Trial Outcomes & Findings for Anti-HIV Drugs for Treating Infants Who Acquired HIV Infection at Birth (NCT NCT00102960)

Last Updated: 2021-11-02

Results Overview

To compare time to failure of first line ART (due to clinical, virological or immunological disease progression, or regimen-limiting ART toxicities) or death among three randomized arms (infants who receive early ART in Arms 2 and 3 and infants in whom ART is deferred until clinical or immunological disease progression in Arm 1) during the study (up to 4.8 years). The number of participants experiencing the events did not reach the 50% survival and thus median time-to-event is not be presented. Therefore we report the number of participants experiencing the events per Arm.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

377 participants

Primary outcome timeframe

From date of randomization up to failure of first-line therapy or death from any cause, whichever came first, assessed up to 4.8 years

Results posted on

2021-11-02

Participant Flow

The results are presented for only 377 participants that were enrolled into the three arms (ART-Def 125, ART-40W 126 and ART-96W 126).

Participant milestones

Participant milestones
Measure	ART-Deferred For participants with a CD4% of at least 25%, ART deferred until necessary. Once ART therapy was initiated, it was taken continously. Zidovudine: First Line Regimen: Given twice daily at a dose of 240 mg/m\^2 of body surface area. Dose was adjusted by age as the children grew older. Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight. Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m\^2 Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol. Didanosine: Second Line Regimen: Either 100 mg/m\^2 or 120 mg/m\^2 taken orally twice daily. Dosage depends on age. Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight. Nevirapine: Second Line Regimen: 150 - 200 mg/m\^2 taken orally twice daily.	Early ART up to 40 Weeks For participants with a CD4% of at least 25%, receive 40 weeks of ART until first birthday Zidovudine: First Line Regimen: 10 mg/mL taken orally twice per day. Dose was adjusted by age as the children grew older. Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight. Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m\^2 Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol. Didanosine: Second Line Regimen: Either 100 mg/m\^2 or 120 mg/m\^2 taken orally twice daily. Dosage depends on age. Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight. Nevirapine: Second Line Regimen: 150 - 200 mg/m\^2 taken orally twice daily.	Early ART up to 96 Weeks For participants with a CD4% of at least 25%, receive ART for 96 weeks until second birthday Zidovudine: First Line Regimen: 10 mg/mL taken orally twice per day. Dose was adjusted by age as the children grew older. Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight. Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m\^2 Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol. Didanosine: Second Line Regimen: Either 100 mg/m\^2 or 120 mg/m\^2 taken orally twice daily. Dosage depends on age. Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight. Nevirapine: Second Line Regimen: 150 - 200 mg/m\^2 taken orally twice daily.
Overall Study STARTED	125	126	126
Overall Study COMPLETED	95	103	98
Overall Study NOT COMPLETED	30	23	28

Reasons for withdrawal

Reasons for withdrawal
Measure	ART-Deferred For participants with a CD4% of at least 25%, ART deferred until necessary. Once ART therapy was initiated, it was taken continously. Zidovudine: First Line Regimen: Given twice daily at a dose of 240 mg/m\^2 of body surface area. Dose was adjusted by age as the children grew older. Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight. Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m\^2 Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol. Didanosine: Second Line Regimen: Either 100 mg/m\^2 or 120 mg/m\^2 taken orally twice daily. Dosage depends on age. Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight. Nevirapine: Second Line Regimen: 150 - 200 mg/m\^2 taken orally twice daily.	Early ART up to 40 Weeks For participants with a CD4% of at least 25%, receive 40 weeks of ART until first birthday Zidovudine: First Line Regimen: 10 mg/mL taken orally twice per day. Dose was adjusted by age as the children grew older. Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight. Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m\^2 Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol. Didanosine: Second Line Regimen: Either 100 mg/m\^2 or 120 mg/m\^2 taken orally twice daily. Dosage depends on age. Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight. Nevirapine: Second Line Regimen: 150 - 200 mg/m\^2 taken orally twice daily.	Early ART up to 96 Weeks For participants with a CD4% of at least 25%, receive ART for 96 weeks until second birthday Zidovudine: First Line Regimen: 10 mg/mL taken orally twice per day. Dose was adjusted by age as the children grew older. Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight. Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m\^2 Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol. Didanosine: Second Line Regimen: Either 100 mg/m\^2 or 120 mg/m\^2 taken orally twice daily. Dosage depends on age. Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight. Nevirapine: Second Line Regimen: 150 - 200 mg/m\^2 taken orally twice daily.
Overall Study Death	23	11	11
Overall Study Lost to Follow-up	6	12	16
Overall Study Withdrawal by Subject	1	0	1

Baseline Characteristics

Anti-HIV Drugs for Treating Infants Who Acquired HIV Infection at Birth

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Deferred Therapy n=125 Participants For participants with a CD4% of at least 25%, ART deferred until necessary. Once ART therapy was initiated, it was taken continously. Zidovudine: First Line Regimen: Given twice daily at a dose of 240 mg/m\^2 of body surface area. Dose was adjusted by age as the children grew older. Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight. Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m\^2 Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol. Didanosine: Second Line Regimen: Either 100 mg/m\^2 or 120 mg/m\^2 taken orally twice daily. Dosage depends on age. Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight. Nevirapine: Second Line Regimen: 150 - 200 mg/m\^2 taken orally twice daily.	Early Therapy up to 40 Weeks n=126 Participants For participants with a CD4% of at least 25%, receive 40 weeks of ART until first birthday Zidovudine: First Line Regimen: 10 mg/mL taken orally twice per day. Dose was adjusted by age as the children grew older. Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight. Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m\^2 Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol. Didanosine: Second Line Regimen: Either 100 mg/m\^2 or 120 mg/m\^2 taken orally twice daily. Dosage depends on age. Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight. Nevirapine: Second Line Regimen: 150 - 200 mg/m\^2 taken orally twice daily.	Early Therapy up to 96 Weeks n=126 Participants For participants with a CD4% of at least 25%, receive ART for 96 weeks until second birthday Zidovudine: First Line Regimen: 10 mg/mL taken orally twice per day. Dose was adjusted by age as the children grew older. Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight. Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m\^2 Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol. Didanosine: Second Line Regimen: Either 100 mg/m\^2 or 120 mg/m\^2 taken orally twice daily. Dosage depends on age. Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight. Nevirapine: Second Line Regimen: 150 - 200 mg/m\^2 taken orally twice daily.	Total n=377 Participants Total of all reporting groups
Age, Continuous	7.1 Weeks n=93 Participants	7.4 Weeks n=4 Participants	7.5 Weeks n=27 Participants	7.3 Weeks n=483 Participants
Sex: Female, Male Female	70 Participants n=93 Participants	76 Participants n=4 Participants	74 Participants n=27 Participants	220 Participants n=483 Participants
Sex: Female, Male Male	55 Participants n=93 Participants	50 Participants n=4 Participants	52 Participants n=27 Participants	157 Participants n=483 Participants
Region of Enrollment South Africa	125 Participants n=93 Participants	126 Participants n=4 Participants	126 Participants n=27 Participants	377 Participants n=483 Participants

PRIMARY outcome

Timeframe: From date of randomization up to failure of first-line therapy or death from any cause, whichever came first, assessed up to 4.8 years

Population: In the analysis of failure of first-line therapy, children enrolled in the ART-Deferred group were used as the reference category in the hazard ratio analysis.

