HIV and Lung health

1. HIV AND LUNG
HEALTH
Presenter: Dr. Arnab Nandy
Moderator: Prof. Rakesh Lodha
Division of pediatric pulmonology and
intensive care, Dept. of Pediatrics,
AIIMS, New Delhi

2. Introduction
▪ Children living with HIV (CLHIV) estimated to be 2.73
million globally in 2021.
▪ Children (<15 years) account for
- 05% of all (PLHIV)
- 10% of new HIV infections
- 15% of all AIDS-related deaths
▪ The largest share of global burden of HIV infection in
children was reported from sub-Saharan Africa (88%).
▪ The burden of HIV in India was estimated 23.19 lakh in
2020 where children (<15 years) accounted for 3.5%.
▪ Respiratory disease had been found to be the major cause
of morbidity and mortality in HIV infected children.
[AIDS related deaths]
UNAIDS. Global Report UNAIDS Report on the Global AIDS Epidemic 2010. Geneva: UNAIDS, 2010.
UNAIDS. Fact sheet-World AIDS Day 2020. 2019 Global HIV Statistics. (2020).

3. Evolution of lung health in HIV
infection
3
▪ Over the past decade, the number of HIV infected children had greatly declined following
incorporation of preventive perinatal transmission measures into the national programs.
▪ The advent of highly active anti-retroviral therapy (HAART) and timely institution of
antimicrobial prophylaxis had helped further in reduction of acute respiratory infections and
mortality in children infected with HIV.
▪ The impact of these could be observed with decline in acute and opportunistic respiratory
infections where HIV-associated chronic lung disease is found to be emerging as the major
healthcare problem in the near future.
Crothers K, Thompson BW,
Burkhardt K, Morris A, Flores
SC, Diaz PT, et al. HIV-
associated lung infections and
complications in the era of
combination antiretroviral
therapy. Proc Am Thorac Soc.
2011;8:275-81

4. Differential transition
Developed vs Developing
4
▪ Stringent perinatal screening, early diagnosis, prophylaxis against opportunistic pathogens
and early ART administration had led to remarkable decline in HIV associated respiratory
infections and mortality in the developed countries.
▪ UNAIDS 2013 global report - 2.9 million children were infected with HIV in sub-Saharan
Africa and <50% of them had the access to anti-retroviral therapy (ART) which could be
attributed to higher pneumoniae specific mortality in HIV infected children.
Mukherjee A, Shah N, Singh
R, Vajpayee M, Kabra SK,
Lodha R. Outcome of highly
active antiretroviral therapy
in HIV-infected Indian
children. BMC Infect Dis.
2014;14:701

5. Impact of Highly Active Antiretroviral Therapy (HAART) on Opportunistic Respiratory Infections [USA]
HIV & lung health 5
Infections
Pre-HAART rate
Incidence rate per
100 child years (CI)
Post-HAART rate
Incidence rate per
100 child years (CI)
Pneumocystis pneumoniae 1.3 (1.1–1.6) 0.1 (0.04–0.2)
Bacterial pneumoniae 11.1 (10.3–12.0) 2.2 (1.8–2.6)
Bacteremia 3.3 (2.9–3.8) 0.4 (0.2–0.5)
Disseminated M. avium
intracellulare complex
1.8 (1.5–2.1) 0.1 (0.1–0.3)
Tracheobronchial or esophageal
candidiasis
1.2 (1.0–1.5) 0.1 (0.03–0.2)
Zar HJ. Chronic lung disease in human immunodeficiency virus (HIV) infected children. Pediatr Pulmonol. 2008;43:1-10

6. Clinical features in HIV infected symptomatic children
HIV & lung health 6
Lodha R, Singhal T, Jain Y, Kabra SK, Seth P, Seth V. Pediatric HIV infection in a tertiary care center in
North India: early impressions. Indian Pediatr. 2000;37:982-6

7. Pathophysiologic basis of
HIV related lung disease
A. HIV mediated impairment of lung immunity
B. HIV mediated lung damage
C. Implications of anti-retroviral therapy on the lungs

8. A. HIV mediated impairment of
lung immunity
(Activation of multiple proinflammatory pathways with ineffective
protection against pathogenic micro-organisms)
o Impaired innate lung immunity
o Impaired adaptive lung immunity
8
Cribbs SK, Crothers K, Morris A. Pathogenesis of HIV-Related Lung Disease: Immunity, Infection, and
Inflammation. Physiol Rev. 2020;100:603-32

