Intervention: Raltegravir
Trial phase: Phase 1 | Phase 2
ATC code: J05AJ01 | J05AR16 | J05AX08
SMILES: Cc1nnc(C(=O)NC(C)(C)c2nc(C(=O)NCc3ccc(F)cc3)c(O)c(=O)n2C)o1
Sex: All
Age groups: Child
Healthy volunteers: No
Participants at risk: 13
Group description: Participants in this cohort received chewable raltegravir tablets (as a dispersible tablet), starting dose of 12 mg/kg (up to a maximum of 800 mg) orally twice daily, in addition to two NRTIs to treat HIV as part of standard of care, and a rifampicin-containing regimen to treat TB. After a study visit at Day 5 to 8, a fourth ARV medication was added to the regimen.

Raltegravir: Chewable raltegravir tablets, initially dosed at 12 mg/kg (up to a maximum of 800 mg) orally twice daily.
Eligibility criteria:
Inclusion Criteria:

Weight greater than or equal to 3.5 kg at entry
Confirmation of HIV-1 infection was defined as positive results from two samples collected at different time points. All samples tested must be whole blood, serum, or plasma. For studies conducted under an Investigational New Drug (IND), all test methods should be Food and Drug Administration (FDA)-approved if available. If FDA-approved methods are not available, test methods should be verified according to good clinical laboratory practice (GCLP) and approved by the International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) Laboratory Center. More information on this criterion can be found in the protocol.
ARV treatment naïve or did not received ARVs for at least 30 days prior to entry. Note: Participants with prior exposure to ARVs for prevention of mother-to-child transmission (PMTCT) or treatment - regardless of duration - were eligible provided the participant did not received ARVs for at least 30 days prior to entry. The reasons for interruption could include drug toxicity, poor adherence, or treatment failure that preceded enrollment and was not imposed by study staff. ARVs should not be withheld for the purposes of enrollment into the study and against the participant's best interest.

ARV treatment eligible as defined by:

Country-specific guidelines OR
World Health Organization (WHO) pediatric treatment algorithm (http://apps.who.int/iris/bitstream/10665/208825/1/9789241549684_eng.pdf?ua=1)
Diagnosis of pulmonary TB or TB adenitis. More information on this criterion can be found in the protocol.
Participant initiated at least a 2-drug TB regimen containing rifampicin, and had tolerated at least 1 week of the TB drug regimen prior to initiation of raltegravir. Note: TB treatment was allowed to be started after being diagnosed by the site investigator. Treatment regimens included isoniazid, pyrazinamide, ethambutol and streptomycin in addition to rifampicin. ART ideally started within 2 weeks of starting TB treatment. A patient who had started therapy for TB elsewhere but was not yet been started on ART was eligible for enrollment provided they did not have greater than 20 weeks of TB therapy. Delay between starting TB treatment and ART was not encouraged, and local or international guidelines should be followed for managing TB and HIV coinfection in infants and children.
Female participant who was of child bearing potential and sexually active agreed to use two reliable methods of contraception, including a medically accepted barrier method of contraception (e.g., female/male condoms, diaphragm or cervical cap with a cream or gel that kills sperm (excluding nonoxydyl-9), intrauterine device [IUD], others) together with another reliable form of contraception while on study and for 4 weeks after stopping raltegravir.
Parent, legal guardian, or designated guardian according to country-specific guidelines provided signed informed consent and to have the participant followed at the clinical site

Exclusion Criteria:

Greater than or equal to Grade 2 aspartate aminotransferase (AST) or alanine aminotransferase (ALT) at screening, which must be within 30 days of entry. Note: Participants were allowed to be re-screened provided that they had at least 4 weeks of TB treatment remaining at the time of entry.
Any greater than or equal to Grade 4 clinical toxicity or laboratory result at screening except fever, chills, fatigue or malaise, unintentional weight loss, and dyspnea or respiratory distress that could be associated with TB
Acute, serious infections other than TB requiring active treatment (e.g., Pneumocystis jirovecii [previously Pneumocystis carinii] pneumonia [PCP], cryptococcal meningitis, etc.). Infants and children diagnosed with acute bacterial pneumonia at time of diagnosis of TB may be included. Prophylaxis against opportunistic infections was allowed.
Diagnosis of Kwashiorkor (less than 80% expected weight-for-age with the presence of edema and hypoalbuminemia)
Current chemotherapy for active malignancy and history of chemotherapy discontinued within 1 year of entry
Rifampicin therapy of greater than 20 weeks duration immediately prior to enrollment
Known or suspected multidrug resistant (MDR) or extensively drug resistant (XDR) TB, including contact with a documented MDR or XDR TB source case, as these may require longer duration of therapy or non-rifampicin containing regimen. Note: Participants found to have MDR or XDR TB before or during the study were informed of their illness and referred for appropriate care as determined by local guidelines.
Current TB regimen containing rifabutin, macrolides, and any other anti-mycobacterial agents with known interactions with raltegravir
Any clinically significant diseases (other than HIV and TB infection) or clinically significant findings during the screening medical history or physical examination that, in the investigator's opinion, would compromise the outcome of this study
Participant who was pregnant or breastfeeding
Participant who was unlikely to adhere to the study procedures or keep appointments
Participant who was planning to relocate during the study to a non-IMPAACT study site
Participant who was taking any disallowed medications.