Table 3.
Studies of latent TB infection treatment in pregnancy.
| Study | Treatment Regimen | Study Site | Population | Study Design | Findings |
|---|---|---|---|---|---|
| Franks et al., Public Health Reports 1989 [67] | 6H | USA | 3681 women during and after pregnancy | Retrospective cohort | A total of 5 pregnant women developed hepatitis; 2 of the 5 died. |
| Moulding et al., Am Rev Resp Disease 1989 [68] | 6H | USA | 24 people who died while taking isoniazid | Retrospective cohort | A total of 20 isoniazid associated deaths, 4 initiated isoniazid in pregnancy. |
| Martinson et al., NEJM 2011 [69] | 3HP vs. 3HR vs. 6H | South Africa | 235 WHIV who became pregnant during treatment or follow-up | Sub-analysis of RCT | Pregnant women on 3HP and 3HR were discontinued off treatment. A total of 26 became pregnant on isoniazid; 10 chose to continue with no toxicity observed. |
| Taylor et al., IDOBGYN 2013 [54] | 6H vs. 36H | Botswana | 103 WHIV who became pregnant during trial (37% on cART, 63% on AZT or AZT/3TC for PMTCT) | Sub-analysis of RCT | No isoniazid-associated hepatitis or other severe isoniazid-associated adverse events were observed. |
| Tiam et al., JAIDS 2014 [70] |
6H | Lesotho | 160 Pregnant WHIV at 1st ANC visit (36% on ART, 65% on AZT for PMTCT) | Prospective cohort | IPT was initiated in 124/158 (78.5%) pregnant WHIV; 64.5% women completed a 6-month IPT regimen; 2 (1.6%) died of causes unrelated to IPT/TB; and 31.5% were lost to follow-up. |
| Moro et al., Ann Am Thorac Soc 2018 [58] |
3HP vs. 9H | USA, Canada, Brazil, Spain, Peru, South Africa, Hong Kong | 126 women who became pregnant during trial | Sub-analysis of 2 RCTs | Of the total 126 pregnancies, fetal loss was reported in 8/54 (15%) and 9/72 (13%), 3HP and 9H, respectively; and congenital anomalies in 1/37 (3%) and 2/56 (4%) live births, 3HP and 9H, respectively. The overall proportions of fetal loss (17/126 (13%)) and anomalies (3/93 (3%)) were similar to those estimated for the United States, 17% and 3%, respectively. |
| Gupta et al., NEJM 2019 [52] | 6H | Botswana, Haiti, India, South Africa, Tanzania, Thailand, Uganda, Zimbabwe | 956 pregnant WHIV, 14–34 weeks gestation, 99% on cART | RCT | A primary outcome event (treatment-related maternal adverse events of grade 3 or higher or permanent discontinuation of the trial regimen because of toxic effects) occurred in 72 of 477 women (15.1%) in the group that IPT was initiated in during pregnancy and in 73 of 479 (15.2%) in the group that IPT was initiated in postpartum. The risks associated with initiation of IPT during pregnancy appeared to be greater than those associated with initiation of therapy during the postpartum period. |
| LaCourse et al., 2019 [71] | 6H | Kenya | 300 postpartum WHIV, 100% on cART | Retrospective cohort | A total of 224 reported previous IPT; 155 (69%) had any IPT use during pregnancy. Six-month IPT completion rates were high (147/160 (91.9%)) among women with sufficient time to complete before infant trial enrollment and similar among preconception or during pregnancy initiators. |
| Kalk et al., Clin Infect Dis 2020 [53] |
6H-12H | South Africa | 43,971 Pregnant WHIV on or initiating cART | Retrospective cohort | A total of 16.6% received IPT during pregnancy. Women who received IPT were less likely to experience poor pregnancy outcomes (adjusted odds ratio (aOR), 0.83); this association strengthened with IPT started after the first trimester compared with none (aOR, 0.71) or with first-trimester exposure (aOR, 0.64). IPT reduced the risk of TB by approximately 30%. |
| Salazar-Austin et al., Clin Infect Dis 2020 [11] | 6H | South Africa | 151 Pregnant WHIV | Prospective cohort | Of the 69 IPT-exposed women, 11 (16%) had an adverse pregnancy outcome compared with 23 (28%) IPT-unexposed women. The adjusted odds of having an adverse pregnancy outcome were 2.5 times higher in IPT-unexposed women compared with IPT-exposed women after controlling for confounding factors. |
| Mathad et al., Clin Infect Dis 2022 [72] |
3HP | Haiti, Kenya, Malawi, Thailand, Zimbabwe | 50 pregnant w/ and w/o HIV | RCT | Among 30 women without HIV, clearance of rifapentine was 28% lower during pregnancy than postpartum. In 20 pregnant WHIV, clearance was 30% higher than women without HIV (p < 0.001). 3HP does not require dose adjustment in pregnancy. There were no drug-related serious adverse events. |
| Singh et al., JAIDS 2022 [73] | 3HP vs. 3HR vs. 6H | South Africa | 216 women who became pregnant during trial | Sub-analysis of RCT | A total of 216/896 women (24%) conceived during the study. A total of 34 women became pregnant while taking preventive treatment (8 rifamycin, 26 isoniazid monotherapy). The odds of pregnancy were higher in women in the rifamycin-isoniazid arms than the isoniazid arms (3HP: 1.73, p = 0.001; 3HR: 1.55, p = 0.017) despite increased contraceptive use compared to the standard 6H therapy. |
Treatments: 6H–12H = Isoniazid daily for 6–12 months, 3HP = Isoniazid and Rifampin weekly for 3 months, 3HR = Isoniazid and Rifampin daily for 3 months, 36H = Isoniazid daily for 36 months. Abbreviations: WHIV = women with HIV; cART = combined antiretroviral therapy; ANC = antenatal care; IPT = Isoniazid preventative therapy; AZT = Azidothymidine; 3CT = Lamivudine; PMTCT = prevention of mother to child transmission; RCT = randomized controlled trial.