Background: Combined ARV has been shown to improve zidovudine (ZDV) monotherapy to reduce perinatal transmission rate of HIV-1 infection. Few data concerning adverse events during pregnancy are available. Objectives were to evaluate toxicity related to ARV in a cohort of HIV infected pregnant women, and to describe the prevalence of birth defects in this cohort.

Methods:  We conducted a retrospective analysis of patients followed at our HIV clinic. The charts of 349 pregnant women were reviewed. Data related with adverse effects and congenital abnormalities were collected. WHO Toxicity Tables were used to evaluate adverse events severity. Two groups were defined:   monotherapy (complete or incomplete ACTG 076 protocol), and combined therapy (2 NRTI alone or combined with NNRTI or PI).

Results:  Mean age was 26.8 years. Mean viral load and CD4⁺ cell count at baseline were 3.61 log (1.6 to 5.7) and 415 cells/cc (27 to 1485), respectively; 271 patients received any ARV,138 monotherapy with ZDV, and 133 combined therapy (54 :2 NRTI,  41: 2 NRTI + 1 NNRTI, and 38: 2 NRTI + 1 PI).  No cases of HIV transmission were detected in the combined therapy group. 187 episodes of adverse events were found in 88 women who received at least one ARV agent: 140 grade I (74.86%), 38 grade II (20.32%), and 9 grade III-IV (4.8%). Distribution of adverse events by group of treatment was:  ZDV alone = 10.16% (19/187), 2NRTI = 35.3% (66/187), 2NRTI + NNRTI = 24.6% (46/187) and 2 NRTI + PI = 29.9% (56/187). More prevalent  adverse events were anemia:  38.5% (72/187), hypercholesterolemia: 17.64% (33/187), hypertrigliceridaemia 10.7% (20/187), increase of ALP: 10.7% (20/187), or ALT/AST: 6.95% (13/187) levels and gastrointestinal upset: 5.34% (10/187). Less frequent toxicity include: thrombocytopenia, neutropenia, rash, hyperglycemia and high levels of amylase and CK. Eight cases of congenital abnormalities were detected (8/349 = 2.3%),6 in the monotherapy group:  renal agenesis (1), imperforate anus (2), gastroschisis (1),harelip (2), myelomeningocele (1) and miocardiopathy (1).

Conclusions: In this cohort combined therapy has improved efficacy of ZDV monotherapy to reduce HIV-1 vertical transmission. No increase in toxicity was observed attributable to ARV, in this retrospective analysis. Prevalence of congenital abnormalities at birth was not different to that expected in the general population. Further follow-up of this pediatric cohort is required to define long term toxicities.

Keywords: antiretroviral; toxicity; pregnancy