9. A1. Impaired innate immunity
• Barrier disruption: Infection of bronchial epithelial cells
through HIV receptors (CD4, CCR5, CXCR4)
- Accelerated ageing
- Tat protein suppress CFTR functions leading to impaired
muco-ciliary clearance
• Dendritic cell and NK cell dysfunction:
- Persistent pro-inflammatory environment by increased
number and activation of DCs, induce T cell activation and
transmission of reactivated HIV to DCs

10. A1. Impaired innate immunity
• Surfactant dysfunction:
- SpA promote attachment of M. tb with AMs
- Abundance of SpD in PCP infection in AIDS
• Alveolar macrophage (AM) dysfunction:
- Reduced viability and phagocytic capacity (↓HLA-DR,
TNF-α)
- Impaired AM-T cell cross talk, aberrant release of
cytokines

11. HIV & lung health 11
Altered circulation of dendritic cells between the lung and lymphoid organs
(vicious cycle of inflammatory cell activation causing T cell exhaustion in
chronic HIV infection)
Memory T
cell
carrying
pro-viral
DNA
Resident
DC
T cell activation

12. A2. Impaired adaptive immunity
• Impaired cell mediated immunity:
- Compartmentalization (Blood and BAL) with higher frequency of
antigen specific CD4 T cells tend to exist in BAL suggested
recruitment of T cells to the lung in response to HIV antigens
(persistence of HIV)
- Influx of dysfunctional HIV specific CD8 T cells causing
lymphocytic alveolitis (↓CD4:CD8 ratio)
- HIV specific CD4 and CD8 T cells in BAL had increased expression
of programmed cell death protein 1 (PD-1) and impaired proliferative
capacity

13. A2. Impaired adaptive immunity
• Impaired humoral immunity:
- Increased B cell activation, Hypergammaglobulinemia
- Higher BAL (non-specific and abnormal) IgG, IgM and IgA in
PLHIV with respiratory symptoms

14. B. HIV mediated lung damage
o Persistence of HIV in the lungs
o Systemic inflammation
o Pulmonary inflammation
o Role of oxidative stress
o Role of lung microbiome
14
Attia EF, Bhatraju PK, Triplette M, Kosamo S, Maleche-Obimbo E, West TE, et al. Endothelial Activation, Innate
Immune Activation, and Inflammation Are Associated With Postbronchodilator Airflow Limitation and Obstruction
Among Adolescents Living With HIV. J Acquir Immune Defic Syndr. 2020;83:267-77

15. o Persistence of HIV in the lungs
- Latent reservoirs, HIV infected AMs live longer low turn over rate which represent a
compartment for continued infection
- TNF-α and IL-6 stimulate HIV replication in lung fibroblasts and release infectious virions
o Systemic inflammation
- Chronic HIV infection substantiate for an aberrant and sustained proinflammatory state as
evidenced with higher inflammatory markers (CRP, sTNF-R1, sICAM-1, IL-6 etc.)
- These correlate with increased risk of AIDS-defining events including recurrent pneumonia
15

16. o Pulmonary inflammation
- HIV-induced release of cytokine and chemokines by AMs and T cells resulted in neighboring lung
cellular damage and dysfunction, increased expression of local inflammatory mediators (sICAM-1)
- Dysfunctional CD8 T cells in the lungs express markers of functional exhaustion (PD-1) but also
secrete effector cytokines in response to HIV antigens, resulting in local pulmonary inflammation and
lung damage
- Release of IL-6 by AMs had been attributed to perivascular inflammation, interstitial pneumonia,
and precipitation of fibrin and edema, impaired TLR4 signaling by infected AMs
- Expression of inflammatory cytokines led to release of MMPs (elastolytic and collagenolytic)
16

17. o Role of oxidative stress
- HIV infection alters cellular (AMs) oxidative stress and phagocytic function like peroxisome
proliferator activated receptor-γ and NADPH oxidase activity whereas HIV related proteins could
inhibit Nrf2, master transcription factors involved in cellular antioxidant response
o Role of lung microbiome
- Microbiota dominated by Haemophilus, Moraxella or Neisseria (HMN) had 1.5 times higher
risk of CLD than harbored Streptococcus or Prevotella (SP) dominated microbiota in children
17
Bhadriraju S, Fadrosh D, Shenoy MK, Lin DL, Lynch KV, MacCauley K, et al. Distinct lung microbiota associate with HIV-associated chronic lung
disease in children. Sci Rep. 2020;10;16186

