Maternal Lopinavir/Ritonavir Is Associated with Fewer Adverse Events in Infants than Nelfinavir or Atazanavir.

Combination antiretroviral therapy (cART) is successfully used for prevention of perinatal HIV transmission. To investigate safety, we compared adverse events (AE) among infants exposed to different maternal cART regimens. We reviewed 158 HIV-uninfected infants born between 1997 and 2009, using logistic regression to model grade ≥1 AE and grade ≥3 AE as a function of maternal cART and confounding variables (preterm, C-section, illicit drug use, race, ethnicity, infant antiretrovirals, and maternal viremia). Frequently used cART regimens included zidovudine (63%), lamivudine (80%), ritonavir-boosted lopinavir (37%), nelfinavir (26%), and atazanavir (10%). At birth, anemia occurred in 13/140 infants (9%), neutropenia in 27/107 (25%), thrombocytopenia in 5/133 (4%), and liver enzyme elevation in 21/130 (16%). Corresponding rates of AE at 4 weeks were 59/141 (42%), 54/130 (42%), 3/137 (2%), and 3/104 (3%), respectively. Serious AE (grade ≥ 3) exceeded 2% only for neutropenia (13% at birth; 9% at 4 weeks). Compared with infants exposed to maternal lopinavir/ritonavir, infants exposed to nelfinavir and atazanavir had a 5-fold and 4-fold higher incidence of AE at birth, respectively. In conclusion, hematologic and hepatic AE were frequent, but rarely serious. In this predominantly protease inhibitor-treated population, lopinavir/ritonavir was associated with the lowest rate of infant AE.

Telehealth Use in a National Pediatric Weight Management Sample During the COVID-19 Pandemic.

Background: This study aimed to assess the implementation and access to telehealth-delivered pediatric weight management (PWM) during the initial phase of the COVID-19 pandemic at six US PWM programs (PWMP) using the RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) framework. Methods: The COVID-19 period (COVID) was defined in this retrospective, multisite study as the time when each site closed in-person care during 2020. The Pre-COVID period (Pre-COVID) was an equivalent time frame in 2019. Patients were stratified by visit completion status. Patient characteristics for COVID and Pre-COVID were compared to examine potential changes/disparities in access to care. Results: There were 3297 unique patients included across the six sites. On average, telehealth was initiated 4 days after in-person clinic closure. Compared with Pre-COVID, COVID (mean duration: 9 weeks) yielded fewer total completed visits (1300 vs. 2157) and decreased revenue (mean proportion of nonreimbursed visits 33.30% vs. 16.67%). Among the completed visits, COVID included a lower proportion of new visits and fewer patients who were male, non-English speaking, Hispanic, or Asian and more patients who were Black or lived ≥20 miles from the program site (p < 0.05 for all). Among no-show/canceled visits, COVID included more patients who had private insurance, older age, or a longer time since the last follow-up. Conclusion: Rapid implementation of telehealth during COVID facilitated continuity of PWM care. Clinic volume and reimbursement were lower during COVID and differences in the patient population reached by telehealth emerged. Further characterization of barriers to telehealth for PWM is needed.

Safety and tolerability of antiretrovirals during pregnancy.

Combination antiretroviral therapy (CART) dramatically decreases mother-to-child HIV-1 transmission (MTCT), but maternal adverse events are not infrequent. A review of 117 locally followed pregnancies revealed 7 grade ≥ 3 AEs possibly related to antiretrovirals, including 2 hematologic, 3 hepatic, and 2 obstetric cholestasis cases. A fetal demise was attributed to obstetric cholestasis, but no maternal deaths occurred. The drugs possibly associated with these AE were zidovudine, nelfinavir, lopinavir/ritonavir, and indinavir. AE or intolerability required discontinuation/substitution of nevirapine in 16% of the users, zidovudine in 10%, nelfinavir in 9%, lopinavir/ritonavir in 1%, but epivir and stavudine in none. In conclusion, nevirapine, zidovudine, and nelfinavir had the highest frequency of AE and/or the lowest tolerability during pregnancy. Although nevirapine and nelfinavir are infrequently used in pregnancy at present, zidovudine is included in most MTCT preventative regimens. Our data emphasize the need to revise the treatment recommendations for pregnant women to include safer and better-tolerated drugs.

Kinetics and determining factors of the virologic response to antiretrovirals during pregnancy.

