Non‐nucleoside reverse transcriptase inhibitor levels among HIV‐exposed uninfected infants at the time of HIV PCR testing – findings from a tertiary healthcare facility in Pretoria, South Africa

Abstract

Introduction To date, very little programmatic data has been published regarding serial antiretroviral ( ARV ) levels in infants exposed to maternal treatment and/or infant prophylaxis during the first months of life. Such data provide the opportunity to describe the proportion of infants exposed to virologically suppressive levels of ARV s and to gauge adherence to the prevention of mother‐to‐child transmission of HIV ( PMTCT ) programme. Methods From August 2014 to January 2016, HIV ‐exposed infants born at Kalafong Provincial Tertiary Hospital in Pretoria, South Africa were enrolled as part of an observational cohort study. Plasma samples from HIV ‐exposed uninfected infants were obtained at birth, 6‐weeks, 10‐weeks and 14‐weeks of age and quantitative efavirenz ( EFV ) and nevirapine ( NVP ) drug level testing performed using liquid chromatography‐mass spectrometry, irrespective of maternal ARV regimen. Descriptive analysis of EFV and NVP levels in relation to self‐reported maternal and infant ARV exposure was performed. EFV levels >500 ng/ mL and NVP levels >100 ng/ mL were reported based on studies suggesting that trough levels above these thresholds are associated with virological suppression and PMTCT respectively. Results Among 66 infants exposed to maternal EFV in utero , 29 (44%) had virologically suppressive plasma EFV levels at birth, with a median level of 1665 ng/ mL ( IQR : 1094 to 3673). Among infants who were exclusively breastfed at 6‐, 10‐ and 14 weeks, 13/48 (27%), 5/25 (25%) and 0/21 (0%) had virologically suppressive EFV levels. Among 64 infants whose mothers reported administering daily infant NVP at time of their 6‐week HIV PCR test, only 45 (70%) had NVP levels above the minimum prophylactic trough level. Conclusions During the first 10‐weeks after delivery, a quarter of breastfed infants born to women on an EFV ‐containing treatment regimen maintained virologically suppressive EFV plasma levels. This finding highlights the importance of both careful monitoring of ARV side effects and repeat HIV PCR after the first few months of life among HIV ‐exposed uni...

Barriers and enablers of adherence to infant nevirapine prophylaxis against HIV 1 transmission among 6-week-old HIV exposed infants: A prospective cohort study in Northern Uganda

“…We relied on the mother or caregiver’s report in measuring adherence of the infant to nevirapine prophylaxis. Studies done in South Africa [ 9 , 13 , 19 ], have reported levels of non-adherence to infant nevirapine prophylaxis ranging from 12.3%–30% within which range the incidence of non-adherence in our study falls. The reported non-adherence rates vary across study contexts because different methods were used while measuring infant adherence.…”

“…The reported non-adherence rates vary across study contexts because different methods were used while measuring infant adherence. Studies that rely on self-reported or caregiver’s report [ 9 , 10 ] have reported higher levels of non-adherence compared to those that have relied on electronic dose monitoring [ 9 ] and plasma concentration of therapeutic levels of nevirapine in the infant’s blood [ 9 , 13 ]. All these studies measure adherence to infant nevirapine prophylaxis at different time points; some at birth and the majority at 6 weeks while factoring in variable recall periods.…”

“…The majority of the women in our cohort who never received nevirapine for the baby actually had a non-clinic delivery, mostly a home delivery. Studies done in Zambia [ 13 ], South Africa [ 19 ] and a systematic review for sub-Saharan Africa [ 12 ] have demonstrated the association between home delivery and non-adherence to infant prophylaxis. Home deliveries have also been associated with the mother not receiving the nevirapine syrup for the baby from the health worker at the time of delivery [ 10 , 12 ].…”

“…Most studies done on adherence to infant nevirapine prophylaxis have been qualitative and were done under previous treatment paradigms and cannot be compared to today’s situation. Furthermore, different methods have been used to measure adherence to infant NVP prophylaxis like relying on caregivers’ report [ 12 ], measuring blood plasma concentrations of NVP therapeutic levels [ 9 , 13 ] and electronic dose monitoring like medication event monitoring systems (MEMs) where bottle caps are fitted with a microchip that records the time and date of each bottle opening [ 14 ].…”

Socio-Demographic, Nutritional and Adherence as Determinants of Nevirapine Plasma Concentration among HIV-1 Patients from Two Geographically Defined Regions of Kenya

“…We reported wide interindividual variability in NVP plasma levels ranging from 4ng/mL to 44,207 ng/mL (median 5179 ng/mL, IQR 2557-7453 ng/mL). This range is far broader than those reported in other studies (Oluka et al, 2015;Mazanderani et al, 2019). There were 255(67.6%) patients with NVP plasma of 3000 to 8000 ng/mL (la Porte et al, 2006) considered within therapeutic range.…”