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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether starting antiretroviral treatment very early in life can help control HIV in infants and maintain strong immune systems. The study includes different groups: some infants begin treatment immediately after birth, while others start shortly after. It uses medications such as Kaletra, Lamivudine (also known as Epivir or Epivir-HBV), Nevirapine (also known as Viramune or Viramune XR), and Zidovudine (also known as Retrovir or AZT). The trial seeks infants with HIV who can begin treatment within a few days of birth and includes a control group of older children who started treatment later. As a Phase 2/3 trial, this study measures the treatment's effectiveness in an initial group and represents the final step before FDA approval, offering a chance to contribute to significant advancements in HIV treatment for infants.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that the treatments used in this trial—Kaletra, Lamivudine, Nevirapine, and Zidovudine—have been studied for safety in infants and young children.

Studies on Kaletra indicate it is generally safe for infants at least 13 days old and born at 34 weeks or later. However, it should not be used in premature newborns immediately after birth due to potential harmful effects.

Lamivudine has been researched in infants and is considered safe when used alone or with other HIV medications. It has been administered to infants as young as one week old, though data is limited.

Nevirapine is shown to be safe for infants born after 34 weeks. It has been successfully used to prevent HIV transmission from mother to child in breastfeeding infants up to six months old.

Zidovudine is also found to be safe and effective when started early in infants. Most infants on this treatment have low levels of the virus in their blood by six months of age.

Overall, these drugs have a history of safe use in infants. However, each infant may react differently, so close monitoring is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about early antiretroviral therapy (ART) for infant HIV/AIDS because it aims to start treatment much earlier than usual, within the first days or weeks of life. This early intervention could potentially suppress the virus more effectively and bolster the infant's immune system from the start. While traditional ART typically begins when symptoms appear, this approach could change the standard by possibly preventing symptoms from developing at all. By using a combination of drugs like Nevirapine, Zidovudine, Lamivudine, and Kaletra, this method targets the virus aggressively before it can establish a strong presence in the body, offering hope for better long-term health outcomes for HIV-positive infants.

What evidence suggests that this trial's treatments could be effective for infant HIV/AIDS?

Research has shown that starting HIV treatment early can be very effective for infants. In this trial, infants in the Antepartum Cohort will initially receive Nevirapine, Zidovudine, and Lamivudine soon after birth, a combination found to be safe and effective in controlling the virus. Infants on these treatments often maintain low virus levels, indicating successful management. Meanwhile, the Peripartum Cohort will primarily start with Kaletra, Zidovudine, and Lamivudine, a combination shown to lower early infant death rates and slow HIV progression. Early treatment links to better survival and health for infants. Overall, starting HIV treatment soon after birth is crucial for managing the virus effectively in infants. ^{6 7 8 9 10}

Who Is on the 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

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6978195/

Early antiretroviral treatment of infants to attain HIV remission Three HIV-infected infants (4.1%) died and nine (12.3%) were lost to follow-up before 48 weeks of age. Of those surviving on study, 52.5% ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7850532/

Safety and Efficacy of Starting Antiretroviral Therapy in the ... Our 3 major findings were that starting NVP, ZDV, and 3TC at treatment dosages was safe and effective; that all infants could be successfully transitioned to ...

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa0800971

Early Antiretroviral Therapy and Mortality among HIV ... Early HIV diagnosis and early antiretroviral therapy reduced early infant mortality by 76% and HIV progression by 75%.

4. clinicalinfo.hiv.gov clinicalinfo.hiv.gov/en/guidelines/pediatric-arv/zidovudine

Pediatric Antiretroviral Drug Information - Zidovudine | NIH Early treatment was found to be safe and effective, with most infants achieving and maintaining viral suppression by 24 weeks of age.16. For ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT00102960

Study Details | NCT00102960 | Anti-HIV Drugs for Treating ... First-line treatment of zidovudine, lamivudine, and lopinavir/ritonavir will continue until infants reach a study endpoint; when this occurs, infants will then ...

6. clinicalinfo.hiv.gov clinicalinfo.hiv.gov/en/guidelines/pediatric-arv/lopinavirritonavir

Pediatric Antiretroviral Drug Information - Lopinavir/Ritonavir The authors concluded that oral LPV/r solution is safe and effective in preterm infants at ≥13 days postnatal age and ≥34 weeks postmenstrual ...

7. fda.gov fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-serious-health-problems-seen-premature-babies-given-kaletra

Serious health problems seen in premature babies given ... Kaletra oral solution should be avoided in preterm neonates in the immediate postnatal period because of possible toxicities. Kaletra oral ...

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38190642/

Safety and Pharmacokinetics of Lopinavir/Ritonavir Oral ... LPV/r oral solution was safely initiated in a relatively small sample size of infants ≥34 weeks PMA and >2 weeks of life.

9. mayoclinic.org mayoclinic.org/drugs-supplements/lopinavir-and-ritonavir-oral-route/description/drg-20063001

Lopinavir and ritonavir (oral route) - Side effects & dosage Lopinavir and ritonavir combination will not keep you from spreading HIV to other people. People who receive this medicine may continue to have ...

10. rxabbvie.com rxabbvie.com/pdf/kaletratabpi.pdf

KALETRA (lopinavir and ritonavir) tablet for oral use ... 8.4 Pediatric Use. The safety, efficacy, and pharmacokinetic profiles of KALETRA in pediatric patients below the age of 14 days have not been established.