AZT Protocols With Breast Feeding : Nevirapine Protocol HIV NET 012

4th Pediatric Infectious Diseases Conference

ISSN 0973 - 0958

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Results

PREVENTION OF PARENT TO CHILD TRANSMISSION OF HIV INFECTION

HIV Infection Prevention From Parent to Child Transmission

Interventions To Decrease PTCT Transmission

Related topics

Magnitude of Problem and Factors Affecting Vertical Transmission Efficacy

Timing of Vertical Transmission and Phases of PTCT Prevention

Dr. Nitin Shah
Hon. Pediatrician- UHC, LTMG Hospital, Mumbai.
Treasurer, Indian Academy of Pediatrics, 1998-2001

Dr. M.R.Lokeshwar
Hon. Pediatrician, U.H.C., LTMG Hospital, Mumbai
and P.D. Hinduja National Hospital, Mumbai
Consultant Pediatric Hematologist-Oncologist, Lilavati Hospital, Mumbai.

Continued...

AZT protocols with breast feeding allowed
Both the 076 and Thai protocols discussed above did not allow breast feeding by mothers. It is obvious that the efficacy of AZT will drop if breast feeding is allowed. There are two protocols that have looked at this problem.
- Cote d'ivoire Abedjan study
  This study was done in 1999 at Abedjan. It compared AZT Vs placebo given as per Thai protocol and allowed breast feeding by mothers. The results showed that at 6 weeks the HIV infection was seen in 21.7% of placebo group and 12.2% of AZT group giving 44% efficacy but at 3 months it was 24.9% in placebo group and 15.7% in AZT group giving it 37% efficacy which is much less as compared to 50% efficacy with Thai protocol.
- Cote d'ivoire and Buskia Faso study (DITRAME study)
  This study was done in 1999. Again AZT was given as per Thai protocol except that 600 mg of AZT was given as first dose during labor and AZT was continued in dose of 300 mg BD orally for 1 week postpartally in mothers. Again they allowed breast feeding to be continued like the above protocol. The results showed that the transmission rate at 6 months was 18% in AZT group and 27.5% in placebo group. This gives efficacy of 38%.
Nevirapine protocol (HIV NET 012)
Nevirapine as monotherapy was used in this protocol in Uganda in 1999. Nevirapine was compared against short course of AZT (as trying placebo will be unethical). Nevirapine was given as single dose of 200 mg orally at the onset of labor to be taken at home with onset of first labor pain. The baby was given single dose of nevirapine in the dose of 2 mg/kg orally at 48-72 hours of birth while in hospital. This was compared with another group given AZT in the dose of 600 mg at onset of labor followed by 300 mg 3 hourly till delivery and then to the baby in the dose of 4 mg/kg/dose BD for 7 days. Elective LSCS was not mandatory and breast feeding was allowed. The initial results are very encouraging. At 6-8 weeks the HIV transmission rate was 21.3% in AZT group and 11.9% in nevirapine group and at 14-16 weeks it was 25.1% in AZT group and 13.1 in nevirapine group. This gives efficacy of around 50% which is same as Thai protocol. However, at 12 months the transmission in nevirapine group was 16% and in AZT group 24% showing only 35% efficacy. There are many advantages of this protocol. Firstly, it involves only a single dose to mother at onset of labor and a single dose to baby while in hospital. This makes the protocol very cost effective, acceptable with good compliance. It also can be administered to mothers who register at last moment or even to unregistered cases. In fact some think that in areas with HIV prevalence as high as 15-25%, like in some African countries, this protocol should be offered to all those come for delivery and who are not tested so that it will benefit many. However, it may be unethical to do so. Elective LSCS is not mandatory and breast feeding is allowed in this protocol. This makes it acceptable by many in developing countries. Only thing is that one needs to await further results on long term follow-up. Secondly, the success of this protocol needs to be duplicated at some other centers to prove the efficacy and safety.

In India during phase II feasibility trial this protocol will be tried soon in a multicentric study. It is exciting to await the results of this protocol whenever it will be over.
Long term safety of AZT
Short term follow up during 076 protocol has shown less than 4% chances of toxicities like anemia, neutropenia or skin rash in mother as well as babies given AZT. These side effects are transient and disappear by 4-6 weeks like anemia.

PACTG 219 is a long term follow up study of the babies enrolled in 076 protocol originally and are planned to be followed up till 21 years of age. The interim results show that at median follow up of 4.6 years the growth parameters, cognitive function, ophthalmic evaluation, immunological function and ECG are similar in AZT group as in placebo group. This proves long term safety of AZT.
Protocols containing combination drugs
In west, protocols containing 2 or more drugs are used and that has reduced the vertical transmission rate to < 5%.
- PETRA Study: This study was conducted in 1999 in 5 sites in Uganda, Tanzania and South Africa. HIV positive women were randomized to four treatment arms.
  
  Arm A: Mother was given AZT and 3TC 12 hourly from 36 weeks of gestation till onset of labor. During labor AZT was given 3 hourly and 3TC 12 hourly. AZT & 3TC were continued at 12 hourly interval for 1 week post partally. AZT and 3TC are given also to baby at 12 hourly interval for 1 week. The HIV transmission rate was 8.6% at 6 weeks giving efficacy of 54% and was 21% at 18 months giving efficacy of only 21%
  
  Arm B: Mother was given AZT + 3TC only during labor as above and post partally for 1 week and to the baby for 1 week as above. The transmission rate was 10.8% at 6 weeks (efficacy 39%) and 25% at 18 weeks (efficacy 7%).
  
  Arm C: Mother was given AZT + 3TC only during labor and post partally for 1 week as above but baby was not given any drug. The transmission rate was 17.7% at 6 weeks (efficacy of 4%) and 28% at 18 weeks (efficacy of -4%).
  
  Arm D: It was the control arm given only placebo. The transmission was 17.2% at 6 weeks and 27% at 18 months.
- SAINT trial : This trial was done in 2000 in South Africa. HIV positive mothers were assigned to one of the two treatment arms. In Arm A, mothers were given nevirapine in dose of 200 mg orally at onset of labor and at 24-48 hrs after delivery and the baby was given 2 mg/kg orally at 24-48 hrs after delivery. In Arm B multiple doses of AZT + 3TC were given during labor and for 1 week and also to baby for 1 week (like in PETRA Arm B).
  
  The results at 6-12 weeks showed transmission rate of 12.7% in Arm A (similar to Uganda Protocol HIV NET O12) and 9.5% in Arm B (similar to PETRA Arm B).