HIV-infected pregnant women with undetectable plasma HIV RNA concentrations at delivery pose a minimal risk of vertical transmission. We studied the kinetics and the determinants of the virologic response to antiretroviral therapy in 117 consecutive pregnancies. Patients who initiated therapy during pregnancy had a VL decrease of 2 and 2.5 log(10) after 4 and 24 weeks, respectively. Therapeutic drug monitoring (TDM) of the protease inhibitors administered in doses recommended for nonpregnant adults resulted in below-target concentrations in 29%, 35%, and 44% of 1st, 2nd, and 3rd trimester measurements, respectively, but low drug concentrations did not correlate with virologic failure. Demographic characteristics, antiretroviral experience prior to pregnancy, baseline VL, or use of specific antiretrovirals did not affect the virologic response. Adherence to >/=95% of prescribed doses and utilization of psychosocial services were associated with undetectable plasma HIV RNA at delivery. In conclusion, the virologic responses of pregnant and nonpregnant adults share similar characteristics.

Serious adverse events are uncommon with combination neonatal antiretroviral prophylaxis: a retrospective case review.

Six weeks of zidovudine (ZDV) is recommended for postnatal prophylaxis of HIV-exposed infants, but combination antiretrovirals are indicated if HIV transmission risk is increased. We investigated the frequency and severity of adverse events (AE) in infants receiving multiple drug prophylaxis compared to ZDV alone. In this retrospective review of 148 HIV-exposed uninfected infants born between 1997-2009, we determined clinical and laboratory AE that occurred between days of life 8-42. Thirty-six infants received combination prophylaxis; among those, a three-drug regimen containing ZDV, lamivudine, and nevirapine was most common (53%). Rates of laboratory AE grade ≥1 were as follows for the combination prophylaxis and ZDV alone groups, respectively: neutropenia 55% and 39%; anemia 50% and 39%; thrombocytopenia 0 and 3%; elevated aspartate aminotransferase 3% and 3%; elevated alanine aminotransferase 0 and 1%; hyperbilirubinemia 19% and 42%. Anemia occurred more frequently in infants who received three-drug prophylaxis compared to infants who received ZDV alone (63% vs. 39%, p = 0.04); all anemia AE were grade 1 or 2 in the three-drug prophylaxis group. Overall, 75% of infants on combination prophylaxis and 66% of infants on ZDV alone developed grade ≥1 AE (p = 0.32), and 17% of infants in either group developed grade ≥3 AE. Stavudine was substituted for ZDV in 23 infants due to anemia or neutropenia. After this antiretroviral change, 50% of evaluable infants demonstrated improvement in AE grade, and 25% had no change. In conclusion, low grade anemia, neutropenia, and hyperbilirubinemia occurred frequently regardless of the prophylactic regimen, but serious AE were uncommon. Although most AE were typical of ZDV toxicity, the combination of ZDV with lamivudine and nevirapine resulted in an increased frequency of low-grade anemia. Further studies are needed to identify prophylactic regimens with less toxicity for infants born to HIV-infected mothers.

Resistance to antiretrovirals in HIV-infected pregnant women.

BACKGROUND: Antiretrovirals suppress HIV replication and prevent mother-to-child-transmission of HIV (PMTCT). Resistance to antiretrovirals may reduce the efficacy of PMTCT and/or complicate treatment of maternal or infant infection. OBJECTIVES: To assess resistance to antiretrovirals during pregnancy. DESIGN: Retrospective chart review of 44 pregnancies. RESULTS: Twenty-two patients were antiretroviral treatment-naïve, 8 were on therapy, and 14 had prior therapy, but were off medication when the genotyping was performed. Major mutations were found in 10 antiretroviral-experienced women, including 5 women with major mutations to 2 classes of drugs (none to 3 classes). Major mutations were most common for lamivudine, nevirapine, zidovudine, stavudine, and abacavir. Three women had significant resistance to zidovudine/lamivudine, a combination recommended in PMTCT guidelines. Despite significant antiretroviral resistance, 6 of 8 women with plasma HIV RNA measured within 4 weeks of delivery achieved <50 copies/mL. All neonates were uninfected. Among 6 women who received antiretrovirals exclusively for PMTCT, there were no remarkable changes of the HIV genotype before and after pregnancy. CONCLUSIONS: Resistance to antiretrovirals was common in antiretroviral-experienced pregnant women, but not in naïve women. The 14% prevalence of resistance to zidovudine and lamivudine in antiretroviral-experienced women suggests that alternative NRTI are desirable for this group of patients.