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Background The rising prevalence of pretreatment drug resistance (PDR) to non-nucleoside reverse-transcriptase inhibitors threatens the effectiveness of ART. In response, the WHO recommends dolutegravir-based ART regimens due to their high genetic barrier to resistance and better treatment outcomes. This is expected to contribute to achieving the Joint United Nations Programme on HIV/AIDS (UNAIDS) target of 95% viral suppression in people on ART. Objectives To estimate the prevalence of PDR among adults initiating ART and assess viral suppression and acquired HIV drug resistance (ADR) among individuals receiving ART in Belize. Patients and methods Nationally representative cross-sectional PDR and ADR surveys were conducted between 2021 and 2022. Sixty-seven adults were included in the PDR survey, and 43 children and adolescents and 331 adults were included in the ADR survey. Demographic and clinic data and blood specimens were collected. HIV drug resistance (HIVDR) was predicted using the Stanford HIVdb tool. Results The prevalence of PDR to efavirenz or nevirapine in adults was 49.3% (95% CI 42.2%–56.4%) and was significantly higher in those with previous antiretroviral exposure (OR: 7.16; 95% CI 2.71–18.95; P  = 0.002). Among children and adolescents receiving ART, 50.0% had viral suppression, with better rates for those receiving dolutegravir-based ART (OR: 5.31; 95% CI 3.02–9.34; P  < 0.001). In adults, 79.6% achieved viral suppression. No resistance to integrase inhibitors was observed in those on dolutegravir-based ART. Conclusions Prioritizing dolutegravir-based ART is critical for achieving HIV epidemic control in Belize. Efforts should focus on retention in care and adherence support to prevent HIVDR. [ABSTRACT FROM AUTHOR]

Mohamed Jayte,1,2 Yahye Mohamed Jama,1,2 Lubega Athanus1,2 1Internal Medicine Department at Kampala International University, Kampala, Uganda; 2Internal Medicine Department at Itogo General Hospital, Itogo, UgandaCorrespondence: Mohamed Jayte, Internal Medicine Department at Kampala International University, P.O. Box 7062, Kampala, Uganda, Tel +256 55272543, Email jaytebuug@gmail.comAbstract: Nevirapine, a non-nucleoside reverse transcriptase inhibitor (NNRTI), is widely prescribed in antiretroviral therapy (ART) for HIV treatment. Although effective, it is associated with rare but severe adverse drug reactions, including Stevens–Johnson syndrome (SJS), a life-threatening mucocutaneous disorder. This case report describes a Middle age HIV-positive man who developed SJS following nevirapine initiation, highlighting the importance of timely recognition, management, and the need for clinician vigilance to prevent adverse outcomes in antiretroviral therapy.Keywords: nevirapine, Stevens–Johnson syndrome, antiretroviral therapy, adverse drug reactions, Hiv

Objectives Methods Results Conclusions This survey was conducted to describe current European postnatal prophylaxis (PNP) and infant feeding policies with the aim of informing future harmonized guidelines.A total of 32 senior clinicians with relevant expertise, working in 20 countries within the European Region, were invited to complete a REDCap questionnaire between July and September 2023.Twenty‐three of the 32 invited paediatricians responded, representing 16/20 countries. There were multiple respondents from the same country for Italy (n = 5), the UK (n = 2), Germany (n = 2) and France (n = 2). All countries use risk stratification to guide PNP regimen selection. Nine out of 16 countries reported three risk categories, six out of 16 reported two, and one country reported differences in categorization. Criteria used to stratify risk varied between and within countries. For the lowest risk category, the PNP regimen reported ranged from no PNP to up to four weeks of one drug; the drug of choice reported was zidovudine, apart from one country which reported nevirapine. For the highest risk category, the most common regimen was zidovudine/lamivudine/nevirapine (20/23 respondents); regimen duration varied from two to six weeks with variation in recommended dosing. Guidelines support breastfeeding for infants born to people living with HIV in eight out of 16 countries; in the other eight, guidelines do not support/specify.Guidelines and practice for PNP and infant feeding vary substantially across Europe and within some countries, reflecting the lack of robust evidence. Effort is needed to align policies and practice to reflect up‐to‐date knowledge to ensure the vertical transmission risk is minimized and unnecessary infant HIV testing and PNP avoided, while simultaneously supporting families to make informed decisions on infant feeding choice. [ABSTRACT FROM AUTHOR]

Doravirine (DOR) is a non-nucleoside reverse transcriptase inhibitor (NNRTI) with efficacy against some NNRTI-resistant mutants. Although DOR resistance mutations are established for HIV-1 subtype B, it is less clear for non-B subtypes. This study investigated prevalent NNRTI resistance mutations on DOR susceptibility in HIV-1 subtype C. Prevalent drug resistance mutations were identified from a South African genotypic drug resistance testing database. Mutations, single or in combination, were introduced into replication-defective pseudoviruses and assessed for DOR susceptibility in vitro. The single V106M and Y188L mutations caused high-level resistance while others did not significantly impact DOR susceptibility. We observed an agreement between our in vitro and the Stanford HIVdb predicted susceptibilities. However, the F227L mutation was predicted to cause high-level DOR resistance but was susceptible in vitro. Combinations of mutations containing K103N, V106M or Y188L caused high-level resistance, in agreement with the predictions. These mutations are frequently observed in patients failing efavirenz- or nevirapine-based first-line regimens. However, they are also observed in those failing a protease inhibitor-based second-line regimen, as we have observed in our database. Genotypic drug resistance testing is therefore vital prior to the initiation of DOR-based treatment for those previously exposed to efavirenz or nevirapine. [ABSTRACT FROM AUTHOR]

