Efficacy and safety of an Albuvirtide-based regimen for preventing mother-to-child transmission of multidrug-resistant HIV: a case report

Abstract

Background

Antiretroviral drugs are essential for preventing mother-to-child transmission (MTCT) of HIV in HIV-infected pregnant women. However, ART treatment for HIV-infected pregnant women with multidrug resistance remains a major challenge. Effective and safe ART regimens for preventing MTCT should be tailored to this special population. Albuvirtide (ABT) is along-acting fusion inhibitor with proven efficacy and safety in adults with multidrug-resistant HIV. Herein, for the first time, we report the use of an ABT-based ART regimen in pregnant women infected with multidrug-resistant HIV.

Case presentation

A 25-year-old female HIV patient with an estimated gestational age of 14 weeks who received the TDF + 3TC + EFV regimen. The tests revealed an HIV- RNA concentration of 1730 copies/mL, a CD4 T lymphocyte (CD4 cell) concentration of 145 cells/µL and genotypic resistance to NRTI and NNRTI. The patient showed a decreased viral load (30 copies/mL) and increased CD4 cells (215 cells/µL) after 12 weeks of ABT + 3TC/DTG treatment. Her physical condition was good, and no drug- related adverse reactions occurred. By the prenatal period (40 weeks), HIV RNA became undetectable, and CD4 cells had risen to 348 cells/µL. Finally, the patient delivered a healthy female baby who was negative for HIV, and the follow-up showed normal growth.

Conclusions

In our case, ABT-based antiretroviral regimen was effective in suppressing viral load (VL) in pregnancy, and there is no reported safety issues for the mother or the baby. Albuvirtide use in pregnancy might represent a strategy to avoid in utero transmission of MDR-HIV, but further investigation is warranted.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12884-025-07156-4.

Background

The infection caused by human immunodeficiency virus- 1 (HIV) continues to pose a significant worldwide health issue. The majority of pediatric HIV infections are caused by mother-to-child transmission (MTCT), which may occur during the second or third trimester of pregnancy, labor, or nursing [1]. In the absence of intervention, the risk of HIV MTCT is high, as 8% of infants contract the virus during pregnancy, 15% during delivery and labor, and 12-26% during breastfeeding [2, 3]. Moreover, implementing antiretroviral therapy (ART), postexposure prophylaxis, and prevention of MTCT services has resulted in a substantial decline in the percentage of MTCT, which is now less than 5% [4].

Presently, there is a collection of more than thirty antiretroviral medications licensed for use by medical professionals. Nevertheless, many of these medications are taken off-label since their pharmacokinetics, effectiveness, and safety for both the mother and the fetus during pregnancy have not been well studied [5]. In addition, with the expansion of a range of therapeutic interventions, prolonged and intense drug exposure has exacerbated HIV drug resistance, which weakens the activity of antiretroviral drugs and reduces the efficacy of antiretroviral therapy. This group of pregnant women exhibits the emergence of drug-resistant viruses, which can facilitate MTCT of HIV throughout both the intrauterine and postnatal periods [6]. Consequently, further investigation into strategies to mitigate this risk during pregnancy remains essential.

Albuvirtide (ABT) is an injectable antiretroviral drug that was approved by the Chinese National Medical Products Administration (NMPA) in 2018. It has a wide range of anti-HIV- 1 activities, with a half-maximal half-life of 12 days. Here, we describe a young, drug-resistant HIV patient who achieved complete viral suppression with alamivudine (3TC)/dolutegravir (DTG)+ABT regimen throughout her pregnancy and gave birth to a healthy, HIV-negative female baby.

Case presentation

A 25-year-old woman with HIV infection visited the gynecology department of the local hospital, and an ultrasound was suggestive of early intrauterine pregnancy. She was admitted to our hospital for "midterm pregnancy, HIV infection" for further diagnosis and treatment in April 2022.

She was diagnosed as HIV-positive in 2018, and her initial antiretroviral regimen was tenofovir (TDF)+3TC+efavirenz (EFV), but she did not take medication regularly. At admission, an ultrasound examination revealed that she was in the middle stage of pregnancy, with a single viable fetus. Her fetal heart rate was 158 beats/min, and her placental maturity was grade 0. The gestation period was estimated to be 14 weeks and 3 days. The viral load and number of CD4 cells were 1730 copies/mL and 145 cells/µL, respectively. The CD4/CD8 ratio was 0.14. A multidrug resistance test (Sanger sequencing) revealed 7 point mutations in the reverse transcriptase region, and no primary drug resistance mutations were detected in the protease and integrase strand transfer inhibitor region (Table 1). Then, an adjusted ART regimen of ABT (320 mg) with 3TC/DTG (300 mg/50 mg) was given. After 12 weeks, the HIV viral load decreased to 30 copies/mL, the number of CD4 cells increased to 215 cells/µL, and the CD4/CD8 T-cell ratio was 0.39. In her 40^th week of gestation, the viral load decreased to undetectable levels after six months of treatment, accompanied by a significant recovery of CD4 cells (348 cells/µL), and the CD4/CD8 T-cell ratio was 0.51 (Fig. 1 and Table 2). Moreover, this ART regimen was well tolerated, without any relevant toxicity, and the patient’s condition improved significantly. The laboratory results at admission and during pregnancy are shown in Table 2.