Outcome measures

Outcome measures
Measure	Deferred Therapy n=125 Participants For participants with a CD4% of at least 25%, ART deferred until necessary. Once ART therapy was initiated, it was taken continuously. Zidovudine: First Line Regimen: Given twice daily at a dose of 240 mg/m\^2 of body surface area. Dose was adjusted by age as the children grew older. Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight. Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m\^2 Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol. Didanosine: Second Line Regimen: Either 100 mg/m\^2 or 120 mg/m\^2 taken orally twice daily. Dosage depends on age. Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight. Nevirapine: Second Line Regimen: 150 - 200 mg/m\^2 taken orally twice daily.	Early Therapy up to 40 Weeks n=126 Participants For participants with a CD4% of at least 25%, receive 40 weeks of ART until first birthday Zidovudine: First Line Regimen: 10 mg/mL taken orally twice per day. Dose was adjusted by age as the children grew older. Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight. Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m\^2 Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol. Didanosine: Second Line Regimen: Either 100 mg/m\^2 or 120 mg/m\^2 taken orally twice daily. Dosage depends on age. Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight. Nevirapine: Second Line Regimen: 150 - 200 mg/m\^2 taken orally twice daily.	Early Therapy up to 96 Weeks n=126 Participants For participants with a CD4% of at least 25%, receive ART for 96 weeks until second birthday Zidovudine: First Line Regimen: 10 mg/mL taken orally twice per day. Dose was adjusted by age as the children grew older. Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight. Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m\^2 Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol. Didanosine: Second Line Regimen: Either 100 mg/m\^2 or 120 mg/m\^2 taken orally twice daily. Dosage depends on age. Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight. Nevirapine: Second Line Regimen: 150 - 200 mg/m\^2 taken orally twice daily.
Time to Failure of First Line Therapy or Death	48 Participants	32 Participants	26 Participants

PRIMARY outcome

Timeframe: This outcome was assessed from the date of randomization to immunological failure. Immunological failure was assessed in the entire study duration of 4.8 years.

This was part of the primary outcome measure above. The primary outcome was a composite endpoint. The primary outcome analysis only considered the initially enrolled children that were 377 in total (ART-Deferred n=125, Early therapy 40 weeks n=126 and Early therapy 96 weeks n=126). This was part of the primary outcome measure that was a composite endpoint.

Outcome measures

Outcome measures
Measure	Deferred Therapy n=125 Participants For participants with a CD4% of at least 25%, ART deferred until necessary. Once ART therapy was initiated, it was taken continuously. Zidovudine: First Line Regimen: Given twice daily at a dose of 240 mg/m\^2 of body surface area. Dose was adjusted by age as the children grew older. Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight. Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m\^2 Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol. Didanosine: Second Line Regimen: Either 100 mg/m\^2 or 120 mg/m\^2 taken orally twice daily. Dosage depends on age. Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight. Nevirapine: Second Line Regimen: 150 - 200 mg/m\^2 taken orally twice daily.	Early Therapy up to 40 Weeks n=126 Participants For participants with a CD4% of at least 25%, receive 40 weeks of ART until first birthday Zidovudine: First Line Regimen: 10 mg/mL taken orally twice per day. Dose was adjusted by age as the children grew older. Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight. Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m\^2 Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol. Didanosine: Second Line Regimen: Either 100 mg/m\^2 or 120 mg/m\^2 taken orally twice daily. Dosage depends on age. Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight. Nevirapine: Second Line Regimen: 150 - 200 mg/m\^2 taken orally twice daily.	Early Therapy up to 96 Weeks n=126 Participants For participants with a CD4% of at least 25%, receive ART for 96 weeks until second birthday Zidovudine: First Line Regimen: 10 mg/mL taken orally twice per day. Dose was adjusted by age as the children grew older. Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight. Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m\^2 Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol. Didanosine: Second Line Regimen: Either 100 mg/m\^2 or 120 mg/m\^2 taken orally twice daily. Dosage depends on age. Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight. Nevirapine: Second Line Regimen: 150 - 200 mg/m\^2 taken orally twice daily.
Number of Participants Who Experienced Immunological Failure Defined as Failure of CD4% to Reach 20% or CD4% Falls Below 20% on Two Occasions, Within 4 Weeks, at Any Time After the First 24 Weeks of Therapy (Initial Therapy or Restart)	9 Participants	14 Participants	11 Participants

PRIMARY outcome

Timeframe: Regimen limiting drug toxicity was monitored from randomization up to the entire study duration of 4.8 years.

Development of toxicity requiring more than one drug substitution within the same class or a switch to a new class of drugs (regimen-limiting toxicity failure) or requiring a permanent treatment discontinuation. This was part of the primary outcome measure that was a composite endpoint.

Outcome measures

Outcome measures
Measure	Deferred Therapy n=125 Participants For participants with a CD4% of at least 25%, ART deferred until necessary. Once ART therapy was initiated, it was taken continuously. Zidovudine: First Line Regimen: Given twice daily at a dose of 240 mg/m\^2 of body surface area. Dose was adjusted by age as the children grew older. Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight. Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m\^2 Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol. Didanosine: Second Line Regimen: Either 100 mg/m\^2 or 120 mg/m\^2 taken orally twice daily. Dosage depends on age. Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight. Nevirapine: Second Line Regimen: 150 - 200 mg/m\^2 taken orally twice daily.	Early Therapy up to 40 Weeks n=126 Participants For participants with a CD4% of at least 25%, receive 40 weeks of ART until first birthday Zidovudine: First Line Regimen: 10 mg/mL taken orally twice per day. Dose was adjusted by age as the children grew older. Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight. Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m\^2 Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol. Didanosine: Second Line Regimen: Either 100 mg/m\^2 or 120 mg/m\^2 taken orally twice daily. Dosage depends on age. Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight. Nevirapine: Second Line Regimen: 150 - 200 mg/m\^2 taken orally twice daily.	Early Therapy up to 96 Weeks n=126 Participants For participants with a CD4% of at least 25%, receive ART for 96 weeks until second birthday Zidovudine: First Line Regimen: 10 mg/mL taken orally twice per day. Dose was adjusted by age as the children grew older. Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight. Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m\^2 Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol. Didanosine: Second Line Regimen: Either 100 mg/m\^2 or 120 mg/m\^2 taken orally twice daily. Dosage depends on age. Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight. Nevirapine: Second Line Regimen: 150 - 200 mg/m\^2 taken orally twice daily.
Number of Participants Who Experienced Regimen-limiting ART Drug Toxicity	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Clinical failure on therapy was assessed at each visit for the entire study duration of 4.8 years.

This included development of severe CDC Stage B or Stage C disease.This was part of the primary outcome measure that was a composite endpoint

Outcome measures

Outcome measures
Measure	Deferred Therapy n=125 Participants For participants with a CD4% of at least 25%, ART deferred until necessary. Once ART therapy was initiated, it was taken continuously. Zidovudine: First Line Regimen: Given twice daily at a dose of 240 mg/m\^2 of body surface area. Dose was adjusted by age as the children grew older. Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight. Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m\^2 Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol. Didanosine: Second Line Regimen: Either 100 mg/m\^2 or 120 mg/m\^2 taken orally twice daily. Dosage depends on age. Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight. Nevirapine: Second Line Regimen: 150 - 200 mg/m\^2 taken orally twice daily.	Early Therapy up to 40 Weeks n=126 Participants For participants with a CD4% of at least 25%, receive 40 weeks of ART until first birthday Zidovudine: First Line Regimen: 10 mg/mL taken orally twice per day. Dose was adjusted by age as the children grew older. Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight. Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m\^2 Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol. Didanosine: Second Line Regimen: Either 100 mg/m\^2 or 120 mg/m\^2 taken orally twice daily. Dosage depends on age. Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight. Nevirapine: Second Line Regimen: 150 - 200 mg/m\^2 taken orally twice daily.	Early Therapy up to 96 Weeks n=126 Participants For participants with a CD4% of at least 25%, receive ART for 96 weeks until second birthday Zidovudine: First Line Regimen: 10 mg/mL taken orally twice per day. Dose was adjusted by age as the children grew older. Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight. Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m\^2 Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol. Didanosine: Second Line Regimen: Either 100 mg/m\^2 or 120 mg/m\^2 taken orally twice daily. Dosage depends on age. Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight. Nevirapine: Second Line Regimen: 150 - 200 mg/m\^2 taken orally twice daily.
Number of Participants Who Experienced Clinical Failure (Defined as Development of Severe CDC Stage B or Stage C Disease.) on Therapy.	8 Participants	6 Participants	5 Participants

PRIMARY outcome

Timeframe: Virological failure was assessed from randomization through the entire study duration of 4.8 years.

