Doravirine/islatravir (DOR/ISL) is a 2-drug, single-tablet regimen in clinical development for once-daily treatment of adults living with HIV-1. We examined the impact of baseline resistance-associated mutations (RAMs) in proviral DNA on the response to DOR/ISL (100/0.25 mg) in virologically suppressed participants in three phase 3 studies.MethodsSamples were collected pre-dose from participants in studies P051 (NCT05631093), P052 (NCT05630755), and P054 (NCT05766501) to evaluate RAMs in proviral DNA at baseline. The prevalence of baseline non-nucleoside reverse transcriptase inhibitor (NNRTI) RAMs and M184I/V, and their impact on virologic suppression (HIV-1 RNA <50 copies/mL) at week 48, as well as on types of viremia (confirmed HIV-1 RNA ≥200 copies/mL, low-level viremia, and transient viremia), was examined. Samples from participants with confirmed HIV-1 RNA ≥200 copies/mL or who discontinued from treatment with HIV-1 RNA ≥200 copies/mL were assessed for viral drug resistance.ResultsAmong 1227 participants who switched to DOR/ISL, 323 (26.3%) had baseline NNRTI RAMs and 70 (5.7%) had baseline M184I/V. At week 48, DOR/ISL maintained HIV-1 RNA <50 copies/mL in ≥88% of participants with and/or without NNRTI RAMs and/or M184I/V detected in proviral DNA at baseline. The percentage of participants in each viremia category was comparable with regard to the presence or absence of NNRTI RAMs and/or M184I/V. No treatment-emergent resistance to DOR or ISL was observed in the 7 participants who met criteria for postbaseline resistance testing.ConclusionsBaseline NNRTI RAMs and M184I/V in proviral DNA did not impact virologic outcomes through 48 weeks after switching to DOR/ISL (100/0.25 mg).Clinical Trials RegistrationClinicalTrials.gov: NCT05631093, NCT05630755, NCT05766501.

Bictegravir–lenacapavir STR demonstrated non-inferior efficacy to complex regimens, with a similar safety profile and increased treatment satisfaction. Bictegravir–lenacapavir offers new opportunities...

Gilead/MSD's once-weekly oral medicine for HIV has been shown to achieve high rates of viral suppression in phase 3, setting up regulatory filings.

Attachment inhibitor fostemsavir (FTR) and postattachment inhibitor ibalizumab (IBA) are used in people with HIV-1 (PWH) who are highly treatment experienced and harboring multidrug-resistant viruses, and real-world data remain limited. We describe population characteristics and pharmacovirologic outcomes of PWH initiating FTR- or IBA-based regimens.MethodsWe conducted a French retrospective observational study within the AIDS Research National Agency | Emerging Infectious Diseases virology and pharmacology network. Virologic failure (VF) was defined as 2 consecutive plasma viral loads (VLs) ≥50 copies/mL; nonvirologic response was considered a VL decrease <1 log10 copies/mL or failure to achieve virologic suppression.ResultsAmong 70 PWH receiving FTR-based treatment, 50% were virologically suppressed at initiation; median VL among viremic cases was 3.6 log10 copies/mL. Resistance to at least 2 antiretrovirals was observed among participants by inhibitor class: 96%, nucleoside reverse transcriptase inhibitor; 94%, nonnucleoside reverse transcriptase inhibitor; 74%, protease inhibitor; and 64%, integrase strand transfer inhibitor. The genotypic susceptibility score was ≤1 in 47%, and median follow-up was 20 months. Eight VFs and 8 nonvirologic responses occurred. At failure, emergence of FTR resistance-associated mutations occurred in 1 case. Suboptimal temsavir concentrations were observed in 2 of 8 participants in failure. Eleven PWH who were viremic initiated IBA-based treatment: the genotypic susceptibility score was ≤1 in 4, and median follow-up was 7 months with 5 VFs and 2 nonvirologic responses. One new resistance mutation (N74D, capsid) was detected at VF; suboptimal plasma concentrations of oral antiretrovirals were observed in 3 of 5 participants.ConclusionsPWH receiving FTR or IBA had extensive multidrug resistance and limited therapeutic options. Among PWH who were viremic and initiating FTR- and IBA-based regimens, virologic success was achieved in 63% and 36%, respectively, and maintained in 91% who were virologically suppressed and starting an FTR-based regimen.

