Effectiveness of a community-based intervention to prevent childhood TB in Lesotho.

BACKGROUND: Child contact management (CCM) is a recognized strategy to prevent TB; however, implementation is suboptimal. PREVENT was a cluster-randomized trial that evaluated the effectiveness and acceptability of a community-based intervention (CBI) to improve CCM in Lesotho.METHODS: Ten health facilities (HFs) were randomized to CBI or standard-of-care (SOC). CBI included nurse training/mentorship, health education by village health workers (VHW), adherence support, and multidisciplinary team meetings. Information on TB cases registered from February 2016 to June 2018 and their child contacts was abstracted. Outcomes were TB preventive treatment (TPT) initiation, TPT completion, and CBI acceptability. Generalized linear mixed models were used to test for differences between study arms and qualitative interview thematic analysis for acceptability.RESULTS: Among 547 registered children (CBI: n = 399; SOC: n = 148) of 426 adult TB patients, 46% were <2 years, 48% female, and 3% HIV-exposed/positive, with no significant differences between study arms. A total of 501 children initiated TPT-98% at CBI and 88% at SOC HFs (P < 0.0001). TPT completion was 82% in CBI vs. 59% in SOC sites (P = 0.048). Caregivers and providers reported that CBI was acceptable.CONCLUSION: The CBI was acceptable and significantly improved TPT initiation and completion in Lesotho, offering the opportunity to mitigate the threat of TB among children.

A window into a public program for prevention of mother to child transmission of HIV: evidence from a prospective clinical trial.

OBJECTIVES: To evaluate efficacy of the antenatal, intra-partum and post-natal antiretroviral components of a public service Prevention of Mother to Child (MTCT) program in infants. DESIGN: Analysis of prospectively collected screening data of demographic and MTCT-related interventions and HIV-infection status of infants identified through HIV-specific DNA polymerase chain reaction. SETTING: Tygerberg Children's Hospital, Western Cape Province, South Africa. SUBJECTS: HIV-infected women and their infants identified through participation in a public service MTCT program were referred for possible participation in a prospective study of isoniazid prophylaxis. INTERVENTIONS: Key components of the Program include voluntary counselling and testing, zidovudine to the mother from between 28 and 34 weeks gestation and to the newborn infant for the first week, single dose nevirapine to the mother in labour and the newborn shortly after birth and free formula for 6 months. MAIN OUTCOME MEASURES: Number and percentage of HIV-infected infants and extent of exposure to antenatal, intrapartum and post-natal antiretrovirals. RESULTS: Of 656 infants with a median age of 12.6 weeks, screened between April 1(st) 2005 through May 2006, 39 were HIV-infected giving a transmission rate of 5.9% (95% CI: 4.4% - 8.0%). Antenatal prophylaxis was significantly associated with reduced transmission (OR: 0.43 (95% CI: 0.21 - 0.94)) as opposed to intrapartum and postpartum components (p=0.85 and p=0.84, respectively). In multivariable analysis the antenatal component remained significant (OR=0.40 (95% CI 0.19 - 0.90)). CONCLUSIONS: The antenatal phase is the most important antiretroviral component of the MTCT program, allowing most opportunity for intervention.

Monosomy 1p36 uncovers a role for OX40 in survival of activated CD4+ T cells.

Monosomy 1p36 is a subtelomeric deletion syndrome associated with congenital anomalies presumably due to haploinsufficiency of multiple genes. Although immunodeficiency has not been reported, genes encoding costimulatory molecules of the TNF receptor superfamily (TNFRSF) are within 1p36 and may be affected. In one patient with monosomy 1p36, comparative genome hybridization and fluorescence in- situ hybridization confirmed that TNFRSF member OX40 was included within the subtelomeric deletion. T cells from this patient had decreased OX40 expression after stimulation. Specific, ex vivo T cell activation through OX40 revealed enhanced proliferation, and reduced viability of patient CD4+ T cells, providing evidence for the association of monosomy 1p36 with reduced OX40 expression, and decreased OX40-induced T cell survival. These results support a role for OX40 in human immunity, and calls attention to the potential for haploinsufficiency deletions of TNFRSF costimulatory molecules in monosomy 1p36.

Tuberculosis exposure in HIV-exposed infants in a high-prevalence setting.

