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Objective: To assess the impact of HIV and antiretroviral exposure without infection on lung growth and function over the first 2 years of life., Design: Prospective observational study of an African birth cohort, Drakenstein Child Health Study., Method: Infants enrolled antenatally had lung function measured at 6 weeks, 1 and 2 years. HIV-infected women received antiretroviral therapy (ART) as per local guidelines. The association between HIV and antiretroviral exposure with lung function was assessed using mixed effects modelling., Results: Of 1143 infants born, two HIV-infected infants were excluded from analysis; 909 (80%) infants had lung function collected at 6 weeks [190 (21%) were HIV-exposed uninfected (HEU)]; 782 (69%) at 1 year and 741 (65%) at 2 years. At 6 weeks HEU infants had larger tidal volume compared with HIV-unexposed infants (1.13 ml, confidence interval: 0.02-2.23, P = 0.045). High maternal viral load was associated with a 17% lower expiratory flow over 2 years (0.17, confidence interval 0.00-0.34, P = 0.046). First-line ART initiated during pregnancy was associated with lower infant tidal volume at 6 weeks compared with those who initiated ART before pregnancy (-2.7 ml, -5.31 to -0.10, P = 0.042), and low maternal CD4 cell counts associated with lower infant tidal over 2 years (-11.1 ml, -18.58-3.58, P = 0.004)., Conclusion: HIV exposure is associated with altered lung function in early life, with a vulnerable HEU subgroup based on maternal disease severity, immunological compromise and ART exposure. These data highlight the importance of ongoing surveillance of respiratory health in HEU children.

Background: Despite increased access to highly active antiretroviral therapy (HAART), lung disease remains common in human immunodeficiency virus (HIV)-infected (HIV+) adolescents. There is limited information on changes in lung function over time in perinatally HIV+ adolescents on HAART. The objective was to investigate the progression of spirometry findings over 2 years in HIV+ adolescents on HAART in a prospective cohort, the Cape Town Adolescent Antiretroviral Cohort (CTAAC)., Methods: HIV+ adolescents aged 9-14 years, with at least 6 months of HAART, and a comparator group of healthy HIV-uninfected (HIV-), age-matched controls were enrolled in CTAAC. Spirometry and bronchodilator testing were done at baseline, 12 months, and 24 months. Mixed-effect models were used to compute longitudinal changes in lung function., Results: Five hundred fifteen HIV+ adolescents, mean age 12 (standard deviation [SD], 1.6) years, 50.4% male, and 110 HIV- adolescents, mean age 11.8 (SD, 1.8) years, 45.6% male, were tested at baseline; 477 (93%) HIV+ and 102 (93%) HIV- adolescents at 12 months; and 473 (92%) HIV+ and 97 (88%) HIV- adolescents at 24 months. Only 5.4% of the HIV+ adolescents had HIV viral load >10 000 copies/mL at baseline. Forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) were lower in the HIV+ compared to the HIV- adolescents and tracked with no deterioration or catch-up over 2 years. Previous pulmonary tuberculosis (PTB) or lower respiratory tract infection (LRTI) was significantly associated with reduced FEV1 and FVC (P < .05 for both)., Conclusions: HIV+ adolescents had lower lung function over 2 years than HIV- adolescents. This study highlights the need for lung function surveillance and prevention of LRTIs and PTB in HIV+ adolescents., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Tuberculosis (TB) is an important cause of illness and death in HIV-positive children living in areas of high TB prevalence. We know that isoniazid prophylaxis prevents TB in HIV-negative children following TB exposure, but there is uncertainty related to its role in TB preventive treatment in HIV-positive children., Objectives: To summarise the effects of TB preventive treatment versus placebo in HIV-positive children with no known TB contact on active TB, death, and reported adverse events., Search Methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE/PubMed, Embase and two trial registers up to February 2017., Selection Criteria: We included trials of HIV-positive children with and without known TB exposure, randomized to receive TB preventive treatment or placebo., Data Collection and Analysis: Two review authors independently used the study selection criteria, assessed risk of bias, and extracted data. We assessed effects using risk, incidence rate and hazard ratios and assessed the certainty of evidence using GRADE., Main Results: We included three trials, involving 991 participants, below the age of 13 years, from South Africa and Botswana. Children were randomized to isoniazid prophylaxis or placebo, given daily or three times weekly. The median length of follow-up ranged from 5.7 to 34 months; some were on antiretroviral therapy (ART).In HIV-positive children not on ART, isoniazid prophylaxis may reduce the risk of active TB (hazard ratio (HR) 0.31, 95% confidence interval (CI) 0.11 to 0.87; 1 trial, 240 participants, low certainty evidence), and death (HR 0.46, 95% CI 0.22 to 0.95; 1 trial, 240 participants, low certainty evidence). One trial (182 participants) reported number of children with laboratory adverse events, which was similar between the isoniazid prophylaxis and placebo groups. No clinical adverse events were reported.In HIV-positive children on ART, we do not know if isoniazid prophylaxis reduces the risk of active TB (risk ratio (RR) 0.76, 95% CI 0.50 to 1.14; 3 trials, 737 participants, very low certainty evidence) or death (RR 1.45, 95% CI 0.78 to 2.72; 3 trials, 737 participants, very low certainty evidence). Two trials (714 participants) reported number of clinical adverse events and three trials (795 participants) reported number of laboratory adverse events; for both categories, the number of adverse events were similar between the isoniazid prophylaxis and placebo groups., Authors' Conclusions: Isoniazid prophylaxis given to all children diagnosed with HIV may reduce the risk of active TB and death in HIV-positive children not on ART in studies from Africa. For children on ART, no clear benefit was detected. .

