Brief Report: Suboptimal Lopinavir Exposure in Infants on Rifampicin Treatment Receiving Double-dosed or Semisuperboosted Lopinavir/Ritonavir: Time for a Change.

BACKGROUND: Although super-boosted lopinavir/ritonavir (LPV/r; ratio 4:4 instead of 4:1) is recommended for infants living with HIV and receiving concomitant rifampicin, in clinical practice, many different LPV/r dosing strategies are applied due to poor availability of pediatric separate ritonavir formulations needed to superboost. We evaluated LPV pharmacokinetics in infants with HIV receiving LPV/r dosed according to local guidelines in various sub-Saharan African countries with or without rifampicin-based tuberculosis (TB) treatment. METHODS: This was a 2-arm pharmacokinetic substudy nested within the EMPIRICAL trial (#NCT03915366). Infants aged 1-12 months recruited into the main study were administered LPV/r according to local guidelines and drug availability either with or without rifampicin-based TB treatment; during rifampicin cotreatment, they received double-dosed (ratio 8:2) or semisuperboosted LPV/r (adding a ritonavir 100 mg crushed tablet to the evening LPV/r dose). Six blood samples were taken over 12 hours after intake of LPV/r. RESULTS: In total, 14/16 included infants had evaluable pharmacokinetic curves; 9/14 had rifampicin cotreatment (5 received double-dosed and 4 semisuperboosted LPV/r). The median (IQR) age was 6.4 months (5.4-9.8), weight 6.0 kg (5.2-6.8), and 10/14 were male. Of those receiving rifampicin, 6/9 infants (67%) had LPV Ctrough <1.0 mg/L compared with 1/5 (20%) in the control arm. LPV apparent oral clearance was 3.3-fold higher for infants receiving rifampicin. CONCLUSION: Double-dosed or semisuperboosted LPV/r for infants aged 1-12 months receiving rifampicin resulted in substantial proportions of subtherapeutic LPV levels. There is an urgent need for data on alternative antiretroviral regimens in infants with HIV/TB coinfection, including twice-daily dolutegravir

Rapid neurodevelopmental recovery after ART initiation in an infant with HIV encephalopathy

While there is ample evidence that antiretroviral therapy (ART) can improve cognitive outcomes in older children living with HIV, encephalopathy in infants has historically been considered an advanced disease presentation with less likelihood of neurodevelopmental recovery on treatment. More recent studies suggest that timely ART can halt encephalopathic disease progression and even lead to symptom resolution. Here we present a case of an HIV-positive infant diagnosed with encephalopathy who experienced impressive and rapid improvement with a multi-disciplinary care approach that included physical and occupational therapy and ART

Suboptimal Lopinavir Exposure in Infants on Rifampicin Treatment Receiving Double-dosed or Semisuperboosted Lopinavir/Ritonavir: Time for a Change

Background: Although super-boosted lopinavir/ritonavir (LPV/r; ratio 4:4 instead of 4:1) is recommended for infants living with HIV and receiving concomitant rifampicin, in clinical practice, many different LPV/r dosing strategies are applied due to poor availability of pediatric separate ritonavir formulations needed to superboost. We evaluated LPV pharmacokinetics in infants with HIV receiving LPV/r dosed according to local guidelines in various sub-Saharan African countries with or without rifampicin-based tuberculosis (TB) treatment. Methods: This was a 2-arm pharmacokinetic substudy nested within the EMPIRICAL trial (#NCT03915366). Infants aged 1-12 months recruited into the main study were administered LPV/r according to local guidelines and drug availability either with or without rifampicin-based TB treatment; during rifampicin cotreatment, they received double-dosed (ratio 8:2) or semisuperboosted LPV/r (adding a ritonavir 100 mg crushed tablet to the evening LPV/r dose). Six blood samples were taken over 12 hours after intake of LPV/r. Results: In total, 14/16 included infants had evaluable pharmacokinetic curves; 9/14 had rifampicin cotreatment (5 received double-dosed and 4 semisuperboosted LPV/r). The median (IQR) age was 6.4 months (5.4-9.8), weight 6.0 kg (5.2-6.8), and 10/14 were male. Of those receiving rifampicin, 6/9 infants (67%) (67%) had LPV Ctrough ,1.0 mg/L compared with 1/5 (20%) in the control arm. LPV apparent oral clearance was 3.3-fold higher for infants receiving rifampicin. Conclusion: Double-dosed or semisuperboosted LPV/r for infants aged 1–12 months receiving rifampicin resulted in substantial proportions of subtherapeutic LPV levels. There is an urgent need for data on alternative antiretroviral regimens in infants with HIV/TB coinfection, including twice-daily dolutegravir.Sin financiación3.6 Q3 JCR 20221.278 Q1 SJR 2022No data IDRUE