Background/objective: The World Health Organization (WHO) recommends routine assessment of antiretroviral treatment outcomes to detect treatment failure early and prevent the development of drug resistance. The aim of this study was to describe treatment outcomes of anti-retroviral therapy (ART) over 2 years in children living with the human immune deficiency virus enrolled in the paediatric HIV clinic at the Lagos University Teaching Hospital (LUTH). Materials and methods: This was a retrospective study of antiretroviral treatment outcomes in 278 children receiving antiretroviral therapy at the paediatric HIV clinic of LUTH. Demographic, clinical and laboratory data were retrospectively collected from clinical records of pediatric patients who received antiretroviral therapy for 2 years ( from November 2015 to December 2017) . Virological failure was defined as viral load > 400 copies/ml and immunological failure was defined as a CD4 count 5000 copies/ml), poor adherence (

Artemisinin-based combination therapies (ACTs) are the primary treatment for malaria. It is essential to characterize the pharmacokinetics (PKs) and pharmacodynamics (PDs) of ACTs in vulnerable populations at risk of suboptimal dosing. We developed a population PK/PD model using data from our previous study of artemether-lumefantrine in HIV-uninfected and HIV-infected children living in a high-transmission region of Uganda. HIV-infected children were on efavirenz-, nevirapine-, or lopinavir-ritonavir-based antiretroviral regimens, with daily trimethoprim-sulfamethoxazole prophylaxis. We assessed selection for resistance in two key parasite transporters, pfcrt and pfmdr1, over 42-day follow-up and incorporated genotyping into a time-to-event model to ascertain how resistance genotype in relation to drug exposure impacts recurrence risk. Two hundred seventy-seven children contributed 364 episodes to the model (186 HIV-uninfected and 178 HIV-infected), with recurrent microscopy-detectable parasitemia detected in 176 episodes by day 42. The final model was a two-compartment model with first-order absorption and an estimated age effect on bioavailability. Systemic lumefantrine exposure was highest with lopinavir-ritonavir, lowest with efavirenz, and equivalent with nevirapine and HIV-uninfected children. HIV status and lumefantrine concentration were significant factors associated with recurrence risk. Significant selection was demonstrated for pfmdr1 N86 and pfcrt K76 in recurrent infections, with no evidence of selection for pfmdr1 Y184F. Less sensitive parasites were able to tolerate lumefantrine concentrations ~ 3.5-fold higher than more sensitive parasites. This is the first population PK model of lumefantrine in HIV-infected children and demonstrates selection for reduced lumefantrine susceptibility, a concern as we confront the threat to ACTs posed by emerging artemisinin resistance in Africa.

Idiosyncratic drug reactions (IDRs) are associated with significant patient morbidity/mortality and lead to considerable drug candidate attrition in drug development. Their idiosyncratic nature makes the study of IDRs difficult. In particular, nevirapine is associated with a relatively high risk of serious skin rash and liver injury. We previously found that nevirapine causes a similar skin rash in female Brown Norway rats, but these animals do not develop significant liver injury. Programmed cell death protein-1 (PD-1) is an immune checkpoint involved in immune tolerance, and anti-PD-1 antibodies have been used to treat cancer. However, they increase the risk of liver injury caused by co-administered drugs. We found that PD-1−/− mice are more susceptible to drug-induced liver injury, but PD-1−/− mice are not a good model for all drugs. In particular, they do not develop a skin rash when treated with nevirapine, at least in part because they lack the sulfotransferase in their skin that forms the reactive metabolite responsible for the rash. Therefore, we developed a PD-1 mutant (PD-1m/m) rat, with an excision in the ligand-binding domain of PD-1, to test whether nevirapine would cause a more serious skin rash in these animals. The PD-1m/m rat was based on a Sprague Dawley background, which has a lower incidence of skin rash than Brown Norway rats. The treated PD-1m/m rats developed more severe liver injury than PD-1−/− mice, but in contrast to expectations, they did not develop a skin rash. Functional knockouts provide a unique tool to study the mechanisms of IDRs. [ABSTRACT FROM AUTHOR]

Introduction: The large number of deaths among children with HIV is driven by poor antiretroviral treatment (ART) coverage among this cohort. The aim of the study was to assess the availability and stock‐outs of paediatric and adult ART formulations in Kenya and Uganda across various regions and types of health facilities. Methods: A survey on availability and stock‐outs of paediatric ART at health facilities was adapted from the standardized Health Action International–WHO Medicine Availability Monitoring Tool. All preferred and limited‐use formulations, and three phased‐out formulations according to the 2021 WHO optimal formulary list were included in the survey, as well as a selection of adult ART formulations suitable for older children, adolescents, and adults. Availability data were collected in June–July 2022 and stock‐out data were obtained over the previous year from randomly selected public and private‐not‐for‐profit (PNFP) facilities registered to dispense paediatric ART across six districts per country. All data were analysed descriptively. Results: In total, 144 health facilities were included (72 per country); 110 were public and 34 PNFP facilities. Overall availabilities of preferred paediatric ART formulations were 52.2% and 63.5% in Kenya and Uganda, respectively, with dolutegravir (DTG) 10 mg dispersible tablets being available in 70.2% and 77.4% of facilities, respectively, and abacavir/lamivudine dispersible tablets in 89.8% and 98.2% of facilities. Of note, availability of both formulations was low (37.5% and 62.5%, respectively) in Kenyan PNFP facilities. Overall availabilities of paediatric limited‐use products were 1.1% in Kenya and 1.9% in Uganda. At least one stock‐out of a preferred paediatric ART formulation was reported in 40.0% of Kenyan and 74.7% of Ugandan facilities. Nevirapine solution stock‐outs were reported in 43.1% of Ugandan facilities, while alternative formulations for postnatal HIV prophylaxis were not available. Conclusions: Recommended DTG‐based first‐line ART for children across all ages was reasonably available at health facilities in Kenya and Uganda, with the exception of Kenyan PNFP facilities. Availability of paediatric ART formulations on the limited‐use list was extremely low across both countries. Stock‐outs were reported regularly, with the high number of reported stock‐outs of neonatal ART formulations in Uganda being most concerning. [ABSTRACT FROM AUTHOR]