Exposure to TB was quantified by screening human immunodeficiency virus (HIV) exposed infants aged 3-4 months for an isoniazid prophylaxis study where tuberculosis (TB) exposure excluded enrolment. Seventy-seven (10.1%, 95%CI 8.0-12.4) of 766 infants had contact with a TB source case. Nurses and lay counsellors identified 52 infants during pre-screening and doctors identified 25 during formal screening. High exposure may contribute to high rates of TB in HIV-exposed infants. Programs to prevent mother-to-child transmission of HIV offer an important opportunity to screen for TB. In-depth assessment is required for evaluating TB exposure.

Tuberculosis preventive treatment preferences among care givers of children in Lesotho: a pilot study.

BACKGROUND: Shorter-duration regimens for preventing drug-susceptible tuberculosis (TB) have been shown to be safe and efficacious in children, and may improve acceptability, adherence, and treatment completion. While these regimens have been used in children in low TB burden countries, they are not yet widely used in high TB burden countries. SETTING: Five health facilities in one district in Lesotho, a high TB burden country. OBJECTIVE: Assess the preventive treatment preferences of care givers of child TB contacts. DESIGN: Qualitative data were collected using in-depth interviews with 12 care givers whose children completed preventive treatment, and analyzed using grounded theory. FINDINGS: Care givers were interested in being involved in the children's treatment decisions. Pill burden, treatment duration and related frequency of dosing were identified as important factors that influenced preventive treatment preferences among care givers. CONCLUSION: Understanding care giver preferences and involving them in treatment decisions may facilitate efforts to implement successful preventive treatment for TB among children in high TB burden countries.

Use of antiretrovirals in HIV-infected children in a tuberculosis prevention trial: IMPAACT P1041.

SETTING: International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) P1041, a tuberculosis (TB) prevention trial conducted among children enrolled from 2004 to 2008 during South Africa's roll-out of combination antiretroviral therapy (ART). OBJECTIVE: To estimate TB incidence and mortality and the effect of ART. DESIGN: Children were pre-screened to exclude TB disease and exposure, actively screened 3-monthly for TB exposure and symptoms, and provided post-exposure isoniazid prophylaxis therapy (IPT). TB diagnoses were definite, probable, or possible, and mortality all-cause. Testing was at the 5% significance level. RESULTS: In 539 children (aged 3-4 months) followed up for a median of 74 weeks (interquartile range [IQR] 48-116), incidence/100 person-years (py) was 10.67 (95%CI 8.47-13.26) for any TB and 2.89 (95%CI 1.85-4.31) for definite/probable TB. Any TB incidence was respectively 9.39, 13.59, and 9.83/100 py before, <180 days after, and 180 days after ART initiation. Adjusted analysis showed a non-significant increase in any TB (HR 1.32, 95%CI 0.71-2.52, P = 0.38) and a significant reduction in mortality (HR 0.39, 95%CI 0.17-0.82, P = 0.017) following ART initiation. CONCLUSIONS: ART reduced mortality but not TB incidence in human immunodeficiency virus (HIV) infected children in IMPAACT P1041, possibly attributable to active screening for TB exposure and symptoms with post-exposure IPT. Research into this as a strategy for TB prevention in high HIV-TB burden settings may be warranted.

Understanding NIH clinical case definitions for pediatric intrathoracic TB by applying them to a clinical trial.

SETTING: Standardized clinical case definitions represent the best option for pediatric tuberculosis (TB) disease diagnosis and classification. OBJECTIVE: To apply published guidelines for intrathoracic TB classification for use in reporting diagnostic studies with passive case finding to presumed TB patients from International Maternal Pediatric Adolescent AIDS Clinical Trials P1041, a trial of isoniazid prophylaxis in healthy human immunodeficiency virus exposed, bacille Calmette-Guérin vaccinated infants which employed active surveillance to assess a novel application of these guidelines in this setting. METHODS: P1041 presumed TB patients were retrospectively cross-classified by protocol-defined and National Institutes of Health (NIH) classifications, and agreement was assessed. RESULTS: Of 219 TB suspects, 166 had signs/symptoms, with 158 considered TB (21 confirmed, 92 probable, 45 possible) and 8 not TB (6 TB unlikely, 2 alternative diagnoses). Weight loss and failure to thrive represented the majority of the observed signs/symptoms. Among those with signs/symptoms, agreement between definitions was poor. Furthermore, 53 TB presumptives were without signs/symptoms, including 33 classified by the P1041 protocol as TB. CONCLUSION: Poor agreement between P1041 and NIH classifications reflects cases identified through active vs. passive surveillance, the latter reflecting the intended use of NIH definitions. Given the interest in standardized definitions for broader application, future efforts could focus on expanding TB disease classification to presumed TB patients identified through active surveillance.