18. C. Implications of ART on the lungs
(Bi-edged sword)
o Impact on innate immunity
o Impact on adaptive immunity
o Immune reconstitution inflammatory syndrome (IRIS)
o Direct toxicity of ART
18

19. o Impact of ART on innate immunity
- Despite reduction in viral load the AMs or DCs can harbor latent HIV for longer periods of
time and could lead to surge in viral load following inflammatory stimulus
- Inhibit transfer of HIV from tissue macrophages to lymphocytes
o Impact of ART on adaptive immunity
- Recovery of BAL CD4 T cell count by proliferation of memory B cells (restoration of
CD4:CD8 ratio), Improved effective antibody response to vaccines against respiratory pathogens
- Reduced expression of Fas receptor and PD-1, improved functionality of lymphocytes
19

20. o Immune reconstitution inflammatory syndrome (IRIS)
- Paradoxical worsening of lung health secondary to ART induced immune recovery predominantly
in the setting of acute opportunistic infections, latent or partially treated pulmonary TB
- ART resulted in activation of AMs against the pathogens dwelling in an immune suppressed state
for longer time, increased proinflammatory mediators and tissue injury mediators (MMPs)
o Direct toxicity of ART
- Rare events except drug interaction like protease inhibitors with inhaled high dose corticosteroids
20

21. Basic summary
of lung pathogenesis in
chronic HIV infection
o Activation of immune pathways which were not
desired/required
o Suppression of immune pathways which were
required for effective microbial killing/clearance

22. Spectrum of HIV related
lung disease
Acute Chronic
Kilborn T, Chu, W.C.W, Das KM, Laya BF, Lee EY. Current updates on HIV-related pulmonary
disease in children: What do radiologists and clinicians need to know? S Afr J Rad. 2015;19:928

23. Lung health abnormalities in HIV
disease
ACUTE LUNG DISEASE
• Infections
- Viral
- Bacterial
- Mycobacterial
- Fungal
- Mixed
CHRONIC LUNG DISEASE
• Chronic infections
• Interstitial pneumoniae
- Lymphoid interstitial pneumoniae
- Nonspecific interstitial pneumoniae
- Desquamative interstitial pneumoniae
• Malignancies
- Kaposi sarcoma
- Lymphoma
• IRIS
• Bronchiectasis
• Bronchiolitis obliterans
• Reactive airway disease
• Pulmonary hypertension
23

24. HIV & lung health 24
Common respiratory morbidities
in HIV disease
o Acute respiratory infections & pneumoniae
o Tuberculosis (TB)
o ​Lymphocytic interstitial pneumoniae (LIP)
o Immune reconstitution inflammatory syndrome (IRIS)
o Malignancy
o ​Chronic lung disease​ (CLD)
Graham SM, Gibb DM. HIV disease and respiratory infection in children. Br Med Bull. 2002;61:133-50

25. HIV & lung health 25
Infectious lung morbidities in
HIV disease
Respiratory infections/disease CD4 cell count
(cells/mm3)
Mycobacterium tuberculosis < 400
Bacterial pneumoniae < 250
Pneumocystis jiroveci (PCP) pneumonia < 200
Mycobacterium avium complex, Cytomegalovirus
(CMV) infection
< 100
Suppurative lung disease and sinus disease < 100

26. • Bacterial respiratory diseases commonly include sinusitis, bronchitis, otitis and pneumonia
• Bacterial pneumoniae is the most common lower respiratory tract infection in both ART naive and
ART exposed children (six times higher risk than HIV uninfected children)
• Highest incidence of pneumoniae during infancy
• Frequently encountered organisms:
• Recurrent bacterial pneumoniae: current episode with one or more during the previous six months
- Streptococcus pneumoniae
(M/C prior to PCV vaccination)
- Staphylococcus aureus
- Haemophilus influenzae
- Escherichia coli
- Bordetella pertussis
- Salmonella species
- Mycoplasma pneumoniae
- Chlamydophila species
- Legionella pneumophila
26
BACTERIAL INFECTIONS
Atypical bacterial
organisms

27. Mycobacterium tuberculosis (MTB) -
• HIV predisposes for TB disease and MTB hastens progression of AIDS; Inflammatory response to TB
increases viral replication (increasing viral load by 6-7 fold)
• Risk of development of TB disease is 15-25 fold higher from fresh TB infection in HIV
Nontuberculous mycobacteria (NTM) -
• Mycobacterium avium complex (MAC) is the commonest opportunistic pathogen amongst NTM;
Nonspecific presentations, respiratory symptoms may be absent
• Disease manifestation involving the lungs often include pneumonitis, abscess formation, adenitis and
pleural nodularity
27
TUBERCULOSIS