The study was designed to develop a simple, precise, rapid and reproducible simultaneous method for fosamprenavir calcium and nevirapine in dendrimer-carbon nanotube conjugates. Reverse phase column C18 was used for the development and validation of the high-performance liquid chromatography method. The method was run on isocratic mode with methanol and water (80:20) with 1 ml/min flow rate and the detection was carried out at 258 nm. Fosamprenavir calcium was shown to have a retention time of 4.255 min whereas nevirapine had a retention time of 6.337 min. The method was validated as per International Council for Harmonisation M10 guidelines. The coefficient of correlation (R2) was found to be 0.9905 for fosamprenavir calcium and 0.9896 for nevirapine. The approach was accurate and precise based on drug recovery (greater than 95 %) and relative standard deviation (less than 2 % among duplicate experiments). Lower, medium and higher quantified concentration of fosamprenavir calcium were found to be 5.98 µg/ml, 7.18 µg/ml and 8.38 µg/ml respectively and for nevirapine the lower, medium and higher quantified concentration were found to be 6.54 µg/ml, 7.74 µg/ml and higher quantified concentration 8.94 µg/ml respectively. Drug loading was found to be 47.59 % for fosamprenavir calcium and 69.65 % for nevirapine when both drugs are loaded together in dendrimer-carbon nanotube conjugates. From the study, it can be concluded that a robust method was developed that qualified different validation parameters and can be used for the determination of fosamprenavir calcium and nevirapine in dendrimer-carbon nanotube conjugates. [ABSTRACT FROM AUTHOR]

Nevirapine, an antiretroviral used in the treatment of HIV, is associated with idiosyncratic drug-induced liver injury (IDILI), a potentially life-threatening adverse drug reaction. Its usage has decreased due to this concern, but it is still widely used in lower-resource settings. In general, the mechanisms underlying idiosyncratic drug reactions (IDRs) are poorly understood, but evidence indicates that most are immune-mediated. There is very limited understanding of the early immune response following administration of drugs associated with IDRs, which likely occurs due to reactive metabolite formation. In this work, we aimed to characterize the links between covalent binding of nevirapine, the development of an early immune response, and the subsequent liver injury using a mouse model. We describe initial attempts to characterize an early immune response to nevirapine followed by the discovery that nevirapine induced the release of corticosterone. Corticosterone release was partially associated with the degree of drug covalent binding in the liver but was also likely mediated by additional mechanisms at higher drug doses. Transcriptomic analysis confirmed metabolic activation, glucocorticoid signaling, and decreased immune activation; GDF-15 also warrants further investigation as part of the immune response to nevirapine. Finally, glucocorticoid blockade preceding the first dose of nevirapine attenuated nevirapine-induced liver injury at 3 weeks, suggesting that acute glucocorticoid signaling is harmful in the context of nevirapine-induced liver injury. This work demonstrates that nevirapine induces acute corticosterone release, which contributes to delayed-onset liver injury. It also has implications for screening drug candidates for IDILI risk and preventing nevirapine-induced IDILI. [ABSTRACT FROM AUTHOR]

Background: Nevirapine prophylaxis has been found to lower the risk of HIV transmission in breastfed infants. While about 95% of HIV positive pregnant and lactating mothers use Antiretroviral therapy in Uganda, a smaller percentage of HIV exposed infants (HEI) receive nevirapine (NVP) prophylaxis. This study aimed to determine the proportion of HEI who missed NVP prophylaxis and associated factors. Methods: This was a cross-sectional study done using quantitative methods, conducted at Mulago National Referral Hospital (MNRH). A total of 228 mother-infant pairs were enrolled. The proportion of HEI who missed NVP, maternal, infant and health facility factors associated were determined using a pre-tested questionnaire. Bivariate analysis and binary logistic regression model were used to determine the proportion and factors associated with missing NVP prophylaxis. Results: The proportion of HEI who missed NVP prophylaxis was 50/228 (21.9%). Factors significantly associated with HEI missing NVP prophylaxis included delivery from outside government health facilities (AOR = 8.41; P = 0.001), mothers not undergoing PMTCT counselling (AOR = 12.01; P = 0.001), not on ART (AOR = 8.47; P = 0.003) and not having disclosed their HIV status to their partners (AOR = 2.80; P = 0.001). The HEI that missed nevirapine and were HIV positive were 35 (70.0%). The HEI that were HIV infected despite receiving nevirapine prophylaxis were 5 out of 40(12.5%). Conclusion: One in five HEI missed NVP prophylaxis and nearly three quarters of those who missed NVP prophylaxis were HIV infected. Improving uptake of nevirapine by HEI will require interventions that can aid to strengthen PMTCT counselling. [ABSTRACT FROM AUTHOR]