First-Line Antituberculosis Drug Concentrations in Infants With HIV and a History of Recent Admission With Severe Pneumonia

Optimal antituberculosis therapy is essential for favorable clinical outcomes. Peak plasma concentrations of first-line antituberculosis drugs in infants with living HIV receiving WHO-recommended dosing were low compared with reference values for adults, supporting studies on increased doses of first-line TB drugs in infants.3.2 Q2 JCR 20221.547 Q1 SJR 2022No data IDR 2022UE

Table1_Prevalence of sexually transmitted infections (STIs), associations with sociodemographic and behavioural factors, and assessment of the syndromic management of vaginal discharge in women with urogenital complaints in Mozambique.docx

In Mozambique, sexually transmitted infections (STIs) are estimated to be prevalent, but diagnosis and treatment of curable STIs rely only on syndromic management. We examined the prevalence of four non-viral STIs and HIV-1/2, based on etiological diagnosis, associations with sociodemographic and behavioural factors, and the STI diagnostic accuracy of the vaginal discharge syndromic management in women with urogenital complaints in Maputo, Mozambique. A cross-sectional study was performed in Maputo, Mozambique, February 2018–January 2019, enrolling 924 women of reproductive age with urogenital complaints. Endocervical/vaginal swabs were sampled and chlamydia, gonorrhoea, trichomoniasis and Mycoplasma genitalium infections were diagnosed using a multiplex real-time PCR (AmpliSens; InterLabServices). Serological testing was performed for HIV-1/2. A structured questionnaire collected metadata. All data were analyzed in STATA/IC 12.1 using descriptive statistics, chi-square tests and logistic regression model. About 40% of the women were less than 24 years old, 50.8% were single, 62.1% had their sexual debut between 12 and 17 years of age, and the main complaint was vaginal discharge syndrome (85%). The prevalence of chlamydia was 15.5%, trichomoniasis 12.1%, gonorrhoea 4.0%, M. genitalium 2.1%, and HIV-1/2 22.3%. The vaginal discharge syndrome flowchart had a sensitivity of 73.0%–82.5% and a specificity of 14%–15% for the detection of any individual non-viral STI in women with urogenital complaints. In total, 19.2% of the symptomatic women with chlamydia, trichomoniasis or gonorrhoea would not be detected and accordingly treated using the vaginal discharge syndromic management (missed treatment) and 70.0% of the women would be treated despite not being infected with any of these three STIs (overtreatment). In conclusion, a high prevalence of especially chlamydia, trichomoniasis, and HIV-1/2 was found in women of childbearing age with urogenital complaints in Maputo, Mozambique. Syndromic management of vaginal discharge revealed low accuracy in the detection of STIs in symptomatic women, especially low specificity, which resulted in under-treatment of STI-positive cases and incorrect or over-treatment of women with urogenital complaints, many of whom were negative for all the non-viral STIs. Etiological diagnosis is imperative for effective management of STIs in symptomatic and asymptomatic women.</p

Brief Report: Suboptimal Lopinavir Exposure in Infants on Rifampicin Treatment Receiving Double-dosed or Semisuperboosted Lopinavir/Ritonavir: Time for a Change