Drug-resistant tuberculosis clinical trials: proposed core research definitions in adults.

Drug-resistant tuberculosis (DR-TB) is a growing public health problem, and for the first time in decades, new drugs for the treatment of this disease have been developed. These new drugs have prompted strengthened efforts in DR-TB clinical trials research, and there are now multiple ongoing and planned DR-TB clinical trials. To facilitate comparability and maximise policy impact, a common set of core research definitions is needed, and this paper presents a core set of efficacy and safety definitions as well as other important considerations in DR-TB clinical trials work. To elaborate these definitions, a search of clinical trials registries, published manuscripts and conference proceedings was undertaken to identify groups conducting trials of new regimens for the treatment of DR-TB. Individuals from these groups developed the core set of definitions presented here. Further work is needed to validate and assess the utility of these definitions but they represent an important first step to ensure there is comparability in clinical trials on multidrug-resistant TB.

A double-blind, randomised, placebo-controlled, dose-finding trial of the novel tuberculosis vaccine AERAS-402, an adenovirus-vectored fusion protein, in healthy, BCG-vaccinated infants.

BACKGROUND: Several novel tuberculosis vaccines are currently in clinical trials, including AERAS-402, an adenovector encoding a fusion protein of Mycobacterium tuberculosis antigens 85A, 85B, and TB10.4. A multicentred trial of AERAS-402 safety and immunogenicity in healthy infants was conducted in three countries in sub-Saharan Africa, using an adaptive design. METHODS: In a double-blind, randomised, placebo-controlled, dose-finding trial, we enrolled BCG-vaccinated, HIV-uninfected infants aged 16-26 weeks. Infants in the safety/dose-finding phase received two doses of AERAS-402 across three dose levels, or placebo, intramuscularly on days 0 and 28. Infants in the expanded safety phase received three doses of the highest dose level, with the 3rd dose at day 280. Follow up for safety and immunogenicity was for up to two years. RESULTS: We enrolled 206 infants (52 placebo and 154 AERAS-402 recipients) into the dose-finding phase and 281 (141 placebo and 140 AERAS-402 recipients) into the expanded safety phase. Safety data were acceptable across all dose levels. No vaccine-related deaths were recorded. A single serious adverse event of tachypnoea was deemed related to study vaccine. Antibodies directed largely against Ag85A and Ag85B were detected. Low magnitude CD4+ and CD8+ polyfunctional T cell responses were observed at all dose levels. The addition of a third dose of AERAS-402 at the highest dose level did not increase frequency or magnitude of antibody or CD8+ T cell responses. CONCLUSIONS: AERAS-402 has an acceptable safety profile in infants and was well tolerated at all dose levels. Response rate was lower than previously seen in BCG vaccinated adults, and frequency and magnitude of antigen-specific T cells were not increased by a third dose of vaccine.

Proteolysis of insulin-like growth factor-binding protein-3 in human immunodeficiency virus-positive children who fail to thrive.

Failure to thrive is a common manifestation of human immunodeficiency virus (HIV) infection in children. Given the role of insulin-like growth factor I (IGF-I) in stimulating postnatal growth, we have examined whether HIV-infected pediatric patients with growth failure have lower serum concentrations of IGF-I than age-matched control subjects. IGF-I was measured in 16 HIV-infected children and 13 HIV-negative controls. Ten of the HIV-infected children failed to thrive based on height and linear growth that was below the National Center for Health Statistics 10th percentile. IGF-I levels were significantly lower in children who failed to thrive compared to those in age-matched controls (20 vs. 60 micrograms/L; P < 0.001). Children who failed to thrive also displayed lower IGF-I levels than HIV-positive children, who exhibited normal growth velocity (20 vs. 91 micrograms/L; P < 0.001). Failure to thrive was associated with a significant reduction in circulating levels of IGF-binding protein-3 (IGFBP-3), as determined by ligand and Western blotting (P < 0.001), enhanced IGFBP-3 proteolysis (P < 0.001), and a decrease in the serum concentration of the acid-labile subunit of the IGFBP-3 ternary complex (P < 0.005). IGFBP-3 proteolysis was negatively correlated with IGF-I (r = 0.78) and IGFBP-3 levels (r = 0.70). Failure to thrive was associated with a reduction in the formation of the ternary complex, but the ternary complex could be restored by the addition of an excess of IGFBP-3 to serum. These results indicate that low levels of IGF-I, IGFBP-3, and acid-labile subunit are associated with a failure to thrive in HIV-infected children.