Rationale: Lung disease is a common cause of mortality and morbidity in HIV-infected adolescents, but there is limited information on the spectrum of lung function impairment in adolescents on antiretroviral therapy., Objectives: To investigate lung function in HIV-infected adolescents on antiretroviral therapy in the Cape Town Adolescent Antiretroviral Cohort (Cape Town, South Africa)., Methods: A total of 515 South African adolescents, aged 9-14 years, stable on antiretroviral therapy for at least 6 months, underwent baseline lung function testing. Measures included spirometry, nitrogen multiple-breath washout, forced oscillation technique, 6-minute walk test, single-breath carbon monoxide diffusion testing, and bronchodilator response testing. A comparator group of 110 age- and ethnicity-matched HIV-uninfected adolescents was also tested., Results: For the HIV-infected adolescents (mean [SD] age 12 [1.6] years, 52% male), the median (interquartile range) duration of antiretroviral therapy was 7.6 (4.6-9.2) years. The median (interquartile range) nadir CD4 was 510.5 (274-903) cells/mm 3 . HIV-infected adolescents had significantly lower FEV 1 , FVC, FEV 1 /FVC, diffusing capacity of carbon monoxide, respiratory system compliance, and functional residual capacity than HIV-uninfected adolescents (P < 0.05 for all associations). HIV-infected adolescents had higher airway resistance and lung clearance index than HIV-uninfected adolescents (P < 0.05 for all associations). Although generally small in magnitude, these differences remained significant after adjusting for age, sex, and height. In addition, age, sex, height, and history of past lower respiratory tract infection or pulmonary tuberculosis were associated with reduced lung function., Conclusions: Perinatally infected South African HIV-infected adolescents on antiretroviral therapy have lower lung function than uninfected adolescents. Prior lower respiratory tract infection or pulmonary tuberculosis is associated with lower lung function.