This was part of the primary outcome measure that was a composite endpoint that included confirmed HIV-1 RNA value of at least 10,000 copies per/ml recorded on two consecutive separate occasions after 24 weeks of treatment (initial therapy or restart).

Outcome measures

Outcome measures
Measure	Deferred Therapy n=125 Participants For participants with a CD4% of at least 25%, ART deferred until necessary. Once ART therapy was initiated, it was taken continuously. Zidovudine: First Line Regimen: Given twice daily at a dose of 240 mg/m\^2 of body surface area. Dose was adjusted by age as the children grew older. Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight. Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m\^2 Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol. Didanosine: Second Line Regimen: Either 100 mg/m\^2 or 120 mg/m\^2 taken orally twice daily. Dosage depends on age. Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight. Nevirapine: Second Line Regimen: 150 - 200 mg/m\^2 taken orally twice daily.	Early Therapy up to 40 Weeks n=126 Participants For participants with a CD4% of at least 25%, receive 40 weeks of ART until first birthday Zidovudine: First Line Regimen: 10 mg/mL taken orally twice per day. Dose was adjusted by age as the children grew older. Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight. Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m\^2 Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol. Didanosine: Second Line Regimen: Either 100 mg/m\^2 or 120 mg/m\^2 taken orally twice daily. Dosage depends on age. Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight. Nevirapine: Second Line Regimen: 150 - 200 mg/m\^2 taken orally twice daily.	Early Therapy up to 96 Weeks n=126 Participants For participants with a CD4% of at least 25%, receive ART for 96 weeks until second birthday Zidovudine: First Line Regimen: 10 mg/mL taken orally twice per day. Dose was adjusted by age as the children grew older. Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight. Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m\^2 Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol. Didanosine: Second Line Regimen: Either 100 mg/m\^2 or 120 mg/m\^2 taken orally twice daily. Dosage depends on age. Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight. Nevirapine: Second Line Regimen: 150 - 200 mg/m\^2 taken orally twice daily.
Number of Participants Who Experienced Virological Failure Defined as Confirmed HIV-1 RNA Value of at Least 10,000 Copies Per/ml Recorded on Two Consecutive Separate Occasions After 24 Weeks of Treatment (Initial Therapy or Restart)	10 Participants	1 Participants	1 Participants

SECONDARY outcome

Timeframe: Occurrence of severe CDC Stage B or Stage C disease or death (cumulative after 3.5 years), whichever came first, was assessed from randomization up to at least 3.5 years.

The outcome measure is defined as a number because it represents the number of children that experienced severe CDC Stage B or Stage C disease or death as defined in the outcome measure title above

Outcome measures

Outcome measures
Measure	Deferred Therapy n=125 Participants For participants with a CD4% of at least 25%, ART deferred until necessary. Once ART therapy was initiated, it was taken continuously. Zidovudine: First Line Regimen: Given twice daily at a dose of 240 mg/m\^2 of body surface area. Dose was adjusted by age as the children grew older. Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight. Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m\^2 Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol. Didanosine: Second Line Regimen: Either 100 mg/m\^2 or 120 mg/m\^2 taken orally twice daily. Dosage depends on age. Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight. Nevirapine: Second Line Regimen: 150 - 200 mg/m\^2 taken orally twice daily.	Early Therapy up to 40 Weeks n=126 Participants For participants with a CD4% of at least 25%, receive 40 weeks of ART until first birthday Zidovudine: First Line Regimen: 10 mg/mL taken orally twice per day. Dose was adjusted by age as the children grew older. Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight. Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m\^2 Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol. Didanosine: Second Line Regimen: Either 100 mg/m\^2 or 120 mg/m\^2 taken orally twice daily. Dosage depends on age. Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight. Nevirapine: Second Line Regimen: 150 - 200 mg/m\^2 taken orally twice daily.	Early Therapy up to 96 Weeks n=126 Participants For participants with a CD4% of at least 25%, receive ART for 96 weeks until second birthday Zidovudine: First Line Regimen: 10 mg/mL taken orally twice per day. Dose was adjusted by age as the children grew older. Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight. Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m\^2 Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol. Didanosine: Second Line Regimen: Either 100 mg/m\^2 or 120 mg/m\^2 taken orally twice daily. Dosage depends on age. Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight. Nevirapine: Second Line Regimen: 150 - 200 mg/m\^2 taken orally twice daily.
Number of Children Experiencing Severe CDC Stage B or Stage C Disease or Death (Cumulative After 3.5 Years)	41 Participants	28 Participants	21 Participants

SECONDARY outcome

Timeframe: 4.8 years

Population: This analysis was only performed on the primary groups including a total of 377 participants

This was a secondary outcome measure that assessed the total count of Grade 3 or 4 (clinical or laboratory) adverse events.

Outcome measures

Outcome measures
Measure	Deferred Therapy n=125 Participants For participants with a CD4% of at least 25%, ART deferred until necessary. Once ART therapy was initiated, it was taken continuously. Zidovudine: First Line Regimen: Given twice daily at a dose of 240 mg/m\^2 of body surface area. Dose was adjusted by age as the children grew older. Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight. Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m\^2 Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol. Didanosine: Second Line Regimen: Either 100 mg/m\^2 or 120 mg/m\^2 taken orally twice daily. Dosage depends on age. Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight. Nevirapine: Second Line Regimen: 150 - 200 mg/m\^2 taken orally twice daily.	Early Therapy up to 40 Weeks n=126 Participants For participants with a CD4% of at least 25%, receive 40 weeks of ART until first birthday Zidovudine: First Line Regimen: 10 mg/mL taken orally twice per day. Dose was adjusted by age as the children grew older. Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight. Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m\^2 Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol. Didanosine: Second Line Regimen: Either 100 mg/m\^2 or 120 mg/m\^2 taken orally twice daily. Dosage depends on age. Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight. Nevirapine: Second Line Regimen: 150 - 200 mg/m\^2 taken orally twice daily.	Early Therapy up to 96 Weeks n=126 Participants For participants with a CD4% of at least 25%, receive ART for 96 weeks until second birthday Zidovudine: First Line Regimen: 10 mg/mL taken orally twice per day. Dose was adjusted by age as the children grew older. Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight. Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m\^2 Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol. Didanosine: Second Line Regimen: Either 100 mg/m\^2 or 120 mg/m\^2 taken orally twice daily. Dosage depends on age. Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight. Nevirapine: Second Line Regimen: 150 - 200 mg/m\^2 taken orally twice daily.
Total Occurrence of Grade 3 or 4 Clinical Events	170 Count of events	118 Count of events	88 Count of events