28. Nocardia masquerading PTB
28
▪ Nocardia asteroids – most common; aerobic actinomycete
▪ Immunocompromised host
▪ Chronic cough, chest pain, dyspnea and hemoptysis
▪ Alveolar infiltrates, multiple pulmonary nodules, cavitation, pleural
effusion
▪ Advanced HIV disease; reticulonodular opacities
Benito N, Moreno A, Miro JM, Torres A. Pulmonary infections in HIV-infected patients: an update in the 21st century. Eur Respir J. 2012;39:730-45

29. • Improvement in coverage of the vaccination (PCV, Hib) is followed by increase with the reports
of viral respiratory illnesses
• Co-infections are common (viral-viral, viral-bacterial, viral-mycobacterial, and viral-fungal)
• Increased severity of illness, prolonged convalescence compared to HIV uninfected children
• Frequently encountered viruses –
• CMV pneumoniae – marker of severe immune suppression; 2.5 fold higher risk of mortality
• Variable response in terms of antibody titer development following vaccination
29
VIRAL INFECTIONS
- Respiratory syncytial virus (M/C)
- Influenza
- Para-influenza
- Human metapneumovirus
- Adenovirus
- Cytomegalovirus (CMV)
- Measles virus
- Varicella zoster virus

30. • PCP pneumoniae has 10 fold higher risk of incidence in HIV infected infants than uninfected
(two thirds of healthy children have antibodies to P. jirovecii by the age of 2-4 years)
• Dry non-productive cough, subacute onset of progressive symptoms like dyspnea and fever
• Disease manifestation involving the lungs is described as development of interstitial pneumoniae,
pulmonary interstitial emphysema, cysts and rarely pneumatocele and pneumothorax
• CD4 cell count as marker is less useful while interrogating clinical suspicion but high plasma
viral load is a strong indicator of PCP
• Mortality ranges between 20-40% in untreated with high serum LDH suggesting bad prognosis
30
FUNGAL INFECTIONS

31. Opportunistic fungal infections other than PCP
31
▪ Opportunistic fungal infections causing severe pulmonary disease are reported in small
numbers
▪ Candida spp. – interpretation requires careful exclusion of the possibility of
contamination
▪ Aspergillus spp. – Aspergillus mycetoma or fungal ball, invasive aspergillosis (usually
found late in the course of HIV disease or neutropenic or use of corticosteroids)
▪ Cryptococcus neoformans, Histoplasma capsulatum, Coccidioides immitis –
pulmonary involvement is uncommon
▪ Talaromycosis (Penicilliosis) – Talaromyces marneffei; spread of infection from
bamboo rats

32. HIV & lung health 32
Non-infectious lung morbidities
in HIV disease
(occupies a major proportion amongst chronic lung disease)
o ​Lymphocytic interstitial pneumoniae (LIP)
o Immune reconstitution inflammatory syndrome (IRIS)
o Bronchiectasis
o Bronchiolitis obliterans
o Malignancy
o ​Airway hyperreactivity/Asthma
Rylance J, Mchugh G, Metcalfe J, Mujuru H, Nathoo K, Wilmore S, et al. Chronic lung disease in HIV-infected children
established on antiretroviral therapy. AIDS. 2016;30:2795-2803

33. Chronic lung disease in HIV
33
Recurrent or persistent infections
- Bacterial
- Mycobacterial (M/C)
- Virus (CMV)
- Fungus (PCP)
- Mixed
Persistent broncho-vascular or reticular markings for 6
months or longer, or consolidation or nodules present for 3
months or longer
Non-infectious morbidities
- LIP
- Bronchiectasis
- Bronchiolitis obliterans
- Pulmonary tumors
- Airway hyper-reactivity
Attia EF, Miller RF, Ferrand RA. Bronchiectasis and other chronic lung diseases in adolescents living with HIV. Curr Opin Infect Dis. 2017;30:21-30

34. • Aetiology is unknown but often attributed to EBV infection (serological data)
• Occurs in 25–30% of vertically HIV-infected children
• Secondary infections are common, may be associated with obstructive airways disease (which may
respond to bronchodilators), OSA
• Diffuse infiltration of lymphocytes into the interstitium and scattered nodules of mononuclear cells
• Insidious course with chronic respiratory symptoms including cough and mild tachypnoea,
clubbing, hypoxemia; latter bronchiectasis and cor-pulmonale may supervene
• Comparatively better prognosis compared with the other lung morbidities in HIV disease
34
LYMPHOCYTIC INTERSTITIAL PNEUMONIAE (LIP)