Population pharmacokinetics of dapsone in children with human immunodeficiency virus infection.

BACKGROUND: Previous studies of dapsone pharmacokinetics in children have been too small to allow assessment of the relationships between dapsone pharmacokinetic parameters and patient characteristics or markers of efficacy and toxicity. METHODS: We used population analysis to estimate dapsone pharmacokinetic parameters in children participating in a phase I/II study of daily and weekly dapsone in children with human immunodeficiency virus (HIV) infection. With use of the program NONMEM and a 1-compartment open model, the influence of demographic and clinical characteristics on oral clearance (CL/F) and oral volume of distribution (V/F) were examined. Measures of drug exposure (area under the concentration-time curve [AUC] and predicted concentrations just before and 2 hours after administration) were estimated for each patient and correlated with markers of efficacy and toxicity. RESULTS: Sixty children (median age, 3 years; age range, 2 months to 12 years) contributed 412 dapsone concentrations collected after 175 study doses. Final parameter estimates were 1.40 L/kg for V/F, 0.0283 L/kg/h for CL/F, and 2.66 for the absorption rate constant. Of the clinical characteristics evaluated, dapsone CL/F was significantly increased by 50% in children taking rifabutin, by 39% in black children, and by 38% in children younger than 2 years old. Although no significant correlations were found between any dapsone exposure parameter and markers of toxicity, increased AUC was associated with a decreased risk of Pneumocystis carinii pneumonia (PCP). CONCLUSION: Ethnicity, age, and concomitant rifabutin use were associated with dapsone CL/F, with more rapid clearance observed in black children, children younger than 2 years old, and children receiving rifabutin. Dapsone pharmacokinetic parameters were not associated with toxicity, but higher dapsone AUC was associated with decreased risk of PCP. Monitoring of serum dapsone levels may be needed for optimal management of dapsone for PCP prophylaxis in children.

Combination nucleoside analog reverse transcriptase inhibitor(s) plus nevirapine, nelfinavir, or ritonavir in stable antiretroviral therapy-experienced HIV-infected children: week 24 results of a randomized controlled trial--PACTG 377. Pediatric AIDS Clinical Trials Group 377 Study Team.

One hundred eighty-one antiretroviral-experienced, protease inhibitor-naive, clinically stable HIV-infected children between 4 months and 17 years of age were randomly assigned to receive one of four combination regimens to evaluate the change in plasma HIV RNA, safety, and tolerance when changing antiretroviral therapy to a protease inhibitor-containing combination regimen. All four regimens contained stavudine; in addition children received nevirapine plus ritonavir, lamivudine plus nelfinavir, nevirapine plus nelfinavir, or lamivudine plus nevirapine plus nelfinavir. Twelve additional children chose to receive stavudine plus lamivudine plus nelfinavir, with nelfinavir given bid, rather than tid as for the main regimens. Overall, 51% (89/176; 95% CI 43-58%) of the children on the randomized portion of the study had an HIV RNA response (< or =400 copies/ml) on at least two of the three HIV RNA determinations taken at Weeks 8, 12, and 16. At Week 24 the proportion of children with an HIV RNA response still on initial therapy was 47% (83/176; 95% CI 40-55%) and ranged from 41 to 61% for the four randomized treatment arms. Rash was frequently seen (27%) on the treatment arms containing nevirapine. At Week 24 64% (7/11, 95% CI 31-89%) of the children on the bid nelfinavir combination regimen were still on initial therapy with an HIV RNA response as compared with 46% (23/50; 95% CI 32-61%) on the corresponding tid nelfinavir combination regimen. A change in antiretroviral therapy to a protease inhibitor-containing regimen was associated with a virological response rate of approximately 50% for this patient population.

Cholestatic hepatitis in children infected with the human immunodeficiency virus.