SECONDARY outcome

Timeframe: From randomization up to 4.8 years

Outcome measures

Outcome measures
Measure	Deferred Therapy n=125 Participants For participants with a CD4% of at least 25%, ART deferred until necessary. Once ART therapy was initiated, it was taken continuously. Zidovudine: First Line Regimen: Given twice daily at a dose of 240 mg/m\^2 of body surface area. Dose was adjusted by age as the children grew older. Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight. Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m\^2 Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol. Didanosine: Second Line Regimen: Either 100 mg/m\^2 or 120 mg/m\^2 taken orally twice daily. Dosage depends on age. Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight. Nevirapine: Second Line Regimen: 150 - 200 mg/m\^2 taken orally twice daily.	Early Therapy up to 40 Weeks n=126 Participants For participants with a CD4% of at least 25%, receive 40 weeks of ART until first birthday Zidovudine: First Line Regimen: 10 mg/mL taken orally twice per day. Dose was adjusted by age as the children grew older. Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight. Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m\^2 Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol. Didanosine: Second Line Regimen: Either 100 mg/m\^2 or 120 mg/m\^2 taken orally twice daily. Dosage depends on age. Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight. Nevirapine: Second Line Regimen: 150 - 200 mg/m\^2 taken orally twice daily.	Early Therapy up to 96 Weeks n=126 Participants For participants with a CD4% of at least 25%, receive ART for 96 weeks until second birthday Zidovudine: First Line Regimen: 10 mg/mL taken orally twice per day. Dose was adjusted by age as the children grew older. Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight. Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m\^2 Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol. Didanosine: Second Line Regimen: Either 100 mg/m\^2 or 120 mg/m\^2 taken orally twice daily. Dosage depends on age. Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight. Nevirapine: Second Line Regimen: 150 - 200 mg/m\^2 taken orally twice daily.
Total Occurrence of Grade 3 or 4 Laboratory Events	35 Count of events	44 Count of events	33 Count of events

SECONDARY outcome

Timeframe: 4.8 years

Time from randomization to starting (deferred therapy Arm) or needing to start continuous therapy (early therapy 40 or 96 weeks)

Outcome measures

Outcome measures
Measure	Deferred Therapy n=125 Participants For participants with a CD4% of at least 25%, ART deferred until necessary. Once ART therapy was initiated, it was taken continuously. Zidovudine: First Line Regimen: Given twice daily at a dose of 240 mg/m\^2 of body surface area. Dose was adjusted by age as the children grew older. Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight. Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m\^2 Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol. Didanosine: Second Line Regimen: Either 100 mg/m\^2 or 120 mg/m\^2 taken orally twice daily. Dosage depends on age. Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight. Nevirapine: Second Line Regimen: 150 - 200 mg/m\^2 taken orally twice daily.	Early Therapy up to 40 Weeks n=126 Participants For participants with a CD4% of at least 25%, receive 40 weeks of ART until first birthday Zidovudine: First Line Regimen: 10 mg/mL taken orally twice per day. Dose was adjusted by age as the children grew older. Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight. Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m\^2 Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol. Didanosine: Second Line Regimen: Either 100 mg/m\^2 or 120 mg/m\^2 taken orally twice daily. Dosage depends on age. Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight. Nevirapine: Second Line Regimen: 150 - 200 mg/m\^2 taken orally twice daily.	Early Therapy up to 96 Weeks n=126 Participants For participants with a CD4% of at least 25%, receive ART for 96 weeks until second birthday Zidovudine: First Line Regimen: 10 mg/mL taken orally twice per day. Dose was adjusted by age as the children grew older. Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight. Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m\^2 Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol. Didanosine: Second Line Regimen: Either 100 mg/m\^2 or 120 mg/m\^2 taken orally twice daily. Dosage depends on age. Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight. Nevirapine: Second Line Regimen: 150 - 200 mg/m\^2 taken orally twice daily.
Time From Randomization to Starting or Needing to Start Continuous Therapy	20 Weeks Interval 16.0 to 25.0	33 Weeks Interval 26.0 to 45.0	70 Weeks Interval 35.0 to 109.0

SECONDARY outcome

Timeframe: 4.8 years

Population: Mutations presented descriptively were 1) Protease inhibitor mutations and 2) Met184Val mutations were reported. Only 32 participants with viral load above 1,000 copies/ml at their last visit while on treatment were analysed.

Resistance testing was performed on samples with a VL≥1000 c/ml together with the matched baseline sample, if available. Reverse transcriptase (NRTI and NNRTI) and protease (PI) inhibitor mutations were analysed using a validated in-house population-based sequencing assay and the IAS 2011 mutation list.

Outcome measures

Outcome measures
Measure	Deferred Therapy n=5 Participants For participants with a CD4% of at least 25%, ART deferred until necessary. Once ART therapy was initiated, it was taken continuously. Zidovudine: First Line Regimen: Given twice daily at a dose of 240 mg/m\^2 of body surface area. Dose was adjusted by age as the children grew older. Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight. Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m\^2 Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol. Didanosine: Second Line Regimen: Either 100 mg/m\^2 or 120 mg/m\^2 taken orally twice daily. Dosage depends on age. Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight. Nevirapine: Second Line Regimen: 150 - 200 mg/m\^2 taken orally twice daily.	Early Therapy up to 40 Weeks n=14 Participants For participants with a CD4% of at least 25%, receive 40 weeks of ART until first birthday Zidovudine: First Line Regimen: 10 mg/mL taken orally twice per day. Dose was adjusted by age as the children grew older. Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight. Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m\^2 Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol. Didanosine: Second Line Regimen: Either 100 mg/m\^2 or 120 mg/m\^2 taken orally twice daily. Dosage depends on age. Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight. Nevirapine: Second Line Regimen: 150 - 200 mg/m\^2 taken orally twice daily.	Early Therapy up to 96 Weeks n=13 Participants For participants with a CD4% of at least 25%, receive ART for 96 weeks until second birthday Zidovudine: First Line Regimen: 10 mg/mL taken orally twice per day. Dose was adjusted by age as the children grew older. Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight. Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m\^2 Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol. Didanosine: Second Line Regimen: Either 100 mg/m\^2 or 120 mg/m\^2 taken orally twice daily. Dosage depends on age. Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight. Nevirapine: Second Line Regimen: 150 - 200 mg/m\^2 taken orally twice daily.
Number of Participants With Indicated Viral Resistance Mutations at the Time of Failure of First Line Therapy PI mutations	1 Participants	1 Participants	0 Participants
Number of Participants With Indicated Viral Resistance Mutations at the Time of Failure of First Line Therapy Met184Val mutations	1 Participants	5 Participants	1 Participants
Number of Participants With Indicated Viral Resistance Mutations at the Time of Failure of First Line Therapy No mutations	3 Participants	8 Participants	12 Participants

SECONDARY outcome

Timeframe: 4.8 years

This was a composite endpoint in which the number of children experiencing the events is reported. The number of participants experiencing the events did not reach the 50% survival and thus median time-to-event is not be presented. Therefore, we report the number of participants experiencing the events per Arm.