The prospective, randomized, multicenter A5391 trial found that switching from INSTI- and TAF-containing antiretroviral therapy to an NNRTI, with or withou

The impact of pre-existing non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance-associated mutations (RAMs) on the effectiveness of long-acting (LA) cabotegravir (CAB) and rilpivirine (RPV) remains poorly defined, particularly for mutations like K103N that do not directly compromise RPV susceptibility (non-RPV NNRTI RAMs).MethodsThis observational substudy within the Spanish RELATIVITY cohort included people with HIV (PWH) who switched to CAB + RPV LA before 2025. We compared virologic outcomes between those with non-RPV NNRTI RAMs and a reference group without NNRTI/INSTI-RAMs or prior NNRTI-based virologic failure (VF). An additional subgroup with RPV-associated RAMs was also analyzed. Confirmed virologic failure (CVF) was defined as 2 consecutive viral loads ≥ 200 copies/mL or 1 ≥500 copies/mL.ResultsAmong 1358 participants, 83 (6.1%) harbored non-RPV NNRTI RAMs (47 with K103N) and 1247 served as the reference group. After a median follow-up of 16.7 months, CVF rates were similar between the non-RPV NNRTI RAMs group and the reference group (1.2% vs 0.8%; HR: 1.39; 95% CI: 0.18–10.84; P = .755). No significant differences were observed in viral blips (6% vs 8.2%; P = .481). Notably, in the subgroup of 28 participants with RPV-associated RAMs (including 5 with high-level resistance), no CVFs occurred over a median of 13.5 months.ConclusionsIn a real-world setting, CAB + RPV LA demonstrated high effectiveness in PWH with pre-existing NNRTI RAMs that do not compromise RPV susceptibility, including K103N. While no failures were seen in those with RPV-associated RAMs, these results should be interpreted with caution due to the small sample size.

Dolutegravir (DTG)-based regimens (DBR) account for >97% of antiretroviral drugs dispensed through President’s Emergency Plan for AIDS Relief. Understanding factors associated with DTG drug resistance (DR) is critical to safeguarding its long-term efficacy.MethodsWe included adults on DBR from cohorts in Malawi, Mozambique, Uganda and Ukraine (2020-2022) with successful genotypes. DTG DR was defined as Stanford HIV Drug Resistance Database genotypic susceptibility score >15. Logistic regression assessed associations between DTG DR and clinical/sociodemographic factors, reporting odds ratios (ORs) and 95% confidence intervals (CIs).ResultsMedian age was 36.2 years; 59% were female; 89% transitioned to DTG from a prior regimen. In a multivariable analyses including findings from genotype test, male sex (OR 2.02, 95% CI 1.10–3.73), any NRTI resistance (OR 31.17, 95% CI 12.93–75.14), and any NNRTI resistance (OR 2.56, 95% CI 1.12–5.88) were associated with DTG DR. After excluding genotype-derived variables, male sex remained associated with DTG DR (OR 2.13, 95% CI 1.28–3.54), while participants receiving zidovudine-containing backbones had higher odds of DTG DR compared with those receiving tenofovir-containing backbones (OR 5.87, 95% CI 2.45–14.07). Among individuals with DTG DR, G118R was the most frequent major mutation. M184V demonstrated high sensitivity (83%) and specificity (91%) for detecting DTG resistance.ConclusionsThese findings identify key clinical correlates of DTG resistance, including concurrent NRTI/NNRTI resistance and zidovudine-containing regimens, which may serve as proxies for prior viral non-suppression and help inform more targeted drug resistance testing and regimen optimization in settings where genotypic testing is not readily available.

While surveillance drug resistance mutations (SDRMs) remain essential for monitoring transmitted drug resistance (TDR), the clinical impact of transmitted resistance for current first-line regimens has become increasingly important. We aimed to update estimates of TDR in Spain and assess its clinical impact over time.MethodsThis is a nationwide observational study within the CoRIS cohort. We estimated the prevalence of SDRMs and clinically meaningful resistance (CMR) among antiretroviral therapy (ART)–naïve individuals with baseline genotypic resistance testing in 2022–2023 and evaluated annual trends in CMR to first-line regimens from 2007 to 2023. Clinically meaningful resistance was defined as Stanford HIVDB resistance level ≥ 3.ResultsIn 2022–2023, 1028 individuals were included; 82.8% were male, 63.2% MSM, and 72.2% subtype B. Surveillance drug resistance mutation prevalence was 14.4% (95% CI 12.2%–16.9%), driven mainly by NNRTI-SDRMs, while INSTI-SDRMs remained rare [0.5% (95% CI 0.1%–1.5%)]; CMR to recommended first-line regimens was very low. Over 2007–2023, CMR declined markedly, coinciding with adoption of second-generation integrase inhibitors. Rilpivirine-associated resistance mutations were detected in 7.0%, largely due to E138A (4.8%). M184V was detected in 0.8%; 6 of 8 cases occurred in persons with current or prior oral pre-exposure prophylaxis (PrEP), although numbers were small.ConclusionsIn Spain, TDR remains stable, but its clinical impact on first-line regimens has markedly declined. These findings support Test & Treat strategies and immediate ART initiation with contemporary triple- or dual-drug regimens, while highlighting the need for targeted resistance assessment for rilpivirine-containing regimens and further research on prior PrEP exposure and selected NRTI resistance patterns.