Background: Mother-to-child transmission (MTCT) of the human immunodeficiency virus (HIV) remains a major public health challenge in Ethiopia. The objective of this review was to assess the pooled magnitude of MTCT of HIV and its risk factors among mother-infant pairs who initiated antiretroviral therapy (ART) after Option B+ in Ethiopia. Methods: A systematic search of literature from PubMed, Hinari, African Journals Online (AJOL), Science Direct, and Google Scholar databases was conducted from June 11, 2013 to August 1, 2023. The authors used the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines to guide the article selection process and reporting. Observational studies that reported the magnitude and/or risk factors on MTCT of HIV among mother-infant pairs who initiated ART after the implementation of Option B+ in Ethiopia were included. We applied a random-effect model meta-analysis to estimate the overall pooled magnitude and risk factors of MTCT of HIV. A funnel plot and Egger's regression test were employed to check publication bias, and heterogeneity was assessed using I2 statistics. The protocol was registered in the PROSPERO database with registration ID number CRD42022325938. Result: Eighteen published articles on the magnitude of MTCT and 16 published articles on its risk factors were included in this review. The pooled magnitude of MTCT of HIV after the Option B+ program in Ethiopia was 4.05% (95% CI 3.09, 5.01). Mothers who delivered their infants at home [OR: 9.74; (95% CI: 6.89–13.77)], had not been on ART intervention [OR: 19.39; (95% CI: 3.91–96.18)], had poor adherence to ART [OR: 7.47; (95% CI: 3.40–16.45)], initiated ART during pregnancy [OR: 5.09; (95% CI: 1.73–14.97)], had WHO clinical stage 2 and above [OR: 4.95; (95% CI: 1.65–14.88]], had a CD4 count below 350 at enrolment [OR: 5.78; (95% CI: 1.97–16.98], had no or low male partner involvement [OR: 5.92; (95% CI: 3.61–9.71]] and whose partner was not on ART [OR: 8.08; (95% CI: 3.27–19.93]] had higher odds of transmitting HIV to their infants than their counterparts. Conclusion: This review showed that the pooled magnitude of MTCT of HIV among mother-infant pairs who initiated ART after the Option B + program in Ethiopia is at the desired target of the WHO, which is less than 5% in breastfeeding women. Home delivery, lack of male partner involvement, advanced HIV-related disease, lack of PMTCT intervention, and poor ARV adherence were significant risk factors for MTCT of HIV in Ethiopia. [ABSTRACT FROM AUTHOR]

IntroductionMaternal antiretroviral therapy (ART) with viral suppression prior to conception, during pregnancy and throughout the breastfeeding period accompanied by infant postnatal prophylaxis (PNP) forms the foundation of current approaches to preventing vertical HIV transmission. Unfortunately, infants continue to acquire HIV infections, with half of these infections occurring during breastfeeding. A consultative meeting of stakeholders was held to review the current state of PNP globally, including the implementation of WHO PNP guidelines in different settings and identifying the key factors affecting PNP uptake and impact, with an aim to optimize future innovative strategies.DiscussionWHO PNP guidelines have been widely implemented with adaptations to the programme context. Some programmes with low rates of antenatal care attendance, maternal HIV testing, maternal ART coverage and viral load testing capacity have opted against risk-stratification and provide an enhanced PNP regimen for all infants exposed to HIV, while other programmes provide infant daily nevirapine antiretroviral (ARV) prophylaxis for an extended duration to cover transmission risk throughout the breastfeeding period. A simplified risk stratification approach may be more relevant for high-performing vertical transmission prevention programmes, while a simplified non-risk stratified approach may be more appropriate for sub-optimally performing programmes given implementation challenges. In settings with concentrated epidemics, where the epidemic is often driven by key populations, infants who are found to be exposed to HIV should be considered at high risk for HIV acquisition. All settings could benefit from newer technologies that promote retention during pregnancy and throughout the breastfeeding period. There are several challenges in enhanced and extended PNP implementation, including ARV stockouts, lack of appropriate formulations, lack of guidance on alternative ARV options for prophylaxis, poor adherence, poor documentation, inconsistent infant feeding practices and in inadequate retention throughout the duration of breastfeeding.ConclusionsTailoring PNP strategies to a programmatic context may improve access, adherence, retention and HIV-free outcomes of infants exposed to HIV. Newer ARV options and technologies that enable simplification of regimens, non-toxic potent agents and convenient administration, including longer-acting formulations, should be prioritized to optimize the effect of PNP in the prevention of vertical HIV transmission.

Background: Adverse drug reactions (ADRs) significantly impact public healthcare, especially among HIV patients. These reactions, which range from mild pruritus to severe conditions such as Steven-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), affect the quality of life and treatment outcomes. Aims and Objectives: The current study was designed to evaluate the various types of cutaneous ADRs (CADRs) in adult HIV patients undergoing antiretroviral therapy (ART). Materials and Methods: A retrospective record-based study was conducted at the Department of Dermatology, Venereology, and Leprosy, Government Medical College/Government General Hospital, Suryapet, Telangana, India. Data from November 2017 to October 2020 were analyzed, focusing on patients over 18 years on ART. Relevant demographic and medical data, including blood tests, liver and renal function, and CD4 counts, were collected. Results: Out of 3532 patients on ART, 568 (16.08%) developed CADRs. Females represented 54.2% of these cases. The age group most affected was between 29 and 48 years. The most common ART regimen was Tenofovir+Lamivudin+Dolutegravir, followed by zidovudine-based combinations. Nevirapine-based regimens had a higher association with CADRs, particularly severe reactions such as SJS and TEN. Conclusion: A significant proportion of HIV patients on ART experience CADRs, with certain drug combinations posing higher risks. This study highlights the need for careful monitoring and selection of ART regimens to minimize the risk of severe CADRs, thereby improving patient outcomes and quality of life in HIV treatment.

