Early Antiretroviral Therapy for Infant HIV/AIDS

(EIT Trial)

Recruiting at 3 trial locations

Age: < 18

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Harvard School of Public Health

Must be taking: Antiretrovirals

Disqualifiers: Life-threatening illness, Survival unlikely, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: 84-96 weeks

67 Participants Needed

Trial Summary

What is the purpose of this trial?

The overall objective of this study is to determine whether very early antiretroviral treatment (ART) initiation in HIV-infected infants limits the seeding of viral reservoirs and maintains immune responses, potentially allowing future periods off ART.

Do I need to stop my current medications to join the trial?

The trial information does not specify whether participants must stop taking their current medications. However, since the trial involves starting antiretroviral therapy (ART) for infants, it is likely that any current medications related to HIV treatment would be adjusted or replaced by the trial's ART regimen.

What data supports the effectiveness of the drug regimen including Kaletra, Lamivudine, Nevirapine, and Zidovudine for treating infant HIV/AIDS?

Research shows that Nevirapine, when used in combination with other antiretroviral drugs, is effective in preventing mother-to-child transmission of HIV during breastfeeding. Additionally, studies indicate that regimens including Zidovudine and Lamivudine can improve health outcomes in HIV-infected children. ^{1 2 3 4 5}

Is early antiretroviral therapy for infant HIV/AIDS safe?

Research shows that antiretroviral therapy, including drugs like zidovudine, lamivudine, and nevirapine, has been used in children and infants to reduce HIV-related health issues. However, some studies have noted potential toxicity and serious side effects, especially with nevirapine in pregnant women, so it's important to discuss these risks with a healthcare provider. ^{2 4 6 7 8}

What makes the early antiretroviral therapy for infant HIV/AIDS unique?

This treatment is unique because it involves a combination of antiretroviral drugs specifically recommended for neonates, including Kaletra, Lamivudine, Nevirapine, and Zidovudine, which are not commonly available in formulations suitable for very young infants. The early initiation of this combination therapy is crucial for preventing the progression of HIV in newborns, despite challenges in developing practical dosage forms for this age group. ^{1 9 10 11 12}

Research Team

Roger L Shapiro, MD, MPH

Principal Investigator

Harvard School of Public Health (HSPH)

Daniel R. Kuritzkes, MD

Principal Investigator

Brigham and Women's Hospital

Mathias Lichterfeld, MD, PhD

Principal Investigator

Ragon Institute of MGH, MIT and Harvard

Eligibility Criteria

This trial is for newborns in Botswana who were born at or after 35 weeks of gestation, weigh at least 2000 grams, and are HIV-infected within their first week of life. They must be able to start antiretroviral therapy (ART) within seven days after birth and have a guardian able to consent.

Inclusion Criteria

You were born after 35 weeks of pregnancy.

You weighed at least 2000 grams at birth.

I can start antiretroviral therapy within 7 days after giving birth.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Treatment

Infants initiate ART with Nevirapine, Zidovudine, Lamivudine, and later switch to Kaletra, Zidovudine, Lamivudine

84-96 weeks

Follow-up

Participants are monitored for virologic and immunologic outcomes after early ART

up to 576 weeks

Treatment Details

Interventions

• Kaletra
• Lamivudine
• Nevirapine
• Zidovudine

Trial Overview The study tests if starting ART very early in HIV-infected infants can limit the virus from establishing itself in the body and maintain immune responses. This could potentially allow breaks from treatment in the future.

Participant Groups

Group I: Peripartum Cohort Experimental Treatment 4 Interventions

10 children who test HIV-negative within 96 hours after birth but test HIV-positive \<57 days after birth (peripartum HIV infection) and who are able to initiate ART \<57 days after birth. This cohort will include at least 10 children who start ART \< 21 days after birth. The majority of infants in the peripartum cohort will be able to start Kaletra, Zidovudine, Lamivudine as their first regimen, but a minority may start Nevirapine, Zidovudine, Lamivudine and then switch to Kaletra, Zidovudine, Lamivudine.

Group II: Antepartum Cohort Experimental Treatment 4 Interventions

40 children who test HIV-positive within 96 hours after birth (antepartum HIV infection) and are able to initiate ART \< 7 days after birth. This cohort will include at least 15 children who start ART \< 3 days after birth. All infants in the antepartum cohort will initiate ART with Nevirapine, Zidovudine, Lamivudine, and later switch to Kaletra, Zidovudine, Lamivudine.

Group III: Control Cohort Active Control 1 Intervention

25 HIV-infected children who initiated ART at later age ranges (30-365 days for antepartum infection, 57-365 days for peripartum infection or for those with unknown timing of infection) will be enrolled for a single visit that will occur between 24 and 36 months of age. These children will serve as a control group for virologic and immunologic comparisons with children in the prospective cohorts.