Doravirine/islatravir (DOR/ISL) is a 2-drug, single-tablet regimen in clinical development for once-daily treatment of adults living with HIV-1. We examined the impact of baseline resistance-associated mutations (RAMs) in proviral DNA on the response to DOR/ISL (100/0.25 mg) in virologically suppressed participants in three phase 3 studies.MethodsSamples were collected pre-dose from participants in studies P051 (NCT05631093), P052 (NCT05630755), and P054 (NCT05766501) to evaluate RAMs in proviral DNA at baseline. The prevalence of baseline non-nucleoside reverse transcriptase inhibitor (NNRTI) RAMs and M184I/V, and their impact on virologic suppression (HIV-1 RNA <50 copies/mL) at week 48, as well as on types of viremia (confirmed HIV-1 RNA ≥200 copies/mL, low-level viremia, and transient viremia), was examined. Samples from participants with confirmed HIV-1 RNA ≥200 copies/mL or who discontinued from treatment with HIV-1 RNA ≥200 copies/mL were assessed for viral drug resistance.ResultsAmong 1227 participants who switched to DOR/ISL, 323 (26.3%) had baseline NNRTI RAMs and 70 (5.7%) had baseline M184I/V. At week 48, DOR/ISL maintained HIV-1 RNA <50 copies/mL in ≥88% of participants with and/or without NNRTI RAMs and/or M184I/V detected in proviral DNA at baseline. The percentage of participants in each viremia category was comparable with regard to the presence or absence of NNRTI RAMs and/or M184I/V. No treatment-emergent resistance to DOR or ISL was observed in the 7 participants who met criteria for postbaseline resistance testing.ConclusionsBaseline NNRTI RAMs and M184I/V in proviral DNA did not impact virologic outcomes through 48 weeks after switching to DOR/ISL (100/0.25 mg).Clinical Trials RegistrationClinicalTrials.gov: NCT05631093, NCT05630755, NCT05766501.

The combination of doravirine (100 mg) and islatravir (0·25 mg) has similar efficacy and safety profiles to bictegravir, emtricitabine, and tenofovir alafenamide, and could provide a two-drug, once da...

Doravirine (MK-1439) is a highly specific HIV-1 nonnucleoside reverse transcriptase inhibitor with IC50s of 4.5 nM, 5.5 nM and 6.1 nM against the wild type and K103N and Y181C reverse transcriptase…

The prospective, randomized, multicenter A5391 trial found that switching from INSTI- and TAF-containing antiretroviral therapy to an NNRTI, with or withou

In the blood mononuclear cells of persons with HIV (PWHs) with a history of virological failure (VF), some viral strains, archived as proviral DNA, can harbor mutations conferring resistance to antiretrovirals.MethodsThis single-center, retrospective study included French PWHs older than 18 years with a history of VF on a non-nucleoside reverse transcriptase inhibitor (NNRTI)-containing regimen and at least one NNRTI resistance-associated mutation (RAM) detected by Sanger sequencing at the time of VF. Next-generation sequencing targeting the reverse transcriptase gene, in combination with proviral DNA quantification, was performed on at least one whole blood sample after years of virological suppression on other antiretroviral regimens. Multivariate analysis identified factors associated with NNRTI RAM persistence.ResultsIn total, 79 PWHs were included. Samples were collected after a median of 10 years of virological suppression and 16 years after VF. Non-nucleoside reverse transcriptase inhibitor RAMs were not detected in the DNA in 39% of patients, and persistence was associated with a higher proviral DNA load and a higher HIV-1 RNA level at the time of VF. The mutational viral load tended to decrease over time (as assessed in 62 people with two samples collected at 3-year intervals).ConclusionsIn contrast to other mutations such as M184V and INSTI RAMs, NNRTI RAMs tended to persist within the HIV-1 DNA reservoir. However, clearance of these archived mutations from the cellular reservoir was observed in some cases (low proviral DNA load, short duration of viral replication, and low HIV RNA level while taking failing NNRTIs).