Table 1.

Genotypic drug resistance interpretation according to the HIV Drug Resistance Database system

Gene coding regions	Mutations		ARV drugs	Interpretation
PR			Atazanavir (ATV/r)	S
			Darunavir (DRV/r)	S
			Fosamprenavir (FPV/r)	S
			Indinavir (IDV/r)	S
			Lopinavir (LPV/r)	S
			Nelfinavir (NFV)	S
			Saquinavir (SQV/r)	S
			Tipranavir (TPV/r)	S
RT	NRTI relevant	D67G, K70E, Y115F, M184V	Abacavir (ABC)	H
			Zidovudine (AZT)	S
			Stavudine (d4T)	L
			Didanosine (DDI)	M
			Emtricitabine (FTC)	H
			Lamivudine (3TC)	H
			Tenofovir (TDF)	M
	NNRTI relevant	V106M, V179DE, G190A	Doravirine (DOR)	M
			Efavirenz (EFV)	H
			Etravirine (ETR)	L
			Nevirapine (NVP)	H
			Rilpivirine (RPV)	L
INSTI			Bictegravir (BIC)	S
			Cabotegravir (CAB)	S
			Dolutegravir (DTG)	S
			Elvitegravir (EVG)	S
			Raltegravir (RAL)	S

Abbreviations: PR Protease region, RT Reverse transcriptase region, INSTI Integrase strand transfer inhibitor, NRTI Nucleoside reverse transcriptase inhibitors, NNRTI Non-nucleoside reverse transcriptase inhibitors, ARV Anti-retroviral, S Susceptible, H Highly resistant, M Moderate resistant, L Lowly resistant

Fig. 1.

Temporal trendsin CD4 cell count and plasma HIV RNA level

Table 2.

Laboratory data

	Baseline	12 weeks after	ante partum
	(14 weeks gestation)	ART (26 weeks gestation)	(40 weeks gestation)
ALT (U/L)	12.9	11.2	10.0
AST (U/L)	19.0	18.6	17.1
GGT (U/L)	17.1	16.6	19.1
Cr (umol/L)	37.3	35.6	41.2
e-GFR (ml/min)	127.6	121.5	118.6
CHOL (mmol/L)	4.32	6.08	6.48
TG (mmol/L)	1.71	1.81	2.70
HDL-C (mmol/L)	1.41	1.98	1.56
GLU (mmol/L)	4.71	4.16	4.70
HbA1c (%)	4.9	5.2	5.5
CD4 (cells/µL)	145	215	348
CD8 (cells/µL)	1032	547	683
CD4/CD8	0.14	0.39	0.51
HIV RNA (copies/mL)	1730	30.2	ND

ND not detectable

A female baby was delivered by cesarean section at 40 weeks and had a birthweight of 2600 g, a length of 50 cm, and anApgar score of 10 at 1 minute, 5 minutes, and 10 minutes. The infant took zidovudine (AZT) at 2 mg/kg (q6h) for six weeks after birth and was formula-fed. HIV RNA tests yielded negative results at 48 and 92 days after birth. The baby was 15 months old with normal growth.

Discussion and conclusions

Pregnant women infected with multidrug-resistant HIV (MDR-HIV) are at high risk of MTCT. The choice of a safe and effective approach in this condition remains a challenge. This is the first reported case of a successful prevention of multidrug resistant HIV- 1 MTCT with Albuvirtide-based regimen use in pregnancy.

The mother’s VL was suppressed within 12 weeks after ABT-based regimen initiation, and the baby was born healthy. Research has shown that maternal viral load is the most significant predictor of perinatal transmission. A viral load of less than 50 copies/ml at birth is linked to a vertical transmission risk of less than 1% [7]. The use of ART has resulted in a notable reduction in HIV MTCT over 25 years [8]. Globally, mother-to-child transmission of HIV is as high as 15-45% without any intervention, and effective mother-to-child blocking interventions can reduce transmission rates to less than 5% [1]. It is vital that pregnant women start ART as soon as possible, regardless of their CD4 cell count and it is essential that they receive the right antiretroviral regimen and that their viral load is monitored continuously to reduce the risk of transmission and to suppress the virus [1, 5, 9].

The World Health Organization (WHO) asserts that the optimal regimen consists of TDF+3TC(or FTC)+DTG. An alternative regimen for pregnant women has been proposed, consisting of TDF, 3TC, and EFV [10]. In contrast, the 2024 Chinese HIV guidelines also recommend that the preferred regimen is FTC/TDF/TAF+3TC or ABC/3TC+DTG(or RAL). Alternative also has been proposed, consisting of TDF, 3TC,AZT,RPV or LPV/r and EFV [11].

