Dolutegravir and rilpivirine as successful initial antiretroviral therapy in a treatment-naive patient with HIV-1: A case report

Summary

Two drug regimens for HIV-1 have been proven effective in attainment of HIV-1 viral suppression in several large trials. Dolutegravir plus lamivudine has been studied and is approved for use in antiretroviral naive patients living with HIV-1, whereas dolutegravir plus rilpivirine has not been studied and is not recommended in this setting. We present the case of an antiretroviral naive patient with low CD4 count, high HIV-1 viral load (VL), a rilpivirine drug-resistance mutation, and cryptococcal meningitis, successfully treated with dolutegravir and rilpivirine, and suggest that further study is warranted to evaluate efficacy of this regimen in antiretroviral therapy naive patients.

Background

Although three-drug regimens (3DR) have been the standard treatment for HIV-1 infection, a 2DR is included as an option for combination antiretroviral therapy (cART) naive patients in the US Department of Health and Human Services HIV treatment guidelines as of 2019. Specifically, the 2DR of dolutegravir (DTG) and lamivudine (3TC) has been shown to be effective and safe as initial treatment for HIV-1 infection based on the GEMINI-1 and GEMINI-2 trials.^1,2 The SWORD-1 and SWORD-2 trials demonstrated that DTG and rilpivirine (RPV) in combination are safe, well-tolerated, and effective in sustaining viral suppression in patients who have achieved viral suppression with a 3DR.^3,4 The combination of DTG + RPV is available as the single-tablet regimen (STR) Juluca™, which is approved in the US for switch therapy in adults who have achieved viral suppression. ⁵ DTG + RPV as initial treatment has not yet been evaluated in large-scale trials and has not been approved for initial treatment in naive patients. Here, we present the case of an ART naive man with newly diagnosed HIV-1 infection, treated effectively with DTG + RPV as the initial cART regimen. The case was previously published in part as an example of delayed cryptococcal meningitis diagnosis. ⁶

Case presentation

A 33-year-old Honduran man presented to a US emergency department with fever, headache, neck stiffness, nausea, vomiting, and sensitivity to light and sound ongoing for 2 weeks. He was diagnosed with HIV-1 and cryptococcal meningitis (CM) based on positive serum HIV-1/2 Ag/Ab, positive HIV-1 VL, positive serum and cerebrospinal fluid (CSF) cryptococcal antigen, Cryptococcus neoformans growth in CSF culture, and an elevated CSF opening pressure on initial lumbar puncture (LP). He was treated with liposomal amphotericin B (L-AMB) and flucytosine (FC) induction therapy for 1-week inpatient in addition to serial LPs to control intracranial pressure. CD4 count was 22 cells/μL and serum HIV-1 VL was 157,065 copies/mL. CM treatment regimen was changed to high dose oral fluconazole due to lack of insurance coverage for outpatient parenteral antimicrobial therapy with L-AMB and FC. Trimethoprim-sulfamethoxazole (TMP-SMX) was prescribed for prophylaxis against Pneumocystis jirovecii and Toxoplasma gondii infection. cART initiation was purposefully delayed due to high risk of immune reconstitution inflammatory syndrome–related mortality. ⁷

Nine weeks after initiation of fluconazole and TMP/SMX, he was admitted for acute pancreatitis, with lipase level peaking at 7011 u/L. Common causes of pancreatitis including alcohol use, gallstones, and hypertriglyceridemia were ruled out. The patient took no other medications apart from what was recently prescribed; TMP/SMX was suspected to be the likely cause of the pancreatitis. TMP/SMX was discontinued and atovaquone initiated for prophylaxis.

Three weeks following the diagnosis of pancreatitis, he was started on DTG + RPV as initial ART, after confirming resolution of elevated lipase level (264 u/L). DTG + RPV was chosen to avoid both nucleoside reverse transcriptase and protease inhibitors given the recent drug-induced pancreatitis. ⁸ After DTG + RPV initiation, resistance genotyping revealed a V179D mutation, which confers low-level resistance to RPV. However, he tolerated DTG + RPV well and had a gradual 4-fold log decline in HIV-1 VL with viral suppression to <100 copies/mL achieved 20 weeks after initiation of ART (Figure 1). The potential increase in rilpivirine concentration due to CYP3A4 inhibition by fluconazole may have been protective against the development of further resistance. Following the 1 week of AMB + FC inpatient, he completed an extended induction with fluconazole 1200 mg daily for a total of 8 weeks, followed by 400 mg daily for consolidation and maintenance for an additional year. Atovaquone was stopped once he achieved viral suppression and a CD4 count of >100 for 3 months.

Figure 1.

CD4 count, CD4 percentage, and HIV-1 viral load trend CD4 Abs, CD4 Absolute; CD4 %, CD4 percentage.

Discussion

The SWORD-1 and SWORD-2 trials demonstrated sustained viral suppression of DTG + RPV in patients previously successfully treated with a 3DR but did not assess whether the combination could be used as initial treatment.^3,4 Current guidelines recommend against using RPV if CD4 count is less than 200 cells/μL or if VL is greater than 100,000 copies/mL, DTG/3TC is advised against with HIV-1 VL over 500,000 copies/mL, and neither RPV-containing regimens nor DTG/3TC are recommended as initial treatment if HIV-1 genotype results are unavailable ⁹ due to higher failure rates (RPV) ¹⁰ and lack of data (DTG/3TC) ¹¹ , respectively. Although these guidelines are evidence-based and appropriate for the vast majority of patients, HIV experts can practice outside of current guidelines in unique situations such as the one presented here.

Here, we demonstrate that the combination of DTG and RPV can be considered as initial ART in treatment-naive patients infected with HIV-1 if there are contraindications to guideline-recommended first-line regimens.

Conclusion

This case suggests that further investigation is warranted to evaluate DTG + RPV for initial treatment in treatment-naive HIV-1 infected patients.