Abstract The antiretroviral drugs (ARVDs) have been reported to be among the emerging water pollutants as a results attention is being paid on their analysis. This work therefore explored for the first time the multi-template MIP for the selective removal of selected ARVDs (abacavir, efavirenz and nevirapine) in wastewater, river water and tap water. The adsorption studies of a multi-template MIP were conducted by determining the effect of an increase in ARVDs concentration in solution and the effect of an increase in contact time between the sorbent and the ARVDs. High adsorption efficiencies were observed for abacavir, efavirenz and nevirapine analytes within 5 min and the maximum adsorption efficiency was observed at 60 min ranging from 94.76 to 96.93%. Adsorption kinetics showed that pseudo-second rate order was the best fitting model, while adsorption isotherms indicated that the Freundlich isotherm (R 2 = 0.94–0.98) best described the adsorption mechanism of ARVDs onto the MIPs. These results indicated that the electrostatic attractions influenced the multilayer coverage and chemisorption process. Selectivity studies conducted in the presence of competitors gave the recoveries between 92 and 98% for the target analytes, while they were 63–79% for competitors indicating good selectivity and strong affinity of the polymer towards the target analytes. Reusability studies showed that the MIP can be reused for up to 8 cycles with recoveries above 92% for all target ARVDs. The application of the MIP-DSPE method to wastewater, river and tap water samples gave concentrations of 28.75–178.02, 1.95–13.15 and 2.17–6.27 µg L−1, respectively. These results indicate the potential unplanned consumption of ARVDs upon drinking contaminated water which could result to their resistance by the human body. Therefore, their continuous monitoring as well as investigation of their removal strategies is of paramount importance.

BackgroundTreatment and prophylaxis options for neonatal HIV are limited. This study aimed to develop a population pharmacokinetic model to characterize the disposition of maraviroc in neonates to inform dosing regimens and expand available options.MethodsUsing maraviroc concentrations from neonates who received either a single dose or multiple doses of 8 mg/kg of maraviroc in the first 6 weeks of life, a population pharmacokinetic model was developed to determine the effects of age, sex, maternal efavirenz exposure and concomitant ARV therapy on maraviroc disposition. The final model was used in Monte Carlo simulations to generate expected exposures with recommended dosing regimens.ResultsA total of 396 maraviroc concentrations, collected in the first 4 days of life, at 1 week, at 4 weeks and at 6 weeks, from 44 neonates were included in the analysis. After allometrically scaling for weight, age less than 4 days was associated with a 44% decreased apparent clearance compared with participants 7 days to 6 weeks of life. There were no differences identified in apparent clearance or volume of distribution from ages 7 days to 6 weeks, sex, maternal efavirenz exposure or concomitant nevirapine therapy. Monte Carlo simulations with FDA-approved weight band dosing resulted in the majority of simulated patients (84.3%) achieving an average concentration of ≥75 ng/mL.ConclusionsWhile maraviroc apparent clearance is decreased in the first few days of life, the current FDA-approved maraviroc weight band dosing provides maraviroc exposures for neonates in the first 6 weeks of life, which were consistent with adult maraviroc exposure range. Maraviroc provides another antiretroviral treatment option for very young infants.

IntroductionContraceptive implants containing etonogestrel and levonorgestrel have emerged as popular contraceptive options among women in areas of high HIV burden in sub-Saharan Africa. However, recent pharmacokinetic data have shown drug-drug interactions between implants and efavirenz-containing antiretroviral therapy (ART), reducing the effectiveness of the implants. Here, we evaluated pregnancy incidence in 6-month intervals following implant initiation among women using efavirenz and contraceptive implants to assess whether the risk of breakthrough pregnancy is higher after specific periods of implant use.MethodsWe used data from a retrospective longitudinal analysis of women living with HIV ages 18-45 years in western Kenya who attended HIV-care facilities between 2011 and 2015. We used Cox proportional hazard models to compute hazard ratios (HRs) for breakthrough pregnancy by implant type and ART regimen. Depending on the model, we adjusted for socio-demographic and clinical factors, programme, site and interaction between calendar time and ART regimen. We utilized inverse probability weights (IPWs) to account for three sampling phases (electronic medical record [EMR], chart review and phone interview) and calculated overall parameter estimates.ResultsWomen contributed 14,768 woman-years from the largest sampling phase (EMR). The median age was 31 years. Women used etonogestrel implants for 26-69% of the time and levonorgestrel implants for 7-31% of the time, depending on the sampling phase. Women used efavirenz, nevirapine or no ART for 27-33%, 40-46% and 15-26% of follow-ups, respectively. When combining sampling phases, there was little evidence to suggest that the relative hazard of pregnancy among efavirenz-containing ART users relative to nevirapine-containing ART changed with length of time on implants: IPW-adjusted HR of 3.1 (CI: [1.5; 6.4]) at 12 months, 3.4 (CI: [1.8; 6.3]) at 24 months, 3.8 (CI: [1.9; 7.7]) at 36 months and 4.2 (CI: [1.6; 11.1]) at 48 months (interaction p-value = 0.88). Similarly, no significant change in HRs over time was found when comparing women not using ART to nevirapine-containing ART users (interaction p-value = 0.49).ConclusionsWe did not find evidence to suggest implants being more fallible from drug-drug interactions with efavirenz at later time intervals of implant use. Thus, we would not recommend shortening the duration of implant use or replacing implants sooner when concomitantly used with efavirenz.