Outcome measures

Outcome measures
Measure	Deferred Therapy n=125 Participants For participants with a CD4% of at least 25%, ART deferred until necessary. Once ART therapy was initiated, it was taken continuously. Zidovudine: First Line Regimen: Given twice daily at a dose of 240 mg/m\^2 of body surface area. Dose was adjusted by age as the children grew older. Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight. Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m\^2 Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol. Didanosine: Second Line Regimen: Either 100 mg/m\^2 or 120 mg/m\^2 taken orally twice daily. Dosage depends on age. Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight. Nevirapine: Second Line Regimen: 150 - 200 mg/m\^2 taken orally twice daily.	Early Therapy up to 40 Weeks n=126 Participants For participants with a CD4% of at least 25%, receive 40 weeks of ART until first birthday Zidovudine: First Line Regimen: 10 mg/mL taken orally twice per day. Dose was adjusted by age as the children grew older. Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight. Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m\^2 Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol. Didanosine: Second Line Regimen: Either 100 mg/m\^2 or 120 mg/m\^2 taken orally twice daily. Dosage depends on age. Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight. Nevirapine: Second Line Regimen: 150 - 200 mg/m\^2 taken orally twice daily.	Early Therapy up to 96 Weeks n=126 Participants For participants with a CD4% of at least 25%, receive ART for 96 weeks until second birthday Zidovudine: First Line Regimen: 10 mg/mL taken orally twice per day. Dose was adjusted by age as the children grew older. Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight. Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m\^2 Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol. Didanosine: Second Line Regimen: Either 100 mg/m\^2 or 120 mg/m\^2 taken orally twice daily. Dosage depends on age. Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight. Nevirapine: Second Line Regimen: 150 - 200 mg/m\^2 taken orally twice daily.
Time to Death Alone or Death Plus Life Threatening Stage C Events or HIV Events Associated With Permanent End-organ Damage.	34 Participants	18 Participants	13 Participants

SECONDARY outcome

Timeframe: 4.8 years

Hospitalisation rates in the three arms enrolled in the CHER study

Outcome measures

Outcome measures
Measure	Deferred Therapy n=125 Participants For participants with a CD4% of at least 25%, ART deferred until necessary. Once ART therapy was initiated, it was taken continuously. Zidovudine: First Line Regimen: Given twice daily at a dose of 240 mg/m\^2 of body surface area. Dose was adjusted by age as the children grew older. Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight. Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m\^2 Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol. Didanosine: Second Line Regimen: Either 100 mg/m\^2 or 120 mg/m\^2 taken orally twice daily. Dosage depends on age. Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight. Nevirapine: Second Line Regimen: 150 - 200 mg/m\^2 taken orally twice daily.	Early Therapy up to 40 Weeks n=126 Participants For participants with a CD4% of at least 25%, receive 40 weeks of ART until first birthday Zidovudine: First Line Regimen: 10 mg/mL taken orally twice per day. Dose was adjusted by age as the children grew older. Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight. Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m\^2 Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol. Didanosine: Second Line Regimen: Either 100 mg/m\^2 or 120 mg/m\^2 taken orally twice daily. Dosage depends on age. Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight. Nevirapine: Second Line Regimen: 150 - 200 mg/m\^2 taken orally twice daily.	Early Therapy up to 96 Weeks n=126 Participants For participants with a CD4% of at least 25%, receive ART for 96 weeks until second birthday Zidovudine: First Line Regimen: 10 mg/mL taken orally twice per day. Dose was adjusted by age as the children grew older. Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight. Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m\^2 Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol. Didanosine: Second Line Regimen: Either 100 mg/m\^2 or 120 mg/m\^2 taken orally twice daily. Dosage depends on age. Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight. Nevirapine: Second Line Regimen: 150 - 200 mg/m\^2 taken orally twice daily.
Hospitalization Rates	27.6 Events per 100 person years	16.4 Events per 100 person years	14.2 Events per 100 person years

SECONDARY outcome

Timeframe: 4.8 years, the study duration

This is the total number of days spent in hospital by the participants and is reported per arm

Outcome measures

Outcome measures
Measure	Deferred Therapy n=125 Participants For participants with a CD4% of at least 25%, ART deferred until necessary. Once ART therapy was initiated, it was taken continuously. Zidovudine: First Line Regimen: Given twice daily at a dose of 240 mg/m\^2 of body surface area. Dose was adjusted by age as the children grew older. Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight. Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m\^2 Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol. Didanosine: Second Line Regimen: Either 100 mg/m\^2 or 120 mg/m\^2 taken orally twice daily. Dosage depends on age. Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight. Nevirapine: Second Line Regimen: 150 - 200 mg/m\^2 taken orally twice daily.	Early Therapy up to 40 Weeks n=126 Participants For participants with a CD4% of at least 25%, receive 40 weeks of ART until first birthday Zidovudine: First Line Regimen: 10 mg/mL taken orally twice per day. Dose was adjusted by age as the children grew older. Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight. Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m\^2 Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol. Didanosine: Second Line Regimen: Either 100 mg/m\^2 or 120 mg/m\^2 taken orally twice daily. Dosage depends on age. Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight. Nevirapine: Second Line Regimen: 150 - 200 mg/m\^2 taken orally twice daily.	Early Therapy up to 96 Weeks n=126 Participants For participants with a CD4% of at least 25%, receive ART for 96 weeks until second birthday Zidovudine: First Line Regimen: 10 mg/mL taken orally twice per day. Dose was adjusted by age as the children grew older. Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight. Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m\^2 Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol. Didanosine: Second Line Regimen: Either 100 mg/m\^2 or 120 mg/m\^2 taken orally twice daily. Dosage depends on age. Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight. Nevirapine: Second Line Regimen: 150 - 200 mg/m\^2 taken orally twice daily.
Duration of Hospitalisation	1018 Days	533 Days	414 Days

SECONDARY outcome

Timeframe: From randomization up to 4.8 years

To compare time to first hospitalization in the three randomized arms (infants who received early ART in Arms 2 and 3 and those who received deferred ART in Arm 1). Not all participants were hospitalized and thus the upper limits could not be evaluated.

Outcome measures

Outcome measures
Measure	Deferred Therapy n=125 Participants For participants with a CD4% of at least 25%, ART deferred until necessary. Once ART therapy was initiated, it was taken continuously. Zidovudine: First Line Regimen: Given twice daily at a dose of 240 mg/m\^2 of body surface area. Dose was adjusted by age as the children grew older. Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight. Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m\^2 Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol. Didanosine: Second Line Regimen: Either 100 mg/m\^2 or 120 mg/m\^2 taken orally twice daily. Dosage depends on age. Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight. Nevirapine: Second Line Regimen: 150 - 200 mg/m\^2 taken orally twice daily.	Early Therapy up to 40 Weeks n=126 Participants For participants with a CD4% of at least 25%, receive 40 weeks of ART until first birthday Zidovudine: First Line Regimen: 10 mg/mL taken orally twice per day. Dose was adjusted by age as the children grew older. Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight. Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m\^2 Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol. Didanosine: Second Line Regimen: Either 100 mg/m\^2 or 120 mg/m\^2 taken orally twice daily. Dosage depends on age. Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight. Nevirapine: Second Line Regimen: 150 - 200 mg/m\^2 taken orally twice daily.	Early Therapy up to 96 Weeks n=126 Participants For participants with a CD4% of at least 25%, receive ART for 96 weeks until second birthday Zidovudine: First Line Regimen: 10 mg/mL taken orally twice per day. Dose was adjusted by age as the children grew older. Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight. Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m\^2 Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol. Didanosine: Second Line Regimen: Either 100 mg/m\^2 or 120 mg/m\^2 taken orally twice daily. Dosage depends on age. Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight. Nevirapine: Second Line Regimen: 150 - 200 mg/m\^2 taken orally twice daily.
Time to First Hospitalization	73.1 Weeks Interval 22.6 to Upper limit of median not estimable	NA Weeks Interval 184.4 to The median is not estimable because the survival curve did not cross the 50% survival	NA Weeks Interval 179.0 to The median is not estimable because the survival curve did not cross the 50% survival

