Advances in the prevention of mother-to-child transmission of HIV and resulting clinical and programmatic implications

Figures & data

Figure 1 Visual representation of the relationship between the efficacy and coverage of PMTCT services.

Notes: This figure is not based on any mathematical modeling. The arrows in the figure demonstrate two dimensions through which PMTCT can be achieved. The vertical arrow signifies transitioning of the PMTCT programs from less effective to more effective PMTCT drug regimens (from sd NVP to Option A, Option B, or Option B+). The horizontal arrow indicates program coverage which can be measured by calculating the number of women completing the cascade of PMTCT services. HIV transmission rate of 2% for effective ARV/ART and 8.4% for less effective ARV (sd NVP as per HIVNET-012 trial) were assumed for making the comparison.
Abbreviations: MTCT, mother-to-child transmission of HIV; PMTCT, prevention of mother-to-child transmission; NVP, nevirapine; ARV, antiretroviral medicine; ART, antiretroviral therapy; sd, single dose.

Table 1 Comparison of current PMTCT guidelines

		WHO Low and middle income countries 2013	DHHS 2012	BHIVA 2013	WHO European region 2012
A	Recommendations for HIV testing
	Recommendations for HIV testing during pregnancy, intrapartum and postpartum	Generalized epidemic: provider initiated testing and counseling as a routine component of the package of care in all antenatal, childbirth, postpartum and pediatric care settings. Re-testing recommended in the third trimester, or during labor or shortly after delivery Low-level and concentrated epidemics: provider-initiated testing and counseling for pregnant women	Include HIV test in routine panel of prenatal screening tests, after notification to the woman (opt out screening) Repeat testing in areas with high HIV prevalence	Offer HIV test along with other antenatal screening tests, repeat test in women with continuing risk of infection	Provider initiated offer and recommendation in antenatal setting
B	Recommendations for ARV interventions in different scenarios
B.1	HIV infected women on ART who become pregnant	Continue current combination ARV regimen If on d4T switch to TDF based regimen	Continue current combination ARV regimen	Continue current combination ARV regimen	Continue current combination ARV regimen
B.2	ARV naïve pregnant women diagnosed with HIV
	Eligibility criteria to start ART Drug resistance studies before initiating ART	CD4 <500/cmm or WHO Stage 3 or 4 (option B) OR All pregnant and lactating women (option B+) Not recommended	All HIV-infected individuals (the strength of recommendation varies by pretreatment CD4 cell count: CD4 count <350/cmm (AI); CD4 count 350–500/cmm (AII); CD4 count >500/cmm (BIII) Recommended	CD4 <350/cmm; AIDS defining illness (consider lifelong ART at CD4=350–500/cmm during pregnancy) Recommended	CD4 ≤350/cmm Recommended If drug sensitivity testing not available and prior exposure to NVP, boosted PI-based therapy is preferred
B.2.1	Pregnant women eligible for ART
	When to initiate ART? What to start?	Start immediately As per guidelines for adults Cautious use of NVP in women with CD4 >250/cmm	Delayed initiation until after first trimester can be considered in women with high CD4 count and low VL As per guidelines for adults NRTI: AZT + 3TC (preferred), TDF (may be considered as alternative) PI: LPV/r, or ATV/r (preferred) NNRTI: avoid initiation of EFV in first trimester, its use after first trimester may be considered, NVP is preferred if CD4 <250/cmm but not to be initiated if CD4 >250/cmm	Start immediately As per guidelines for adults EFV in the first trimester of pregnancy not contraindicated, cautious use of NVP in women with CD4 >250/cmm	Defer to after first trimester unless high risk of OI Preferred option: fixed dose combination of ZDV plus 3TC with NVP (CD4 <250/cmm) or boosted PI (CD4 >250/cmm)
B.2.2	Pregnant women not eligible for ART
	When to start ARV prophylaxis? What to start When to stop?	cARV from 14 weeks Preferred regimen: TDF + 3TC/FTC + EFV Continue oral ART during labor If option B, 1 week after cessation of BF If option B^+, to be continued lifelong	cARV from 12 weeks Dual NRTI (at least one or more of AZT, TDF, 3TC/FTC, ABC) plus ATV/r or LPV/r (preferred) IV AZT to be added during labor if VL >400 copies/mL After delivery (after assessing the need to continue ART postpartum)^b	cARV initiated by 24 weeks Dual NRTI (TDF + FTC/ABC + 3TC/3TC + AZT) plus boosted PI^a Intrapartum IV AZT if VL > 10,000 copies/mL or untreated women with unknown VL After delivery	cARV initiated between 14–24 weeks Dual NRTI (AZT + 3TC) + ritonavir boosted PI or triple nucleoside Continue oral ART during labor 1 week after cessation of BF^b Or after delivery
C	Recommendations for mode of delivery
		ECS recommended only for obstetric and other medical indications	ECS at 38 weeks if HIV RNA levels > 1,000 copies/mL or unknown HIV levels near or at the time of delivery, irrespective of ARV	ECS at 38–39 weeks if VL ≥400 HIV RNA copies/mL at 36 weeks	Vaginal delivery if HIV-VL <50 copies/mL at week 36
D	Recommendations for ARV interventions for baby
		BF: 6 weeks daily NVP replacement feeding: 4–6 weeks NVP or twice-daily AZT	6 weeks AZT	4 weeks AZT/cARV as per mother’s VL	AZT + 3TC for 4 weeks plus NVP for 2 weeks
E	Recommendations for infant feeding methods
		BF with ARV interventions (EBF for 6 months and continue BF for first 12 months of life), or avoid all BF (counseling option to be decided at national/subnational level	Avoid BF	Avoid BF	If AFASS: formula milk is the preferred option If not AFASS: maternal ART should be continued until completion of weaning by 12 months infant age
F	Recommendations for early infant diagnosis
		Virological test: first test at or around birth or at the first postnatal visit (usually 4–6 weeks) Breastfed infant: repeat HIV antibody test at 9 months, 18 months and/or 6 weeks after cessation of BF Note: confirm a positive antibody test at 9 months by virological test	Virological test: within the first 14–21 days, at 1–2 months and 4–6 months of age	Virological test: within 48 hours of life, at 6 and 12 weeks of age Breastfed infant: infant viral diagnostic tests monthly then twice between 2 and 8 weeks after weaning Definitive diagnosis by HIV antibody test at 18–24 months	Virological test: within 48 hours of life, at 6 and 12 weeks of age Definitive diagnosis by HIV Antibody test at 15–18 months