Dolutegravir or Raltegravir-based regimens are currently considered effective and safe medications during pregnancy for HIV-positive pregnant women [9]. Furthermore, in situations where drug resistance is present, DTG to be a highly regarded option due to its ability to overcome resistance barriers more effectively compared to RAL [9].

In this case, a genotypic resistance test evidenced 4 NRTI mutations and 3 NNRTI mutations.Therefore, The decision of switching to antiretroviral therapy was made by personalized therapy strategy:

Firstly, LPV/r may be another choice of antiretroviral drug based on the results of genotypic resistance test, its use is associated with significant gastrointestinal side effects and an increased risk of preterm birth and low birth weight [11]. Given that the patient in this case suffered from severe morning sickness during pregnancy, the introduction of LPV/r could potentially exacerbate these gastrointestinal issues [11]. Taking these possible factors into account, we believed that LPV/r was not the preferred treatment option for this case.

Secondly, this case exhibited high level resistance to 3TC. Previous research has shown that even in instances of 3TC resistance, the combination therapy of dolutegravir (DTG) and lamivudine (3TC) is still effective, which can reduce viral load and maintain virological inhibition [12]. At the same time, Based on the availability of drugs and Chinese medical reimbursement policy , the DTG/3TC regimen was chosen.

Finally, ABT is known as a long-lasting HIV fusion inhibitor. It is active against 28 distinct clinically isolated strains of HIV- 1 in China, with IC50 values varying from 1.3 to 18.1 nmol/L [13–15]. In addition, preclinical studies in rats and rabbits showed no toxicity to fertility and embryonic development at doses up to 4 and 3.9 times the adult dose [16]. There is a large amount of evidence-based medical evidence to confirm DTG/3TC combined with ABT to improve virologic and immunological outcomes in treatment-experienced people with HIV infection and viral resistance and promptly reduced viral loads in treatment-naive individuals [13–15]. These study results demonstrate that ABT has potent antiviral activities and good safety profile. Besides, this case had low CD4⁺ cell counts. It was important for her to reconstruct immune function in the short time. Previous studies have shown that the treatment regimen containing ABT has immunomodulatory effects [17], choosing ABT as one of the treatment regimen may bring more therapeutic benefits for this case.

Therefore, We chose ABT combined with 3TC/DTG regimen for antiviral therapy. Hence, patients with specific conditions face a scarcity of available therapeutic options. For instance, individuals who seek medical intervention during different stages of pregnancy or exhibit resistance to several drugs may require additional drug options to effectively decrease their viral load and thereby limit the possibility of transmitting the virus from mother to child [9]. It is essential to delineate more appropriate initial or secondary treatment options for pregnant individuals with multidrug-resistant HIV. Nevertheless, due to the lack of extensive research evidence on the use of ABT in pregnant women, we believe that more research is needed to support the safety and efficacy of ABT in pregnant women and to monitor key indicators such as blood concentrations of ABT in pregnant women to ensure the health and safety of both mother and child.

In conclusion,although it is not possible to draw definitive conclusions from a single case report, our findings may indicate that the use of ABT during pregnancy can be served as a potential strategy to inhibit viral load and prevent MTCT of HIV. This case may provide valuable insights for clinicians facing similar challenges.

Abbreviations

ABC

Abacavir

ABT

Albuvirtide

AIDS

Acquired immunodeficiency syndrome

ART

Antiretroviral therapy

ARV

Antiretroviral

AZT

Zidovudine

DTG

Dolutegravir

EFV

Efavirenz

FTC

Emtricitabine

HIV

Human immunodeficiency virus

MDR-HIV

Multidrug-resistant HIV

MTCT

Mother-to-child transmission

ND

Not detectable

NMPA

National Medical Products Administration

NNRTI

Non-nucleoside reverse transcriptase inhibitors

NRTI

Nucleoside reverse transcriptase inhibitors

RAL

Raltegravir

TDF

Tenofovir disoproxil fumarate

WHO

World Health Organization

3TC

Lamivudine

Authors’ contributions

Na Li: article writing; Shifei Wen: data collection; Fangfang Zhu, Guirong Liu: writing guidance; Daqing Zhu: article review and revision.

Funding

Not applicable.

Data availability

Data is provided within the manuscript or supplementary information files.

Declarations

Ethics approval and consent to participate

The study protocol was approved by the Hospital Ethics Committee of Ganzhou Fifth People's Hospital, Grant No.GAN-EC2023053. This study was conducted in accordance with the principles of the Declaration of Helsinki.

Consent for publication

Written informed consent was obtained from the patient for publication of this case report and accompanying images.

Competing interests

The authors declare no competing interests.