Antiretroviral therapy, pregnancy, and birth defects: a discussion on the updated data

Figures & data

Table 1 Antiretroviral treatment options recommended for HIV-infected pregnant women who are eligible for treatment

Maternal ART + infant ARV prophylaxis
Mother
Meternal antepartum daily ART, starting as soon as possible irrespective of gestational age, and continued during pregnancy, delivery and thereafter. Recommended regimens include:
AZT + 3TC + NVP or
AZT + 3TC + EFV* or
TDF + 3TC (or FTC) + NVP or
TDF + 3TC (or FTC) + EFV*
Infant
Daily NVP or twice-daily AZT from birth until 4 to 6 weeks of age (irrespective of the mode of infant feeding).

Note: *Avoid use of EFV in the first trimester and use NVP instead. For all exposed infants, regardless of infant feeding, reprinted with permission World Health Organization (Antiretroviral drugs for treating pregnant women and preventing HIV infection in infants, 2010 version. Available from: http://whqlibdoc.who.int/publications/2010/9789241599818_eng.pdf. March 20, 2013).⁷

Abbreviations: ART, antiretroviral therapy; ARV, antiretroviral; AZT, zidovudine; NVP, nevirapine; TDF, tenofovir; EFV, efavirenz; 3TC, lamivudine; FTC, emtricitabine; XTC, 3TC lamivudine.

Table 2 ARV-prophylaxis options recommended for HIV-infected pregnant women who do not need treatment for their own health

Maternal AZT + infant ARV prophylaxis (Option A)	Maternal triple ARV prophylaxis (Option B)
Mother	Mother
Antepartum twice-daily AZT starting from as early as 14 weeks of gestation and continued during pregnancy. At onset of labour, sd-NVP and initiation of twice daily AZT + 3TC for 7 days postpartum.	Triple ARV prophylaxis starting from as early as 14 weeks of gestation and continued until delivery, or, if breastfeeding, continued until 1 week after all infant exposure to breast milk has ended. Reecommended regimens include:
(Note: If maternal AZT was provided for more than 4 weeks antenatally, omission of the sd-NVP and AZT + 3TC tail can be considered; in this case, continue maternal AZT during labour and stop at delivery).	AZT + 3TC + LPV/r or
	AZT + 3TC + ABC or
	AZT + 3TC + EFV or
	TDF + 3TC (or FTC) + EFV
Infant	Infant
For breastfeeding infants Daily NVP from birth for a minimum of 4 to 6 weeks, and until 1 week after all exposure to breast milk has ended.	Irrespective of mode of infant feeding Daily NVP or twice-daily AZT from birth until 4 to 6 weeks of age.
Infants receiving replacement feeding only Daily NVP or sd-NVP + twice-daily AZT from birth until 4 to 6 weeks of age.

Notes: Single-dose NVP and AZT + 3TC can be omitted if mother receives >4 weeks’ AZT antepartum. Begin as early as 14 weeks’ gestation (second trimester) or as soon as possible thereafter. Reprinted with permission World Health Organization (Antiretroviral drugs for treating pregnant women and preventing HIV infection in infants, 2010 version. Available from: http://whqlibdoc.who.int/publications/2010/9789241599818_eng.pdf. Accessed March 20, 2013).⁷

Abbreviations: ARV, antiretroviral; AZT, zidovudine; ART, antiretroviral therapy; NVP, nevirapine; LPV, lopinavir; ABC, abacavir; EFV, efavirenz; 3TC, lamivudine; FTC, emtricitabine; SD, single dose; TDF, tenofovir.

Table 3 Results of major studies associated with birth defects on zidovudine monotherapy and zidovudine-containing regimen exposure in utero

Study	Antiretroviral therapy	Number enrolled	Number exposed	(%)*	Rates compared to controls
Sperling et al^Citation4	ZDV	437	437	0.7	Lower than APR and US pediatric population
Mandelbrot et al^Citation21	ZDV ZDV + 3TC	1344	1344	3	Similar to newborns in Paris (2.7%)
Patel et al^Citation22	ZDV ZDV + 3TC + HAART	3740	1973	1.6	Similar compared to controls not exposed (1.4%)
Watts et al^Citation23	ZDV ZDV + NRTI ZDV + NRTI + NNRTI	2527	2527	3.5	Similar to US pediatric population (2.7%)
Townsend et al^Citation24	ZDV ZDV + 3TC ZDV + NRTI + NNRTI	8242	8242	2.8	Similar to Europe newborns (2.2%)
Gibb et al^Citation30	ZDV ZDV + NRTI	1867	226	3	Similar to international data (1.4%–3.9%)
Nielsen-Saines et al^Citation29	ZDV ZDV + NRTI + NNRTI	236	236	7.6	High compared to international data
Newschaffer et al^Citation10	ZDV	1932	1917	10.5	2.79 times higher than New York newborns
Joao et al^Citation25	ZDV	974	954	6.0	High compared to newborns of Rio de Janeiro, Brazil (2.2%)
Brogly et al^Citation26 Watts et al^Citation27	ZDV ZDV ZDV + NRTI ZDV + NRTI + PI	2202 1414	33 1113	5.5 3.5	High compared to APR (2.9%) High compared to CDC (2.2%)
Knapp et al^Citation28	ZDV	1112	944	5.5	High compared to APR (2.9%)

Note:

* Prevalence per 100 live births.

Abbreviations: ZDV, zidovudine; NRTI, nucleoside analog reverse-transcriptase inhibitor; NNRTI, non- nucleoside analog reverse-transcriptase inhibitor; 3TC, lamivudine; PI, protease inhibitor; HAART: highly active antiretroviral therapy, APR, antiretroviral pregnancy register; US, United States; CDC, Centers of Disease Control and Prevention.

Table 4 Results of major studies associated with birth defects on efavirenz-containing regimen exposure in utero

Study	Number enrolled	Number antenatal exposure	(%)*	Rates compared to controls or international data
Bera et al^Citation37	623	623	2.6	Similar to international data (1.4%–3.9%)
Townsend et al^Citation24	8242	205	2.4	Similar to Europe newborns (2.2%)
Ford et al^Citation32	8295	1132	3.0	Similar to APR (2.9%)
Antiretroviral Pregnancy Register^Citation11	679	679	2.7	Similar to US newborns (2.0%)
Ekouevi et al^Citation36	344	213	0	Lower than APR
Brogly et al^Citation26	105	5	15.6	Higher than APR and CDC data
Knapp et al^Citation38	1112	56	10.7	Higher than APR and CDC data

Note:

* Prevalence per 100 live births.

Abbreviations: APR, Antiretroviral Pregnancy Register; CDC, Centers for Disease Control and Prevention.

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