Reconsidering first-line antiretroviral therapy in the pregnant population
Too many children are still being newly infected with HIV. The Global Plan is to eliminate new HIV infections among children by 2015 and keep their mothers alive. The rate of MTCT of HIV-1 has fallen to less than 2% in countries with the implementation of recommendations. The best documented factor that correlates to higher rates of transmission is the maternal level of plasma viremia. Therefore it is important to maximally inhibit HIV replication in order to prevent HIV-associated morbidity and mortality and to prevent MTCT. Durable viral suppression prolongs life by improving immune function and overall quality of life, lowering the risk of both AIDs-defining and non-AIDS-defining complications. Clinical data are more limited on antiretroviral drugs in pregnant women than in non-pregnant individuals due to concerns for maternal and fetal safety, ethical considerations, the difficulty in designing appropriate trials to assess the study objectives, and funding limitations. However there are sufficient data to base recommendations for drug choice for many of the available antiretroviral drugs. Preferred drugs must show durable viral suppression, increased CD4 cell count, and a favorable safety profile. In addition to the aforementioned characteristics of a preferred drug, preferred antiretroviral drugs for pregnant individuals must pay special attention to maternal toxicity, potential teratogenicity, and fetal safety, efficacy of reducing perinatal transmission, and pharmacokinetics data during the perinatal transmission of HIV. Currently the optimal initial antiretroviral regimens to treat antiretroviral-naïve patients in high resource regions consist of two nucleoside/tide reverse transcription inhibitors in combination with either a nonnucleoside reverse transcriptase inhibitor or a protease inhibitor boosted with RTV. Continually re-evaluation is recommended to challenge current paradigms. Treatment advances may lead to safer and even superior alternatives to current first-line therapy. The WHO current first-line therapy in less developed or developing regions includes the nonnucleoside reverse transcriptase inhibitor, EFV and considerations of poorer overall efficacy compared to newer drugs, toxicity, resistance, and adverse effects suggest that EFV should be reconsidered for use in first-line therapy. Although preferred protease inhibitors are as effective as EFV with fewer adverse effects, serious issues arise when patients are on concomitant medications with drug interactions. Currently raltegravir is the only integrase strand transfer inhibitor drug (INSTI) with data during pregnancy. Raltegravir is an attractive alternative or additional drug for pregnant women requiring medications with resistance, incomplete virologic response, or significant interactions with current first-line regimen drugs. Furthermore, based on recent data, raltegravir could provide pre-exposure prophylaxis in the fetus. DTG is a newer generation INSTI with clinical trials data showing safety and efficacy in nonpregnant adults. These studies suggest great promise for DTG and justify its role as first-line therapy for the nonpregnant population with relatively few drug interactions; in addition, it offers the only single tablet regimen for patient with or at risk for renal dysfunction. Although more data must be collected to ensure the safety and efficacy of INSTI as a first-line therapy in pregnant women, current studies show promise and with increasing experience INSTI agents may become part of the recommended first-line regimen for pregnant women.