ABSTRACTHIV-1 treatment has advanced with various antiretroviral regimens. Although efavirenz (EFV)-based regimens have been widely used, current guidelines recommend integrase strand transfer inhibitor (INSTI)-based therapy as first-line. However, INSTI may cause weight gain and adverse lipid changes, creating new unmet metabolic needs. Novel agents like ainuovirine (ANV), a non-nucleoside reverse transcriptase inhibitor (NNRTI), may offer effective virological suppression (VS) with improved tolerability, but their long-term real-world safety and effectiveness remain unclear. This was a multicenter, retrospective observational cohort study. Virologically suppressed adults on a tenofovir disoproxil fumarate (TDF)/3TC+EFV regimen were either switched to TDF/3TC+ANV (ANV group) based on the physician’s discretion or continued on TDF/3TC+EFV (EFV group). Baseline demographic and clinical data were collected, and participants were followed for 48 weeks. The primary effectiveness outcome was the proportion of patients achieving HIV-1 RNA levels below the limit of quantification (LOQ) at week 48. Secondary outcomes included absolute or percentage changes from baseline in CD4+ T-cell count, CD4+/CD8+ ratio. Key secondary safety outcomes included absolute changes from baseline in body weight, BMI, fasting lipid profiles (total cholesterol [TC], triglycerides [TG], high-density lipoprotein cholesterol [HDL-C], low-density lipoprotein cholesterol [LDL-C]), and parameters of liver and renal function. A total of 350 participants who completed the 48-week follow-up were included, comprising 170 patients in the ANV group and 180 patients who remained on EFV. At week 48, the proportion of VS was 96.5% in the ANV group and 96.1% in the EFV group (difference: 1.00 percentage points; 95% CI: –2.77 to 2.77), confirming non-inferiority. No significant differences in CD4+ T-cell recovery or CD4+/CD8+ ratios were observed. The ANV group experienced significantly less weight gain than the EFV group (estimated treatment difference [ETD]: –0.79 kg; P < 0.001). A corresponding trend in BMI change was observed but did not reach statistical significance. ANV also led to more favorable lipid changes, including a significant reduction in total cholesterol (ETD: –0.52 mmol/L; P < 0.001) and triglycerides (ETD: –0.83 mmol/L; P < 0.001) compared to EFV. Liver and renal function profiles remained stable in both groups. Switching from EFV- to an ANV-based regimen effectively maintained VS and led to improved metabolic parameters, including less weight gain and a more favorable lipid profile. As an alternative switch strategy, the ANV-based regimen may be a more beneficial option for people living with HIV (PLWH) who are at high risk of weight-related or dyslipidemia-associated comorbidities.

This study reveals high rates of HIV-1 drug resistance mutations in individuals failing first-line NNRTI-based regimens across multiple low- and middle-inc

**Randomly Selected Sub-Field:** *Quantitative Structure-Activity Relationship (QSAR) Modeling of Prodrug Activation for Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)* This sub-field combines the established areas of QSAR, prodrug design, and NNRTI drug development, focusing on predicting the activation efficiency of NNRTI prodrugs based on their chemical structure. Prodrugs are inactive precursors of a drug that are converted into the active form in the body.

Despite rising NNRTI resistance among pretreatment people with HIV, overall population prevalence of pretreatment HIV drug-resistant viraemia decreased due to increasing ART uptake and viral suppressi...