This study focused on the efficacy of a calcined layered double hydroxide (CLDH) clay in adsorbing two antiretroviral drugs (ARVDs), namely efavirenz (EFV) and nevirapine (NVP), from wastewater. The clay was synthesized using the co-precipitation method, followed by subsequent calcination in a muffle furnace at 500 °C for 4 h. The neat and calcined clay samples were subjected to various characterization techniques to elucidate their physical and chemical properties. Response surface modelling (RSM) was used to evaluate the interactions between the solution's initial pH, adsorbent loading, reaction temperature, and initial pollutant concentration. Additionally, the adsorption kinetics, thermodynamics, and reusability of the adsorbent were evaluated. The results demonstrated that NVP exhibited a faster adsorption rate than EFV, with both reaching equilibrium within 20–24 h. The pseudo-second order (PSO) model provided a good fit for the kinetics data. Thermodynamics analysis revealed that the adsorption process was spontaneous and exothermic, predominantly governed by physisorption interactions. The adsorption isotherms followed the Freundlich model, and the maximum adsorption capacities for EFV and NVP were established to be 2.73 mg/g and 2.93 mg/g, respectively. Evaluation of the adsorption mechanism through computational analysis demonstrated that both NVP and EFV formed stable complexes with CLDH, with NVP exhibiting a higher affinity. The associated adsorption energies were established to be −731.78 kcal/mol for NVP and −512.6 kcal/mol for EFV. Visualized non-covalent interaction (NCI) graphs indicated that hydrogen bonding played a significant role in ARVDs-CLDH interactions, further emphasizing physisorption as the dominant adsorption mechanism. [ABSTRACT FROM AUTHOR]

Background: Adverse drug reactions (ADRs) significantly impact public healthcare, especially among HIV patients. These reactions, which range from mild pruritus to severe conditions such as Steven-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), affect the quality of life and treatment outcomes. Aims and Objectives: The current study was designed to evaluate the various types of cutaneous ADRs (CADRs) in adult HIV patients undergoing antiretroviral therapy (ART). Materials and Methods: A retrospective record-based study was conducted at the Department of Dermatology, Venereology, and Leprosy, Government Medical College/Government General Hospital, Suryapet, Telangana, India. Data from November 2017 to October 2020 were analyzed, focusing on patients over 18 years on ART. Relevant demographic and medical data, including blood tests, liver and renal function, and CD4 counts, were collected. Results: Out of 3532 patients on ART, 568 (16.08%) developed CADRs. Females represented 54.2% of these cases. The age group most affected was between 29 and 48 years. The most common ART regimen was Tenofovir+Lamivud in+Dolutegravir, followed by zidovudine-based combinations. Nevirapine-based regimens had a higher association with CADRs, particularly severe reactions such as SJS and TEN. Conclusion: A significant proportion of HIV patients on ART experience CADRs, with certain drug combinations posing higher risks. This study highlights the need for careful monitoring and selection of ART regimens to minimize the risk of severe CADRs, thereby improving patient outcomes and quality of life in HIV treatment. [ABSTRACT FROM AUTHOR]

In utero/peripartum antiretroviral therapy (IPA) exposure type was examined in relationship to mental health symptoms among 577 children with perinatally acquired HIV (CPHIV), children perinatally HIV exposed but uninfected (CHEU), and children HIV unexposed uninfected (CHUU). IPA exposure was categorized for CPHIV and CHEU as none, single‐dose nevirapine with or without zidovudine (sdNVP±AZT), sdNVP+AZT+lamivudine (3TC), or combination antiretroviral therapy (cART). Anxiety and depressive symptoms were reported at baseline, 6‐, and 12‐month follow‐up per behavioral assessment system for children. Multivariable linear mixed models were used to estimate differences (b) with 95% confidence intervals (95% CI) for IPA exposure types versus CHEU without IPA exposure. Depressive and anxiety symptoms were lower in CHUU relative to CHEU and CPHIV but did not differ between CPHIV and CHEU. CHEU with sdNVP±AZT exposure had greater anxiety (b = 0.51, 95% CI: [0.06, 0.96]) and depressive symptoms (b = 0.48, 95% CI: [0.07, 0.89]) than CHEU without IPA exposure. CHEU with sdNVP+AZT+3TC exposure had higher anxiety (b = 0.0.45, 95% CI: [0.03, 0.86]) and depressive symptoms (b = 0.72, 95% CI: [0.27, 1.17]) versus CHEU without IPA exposure. Depressive and anxiety symptoms were not different for CHEU and CPHIV exposed to cART (b = 0.12–0.60, 95% CI: [−0.41, 1.30]) and CHEU and CHUU (b = −0.04 to 0.08, 95% CI: [−0.24, 0.29]) without IPA exposure. Among CHEU, peripartum sdNVP±AZT and sdNVP+AZT+3TC but not cART compared to no IPA exposure was associated with clinically important elevations in anxiety and depressive symptoms. Monitoring of mental health trajectory of HIV‐affected children considering IPA is needed to inform mental health interventions. Patient Contribution: Caregivers and their dependents provided consent for participation and collaborated with study team to identify mutually convenient times for protocol implementation. [ABSTRACT FROM AUTHOR]