Notes:

a The prolonged half-life of NNRTIs makes them less suitable as part of a short course of treatment for PMTCT only. Therefore, boosted Pls are preferred

b on NNRTI based regimen, continue NRTI tail for 7 days after stopping NNRTI.

Abbreviations: AFASS, affordable, feasible, accessible, sustainable and safe; EBF, exclusive breast feeding; ABC, abacavir; ZDV, zudovudine; OI, opportunistic infections; ATV/r, atazanavir/ritonavir; d4t, stavudine; PMTCT, prevention of mother-to-child transmission; WHO, World Health Organization; DHHS, US Department of Health and Human Services; BHIVA, British HIV Association; ARV, antiretroviral medicine; cARV, combination ARV; TDF, tenofovir; ART, antiretroviral therapy; NPTI, nucleotide analog reverse transcriptase inhibitor; NNRTI, non-nucleotide analog reverse transcriptase inhibitor; LPV/r, lopinavir/ritonavir; EFV, efavirenz; NVP, nevirapine; PI, protease inhibitor; AZT, azidothymidine; 3TC, lamivudine; FTC, emtricitabine; IV, intravenous; VL, viral load; BF, breastfeeding; ECS, elective cesarian section.

Figure 2 Possible effect of combination antiretroviral therapy (cART) on barriers to accessing continuing care due to increased number of visits to the counselor and improved monitoring.

Abbreviation: PMTCT, prevention of mother-to-child transmission.