The excellent clinical and virologic efficacy, more rapid achievement of viral suppression, and improved tolerability associated with integrase strand transfer inhibitor (INSTI)–based antiretroviral therapy (ART) compared with nonnucleoside reverse transcriptase inhibitor (NNRTI)– or protease inhibitor (PI)–based ART have led to INSTIs being designated as the preferred option for treatment among children and adults. However, for millions of pregnant women with HIV, the journey toward INSTI access has been challenging. The first-generation INSTI raltegravir has a low resistance threshold and lacks pharmacokinetic data to allow once daily dosing and therefore is recommended as an alternative INSTI in pregnancy.1 Pharmacokinetic data on the INSTI coformulation elvitegravir with cobicistat, emtricitabine, and tenofovir alafenamide fumarate in pregnancy demonstrate suboptimal elvitegravir and cobicistat plasma concentrations during the second and third trimesters, and it is not recommended as an initial regimen in pregnancy.1 For the second-generation INSTI dolutegravir, an initial neural tube defect safety signal with exposure at conception based on small number of exposures led to limited use in pregnancy, but the signal was refuted with expanded data collection. Currently, the second-generation INSTIs dolutegravir and bictegravir are recommended as preferred INSTIs for the initial HIV treatment in pregnancy.1 The dolutegravir safety signal played a critical role in advancing advocacy and global framework for the clinical studies and pharmacovigilance of the antiretroviral drugs and other therapeutic agents in pregnant and breastfeeding women.2 An excellent example of a high-quality postmarketing surveillance research following antiretroviral drug exposure during conception and pregnancy is the study by Williams et al3 from the US-based prospective Pediatric HIV/AIDS Cohort Study (PHACS). The study conducted detailed assessments of cognition, language, and motor development among 1006 infants aged 1 year who were exposed to but uninfected with HIV and whose mothers received ART during pregnancy (531 [52.8%] from conception). The investigators found no clinically meaningful differences in neurodevelopmental outcomes between those with in utero exposure to INSTI- vs NNRTI- or PI-based ART. Importantly, the mean scores in each domain were comparable and close to the standard US population mean (SD) of 100 (50) within each ART exposure group.3 The PHACS study findings3 complement recently published data from the Motheo Study,4 a prospective, observational, longitudinal study of 3 cohorts of children in Botswana designed to evaluate the association of in utero exposure to maternal dolutegravir- or efavirenz-based ART regimens with child neurodevelopmental outcomes at 2 and 5 years of age. The Motheo Study enrolled 404 children exposed to but not infected with HIV and with in utero dolutegravir (n = 202) and efavirenz (n = 202) exposures (179 [89%] and 183 [91%] with preconception treatment and first trimester exposure, respectively) and a control group of 160 children without HIV or ART exposure. Similar to PHACS study results at 1 year of age,3 the neurodevelopmental outcomes among children in Botswana at 2 years of age in these 3 cohorts were comparable, with the exception that efavirenz-exposed children had a slightly higher risk of having a raw score 1 SD below the mean in cognitive and expressive language domains compared with dolutegravir-exposed children.4 To ensure comprehensive assessment of the risks and benefits of antiretroviral drugs, studies of antiretroviral and other drugs in pregnant women need to evaluate both short-term (pregnancy and birth) and long-term (neurodevelopmental, growth, metabolic, and cardiovascular) safety outcomes following maternal, fetal, and infant exposures during conception, pregnancy, and breastfeeding. Currently, pregnancy and birth outcome data on maternal INSTI use are reassuring.1 The PHACS and Motheo studies fill the evidence gap on the long-term consequences of INSTI exposure during conception and pregnancy for the child.5,6 Both studies used similar neurodevelopmental methodologies (PHACS adding or substituting Bayley Scales of Infant and Toddler Development–3rd Edition [Bayley-III] with the MacArthur Bates Communication Development Inventory Words and Gestures Assessment) and had comparable numbers of infants and children with dolutegravir exposure in utero (202 for Motheo and 152 for PHACS). These data support continued use of dolutegravir as a preferred antiretroviral anchor drug for ART treatment regimens in women of child-bearing age or pregnant as recommend in the US and World Health Organization HIV management guidelines.1,7 In the exploratory analysis within the PHACS study, the investigators did not observe an association of any individual INSTI or INSTI exposure overall with Bayley-III cognitive or language domain scores.3 However, data on neurodevelopmental outcomes following in utero bictegravir exposure, most recently moved to the preferred choice in pregnancy in US guidelines, remain scarce and were limited to 45 infants in PHACS cohort.3 Some studies have suggested that infants and children exposed to but not infected with HIV have a