A distinct clinical syndrome of cholestasis and hepatitis occurred during early infancy in seven infants with perinatally acquired human immunodeficiency virus 1 infection. In five infants hepatitis was the first manifestation of human immunodeficiency virus 1 infection. The median age of onset of hepatitis was 7 months (range, 5 to 10 months). The mean total bilirubin concentration at presentation was 7.4 mg/dl (range, 3.9 to 11 mg/dl), the mean aspartate aminotransferase was 1512 IU/liter (range, 782 to 2960 IU/liter) and the mean alanine amino-transferase 512 IU/liter (range, 92 to 1247 IU/liter). The absolute CD4 count at the time of onset of hepatitis ranged from 191 to 2298 cells/mm3 (mean, 766 cells/mm3). Six of the seven children died within 12 weeks of onset of hepatitis, three as a result of complications of Pneumocystis carinii pneumonia, and two died of complications secondary to cytomegalovirus. In only one infant was the cause of death the direct consequence of liver failure. The seventh infant died 17 months after the onset of hepatitis of dilated cardiomyopathy. No specific etiologic agent has been identified as the cause of cholestatic hepatitis in these infants. In situ hybridization studies to detect human immunodeficiency virus 1 messenger RNA was negative in the liver tissue obtained at biopsy and autopsy in five of the samples tested.

Toxicity and efficacy of daily vs. weekly dapsone for prevention of Pneumocystis carinii pneumonia in children infected with human immunodeficiency virus. ACTG 179 Study Team. AIDS Clinical Trials Group.

BACKGROUND: Dapsone is an alternative drug for Pneumocystis carinii pneumonia (PCP) prophylaxis in individuals intolerant to trimethoprim-sulfamethoxazole (T/S). There are, however, few data on the pharmacokinetics, toxicity or efficacy of dapsone in children. Design. Randomized, multicenter trial comparing daily (1 or 2 mg/kg) with weekly (4 mg/kg) dapsone regimens in 94 HIV-infected children intolerant to T/S. METHODS: Hematologic and hepatic toxicity was monitored, as well as the occurrence of skin rash, PCP or death. RESULTS: Initial pharmacokinetic data indicated that adequate serum dapsone concentrations were not achieved with the daily 1-mg/kg regimen; the daily dose was then increased to 2 mg/kg. Both short and long term hematologic toxicities were marginally greater in children receiving the daily 2 mg/kg compared with the weekly regimen. Allergic skin rashes were similar in children receiving the daily and weekly regimens (17% in both) and were not associated with prior history of rash with T/S. PCP occurred most frequently with the daily 1-mg/kg regimen (22.0 cases/100 patient years), least frequently with the daily 2-mg/kg regimen (0 case/100 patient years) and at intermediate frequency with the weekly regimen (9.5 cases/100 patient years). More deaths were observed in patients receiving the daily than the weekly regimen (8 vs. 2, respectively), although the deaths were not directly attributable to dapsone treatment. CONCLUSION: Although a weekly dapsone regimen of 4 mg/kg produced less hematologic toxicity than a daily regimen of 2 mg/kg, this advantage was offset by a trend toward higher breakthrough rates of PCP.

Testing cord blood human chorionic gonadotropin as a surrogate marker for early identification of human immunodeficiency virus-1 infection in children.

We measured human chorionic gonadotropin (hCG) in cord sera of 22 infants born to women infected with the human immunodeficiency virus-1 (HIV-1). hCG was also determined in cord sera from 173 infants born at a suburban hospital to HIV-1-seronegative women. The findings indicate that 16 (9%) of 173 HIV-1-seronegative samples had hCG levels greater than 90 IU/L (values were distributed as a Poisson curve). In contrast, 8 (36%) of the 22 infants born to HIV-1-infected women had hCG levels in excess of 90 IU/L, and 7 (88%) of these were shown to be HIV-infected. The remaining 14 infants born to HIV-1-infected women had low hCG levels, and 3 (21%) of the 14 had HIV infection. Mean follow-up time for HIV-uninfected infants was 17.5 months (range 9 months to 3 years). A statistically significant association between maternal-fetal HIV-1 transmission and hCG levels > or = 90 IU/L in cord sera was observed (p = 0.02). The difference between CD4 counts among mothers who transmitted HIV and those who did not was also statistically significant (p = 0.025). On the basis of this study's findings, we propose that cord blood hCG may serve as a surrogate marker for HIV-1 infection. Testing hCG levels in cord sera is an inexpensive and readily available screening test for early identification of infants at increased risk for getting HIV-1 from their mothers.

Left ventricular outflow tract pulmonary artery fistula in endocarditis.

