Cover Image
close this bookPost-Durban Update on ARVs for MTCT-prevention (UNAIDS, 2000, 8 p.)
View the document(introduction...)
View the documentShort term efficacy (6 weeks to 3 months)
View the documentLong-term efficacy (12 to 24 months)
View the documentARV and transmission through breast feeding
View the documentDrug resistance with Nevirapine
View the documentConclusion
View the documentReferences

Short term efficacy (6 weeks to 3 months)

A number of different antiretroviral (ARV) regimens have been shown to reduce the transmission of HIV from mother to child (Tables 1 and 2):

· Long course ACTG076/ANRS024 ZDV regimen starting from early pregnancy1

· Short course ARV regimens (ZDV, other ARV, combination of different ARVs), starting generally one month before delivery2-7

· Regimens starting in labour (combination ZDV+3TC or NVP regimens).8,9

Each regimen has advantages and disadvantages with respect to efficacy, potential toxicity, concerns for future treatment options, practicality and feasibility for implementation.


Table 1: Clinical Trials of Antiretroviral Regimens to Reduce Mother-to-Child Transmission Compared with Placebo

Notes

a ZDV: Zidovudine, 3TC: Lamivudine

b Original dosing regimen. Current practice is 300 mg Q12h for mother.

c Maternal antenatal and postpartum doses: ZDV 300 mg, 3TC 150 mg;

Intrapartum dose: Arm A: ZDV 300 mg, 3TC 150 mg; Arms B and C: ZDV first dose 600 mg subsequent doses 300 mg, 3TC 150 mg

Infant dose: ZDV 4 mg/kg, 3TC 2 mg/kg

References (numbers according to final reference list)

1 Connor, NEJM, 1994; 331: 1173
2 Shaffer, Lancet 1999; 353: 773-80
4 Dabis, Lancet 1999; 353: 786-92
3 Wiktor, Lancet 1999; 353: 781-5.
5 Gray, Durban LbOr5


Table 2: Equivalence Trials of Short Course Antiretroviral Regimens to Reduce Mother-to-Child Transmission

Notes

a ZDV: Zidovudine, 3TC: Lamivudine, NVP: Nevirapine, ddI: Didanosine, d4T: Stavudine

b Short-Short arm (35w mother, 3d infant) dropped at first interim analysis since transmission rate significantly worse than Long-Long arm (28w mother, 6w infant).

c Intrapartum dose: ZDV first dose 600 mg subsequent doses 300 mg, 3TC 150 mg.
Maternal postpartum dose: ZDV 300 mg, 3TC 150 mg.
Infant dose: ZDV 4 mg/kg, 3TC 2 mg/kg.

References (numbers according to final reference list)

6 Lallemant Durban LbOr3
7 Gray, Durban TuOrB355
9 Guay, Lancet 1999; 354: 795-802
8 Moodley, SAINT, Durban LbOr2

The early studies compared the efficacy of the ARV regimens against placebo (Table 1) and showed that short course regimens can reduce early transmission rates by 35% to 70% (that is, from about 25% to between 8% and 17%). The efficacy in breastfeeding populations3,4 is lower than in populations where breastfeeding can be avoided.2 The similarity of the results from the two West African studies which both started ZDV from 36 weeks suggests that the addition of the 1 week post-partum dose for the mother in DITRAME did not confer any additional benefit. In the PETRA study10 which compared combination ZDV + 3TC in three different regimens against placebo, Arm A (starting from 36 weeks) was more effective than Arm B (starting in labour), though not significantly so. Arm C (intrapartum only) showed no reduction in transmission rate compared with placebo.

More recent studies did not use a placebo control group, but studied the equivalence of different ARV regimens, most often including a short ZDV regimen (Table 2).

· The short-short arm of the PHPT study (from 35 weeks to 3 days postnatal) was significantly less effective than the long-long regimen(from 28 weeks to 6 weeks postnatal), and was dropped at the first interim analysis. At that time the transmission rates were 10.6% and 4.1%, respectively. The other three arms (long-short, short-long, long-long) showed comparable transmission rates (between 6% and 8%), except that the intrauterine transmission rate for the regimens starting at week 28 was 1.8%, significantly lower than the 5.0% observed with the short-long regimen starting from week 35. The authors concluded that while 6 weeks ZDV in infants may not add benefit when mothers had received the long antenatal treatment, it may prevent some infections when mothers receive only the shorter treatment.6

· The BMS A455-094 study presented preliminary results based on the first 204 women randomised. The preliminary results do not suggest any clear differences between the four regimens studied. The final study is anticipated to include a total of 360 women.7

· The HIVNET012 study showed that NVP was significantly more effective than an intrapartum-only ZDV regimen. This particular ZDV regimen has not been included in other studies. The study originally included a placebo arm that was dropped after results from the CDC Thailand study2 became available. The transmission rate was 37% in women assigned placebo, compared with 20% among those concurrently assigned to the ZDV arm, based on 19 and 15 women respectively (P = 0.45), suggesting that the ZDV regimen may have had some benefit.9

· The SAINT study, involving two regimens starting in labour, showed that the PETRA Arm B regimen (from onset of labour to 1 week postpartum and postnatal) was equivalent to a NVP regimen slightly different from that used in HIVNET012.8

An observational study from the USA in women receiving combination ARV treatments reported very low transmission rates - 1.1% among those receiving HAART and 3.9% among those receiving combination therapy which did not include a protease inhibitor.11