heightened risk of subtle impairments in expressive language and gross motor development (but not cognitive, receptive language, or fine motor defects) by 2 years of age compared with HIV-unexposed children.6 In the Matheo study, children exposed to HIV and ART generally performed similarly to HIV-unexposed children on most neurodevelopmental and socioemotional outcomes at 2 years of age. However, children exposed to but not infected with HIV had slightly lower mean gross motor scores and were more likely to have expressive language scores 1 SD below the mean than HIV-unexposed infants.4 When stratifying children exposed to but not infected with HIV by type of ART exposure, those exposed to dolutegravir performed comparably to HIV-unexposed children on all neurodevelopmental measures.4 In utero exposure to efavirenz, however, was associated with a higher risk of adverse cognitive and expressive language outcomes (defined as ≥1 SD below the mean or inability to complete the relevant Bayley-III subtest) compared with dolutegravir exposure, supporting the universal switch from NNRTI-based to dolutegravir-based ART in pregnancy. Within the PHACS study, there was no difference in mean Bayley-III cognitive, language, or motor development domain scores between those exposed to INSTI- vs PI-based ART and only a very small mean difference (approximately 3 points) favoring NNRTI (257 participants, with 41 receiving efavirenz) to INSTI-based ART (389 participants), with the differences attenuated in sensitivity analyses adjusting for maternal CD4 count and viral load.3 While it is reassuring that no association between neurodevelopmental delays and currently used INSTI and other maternal ART regimens has been established, given the availability of new antiretroviral drugs, it is vital to continue exploring both the short-term outcomes and the longer-term developmental trajectories and underlying mechanisms of any delays among children with perinatal HIV and ART exposure. Longitudinal cohort studies incorporating smart research strategies such as modeling and sensitivity analyses as conducted by Williams et al3 and the PHACS investigators are critical to assess risk-benefit ratios of novel antiretroviral drugs, including long-acting injectables and biologics. These studies, however, are only feasible with the collaboration of multiple stakeholders and ongoing and future funding of multidisciplinary, collaborative research involving women with HIV and their children on a global basis. Back to top Article Information Published: November 26, 2025. doi:10.1001/jamanetworkopen.2025.45661Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2025 Rakhmanina N et al. JAMA Network Open.Corresponding Author: Natella Rakhmanina, MD, PhD, Division of Infectious Diseases, Childrens’ National Hospital, 111 Michigan Ave NW, West Wing Level 3.5, Ste 100, Washington, DC, 20010 (nrakhman@childrensnational.org).Conflict of Interest Disclosures: Dr Rakhmanina reported receiving research support from ViiV Healthcare, Gilead Sciences Inc, and Chembio Diagnostics outside the submitted work. Dr Mofenson reported receiving consulting fees from the World Health Organization on safety of drugs in pregnancy outside the submitted work. No other disclosures were reported. References 1.Recommendations for the use of antiretroviral drugs during pregnancy and interventions to reduce perinatal HIV transmission in the United States. Dept of Health and Human Services.Updated June 12, 2025. Accessed September 27, 2025. https://clinicalinfo.hiv.gov/en/guidelines/perinatal/whats-new2.Mofenson  LM, Pozniak  AL, Wambui  J,  et al.  Optimizing responses to drug safety signals in pregnancy: the example of dolutegravir and neural tube defects.   J Int AIDS Soc. 2019;22(7):e25352. doi:10.1002/jia2.25352 PubMedGoogle ScholarCrossref3.Williams  PL, Boahene  M, Mash  LE,  et al.  Maternal use of integrase strand inhibitors during pregnancy and infant neurodevelopment.   JAMA Netw Open. 2025;8(11):e2545652. doi:10.1001/jamanetworkopen.2025.45652ArticleGoogle Scholar4.Cassidy  AR, Mayondi  G, Williams  PL,  et al.  Neurodevelopmental outcomes in children exposed in utero to dolutegravir- or efavirenz-based antiretroviral treatment.   AIDS. 2025;39(5):609-617. doi:10.1097/QAD.0000000000004111 PubMedGoogle ScholarCrossref5.Foster  EG, Gendelman  HE, Bade  AN.  HIV-1 integrase strand transfer inhibitors and neurodevelopment.   Pharmaceuticals (Basel). 2022;15(12):1533. doi:10.3390/ph15121533 PubMedGoogle ScholarCrossref6.Wedderburn  CJ, Weldon  E, Bertran-Cobo  C,  et al.  Early neurodevelopment of HIV-exposed uninfected children in the era of antiretroviral therapy: a systematic review and meta-analysis.   Lancet Child Adolesc Health. 2022;6(6):393-408. doi:10.1016/S2352-4642(22)00071-2 PubMedGoogle ScholarCrossref7.Overview of WHO recommendations on HIV and sexually transmitted infection testing, prevention, treatment, care and service delivery. World Health Organization. July 14, 2025. Accessed September 29, 2025. https://www.who.int/publications/i/item/B09471

Despite rising NNRTI resistance among pretreatment people with HIV, overall population prevalence of pretreatment HIV drug-resistant viraemia decreased due to increasing ART uptake and viral suppressi...