Adverse Events

ART-Deferred

Serious events: 79 serious events

Other events: 123 other events

Deaths: 23 deaths

Early ART up to 40 Weeks

Serious events: 60 serious events

Other events: 122 other events

Deaths: 11 deaths

Early ART up to 96 Weeks

Serious events: 53 serious events

Other events: 125 other events

Deaths: 11 deaths

Serious adverse events

Other adverse events

Additional Information

Dr Avy Violari and Prof Mark Cotton

Perinatal HIV Research Unit, Johannesburg and Children's Infectious Diseases Clinical Research Unit, Cape Town all in South Africa

Phone: 27 11 989 9702/27 21 938 4219

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	ART-Deferred n=125 participants at risk For participants with a CD4% of at least 25%, ART deferred until necessary. Once ART therapy was initiated, it was taken continuously. Zidovudine: First Line Regimen: Given twice daily at a dose of 240 mg/m\^2 of body surface area. Dose was adjusted by age as the children grew older. Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight. Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m\^2 Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol. Didanosine: Second Line Regimen: Either 100 mg/m\^2 or 120 mg/m\^2 taken orally twice daily. Dosage depends on age. Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight. Nevirapine: Second Line Regimen: 150 - 200 mg/m\^2 taken orally twice daily.	Early ART up to 40 Weeks n=126 participants at risk For participants with a CD4% of at least 25%, receive 40 weeks of ART until first birthday Zidovudine: First Line Regimen: 10 mg/mL taken orally twice per day. Dose was adjusted by age as the children grew older. Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight. Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m\^2 Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol. Didanosine: Second Line Regimen: Either 100 mg/m\^2 or 120 mg/m\^2 taken orally twice daily. Dosage depends on age. Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight. Nevirapine: Second Line Regimen: 150 - 200 mg/m\^2 taken orally twice daily.	Early ART up to 96 Weeks n=126 participants at risk For participants with a CD4% of at least 25%, receive ART for 96 weeks until second birthday Zidovudine: First Line Regimen: 10 mg/mL taken orally twice per day. Dose was adjusted by age as the children grew older. Lamivudine: First Line Regimen: 4 mg/kg taken orally twice daily Lopinavir/Ritonavir: First Line Regimen: taken orally twice daily. Dosage depends on age and weight. Ritonavir: First Line Regimen taken orally twice a day. Started at 250 mg/m\^2 Abacavir sulfate: Second Line Regimen: 8 mg/kg taken orally twice daily. Guidelines for switching from first line to second line therapy are available in the protocol. Didanosine: Second Line Regimen: Either 100 mg/m\^2 or 120 mg/m\^2 taken orally twice daily. Dosage depends on age. Efavirenz: Second Line Regimen: taken orally once daily. Dosage depends on weight. Nevirapine: Second Line Regimen: 150 - 200 mg/m\^2 taken orally twice daily.
Blood and lymphatic system disorders Lymphadenopathy	30.4% 38/125 • Number of events 46 • 4.8 years, the study duration Only System Organ Class and Higher Level Terms are reported for 377 participants (ART-Def 125, ART-40W 126 and ART-96W 126)	41.3% 52/126 • Number of events 64 • 4.8 years, the study duration Only System Organ Class and Higher Level Terms are reported for 377 participants (ART-Def 125, ART-40W 126 and ART-96W 126)	31.0% 39/126 • Number of events 42 • 4.8 years, the study duration Only System Organ Class and Higher Level Terms are reported for 377 participants (ART-Def 125, ART-40W 126 and ART-96W 126)
Blood and lymphatic system disorders Neutropenia	4.0% 5/125 • Number of events 7 • 4.8 years, the study duration Only System Organ Class and Higher Level Terms are reported for 377 participants (ART-Def 125, ART-40W 126 and ART-96W 126)	7.1% 9/126 • Number of events 10 • 4.8 years, the study duration Only System Organ Class and Higher Level Terms are reported for 377 participants (ART-Def 125, ART-40W 126 and ART-96W 126)	11.1% 14/126 • Number of events 17 • 4.8 years, the study duration Only System Organ Class and Higher Level Terms are reported for 377 participants (ART-Def 125, ART-40W 126 and ART-96W 126)
Blood and lymphatic system disorders Splenomegaly	25.6% 32/125 • Number of events 36 • 4.8 years, the study duration Only System Organ Class and Higher Level Terms are reported for 377 participants (ART-Def 125, ART-40W 126 and ART-96W 126)	18.3% 23/126 • Number of events 28 • 4.8 years, the study duration Only System Organ Class and Higher Level Terms are reported for 377 participants (ART-Def 125, ART-40W 126 and ART-96W 126)	7.9% 10/126 • Number of events 14 • 4.8 years, the study duration Only System Organ Class and Higher Level Terms are reported for 377 participants (ART-Def 125, ART-40W 126 and ART-96W 126)
Gastrointestinal disorders Gastroenteritis	64.0% 80/125 • Number of events 160 • 4.8 years, the study duration Only System Organ Class and Higher Level Terms are reported for 377 participants (ART-Def 125, ART-40W 126 and ART-96W 126)	67.5% 85/126 • Number of events 214 • 4.8 years, the study duration Only System Organ Class and Higher Level Terms are reported for 377 participants (ART-Def 125, ART-40W 126 and ART-96W 126)	64.3% 81/126 • Number of events 178 • 4.8 years, the study duration Only System Organ Class and Higher Level Terms are reported for 377 participants (ART-Def 125, ART-40W 126 and ART-96W 126)
Hepatobiliary disorders Hepatomegaly	42.4% 53/125 • Number of events 72 • 4.8 years, the study duration Only System Organ Class and Higher Level Terms are reported for 377 participants (ART-Def 125, ART-40W 126 and ART-96W 126)	39.7% 50/126 • Number of events 72 • 4.8 years, the study duration Only System Organ Class and Higher Level Terms are reported for 377 participants (ART-Def 125, ART-40W 126 and ART-96W 126)	41.3% 52/126 • Number of events 79 • 4.8 years, the study duration Only System Organ Class and Higher Level Terms are reported for 377 participants (ART-Def 125, ART-40W 126 and ART-96W 126)
Infections and infestations AIDS encephalopathy	8.0% 10/125 • Number of events 10 • 4.8 years, the study duration Only System Organ Class and Higher Level Terms are reported for 377 participants (ART-Def 125, ART-40W 126 and ART-96W 126)	11.9% 15/126 • Number of events 15 • 4.8 years, the study duration Only System Organ Class and Higher Level Terms are reported for 377 participants (ART-Def 125, ART-40W 126 and ART-96W 126)	7.9% 10/126 • Number of events 10 • 4.8 years, the study duration Only System Organ Class and Higher Level Terms are reported for 377 participants (ART-Def 125, ART-40W 126 and ART-96W 126)
Infections and infestations Bronchiolitis	46.4% 58/125 • Number of events 83 • 4.8 years, the study duration Only System Organ Class and Higher Level Terms are reported for 377 participants (ART-Def 125, ART-40W 126 and ART-96W 126)	52.4% 66/126 • Number of events 104 • 4.8 years, the study duration Only System Organ Class and Higher Level Terms are reported for 377 participants (ART-Def 125, ART-40W 126 and ART-96W 126)	38.1% 48/126 • Number of events 76 • 4.8 years, the study duration Only System Organ Class and Higher Level Terms are reported for 377 participants (ART-Def 125, ART-40W 126 and ART-96W 126)