Who Is Running the Clinical Trial?

Harvard School of Public Health

Lead Sponsor

Trials

123

Recruited

1,938,000+

Harvard School of Public Health (HSPH)

Lead Sponsor

Trials

283

Recruited

17,030,000+

Botswana Harvard Health Partnership

Collaborator

Trials

2

Recruited

820+

Ragon Institute of MGH, MIT and Harvard

Collaborator

Trials

9

Recruited

1,600+

University of California, San Diego

Collaborator

Trials

1,215

Recruited

1,593,000+

Brigham and Women's Hospital

Collaborator

Trials

1,694

Recruited

14,790,000+

Findings from Research

In a study of 183 HIV-1 infected children, both the nevirapine (NVP) and efavirenz (EFV) based ART regimens showed similar improvements in CD4 cell counts after six months, indicating comparable immunological efficacy.

Both regimens achieved optimal viral suppression rates of around 82-83%, demonstrating that either NVP+AZT+3TC or EFV+AZT+3TC can be effective treatment options for pediatric patients with HIV-1.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical, Immunological and Virological Responses of Zidovudine-Lamivudine-Nevirapine versus Zidovudine-Lamivudine-Efavirenz Antiretroviral Treatment (ART) Among HIV-1 Infected Children: Asella Teaching and Referral Hospital, South-East Ethiopia. Sorsa, A.[2022]

In a trial involving 480 children in Zambia and Uganda, all three nucleoside reverse-transcriptase inhibitors (NRTIs) - stavudine, zidovudine, and abacavir - showed low toxicity and effective viral load suppression, with no significant differences in adverse events among the groups.

Abacavir was favored due to its absence of hypersensitivity reactions, better resistance profile, and once-daily dosing, supporting its use in line with WHO 2013 guidelines for treating HIV-infected children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abacavir, zidovudine, or stavudine as paediatric tablets for African HIV-infected children (CHAPAS-3): an open-label, parallel-group, randomised controlled trial. Mulenga, V., Musiime, V., Kekitiinwa, A., et al.[2022]

The development of antiretroviral therapy has greatly improved the health outcomes for children with HIV, with 21 FDA-approved agents available, though only a few are suitable for those under 18.

Among the 7 newer antiretroviral agents approved since 2000, only 3 are currently approved for pediatric use, but studies are ongoing to evaluate the safety and efficacy of the others in children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Antiretroviral Therapies for Pediatric HIV Infection. Morris, JL., Kraus, DM.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

Nevirapine Pharmacokinetics and Safety in Neonates Receiving Combination Antiretroviral Therapy for Prevention of Vertical HIV Transmission. [2020]

2. United States pubmed.ncbi.nlm.nih.gov

Efficacy and safety of an extended nevirapine regimen in infants of breastfeeding mothers with HIV-1 infection for prevention of HIV-1 transmission (HPTN 046): 18-month results of a randomized, double-blind, placebo-controlled trial. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

CD4, viral load response, and adherence among antiretroviral-naive breast-feeding women receiving triple antiretroviral prophylaxis for prevention of mother-to-child transmission of HIV in Kisumu, Kenya. [2020]

4. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Clinical, Immunological and Virological Responses of Zidovudine-Lamivudine-Nevirapine versus Zidovudine-Lamivudine-Efavirenz Antiretroviral Treatment (ART) Among HIV-1 Infected Children: Asella Teaching and Referral Hospital, South-East Ethiopia. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Abacavir, zidovudine, or stavudine as paediatric tablets for African HIV-infected children (CHAPAS-3): an open-label, parallel-group, randomised controlled trial. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Short-term toxicity assessment of combined use of zidovudine, lamivudine and lopinavir/ritonavir in vitro and in vivo. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Serious toxicity associated with continuous nevirapine-based HAART in pregnancy. [2013]

8. United States pubmed.ncbi.nlm.nih.gov

New Antiretroviral Therapies for Pediatric HIV Infection. [2021]

9. United States pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Starting Antiretroviral Therapy in the First Week of Life. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Nucleoside-analogue reverse-transcriptase inhibitors plus nevirapine, nelfinavir, or ritonavir for pretreated children infected with human immunodeficiency virus type 1. [2013]

11. England pubmed.ncbi.nlm.nih.gov

Prevention and treatment of HIV infection in neonates: evidence base for existing WHO dosing recommendations and implementation considerations. [2022]

12. France pubmed.ncbi.nlm.nih.gov

First-line antiretroviral treatment of HIV-infected children. A choice largely based on adult data. [2011]