Safety and efficacy of Option B+ ART in Malawi: few severe maternal toxicity events or infant HIV infections among pregnant women initiating tenofovir/lamivudine/efavirenz

Abstract

Objectives Malawi's Option B+ universal antiretroviral therapy (ART) program for pregnant and breastfeeding women does not include routine laboratory monitoring. We report safety outcomes of pregnant women who initiated ART through Option B+. Methods We analysed 12‐month data from an observational cohort study on Option B+ among women newly initiating tenofovir/lamivudine/efavirenz (TDF/3TC/EFV) at a government antenatal clinic in Lilongwe, Malawi. Proportions of women engaged in care, incidence of DAIDS grade ≥ 2 laboratory toxicity, grade ≥ 3 adverse events (AEs), viral suppression (<1000 copies/mL), birth outcomes and infant HIV infections are reported. Results At ART initiation, participants (n = 299) had a median age of 26 years (IQR 22–30), median CD4 count of 352 cells/μl (IQR 231–520) and 94% were in WHO Stage 1. We noted 76 incident DAIDS Grade ≥ 2 laboratory results among 58 women, most commonly elevated liver function tests (n = 30 events) and low haemoglobin (n = 27). No women had elevated creatinine. Clinical AEs (n = 45) were predominantly infectious diseases and Grade 3. Five participants (2%) discontinued TDF/3TC/EFV due to virologic failure (3) or toxicity (2). Twelve months after ART initiation, most women were engaged in care (89%) and had HIV RNA < 1000 copies/ml (90%). 8% of pregnancies resulted in preterm birth, 9% were low birthweight (<2500 g), and 2% resulted in infant HIV infection at 6 weeks post‐delivery. Conclusion Most women remained on ART and were virally suppressed 12 months after starting Option B+. Few infants contracted HIV perinatally. While some women experienced adverse laboratory events, clinical symptom monitoring is likely reasonable.

Short‐term toxicity assessment of combined use of zidovudine, lamivudine and lopinavir/ritonavir in vitro and in vivo

“…After treatment with AZT + 3TC + LPV/r, HGB and RBC counts significantly decreased in rats, which may be related to the inhibition of erythrocytes by damaging the chromosomes. Patients can also develop anaemia after treatment with AZT, 3TC or LPV/r 26,31 . The increased apoptosis associated with DNA strand breaks further confirmed the genotoxicity of AZT + 3TC + LPV/r, which also decreased the lymphocyte percentage in rats.…”

“…However, some studies have reported that PMTCT drugs may adversely affect the body. Some patients who received AZT, 3TC and LPV/r alone or in combination experienced side effects such as headache, fatigue, nausea and vomiting, bone marrow suppression, leukopenia and anaemia 12,13,26 . Although for the most commonly used triple drug for AIDS PMTCT, systemic safety evaluation information for AZT + 3TC + LPV/r is scarce.…”

“…received AZT, 3TC and LPV/r alone or in combination experienced side effects such as headache, fatigue, nausea and vomiting, bone marrow suppression, leukopenia and anaemia. 12,13,26 Although for the most commonly used triple drug for AIDS PMTCT, systemic safety evaluation information for AZT + 3TC + LPV/r is scarce. In this study, the LD 50 of AZT + 3TC + LPV/r was greater than 2000 mg/kg BW in mice, indicating that AZT + 3TC + LPV/r is a non-toxic drug.…”

The impact of Option B+ on mother‐to‐child transmission of HIV in Africa: A systematic review

“…Data collected for this review were summarised in Table 2, which identified 22 studies from 11 African Countries that met inclusion criteria (Cameroon, Ethiopia, Lesotho, Malawi, Rwanda, South Africa, Swaziland, Tanzania, Uganda, Zambia and Zimbabwe). Study designs varied as follows: there were 13 retrospective cohort studies [23][24][25][26][27][28][29][30][31][32][33][34][35][36] ; five prospective cohort studies [37][38][39][40]45 ; two cross-sectional studies 41,42 and one randomised control trial (RCT). 43 Sample sizes ranged from 124 13,15 to 2505 women.…”

“…A total of 16 studies reported MCTC rates of >2% to 5% with Option B+ implementation. Studies were from Cameroon, 24 Ethiopia at 2 years, 25,27 Lesotho at 2 years, 44 Malawi, 28,29,30,41,42 Rwanda at 2 years, 31 Swaziland, 37 Tanzania, 42 Zambia 33,34,40 and Zimbabwe. 36 A study from Uganda 32 and a study from Zambia 34 reported MTCT rates of above 5%, surpassing the WHO target for elimination of HIV transmissions from mother to child.…”