The antiretroviral drugs (ARVDs) have been reported to be among the emerging water pollutants as a results attention is being paid on their analysis. This work therefore explored for the first time the multi-template MIP for the selective removal of selected ARVDs (abacavir, efavirenz and nevirapine) in wastewater, river water and tap water. The adsorption studies of a multi-template MIP were conducted by determining the effect of an increase in ARVDs concentration in solution and the effect of an increase in contact time between the sorbent and the ARVDs. High adsorption efficiencies were observed for abacavir, efavirenz and nevirapine analytes within 5 min and the maximum adsorption efficiency was observed at 60 min ranging from 94.76 to 96.93%. Adsorption kinetics showed that pseudo-second rate order was the best fitting model, while adsorption isotherms indicated that the Freundlich isotherm (R2 = 0.94–0.98) best described the adsorption mechanism of ARVDs onto the MIPs. These results indicated that the electrostatic attractions influenced the multilayer coverage and chemisorption process. Selectivity studies conducted in the presence of competitors gave the recoveries between 92 and 98% for the target analytes, while they were 63–79% for competitors indicating good selectivity and strong affinity of the polymer towards the target analytes. Reusability studies showed that the MIP can be reused for up to 8 cycles with recoveries above 92% for all target ARVDs. The application of the MIP-DSPE method to wastewater, river and tap water samples gave concentrations of 28.75–178.02, 1.95–13.15 and 2.17–6.27 µg L−1, respectively. These results indicate the potential unplanned consumption of ARVDs upon drinking contaminated water which could result to their resistance by the human body. Therefore, their continuous monitoring as well as investigation of their removal strategies is of paramount importance. [ABSTRACT FROM AUTHOR]

Background HIV-1 drug resistance is a huge challenge in the era of ART. Objectives To investigate the prevalence and characteristics of acquired HIV-1 drug resistance (ADR) in Shanghai, China. Methods An epidemiological study was performed among people living with human immunodeficiency virus (PLWH) receiving ART in Shanghai from January 2017 to December 2021. A total of 8669 PLWH were tested for drug resistance by genotypic resistance testing. Drug resistance mutations (DRMs) were identified using the Stanford University HIV Drug Resistance Database program. Results Ten HIV-1 subtypes/circulating recombinant forms (CRFs) were identified, mainly including CRF01_AE (46.8%), CRF07_BC (35.7%), B (6.4%), CRF55_01B (2.8%) and CRF08_BC (2.4%). The prevalence of ADR was 48% (389/811). Three NRTI-associated mutations (M184V/I/L, S68G/N/R and K65R/N) and four NNRTI-associated mutations (V179D/E/T/L, K103N/R/S/T, V106M/I/A and G190A/S/T/C/D/E/Q) were the most common DRMs. These DRMs caused high-level resistance to lamivudine, emtricitabine, efavirenz and nevirapine. The DRM profiles appeared to be significantly different among different subtypes. Conclusions We revealed HIV-1 subtype characteristics and the DRM profile in Shanghai, which provide crucial guidance for clinical treatment and management of PLWH. [ABSTRACT FROM AUTHOR]

The article focuses on a 5-day-old baby girl in the NICU exposed to HIV, syphilis, and maternal drug use, presenting with diarrhea possibly due to neonatal abstinence syndrome. Topics include the infant's treatment regimen for HIV prophylaxis and withdrawal symptoms, along with the management of a rash possibly caused by nevirapine, leading to a change in medication and successful completion of prophylactic treatment before discharge.

Objectives Mitochondrial mutations in HIV-exposed uninfected (HEU) infants after cessation of ART are rarely studied. We analysed a group of HEU newborns born to mothers with late HIV diagnosis who received three doses of ART immediately after birth. We observed mitochondrial DNA (mtDNA) mutations at different times of withdrawal. Methods The study was based on a clinical trial conducted from 2015 to 2020. Newborns of the intervention group who met the criteria for this study received triple antiretroviral drugs, zidovudine + lamivudine + nevirapine, within 2 h after the birth, as post-partum prophylaxis, and at 14 days were switched to zidovudine + lamivudine + lopinavir/ritonavir, which was continued until 6 weeks of age. From August to November 2019, blood samples from HEU infants were also collected after ceasing 12 months of ART, and analysed for mtDNA. Results Our study found that mtDNA mutations remained prevalent in HEU infants a few years after three ARTs were stopped immediately after birth. Among them, D-loop, ND1 and CYTB are the first three mutated regions during different withdrawal periods. This pattern of mutations is similar to, but not exactly consistent with, HIV-infected children receiving standard ART. Conclusions Further studies are needed to determine the effects of these mutations on the development of HEU infants and whether stopping ART leads to the restoration of mitochondrial function. [ABSTRACT FROM AUTHOR]

Context: Combating human immunodeficiency virus/acquired immunodeficiency syndrome epidemic has been possible due to advances in prevention strategies and Antiretroviral therapy (ART). Optimal adherence to ART is a major factor in achieving the desired immunological, virological, and patient well‑being outcomes. Several socio‑demographic, patient, treatment, and health‑care system‑related factors influence nonadherent behavior to ART. Aims: This study was planned to assess (1) ART adherence level, (2) factors and reasons associated with nonadherence, and (3) impact of suboptimal adherence on treatment outcomes. Settings and Design: This was a cross‑sectional analytical study of 300 patients in a tertiary care hospital in Puducherry, India. Methods: Random sampling was used to collect data from patient treatment cards and a predesigned structured questionnaire. The pill count method was used to calculate adherence level. Statistical Analysis Used: Nonadherence was chosen as a dependent variable and factors affecting adherence were chosen as independent variables. Test for significance was carried out by Chi‑square test and Fisher’s exact test. Results: Optimal adherence was seen in 68.3%. Factors significantly associated with nonadherence were lower education level, high prior CD4 count, irregular follow‑up, missing doses in the past, and being late for pharmacy pill refills. Adherence was positively associated with mean increase in CD4 count over 6 months. Conclusions: In our study, the adherence rate is suboptimal which can lead to failure of ART. Nonadherence was associated with a decrease in CD4 count overtime. Most of the factors significantly affecting ART adherence were patient behavior related. These factors can be used for target intervention during reinforcement adherence counseling. [ABSTRACT FROM AUTHOR]

