maintain daily adherence even with provider support services, and fear of prejudice/external stigma from status disclosure with oral ART remain significant barriers.^1–3 ART guidelines recommend against using long-acting (LA) ART [cabotegravir/rilpivirine (CAB/RPV)] in patients with adherence concerns and only recommend monthly/bimonthly parenteral treatment in virally suppressed PLWH.^1,2,4–6 Recent data support CAB/RPV use in PLWH with viremia and demonstrate successful viral load (VL) suppression with some patients necessitating addition of lenacapavir (LEN) secondary to historical HIV resistance.^3,7 Expert opinion now recommends CAB/RPV in PLWH with viremia with optimal support services. ⁸ We present two cases of PLWH with multidrug-resistant (MDR) HIV who were unable to maintain virologic suppression with a daily oral ART, but achieved virologic control with CAB/RPV + LEN.

Case report

Patient A has a history of pill aversion, numerous socioeconomic barriers making daily adherence difficult (Table 1). With daily nursing text message reminders, VL suppression was briefly achieved on bictegravir/emtricitabine/tenofovir alafenamide but was not sustained. Patient B has a long history of severe dysphagia secondary to candidiasis and esophageal strictures requiring frequent dilations and periodically was unable to even swallow crushed medications. Previously having a percutaneous endoscopic gastrostomy tube, she eventually refused tube replacement and was malnourished [body mass index (BMI) of 13.8 kg/m²]. Both patients developed significant HIV resistance on compiled genotypic history (Table 1) with baseline viremia (Table 2). Patient A had non-nucleoside reverse transcriptase inhibitor (NNRTI) mutations (K103N and P225H) preventing use of CAB/RPV as a complete regimen. Patient B had suspected historical mutations (M184V) with incomplete records, but a documented integrase-strand transfer inhibitor (INSTI) mutation (E138D) was concerning for incomplete activity especially with prior CAB failure reports.^9,10

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Table 1.

Baseline HIV resistance.

	Patient A	Patient B
Age	48	64
Gender	Transgender female	Female at birth
Years living with HIV	30	23
Compiled genotype	RT: K103N, V118I, M184V, T215T, P225H, M41L	RT: Suspected M184V
	PI: None	PR: M36T, N37D, I62V, L63P
	IN: None	IN: M50I, E138D/M

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Table 2.

Patient Characteristics.

	Patient A	Patient B
	Viral load (copies/mL)	Viral load (copies/mL)	BMI (kg/m2)	RPV concentration (ng/mL)
Pre-dose VL	112,000	36,900	13.8	Not collected
First injection	440	Not collected	13.2	Not collected
Second injection	34	35	13.8	40
Third injection	<20	Not collected	15.0	70
Fourth injection	Undetectable	37	16.9	Not collected
Fifth injection	Not checked	Undetectable	16.6	Not collected
Sixth injection	Undetectable	Undetectable	17.2	Not collected

Both patients received oral LEN lead in (600 mg on day 1 and 2) and two 463.5 mg abdominal subcutaneous injections with gluteus intramuscular CAB/RPV 600/900 mg followed by monthly 400/600 mg doses. Patient B erroneously received CAB/RPV 400/600 mg injections on her first appointment but received the loading dose (600/900 mg) at month 2. Patient B received injections in the vastus lateralis secondary to low BMI until reverting to gluteus administration on injection 5.^11,12 Patient A was on-time with all monthly CAB/RPV injections, but patient B had concurrent health challenges (recurrent cystitis with a suprapubic catheter necessitating emergency department visits) and had 67 days between the third and fourth doses but maintained VL suppression (<50 copies/mL). Patient B was anorexic at treatment initiation but regained appetite with a 20.9% BMI increase over 23 weeks. Both patients had palpated subcutaneous abdominal nodules without significance. At month 6 with the second LEN injection, both transitioned to bimonthly CAB/RPV and remain virologically suppressed.

Discussion

Three LA ARTs are available for PLWH with VL suppression (CAB/RPV) or with MDR HIV (LEN). This case series demonstrates VL suppression with CAB/RPV + LEN in MDR HIV, baseline viremia, and daily oral ART nonadherence and adds to previously reported experiences.^3,7,13,14 Hickey et al. reported VL suppression (N = 59 PLWH) at 48 weeks in 81% on CAB/RPV and 93% when LEN was added with baseline VL > 50 copies/mL. ¹³ Gandhi et al. reported similar results with CAB/RPV + LEN or CAB + LEN in MDR PLWH with NNRTI mutations. ³ Of 34 PLWH, 94% achieved virologic suppression compared to 47% at baseline. ³

Unique to our report is the successful use of CAB/RPV + LEN in patient B with a BMI of 13 kg/m². Because of low muscle mass, there was concern for CAB/RPV absorption and distribution. RPV trough concentrations collected at the second/third injections were similar to the phase 3 trial results, which had a median BMI 26 kg/m² (15–58 kg/m²). ⁵ The CAB/RPV pharmacokinetic values in adolescent patients [median BMI 19.9 (18.0-24.1)] demonstrated similar trough concentrations. ¹⁴ To our knowledge, LA ART use in PLWH with BMI < 15 kg/m² has not been previously reported. While there was concern about patient B exceeding the dosing window (1 month ± 7 days), she remained virologically suppressed. Both cases correlate with prior reports of PLWH and late injections. ¹⁵ Missing clinic visits in the year prior to switching to CAB/RPV is associated with at least one injection no-show appointment with 30.4% of patients with late injections having at least one no-show. No-show or late injections did not result in detectable VL. ¹⁵ Patient B had two missed visits and a delayed injection but remained suppressed. Although our two patients did not meet the strict initiation requirements for LA ART, the results add to the literature demonstrating MDR PLWH with uncontrolled viremia and historical nonadherence may achieve VL suppression with a return to health and should now be considered a therapeutic option for persons with similar treatment barriers.