To study the safety and effectiveness of protease inhibitors and non-nucleoside reverse transcriptase inhibitors for pregnant women, and assume that protease inhibitors are more effective and safer in the treatment of HIV.

The Safety and Effectiveness of Protease Inhibitors and Non-Nucleoside Reverse Transcriptase Inhibitors for Pregnant Women Student Name* State *Corresponding author: Email Abstract Background. This article investigated the efficacy and safety of antiretroviral medication (ART), namely protease inhibitors (PI) and non-nucleoside reverse transcriptase inhibitors (NNRTI), used by HIV/AIDS pregnant women. It emphasizes the relevance of ART management throughout pregnancy for maternal and child health, aiming to teach doctors and improve outcomes at the maternal and child levels. Objective. To study how HIV-infected pregnant women’s PI and NNRTI efficacy and clarity affect mother’s and baby’s health. Method. A systematic review was undertaken between 2002 and 2021 to assess the similarity groups of HIV-positive pregnant women and their fetuses. The analysis compared the effects of PI-containing and NNRTI-based ART. Over 45,000 pregnant women from 27 nations were analyzed in studies, with each receiving a distinct technique rating. Results. The systematic review included 10 studies in total, with 45,427 women participating. The findings revealed that there was no significant connection between PIs and NNRTIs for various fetal/neonatal outcomes. Therapeutic drug monitoring should be performed on PIs and NNRTI regimens with a small therapeutic window, respectively. The study of antiretroviral medicines with pregnant women indicated that both drug classes were safe throughout pregnancy, with PI-based regimens showing greater efficiency in achieving viral suppression. Hearing early ART initiation resulted in better neonatal outcomes. Conclusion. ART therapy for HIV-positive pregnant women must prevent toxicity and inadequate medication distribution. PIs reduce perinatal risk and inhibit viruses. Understanding patient-drug interactions is crucial because starting ARTs late is dangerous. Go-ahead tracking enhances mother and infant health, HIV-related pregnancy outcomes, and HIV management. Key words: protease inhibitors; non-nucleoside reverse transcriptase inhibitors; pregnancy; antiretroviral therapy 1. Introduction Human immunodeficiency virus (HIV) remains a major disease worldwide. Antiretroviral therapy (ART) has been demonstrated to be a viable technique for improving the prognosis of patients in various HIV populations, including pregnant women who have received education and now have the opportunity to get this treatment [1]. On the other hand, the security and confidence of this ART application during pregnancy are ranked alongside safety and dependability. This study will conduct a review of the literature on the effectiveness and severity of PIs and NNRTIs used by HIV mothers. Human immunodeficiency virus (HIV) continues to pose a global health burden, and one of the most advanced discoveries in the healthcare system is the present treatment of HIV-positive pregnant women, known as antiretroviral therapy (ART). Effective HIV management during the prenatal period is critical to both the mother's health and the prevention of transmission from mother to child (MTCT) [2]. The physical changes that the body undergoes during pregnancy will certainly alter the pharmacokinetics of antiretrovirals used to treat HIV, resulting in increased blood levels and prolonged drug retention in the body [3]. The changes cause drug concentrations to become high and possibly fall outside the acceptable range of drug safety and efficacy. TDM has been recognized as an important method of adjusting doses to ensure that antiretroviral levels do not exceed their therapeutic windows, particularly in the case of PI and NNRTI medicines, which frequently have limited therapeutic windows [4]. Several reports, including pregnancy studies, show that PIs and NNRTIs are both safe for both mothers and their offspring [5]. A review of reported cases revealed that PIs and NNRTIs were found to be effective by a study that showed a reduction in preterm birth and weight at birth compared to other treatments. However, in another study by Roustit et al. (2008) [6], there was no relationship seen in cases of congenital disabilities in newborns exposed to PIs or NNRTIs, fetching caution in the case of mood-altering problems that may occur from individual efavirenz. From the efficacy viewpoint, the study established that PI antiretroviral regimens could be the best as opposed to NNRTIs, including the poor response to antiretroviral therapy and MTCT prevention [7]. NNRTI resistance manifested could be reduced, and the chances of its emergence decreased as a consequence of the higher genetic barrier to resistance of PIs. This factor has been proposed as a fundamental explanation of the enhanced anti-HIV activity of PIs, particularly in settings manifesting high levels of pre-existing NNRTI resistance [8]. Research showed that earlier medical assistance of ART, ideally before pregnancy or during the first trimester, is connected with the rate of MTCT at a reduced level with better perinatal outcomes, while later initiation of ART is connected with the rate of MTCT at a higher level with worse perinatal outcomes [9]. Late ART start makes it more likely to have premature delivery, low birth weight, and difficulty in adequately managing viral load [10]. Customized treatment should be made by taking into account the specific biological markers of the patient, the resistance factors that the pathogen has developed to unique drugs, expected side effects, and drug interactions. 2. Methodology The research was conducted using a systematic examination of PubMed, Reprotox, the Clinical Trial Registry (clinicaltrials.gov), and abstracts from HIV conferences held between January 1, 2002, and October 29, 2021. The study examined perinatal outcomes such as spontaneous abortion, stillbirth, congenital abnormalities, PTB (<37 weeks of gestation), VPTB (<32 weeks of gestation), LBW (<2500 grs), VLBW (<1500 g), SGA, and VSGA. The connection between prenatal exposures to PI-based ART versus NNRTI-based ART was assessed for each adverse perinatal outcome. The researcher selected 49,171 articles for a full reading. The selected studies involved 45,427 pregnant women from 27 different nations. Nineteen studies were undertaken in high-income countries and thirteen in low-income countries. Only one randomized controlled study was chosen, with the remainder being cohort studies. Overall, thirteen research received a high rating for methodological quality. The study sample included 75 to7, 009 pregnant women aged 26 to 33, with a median CD4+ count of 154-638 cells/mm3. Figure 1: Flow-chart of study selection process according to PRISMA guidelines *Four articles had low methodological quality’s score  3. Results This systematic assessment included 1,885 published papers that evaluated 45,427 pregnant women. There was no significant difference between PI and NNRTI prenatal exposure for VPTB, LBW, SGA, stillbirth, and congenital anomalies. However, it was equivocal for PTB, and PI-based ART is associated with a considerably higher incidence of VSGA than NNRTIs. Therapeutic drug monitoring (TDM) is critical, especially for protease inhibitors (PIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs), which have a limited therapeutic window, to ensure optimal drug exposure while avoiding unwanted effects or therapy failure. PIs and NNRTIs are safe to use during pregnancy, with no substantial increase in the incidence of congenital impairments in exposed infants. PI-based regimens were more effective than NNRTI-based regimens in suppressing viral load, which could be attributed to PIs' stronger genetic resistance. Early beginning of antiretroviral medication (ART), ideally before pregnancy or during the first trimester, was linked to decreased incidence of MTCT and better perinatal outcomes, including a lower risk of preterm birth and low birth weight. The table below summarizes the findings. Table 1: Characteristics of included trials Study Setting Sample Size Measuring Outcomes Key Findings Saint-Lary et al. (2021) [1] Pharmacovigilance database analysis 45,427 pregnant women from 27 countries Spontaneous abortion, stillbirth, congenital abnormalities, preterm birth, low birth weight, small for gestational age No significant association between PI vs. NNRTI exposure for most outcomes, but increased risk of very small for gestational age with PI-based ART. Saint-Lary et al. (2023) [2] Systematic review and meta-analysis 45,427 pregnant women Adverse perinatal outcomes PI-based ART associated with increased risk of very...