BackgroundAlthough super-boosted lopinavir/ritonavir (LPV/r; ratio 4:4 instead of 4:1) is recommended for infants living with HIV and receiving concomitant rifampicin, in clinical practice, many different LPV/r dosing strategies are applied due to poor availability of pediatric separate ritonavir formulations needed to superboost. We evaluated LPV pharmacokinetics in infants with HIV receiving LPV/r dosed according to local guidelines in various sub-Saharan African countries with or without rifampicin-based tuberculosis (TB) treatment.MethodsThis was a 2-arm pharmacokinetic substudy nested within the EMPIRICAL trial (#NCT03915366). Infants aged 1-12 months recruited into the main study were administered LPV/r according to local guidelines and drug availability either with or without rifampicin-based TB treatment; during rifampicin cotreatment, they received double-dosed (ratio 8:2) or semisuperboosted LPV/r (adding a ritonavir 100 mg crushed tablet to the evening LPV/r dose). Six blood samples were taken over 12 hours after intake of LPV/r.ResultsIn total, 14/16 included infants had evaluable pharmacokinetic curves; 9/14 had rifampicin cotreatment (5 received double-dosed and 4 semisuperboosted LPV/r). The median (IQR) age was 6.4 months (5.4-9.8), weight 6.0 kg (5.2-6.8), and 10/14 were male. Of those receiving rifampicin, 6/9 infants (67%) had LPV Ctrough &lt;1.0 mg/L compared with 1/5 (20%) in the control arm. LPV apparent oral clearance was 3.3-fold higher for infants receiving rifampicin.ConclusionDouble-dosed or semisuperboosted LPV/r for infants aged 1-12 months receiving rifampicin resulted in substantial proportions of subtherapeutic LPV levels. There is an urgent need for data on alternative antiretroviral regimens in infants with HIV/TB coinfection, including twice-daily dolutegravir

Twice-Daily Dosing of Dolutegravir in Infants on Rifampicin Treatment: A Pharmacokinetic Substudy of the EMPIRICAL Trial.

BACKGROUND: We evaluated dolutegravir pharmacokinetics in infants with human immunodeficiency virus (HIV) receiving dolutegravir twice daily (BID) with rifampicin-based tuberculosis (TB) treatment compared with once daily (OD) without rifampicin. METHODS: Infants with HIV aged 1-12 months, weighing ≥3 kg, and receiving dolutegravir BID with rifampicin or OD without rifampicin were eligible. Six blood samples were taken over 12 (BID) or 24 hours (OD). Dolutegravir pharmacokinetic parameters, HIV viral load (VL) data, and adverse events (AEs) were reported. RESULTS: Twenty-seven of 30 enrolled infants had evaluable pharmacokinetic curves. The median (interquartile range) age was 7.1 months (6.1-9.9), weight was 6.3 kg (5.6-7.2), 21 (78%) received rifampicin, and 11 (41%) were female. Geometric mean ratios comparing dolutegravir BID with rifampicin versus OD without rifampicin were area under curve (AUC)0-24h 0.91 (95% confidence interval, .59-1.42), Ctrough 0.95 (0.57-1.59), Cmax 0.87 (0.57-1.33). One infant (5%) receiving rifampicin versus none without rifampicin had dolutegravir Ctrough &lt;0.32 mg/L, and none had Ctrough &lt;0.064 mg/L. The dolutegravir metabolic ratio (dolutegravir-glucuronide AUC/dolutegravir AUC) was 2.3-fold higher in combination with rifampicin versus without rifampicin. Five of 82 reported AEs were possibly related to rifampicin or dolutegravir and resolved without treatment discontinuation. Upon TB treatment completion, HIV viral load was &lt;1000 copies/mL in 76% and 100% of infants and undetectable in 35% and 20% of infants with and without rifampicin, respectively. CONCLUSIONS: Dolutegravir BID in infants receiving rifampicin resulted in adequate dolutegravir exposure, supporting this treatment approach for infants with HIV-TB coinfection

First-Line Antituberculosis Drug Concentrations in Infants With HIV and a History of Recent Admission With Severe Pneumonia.

Optimal antituberculosis therapy is essential for favorable clinical outcomes. Peak plasma concentrations of first-line antituberculosis drugs in infants with living HIV receiving WHO-recommended dosing were low compared with reference values for adults, supporting studies on increased doses of first-line TB drugs in infants