Infections and infestations Bronchopneumonia	7.2% 9/125 • Number of events 10 • 4.8 years, the study duration Only System Organ Class and Higher Level Terms are reported for 377 participants (ART-Def 125, ART-40W 126 and ART-96W 126)	9.5% 12/126 • Number of events 13 • 4.8 years, the study duration Only System Organ Class and Higher Level Terms are reported for 377 participants (ART-Def 125, ART-40W 126 and ART-96W 126)	9.5% 12/126 • Number of events 14 • 4.8 years, the study duration Only System Organ Class and Higher Level Terms are reported for 377 participants (ART-Def 125, ART-40W 126 and ART-96W 126)
Infections and infestations Candida nappy rash	13.6% 17/125 • Number of events 19 • 4.8 years, the study duration Only System Organ Class and Higher Level Terms are reported for 377 participants (ART-Def 125, ART-40W 126 and ART-96W 126)	12.7% 16/126 • Number of events 19 • 4.8 years, the study duration Only System Organ Class and Higher Level Terms are reported for 377 participants (ART-Def 125, ART-40W 126 and ART-96W 126)	11.1% 14/126 • Number of events 18 • 4.8 years, the study duration Only System Organ Class and Higher Level Terms are reported for 377 participants (ART-Def 125, ART-40W 126 and ART-96W 126)
Infections and infestations Candidiasis	23.2% 29/125 • Number of events 41 • 4.8 years, the study duration Only System Organ Class and Higher Level Terms are reported for 377 participants (ART-Def 125, ART-40W 126 and ART-96W 126)	25.4% 32/126 • Number of events 38 • 4.8 years, the study duration Only System Organ Class and Higher Level Terms are reported for 377 participants (ART-Def 125, ART-40W 126 and ART-96W 126)	13.5% 17/126 • Number of events 21 • 4.8 years, the study duration Only System Organ Class and Higher Level Terms are reported for 377 participants (ART-Def 125, ART-40W 126 and ART-96W 126)
Infections and infestations Gastroenteritis	41.6% 52/125 • Number of events 72 • 4.8 years, the study duration Only System Organ Class and Higher Level Terms are reported for 377 participants (ART-Def 125, ART-40W 126 and ART-96W 126)	33.3% 42/126 • Number of events 61 • 4.8 years, the study duration Only System Organ Class and Higher Level Terms are reported for 377 participants (ART-Def 125, ART-40W 126 and ART-96W 126)	37.3% 47/126 • Number of events 64 • 4.8 years, the study duration Only System Organ Class and Higher Level Terms are reported for 377 participants (ART-Def 125, ART-40W 126 and ART-96W 126)
Infections and infestations Impetigo	21.6% 27/125 • Number of events 37 • 4.8 years, the study duration Only System Organ Class and Higher Level Terms are reported for 377 participants (ART-Def 125, ART-40W 126 and ART-96W 126)	20.6% 26/126 • Number of events 31 • 4.8 years, the study duration Only System Organ Class and Higher Level Terms are reported for 377 participants (ART-Def 125, ART-40W 126 and ART-96W 126)	16.7% 21/126 • Number of events 24 • 4.8 years, the study duration Only System Organ Class and Higher Level Terms are reported for 377 participants (ART-Def 125, ART-40W 126 and ART-96W 126)
Infections and infestations Molluscum Contagiosum	7.2% 9/125 • Number of events 10 • 4.8 years, the study duration Only System Organ Class and Higher Level Terms are reported for 377 participants (ART-Def 125, ART-40W 126 and ART-96W 126)	7.9% 10/126 • Number of events 11 • 4.8 years, the study duration Only System Organ Class and Higher Level Terms are reported for 377 participants (ART-Def 125, ART-40W 126 and ART-96W 126)	7.9% 10/126 • Number of events 12 • 4.8 years, the study duration Only System Organ Class and Higher Level Terms are reported for 377 participants (ART-Def 125, ART-40W 126 and ART-96W 126)
Infections and infestations Mucocutaneous Herpes Simplex	6.4% 8/125 • Number of events 9 • 4.8 years, the study duration Only System Organ Class and Higher Level Terms are reported for 377 participants (ART-Def 125, ART-40W 126 and ART-96W 126)	5.6% 7/126 • Number of events 8 • 4.8 years, the study duration Only System Organ Class and Higher Level Terms are reported for 377 participants (ART-Def 125, ART-40W 126 and ART-96W 126)	7.1% 9/126 • Number of events 10 • 4.8 years, the study duration Only System Organ Class and Higher Level Terms are reported for 377 participants (ART-Def 125, ART-40W 126 and ART-96W 126)
Infections and infestations Oral Candidiasis	48.0% 60/125 • Number of events 101 • 4.8 years, the study duration Only System Organ Class and Higher Level Terms are reported for 377 participants (ART-Def 125, ART-40W 126 and ART-96W 126)	36.5% 46/126 • Number of events 81 • 4.8 years, the study duration Only System Organ Class and Higher Level Terms are reported for 377 participants (ART-Def 125, ART-40W 126 and ART-96W 126)	39.7% 50/126 • Number of events 58 • 4.8 years, the study duration Only System Organ Class and Higher Level Terms are reported for 377 participants (ART-Def 125, ART-40W 126 and ART-96W 126)
Infections and infestations Otitis Media	56.0% 70/125 • Number of events 140 • 4.8 years, the study duration Only System Organ Class and Higher Level Terms are reported for 377 participants (ART-Def 125, ART-40W 126 and ART-96W 126)	64.3% 81/126 • Number of events 220 • 4.8 years, the study duration Only System Organ Class and Higher Level Terms are reported for 377 participants (ART-Def 125, ART-40W 126 and ART-96W 126)	61.9% 78/126 • Number of events 154 • 4.8 years, the study duration Only System Organ Class and Higher Level Terms are reported for 377 participants (ART-Def 125, ART-40W 126 and ART-96W 126)
Infections and infestations Persistent Generalised Lymphadenopathy	10.4% 13/125 • Number of events 14 • 4.8 years, the study duration Only System Organ Class and Higher Level Terms are reported for 377 participants (ART-Def 125, ART-40W 126 and ART-96W 126)	13.5% 17/126 • Number of events 19 • 4.8 years, the study duration Only System Organ Class and Higher Level Terms are reported for 377 participants (ART-Def 125, ART-40W 126 and ART-96W 126)	16.7% 21/126 • Number of events 23 • 4.8 years, the study duration Only System Organ Class and Higher Level Terms are reported for 377 participants (ART-Def 125, ART-40W 126 and ART-96W 126)
Infections and infestations Pharyngitis	55.2% 69/125 • Number of events 112 • 4.8 years, the study duration Only System Organ Class and Higher Level Terms are reported for 377 participants (ART-Def 125, ART-40W 126 and ART-96W 126)	51.6% 65/126 • Number of events 139 • 4.8 years, the study duration Only System Organ Class and Higher Level Terms are reported for 377 participants (ART-Def 125, ART-40W 126 and ART-96W 126)	49.2% 62/126 • Number of events 118 • 4.8 years, the study duration Only System Organ Class and Higher Level Terms are reported for 377 participants (ART-Def 125, ART-40W 126 and ART-96W 126)