Patients with infective endocarditis are at risk for the development of a fistulous communication between chambers or great vessels of the heart. The presence of a continuous murmur may suggest the diagnosis. The first case of aortic valve endocarditis complicated by the development of a fistulous communication between the left ventricular outflow tract and the pulmonary artery is reported. Transesophageal Doppler echocardiography did not detect the defect preoperatively. However, pulmonary artery catheterization revealed very high mixed venous oxygen saturation which supported the presence of a left-to-right shunt.

Implications and management of oral diseases in children and adolescents with HIV infection.

The impact of human immunodeficiency virus (HIV) infection on children continues to be felt worldwide. Since 1981, when the first patients with HIV were recognized, to 1996, when it was estimated that more than 14 million men, women and children were infected with the virus, no other infectious disease has had such a strong impact on the medical community. With the advent of better methods of detection and better therapies we are beginning to see HIV-infected children surviving longer, and thus coming under the care of a host of affiliated medical personnel, including dentists. This article will serve as a brief update on pediatric HIV and its impact on the oral health of infected children.

Loss to follow-up among infants in a study of isoniazid prophylaxis (P1041) in South Africa.

OBJECTIVE: To assess risk factors for loss to follow-up (LFU) from the IMPAACT P1041 study, an isoniazid (INH) prophylaxis study conducted in southern Africa. DESIGN: Infants in two cohorts, human immunodeficiency virus-infected (HIV+) and HIV-exposed but non-infected (HIV-), were randomized to INH or placebo for 96 weeks. LFU was evaluated at week 96. RESULTS: Of 1351 infants, 12.9% were LFU (10.4% HIV+, 14.7% HIV-); 65% of the HIV+ cohort was asymptomatic. Among HIV+ infants, large household size (>6 vs. <4 members, P = 0.035) and presence of an elder (≥55 years, P = 0.05) were associated with better retention. Although attenuated in adjusted analysis, these associations held among HIV- infants. Among HIV- infants, having a younger mother increased the risk (P = 0.008) and maternal history of TB reduced the risk of LFU, the latter by nearly 70% (P = 0.048 univariate, 0.09 adjusted). LFU was largely due to inability to contact the participant (58% HIV+, 30% HIV-), and inability to attend the clinic and withdrawal of consent (HIV-). CONCLUSIONS: Household support was an important factor in participant retention, particularly for the non-HIV-infected cohort, as young maternal age was a risk factor for LFU. Retaining study participants from this mobile population can be challenging and may warrant additional support.

Requirements for the clinical evaluation of new anti-tuberculosis agents in children.

The ultimate goal of evidence-based drug treatment is to produce a desired pharmacological response in a predictable manner and also to minimise adverse effects. This goal requires not only an increased awareness of the need to provide specific dosing recommendations aimed at specific patient groups, but also the implementation of a consistent integrative approach to recognise all factors contributing to the within- and between-subject variability in drug disposition and response. The assessment of new anti-tuberculosis agents and regimens in children requires a specific programme of investigation, and should be included early in human drug evaluation programmes. Appreciation of this principle is an important step forward towards the full integration of children into the tuberculosis research agenda and control programmes. The development of anti-tuberculosis drug formulations and regimens tailored to the requirements of children needs to consider physiological age-related differences for pharmacokinetics and toxicity between adults and children. Research based on these principles will create an evidence base that will inform the appropriate treatment of children with novel agents and regimens and will also inform future research, including the use of chemoprophylaxis and treatment-shortening strategies in children.

High prevalence of drug resistance amongst HIV-exposed and -infected children in a tuberculosis prevention trial.

An emergence of drug-resistant tuberculosis (DR-TB) in settings affected by human immunodeficiency virus (HIV) and tuberculosis (TB) has been observed. We investigated the prevalence of DR-TB in P1041, a multicentered, randomised, double-blind trial which compared the administration of isoniazid (INH) to placebo, in HIV-exposed, non-infected and -infected African infants in the absence of any documented TB exposure. The prevalence of multidrug-resistant TB (MDR-TB) was 22.2% (95%CI 8.5-45.8) and INH monoresistance 5.6% (95%CI 0.1-27.6) among culture-confirmed cases, with all MDR-TB occurring in a single site. There was no association between INH treatment or placebo group, or between HIV infection status, and DR-TB prevalence. There was a high prevalence of DR-TB among HIV-exposed and -infected children. Surveillance of DR-TB among children in high-burden TB-HIV settings should be routine.