Toward a universal antiretroviral regimen

Abstract

Purpose of review As optimized antiretroviral therapy (ART) regimens are prepared for introduction in low and middle income countries (LMIC), we consider the current evidence related to dosing, efficacy and safety during pregnancy and breastfeeding of next generation first- and second-line ART regimens proposed for imminent introduction in the global marketplace. Recent findings Pregnancy pharmacokinetic considerations include potentially insufficient efavirenz exposure if dosed at 400mg/day, the need for twice daily darunavir dosing and the paucity of data related to tenofovir alafenamide and dolutegravir dosing, safety and efficacy. Increasingly evidence suggests an association with adverse birth outcomes, particularly in women conceiving on ART, and with varying risk by drug and drug combination. Clinical trials and studies are in progress or planned that aim to determine dosing, safety and efficacy of several new antiretrovirals. Summary Having a universal, highly potent and safe ART regimen for all individuals living with HIV in LMIC including pregnant women is clearly the most beneficial strategy to keep mothers alive and healthy and to prevent transmission of HIV to their children. It will have to be determined whether use of this next generation of optimized antiretrovirals will also optimize health outcomes of pregnant women and their children.

Lower birth weight-for-age and length-for-age z-scores in infants with in-utero HIV and ART exposure: a prospective study in Cape Town, South Africa

“…Unfortunately, a stratified analysis by ARV drug class was not practical, as most of the women in our study sample (80%), were on a first line efavirenz-based (EFV) regimen. Studies that can be stratified by ARV drug class are urgently needed to establish the safest ARV drugs for use in pregnancy and breastfeeding period [ 25 , 26 ]. In analyzing anthropometrics of infants who were HEU, we were unpowered to evaluate outcomes by gestational duration of ARV exposure, and therefore derived a dichotomous variable.…”

“…Linear regression was used to compare mean z-scores adjusting for maternal and pregnancy characteristics.Results: Among 888 infants, 49% (n = 431) were HEU and 51% (n = 457) HU. Of 431 HEU infants, 62% (n = 268) were exposed to HIV and antiretrovirals (ARVs) from conception and 38% (n = 163) were exposed to ARVs during gestation but after conception (median fetal ARV exposure of 21 weeks [IQR;[17][18][19][20][21][22][23][24][25][26]). In univariable analysis, infants who were HEU had lower mean WAZ compared with HU [β = − 0.15 (95% Confidence Interval (CI): − 0.28, − 0.020)].…”

Dolutegravir for first-line antiretroviral therapy in low-income and middle-income countries: uncertainties and opportunities for implementation and research

“…12 Evidence from randomised clinical trials will be necessary to compare maternal and infant outcomes including safety, pharmacokinetics and virological efficacy between dolutegravir and other regimens. 13 Two large trials have recently begun, but are only enrolling ART naïve pregnant women in the second and third trimesters. 14,15 Therefore, surveillance of maternal and infant outcomes, particularly amongst women who conceive while receiving dolutegravir, will be important to confirm safety in pregnancy and whether dolutegravir can be recommended for use in women of child-bearing age..…”

Propelling the Pediatric HIV Therapeutic Agenda With Science, Innovation, and Collaboration

“…High rates of prematurity, low birth weight, and concomitant health conditions among infants born to women living with HIV infection add another set of considerations when determining dosing and safety of new agents. 75 , 76 The need for formulations other than liquids that are safe, acceptable, and feasible for use in low- and middle-income settings has further delayed access to new medications for infants.…”