Despite the advent of antiretroviral therapy (ART), the human immunodeficiency virus (HIV) epidemic remains a global health crisis with a high burden of respiratory disease among infected persons. While the early complications of the epidemic were dominated by opportunistic infections, improved survival has led to the emergence of non-infectious conditions that are associated with chronic respiratory symptoms and pulmonary disability. Obstructive ventilatory defects and reduced diffusing capacity are common findings in adults, and the association between HIV and chronic obstructive pulmonary disease is increasingly recognized. There is synergism between viral factors, opportunistic infections, conventional influences like tobacco smoke and biomass fuel exposure, and potentially, the immunological effects of ART on the development of HIV-associated chronic obstructive lung disease. Pulmonary function data for HIV-infected infants and children are scarce, but shows that bronchiectasis and obliterative bronchiolitis with severe airflow limitation are major problems, particularly in the developing world. However, studies from these regions are sorely lacking. There is thus a major unmet need to understand the influences of chronic HIV infection on the lung in both adults and children, and to devise strategies to manage and prevent these diseases in HIV-infected individuals. It is important for clinicians working with HIV-infected individuals to have an appreciation of their effects on measurements of lung function. This review therefore summarizes the lung function abnormalities described in HIV-positive adults and children, with an emphasis on obstructive lung disease, and examines potential pathogenic links between HIV and the development of chronic pulmonary disability., (© 2014 Asian Pacific Society of Respirology.)

Background: Children with HIV are at increased risk of acquiring tuberculosis (TB), a common cause of acute and chronic respiratory disease and death in HIV-infected children living in areas where prevalence of the disease is high. Children infected with HIV and TB have worse outcomes than HIV-uninfected children who have TB; thus, preventing the infection and disease in HIV-infected children is potentially an important public health intervention. Isoniazid, an anti-tuberculosis medication, has been used effectively to prevent TB in HIV-uninfected children, but currently there are no guidelines on the use of TB preventive therapy in HIV-infected children., Objectives: To determine the impact of TB preventive therapy on TB-related incidence and death in HIV-infected children, Search Strategy: We searched the Cochrane Controlled Trials Register (CENTRAL/CCTR), Cochrane HIV/AIDS Group Specialized Register, MEDLINE/PubMed, EMBASE, and AIDSearch. In addition, we scanned reference lists, manually searched conference abstracts, and contacted content experts., Selection Criteria: We included studies of HIV-infected children randomised to receive TB preventive therapy or placebo, or an alternative TB preventive regimen. Participants could have tuberculin skin test results that were positive or negative., Data Collection and Analysis: Two authors independently used the study selection criteria, assessed methodological quality and extracted data. Effects were assessed using hazard ratios., Main Results: One trial met the selection criteria for the review. The trial participants were HIV-infected children, most of whom were not taking antiretroviral therapy. Subjects were randomised to isoniazid and cotrimoxazole or placebo and cotrimoxazole, given daily or three times a week. The trial showed a marked reduction in TB incidence and death in the isoniazid group. As yet, however, there are no long-term follow-up data on the durability of the protective effect or on possible long-term adverse events. This trial also was unable to assess the impact of isoniazid prophylaxis on children receiving antiretroviral therapy., Authors' Conclusions: Isoniazid prophylaxis in HIV-infected children has the potential to play a major public health role by reducing TB incidence and death. As yet, however, data are insufficient to guide the duration of prophylaxis and to support its use in children using highly active antiretroviral therapy (HAART) and in those living in areas of low TB prevalence. Further studies are needed to assess whether TB preventive therapy is of benefit in all HIV-infected children, irrespective of use of antiretroviral treatment, the optimal duration of preventive therapy, or long-term adverse events.

It is becoming increasingly clear that human immunodeficiency virus ( HIV) infection, either independently or in concert with opportunistic infections like pulmonary tuberculosis, is a risk factor for the development of chronic airflow limitation. In the majority of patients the etiology of this obstructive ventilatory defect is multifactorial. Post-infectious obliterative bronchiolitis, post-tuberculous lung damage (including bronchiectasis), immune reconstitution and the direct effects of HIV viral infection may all play a role. With increases in life expectancy and decreases in infectious complications in patients taking antiretroviral medications, the importance of HIV-associated chronic lung disease as a cause of pulmonary disability is likely to increase. This is particularly relevant in regions like sub- Saharan Africa, where both HIV infection and tuberculosis are highly prevalent. Here, to illustrate the complexity of this interaction, we present the case of a 15-year-old girl with vertically acquired HIV infection, multiple episodes of pulmonary infection, and severe airflow obstruction. [ABSTRACT FROM AUTHOR]