Abstract
Objectives
Long‐acting (LA) intramuscular injections of cabotegravir (CAB) and rilpivirine (RPV) are an effective maintenance therapy for people living with HIV who are virologically suppressed. However, virological failures (VFs) have been reported, often associated with elevated body mass index (BMI), potentially due to inadequate intramuscular drug delivery. Current recommendations mainly rely on BMI to guide needle length selection and do not routinely incorporate imaging techniques. Furthermore, they do not recommend the use of ultrasound as an investigative tool in cases of LA treatment failure.
Methods
We retrospectively reviewed anonymized records of two patients experiencing virological rebound under LA CAB/RPV. Clinical, virological and resistance data were extracted from their medical records.
Results
The first case involves an obese patient. Ultrasound revealed subcutaneous adipose tissue thickness >3 cm and intra‐adipose injection granulomas, suggesting non‐intramuscular injections. After adapting needle length, virological suppression was restored. The second case involves a patient with a normal BMI in whom ultrasound revealed a gluteal subcutaneous adipose tissue thickness of 45 mm and bilateral subcutaneous granulomas.
Conclusion
Ultrasound is a simple and accessible tool to help optimize drug injection in case of obesity or gynoid fat distribution and investigate injection technique–related issues in cases of VF.
Keywords: anti‐HIV agents, cabotegravir, HIV, intramuscular injections, rilpivirine, ultrasonography
INTRODUCTION
Since 2020, international guidelines endorse long‐acting (LA) intramuscular injections of rilpivirine (RPV) and cabotegravir (CAB) as maintenance therapy for virally suppressed people living with HIV [1]. Observational cohorts report virological failure (VF) rates of 0%–2.4%, associated with body mass index (BMI) ≥30 kg/m2, possibly due to pharmacokinetic alterations and unintentional subcutaneous rather than intramuscular administration due to insufficient needle length [2, 3].
We report two VF cases where ultrasound identified inappropriate injection sites and led to needle length adjustment.
METHODS
We conducted a retrospective descriptive analysis at the Department of Infectious Diseases, CHU Saint‐Pierre, Brussels. Clinical, virological and resistance data were extracted from anonymized medical records. Injections were performed by a dedicated team of trained nurses using 21‐gauge needles at ventrogluteal sites with RPV and CAB in opposite gluteal locations. VF was defined as >200 copies/mL [1]. Ultrasound was performed by the same radiologist using an 11–17‐MHz linear probe in prone position at the ventrogluteal site. Viral RNA genotyping was performed on plasma.
RESULTS
Case 1
A 47‐year‐old woman (BMI = 38 kg/m2) with prior low‐level viraemia (137 copies/mL) due to suboptimal adherence was switched to LA CAB/RPV in November 2023 using 38‐mm needles. Despite three on‐time injections, viral load (VL) increased to 388 copies/mL. Genotyping showed no resistance to CAB or RPV. Ultrasound revealed bilateral adipose tissue thickness >3 cm and post‐injection granulomas within adipose tissue (Figure 1). Injections resumed in May 2024 using 51‐mm needles. VL was <50 copies/mL thereafter (Table 1).
FIGURE 1.
Case 1: granuloma in subcutaneous tissue; Case 2: granuloma in subcutaneous tissue.
TABLE 1.
Demographic and clinical characteristics of patients.
| Characteristics | Case 1 | Case 2 |
|---|---|---|
| Sex | Female | Female |
| Weight (kg) | 108 | 59 |
| BMI (kg/m2) | 38 | 19 |
| Initial needle length (mm) | 38 | 38 |
| Prior resistance | No |
NRTI NNRTI |
| Initial VL (cp/mL) | 137 | <20 |
| VL at VF (cp/mL) | 388 | 207 |
| Duration of LA ART before first VF | 3 months | 6 months |
| Resistance to CAB/RPV at first VF | No | No |
| US findings | Granulomas in subcutaneous adipose tissue | Granulomas in subcutaneous adipose tissue |
| US thickness of adipose tissue (mm) |
31 (right) 38 (left) |
45 (right) 45 (left) |
| Adjusted needle length (mm) | 51 | 51 |
| VL at M3 post‐needle adjustment (cp/mL) | <50 | 28 |
| Follow‐up VL | <50 at M12 | Second VF at M4 post‐needle adjustment; RPV resistance acquired on RNA genotyping |
Abbreviations: ART, antiretroviral therapy; BMI, body mass index; CAB, cabotegravir; cp/mL, copies/mL; LA, long acting; M3, month 3; NNRTI: non‐nucleosidic reverse transcriptase inhibitors; NRTI, nucleosidic reverse transcriptase inhibitors; RPV, rilpivirine; US, ultrasound; VF, virological failure; VL, viral load.
Case 2
A 42‐year‐old woman with multidrug‐resistant HIV affecting nucleoside reverse transcriptase inhibitors and non‐nucleoside reverse transcriptase inhibitors but susceptible to RPV and Integrase Inhibitors requested LA therapy. BMI was 19 kg/m2 and VL <20 copies/mL. Injections began in July 2024 using 38‐mm needles. After four injections, VL rose to 102 copies/mL and reached 207 copies/mL 6 months later leading to reintroduction of oral ART during investigation. Genotyping showed no resistance to RPV or CAB. Ultrasound revealed granulomas in 45‐mm‐deep subcutaneous adipose tissue (Figure 1). Injections resumed in July 2025 with 51‐mm needles. VL initially decreased, but VF with acquired RPV resistance occurred in November 2025 (Table 1).
CONCLUSION
These two cases highlight the poor correlation between BMI and gluteal adipose tissue distribution and suggest ultrasound as a reactive tool to investigate injection‐related issues in case of VF during LA CAB/RPV therapy. Given its ease of use and learnability, point‐of‐care ultrasound may help assess adipose thickness and optimize injection sites in obese patients or those with gynoid fat distribution despite normal BMI [4].
Key limitations include the lack of pharmacokinetic data, as plasma RPV/CAB concentrations were not measured to confirm inadequate drug exposure. However, subtherapeutic levels alone do not fully explain VF, which results from multiple factors including HIV subtype, injection technique, obesity‐altered pharmacokinetic alterations and archived proviral resistance. VF in case 2 was therefore likely not solely attributable to needle length [4, 5]. Finally, operator variability may have influenced drug delivery despite needle adjustment, and follow‐up duration limits long‐term outcome assessment.
AUTHOR CONTRIBUTIONS
All authors contributed to the interpretation of the data and the findings of the study. All authors revised and approved the final version of the manuscript.
CONFLICT OF INTEREST STATEMENT
The authors declare no conflicts of interest.
ACKNOWLEDGEMENTS
We thank all authors, colleagues and reviewers who contributed to the development of this case series.
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available on request from the corresponding author upon reasonable request.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The data that support the findings of this study are available on request from the corresponding author upon reasonable request.