BackgroundWith increasing intention to treat HIV as early as possible, evidence to confirm the safety and therapeutic drug concentrations of a nevirapine-based antiretroviral regimen in the early neonatal period is needed. This study aims to establish dosing of nevirapine for very early treatment of HIV-exposed neonates at high risk of HIV acquisition.MethodsIMPAACT P1115 is a multinational phase 1/2 proof-of-concept study in which presumptive treatment for in-utero HIV infection is initiated within 48 h of birth in HIV-exposed neonates at high risk of HIV acquisition. Participants were neonates who were at least 34 weeks gestational age at birth and enrolled within 48 h of birth, born to women with presumed or confirmed HIV infection who had not received antiretrovirals during this pregnancy. The regimen consisted of two nucleoside reverse transcriptase inhibitors plus nevirapine dosed at 6 mg/kg twice daily for term neonates (≥37 weeks gestational age) or 4 mg/kg twice daily for 1 week and 6 mg/kg twice daily thereafter for preterm neonates (34 to

BackgroundThere is limited information on perinatal outcomes in HIV-hepatitis B virus (HBV) coinfection.MethodsHIV Prevention Trials Network (HPTN) 046 was a randomized double-blind placebo-controlled trial of perinatal transmission that evaluated 6 months of infant nevirapine versus placebo among breast-fed infants. Women living with HIV and their infants enrolled in sub-Saharan Africa from 2007 to 2010; 78% received antiretroviral therapy (ART). Maternal samples were tested for hepatitis B surface antigen (HBsAg). High and low HBV viral load (VL) was defined as ≥106 IU/mL and

The rise of HIV‐1 drug resistance to nonnucleoside reverse transcriptase inhibitors (NNRTIs) threatens the long‐term success of NNRTI‐based therapies. Our study aims to describe the circulation of major resistance‐associated mutations (RAMs) for NNRTIs in people living with HIV (PLWH) in Italy from 2000 to 2020. We included 5982 naïves and 28 505 genotypes from 9387 treatment‐experienced PLWH from the Antiviral Response Cohort Analysis (ARCA) cohort. Transmitted drug resistance (TDR) was found in 12.5% and declined from 17.3% in 2000–2003 to 10.9% in 2016–2020 (p = 0.003). Predictors of TDR were viral subtype B [vs. non‐B, adjusted odds ratio (aOR) = 1.94, p < 0.001], zenith viral load (VL) (per 1 log10 higher, aOR = 0.86, p = 0.013), nadir CD4 cell count (per 100 cells/μL increase aOR = 0.95, p = 0.013). At least one RAM for NNRTIs among treatment experienced PLWH was detected in 33.2% and pre‐treatment drug resistance (PDR) declined from 43.4% in 2000–2003 to 20.9% in 2016–2020 (p < 0.001). Predictors of PDR were sexual transmission route (vs. others, aOR = 0.78, p < 0.001), time since HIV diagnosis (per 1 month longer, aOR = 1.002, p < 0.001), viral subtype B (vs. non B, aOR = 1.37, p < 0.001), VL (per 1 log10 higher, aOR = 1.12, p < 0.001), nadir CD4 count (per 100 cells/μL increase, aOR = 0.91, p < 0.001), previous exposure to any NNRTI (aOR = 2.31, p < 0.001) and a more recent calendar year sequence (any time span > 2008 vs. 2000–2003, any aOR <1, p < 0.001). Circulation of RAMs to NNRTIs declined during the last 20 years in Italy. NNRTIs remain pivotal drugs for the management of HIV‐1 due to safety concerns and long‐acting options. [ABSTRACT FROM AUTHOR]

Background: Feline immunodeficiency virus (FIV) causes an acquired immunodeficiency-like syndrome in cats. FIV is latent. No effective treatment has been developed for treatment the infected cats. The first and second generations non-nucleoside reverse transcriptase inhibitors (NNRTIs) for HIV treatment, nevirapine (NVP) and efavirenz (EFV), and rilpivirine (RPV), were used to investigate the potential of NNRTIs for treatment of FIV infection. Objective: This study aims to use experimental and in silico approaches to investigate the potential of NNRTIs, NVP, EFV, and RPV, for inhibition of FIV reverse transcriptase (FIV-RT). Methods: The FIV-RT and human immunodeficiency virus reverse transcriptase (HIV-RT) were expressed and purified using chromatography approaches. The purified proteins were used to determine the IC50 values with NVP, EFV, and RPV. Surface plasmon resonance (SPR) analysis was used to calculate the binding affinities of NNRTIs to HIV-RT and FIV-RT. The molecular docking and molecular dynamic simulations were used to demonstrate the mechanism of FIV-RT and HIV-RT with first and second generation NNRTI complexes. Results: The IC50 values of NNRTIs NVP, EFV, and RPV against FIV-RT were in comparable ranges to HIV-RT. The SPR analysis showed that NVP, EFV, and RPV could bind to both enzymes. Computational calculation also supports that these NNRTIs can bind with both FIV-RT and HIV-RT. Conclusions: Our results suggest the first and second generation NNRTIs (NVP, EFV, and RPV) could inhibit both FIV-RT and HIV-RT. [ABSTRACT FROM AUTHOR]