Infections and infestations Pneumonia	39.2% 49/125 • Number of events 81 • 4.8 years, the study duration Only System Organ Class and Higher Level Terms are reported for 377 participants (ART-Def 125, ART-40W 126 and ART-96W 126)	34.9% 44/126 • Number of events 78 • 4.8 years, the study duration Only System Organ Class and Higher Level Terms are reported for 377 participants (ART-Def 125, ART-40W 126 and ART-96W 126)	35.7% 45/126 • Number of events 78 • 4.8 years, the study duration Only System Organ Class and Higher Level Terms are reported for 377 participants (ART-Def 125, ART-40W 126 and ART-96W 126)
Infections and infestations Scabies	10.4% 13/125 • Number of events 15 • 4.8 years, the study duration Only System Organ Class and Higher Level Terms are reported for 377 participants (ART-Def 125, ART-40W 126 and ART-96W 126)	22.2% 28/126 • Number of events 38 • 4.8 years, the study duration Only System Organ Class and Higher Level Terms are reported for 377 participants (ART-Def 125, ART-40W 126 and ART-96W 126)	15.9% 20/126 • Number of events 25 • 4.8 years, the study duration Only System Organ Class and Higher Level Terms are reported for 377 participants (ART-Def 125, ART-40W 126 and ART-96W 126)
Infections and infestations TB	18.4% 23/125 • Number of events 24 • 4.8 years, the study duration Only System Organ Class and Higher Level Terms are reported for 377 participants (ART-Def 125, ART-40W 126 and ART-96W 126)	22.2% 28/126 • Number of events 31 • 4.8 years, the study duration Only System Organ Class and Higher Level Terms are reported for 377 participants (ART-Def 125, ART-40W 126 and ART-96W 126)	19.8% 25/126 • Number of events 25 • 4.8 years, the study duration Only System Organ Class and Higher Level Terms are reported for 377 participants (ART-Def 125, ART-40W 126 and ART-96W 126)
Infections and infestations Tinea	39.2% 49/125 • Number of events 63 • 4.8 years, the study duration Only System Organ Class and Higher Level Terms are reported for 377 participants (ART-Def 125, ART-40W 126 and ART-96W 126)	39.7% 50/126 • Number of events 78 • 4.8 years, the study duration Only System Organ Class and Higher Level Terms are reported for 377 participants (ART-Def 125, ART-40W 126 and ART-96W 126)	42.1% 53/126 • Number of events 81 • 4.8 years, the study duration Only System Organ Class and Higher Level Terms are reported for 377 participants (ART-Def 125, ART-40W 126 and ART-96W 126)
Infections and infestations Tonsilitis	32.8% 41/125 • Number of events 72 • 4.8 years, the study duration Only System Organ Class and Higher Level Terms are reported for 377 participants (ART-Def 125, ART-40W 126 and ART-96W 126)	38.9% 49/126 • Number of events 89 • 4.8 years, the study duration Only System Organ Class and Higher Level Terms are reported for 377 participants (ART-Def 125, ART-40W 126 and ART-96W 126)	31.0% 39/126 • Number of events 68 • 4.8 years, the study duration Only System Organ Class and Higher Level Terms are reported for 377 participants (ART-Def 125, ART-40W 126 and ART-96W 126)
Infections and infestations Urinary tract infection	8.0% 10/125 • Number of events 12 • 4.8 years, the study duration Only System Organ Class and Higher Level Terms are reported for 377 participants (ART-Def 125, ART-40W 126 and ART-96W 126)	11.9% 15/126 • Number of events 21 • 4.8 years, the study duration Only System Organ Class and Higher Level Terms are reported for 377 participants (ART-Def 125, ART-40W 126 and ART-96W 126)	4.8% 6/126 • Number of events 7 • 4.8 years, the study duration Only System Organ Class and Higher Level Terms are reported for 377 participants (ART-Def 125, ART-40W 126 and ART-96W 126)
Infections and infestations Varicella Zoster	5.6% 7/125 • Number of events 7 • 4.8 years, the study duration Only System Organ Class and Higher Level Terms are reported for 377 participants (ART-Def 125, ART-40W 126 and ART-96W 126)	12.7% 16/126 • Number of events 16 • 4.8 years, the study duration Only System Organ Class and Higher Level Terms are reported for 377 participants (ART-Def 125, ART-40W 126 and ART-96W 126)	4.0% 5/126 • Number of events 5 • 4.8 years, the study duration Only System Organ Class and Higher Level Terms are reported for 377 participants (ART-Def 125, ART-40W 126 and ART-96W 126)
Investigations ALT Increased	8.8% 11/125 • Number of events 12 • 4.8 years, the study duration Only System Organ Class and Higher Level Terms are reported for 377 participants (ART-Def 125, ART-40W 126 and ART-96W 126)	6.3% 8/126 • Number of events 10 • 4.8 years, the study duration Only System Organ Class and Higher Level Terms are reported for 377 participants (ART-Def 125, ART-40W 126 and ART-96W 126)	3.2% 4/126 • Number of events 5 • 4.8 years, the study duration Only System Organ Class and Higher Level Terms are reported for 377 participants (ART-Def 125, ART-40W 126 and ART-96W 126)
Investigations Gamma GT Increased	5.6% 7/125 • Number of events 7 • 4.8 years, the study duration Only System Organ Class and Higher Level Terms are reported for 377 participants (ART-Def 125, ART-40W 126 and ART-96W 126)	3.2% 4/126 • Number of events 6 • 4.8 years, the study duration Only System Organ Class and Higher Level Terms are reported for 377 participants (ART-Def 125, ART-40W 126 and ART-96W 126)	1.6% 2/126 • Number of events 3 • 4.8 years, the study duration Only System Organ Class and Higher Level Terms are reported for 377 participants (ART-Def 125, ART-40W 126 and ART-96W 126)
Metabolism and nutrition disorders Failure to thrive	29.6% 37/125 • Number of events 41 • 4.8 years, the study duration Only System Organ Class and Higher Level Terms are reported for 377 participants (ART-Def 125, ART-40W 126 and ART-96W 126)	24.6% 31/126 • Number of events 37 • 4.8 years, the study duration Only System Organ Class and Higher Level Terms are reported for 377 participants (ART-Def 125, ART-40W 126 and ART-96W 126)	15.1% 19/126 • Number of events 23 • 4.8 years, the study duration Only System Organ Class and Higher Level Terms are reported for 377 participants (ART-Def 125, ART-40W 126 and ART-96W 126)
Skin and subcutaneous tissue disorders Dermatitis	82.4% 103/125 • Number of events 320 • 4.8 years, the study duration Only System Organ Class and Higher Level Terms are reported for 377 participants (ART-Def 125, ART-40W 126 and ART-96W 126)	76.2% 96/126 • Number of events 223 • 4.8 years, the study duration Only System Organ Class and Higher Level Terms are reported for 377 participants (ART-Def 125, ART-40W 126 and ART-96W 126)	70.6% 89/126 • Number of events 206 • 4.8 years, the study duration Only System Organ Class and Higher Level Terms are reported for 377 participants (ART-Def 125, ART-40W 126 and ART-96W 126)
Skin and subcutaneous tissue disorders Nappy rash	7.2% 9/125 • Number of events 10 • 4.8 years, the study duration Only System Organ Class and Higher Level Terms are reported for 377 participants (ART-Def 125, ART-40W 126 and ART-96W 126)	15.1% 19/126 • Number of events 31 • 4.8 years, the study duration Only System Organ Class and Higher Level Terms are reported for 377 participants (ART-Def 125, ART-40W 126 and ART-96W 126)	5.6% 7/126 • Number of events 10 • 4.8 years, the study duration Only System Organ Class and Higher Level Terms are reported for 377 participants (ART-Def 125, ART-40W 126 and ART-96W 126)