35. 35
BRONCHIECTASIS
BRONCHIOLITIS OBLITERANS
• Important cause of irreversible CLD in children with HIV in post-ART era; associated with
severity of immunosuppression; productive cough, clubbing and persistent CXR abnormalities
• Frequency of acute exacerbations in HIV-bronchiectasis was found independent of the lung
microbiome but overall it has a reduced diversity (Proteobacteria)
• Proposed as continuum of disease process involving small and large airways or sequel of acute
lower respiratory tract infections; patchy involvement of the bronchioles
• Extent of mosaic pattern of decreased attenuation inversely correlated with lung function
Masekela R, Vosloo S,
Venter SN, de Beer WZ,
Green RJ. The lung
microbiome in children
with HIV-bronchiectasis: a
cross-sectional pilot study.
BMC Pulm Med.
2018;18:87

36. • Non-Hodgkins lymphoma>Kaposi’s sarcoma (KS)>leiomyosarcoma & Hodgkins lymphoma
• Prevalence of KS was reported more in children from Africa (HHV-8)
36
MALIGNANCIES
AIRWAY HYPERREACTIVITY/ASTHMA
• In perinatally HIV-infected adolescents from USA, only 30% of those with airflow obstruction
had bronchodilator reversibility (3-5% in HIV infected children from African country)

37. Basic summary
of lung disease in
chronic HIV infection
o Respiratory infections are still contributing for a
good proportion of lung morbidities in CLHIV
o Improved survival of CLHIV is driving for more
studies to come up on CLD

38. Impact of HIV on lung
health in children
o Perinatal transmission
o Post-natal acquisition
o Transition to adolescence and adulthood
Rylance S, Rylance J, McHugh G, Majonga E, Bandason T, Mujuru H, et al. Effect of
antiretroviral therapy on longitudinal lung function trends in older children and
adolescents with HIV-infection. PLoS One. 2019;14:e0213556

39. PERINATAL TRANSMISSION
(Early involvement of the lungs)
39
▪ Unexposed healthy (HU) vs infected infants
HIV infected infants had higher airway resistance in comparison to growth
associated decline in resistance in healthy uninfected infants
▪ Exposed but uninfected (HEU) vs infected infants
HIV infected infants had early alveolar interstitial inflammation (increased
99mTc DTPA radio aerosol clearance)
▪ Non-symptomatic vs symptomatic infants with HIV infection
No significant difference in airway resistance was observed
Gie A, Morrison J, Maree D, Laughton B, Browne SH, Cotton MF, Goussard P, Innes S. Childhood lung function
following perinatal HIV infection and early antiretroviral therapy initiation: a cross-sectional study. ERJ Open Res. 2022;8:00691-2021

40. • Lower tidal volume
• Expiratory air flow limitation
• Early compromise of lung function
40
Effect of maternal immunosuppression, viral load and timing of ART
initiation -
Effect of early initiation of ART in HIV infected infants -
• Achieve normal spirometry by school age in majority
• Certain groups are observed to experience small airway dysfunction
• Attention towards the associated modifiable risk factors are important to preserve lung function
Gray DM, Wedderburn CJ, MacGinty RP, McMillan L, Jacobs C, Stadler JAM, Hall GL, Zar HJ. Impact of HIV and antiretroviral drug exposure on lung growth and
function over 2 years in an African Birth Cohort. AIDS. 2020;34:549-58

41. POSTNATAL ACQUISITION
(ART naive has advanced lung disease)
41
▪ Early administration of ART defers the decline in lung function
▪ Improvement in lung function may not be able to sustain following
2 years of ART initiation
▪ Repeated hospitalizations, higher respiratory rate, clubbing, chest
hyperinflation and hyperpigmented skin lesions are reported as poor
outcome variable of lung function
▪ However children on ART had less severe airway obstruction and
reduced exercise intolerance
Rylance S, Rylance J, McHugh G, Majonga E, Bandason T, Mujuru H, et al. Effect of antiretroviral therapy
on longitudinal lung function trends in older children and adolescents with HIV-infection. PLoS One. 2019;14:e0213556

42. TRANSITION TO ADOLESCENCE AND
ADULTHOOD
(CLD has set in the majority)
42
▪ Recipients of ART may experience decline in FEV1 and FVC though their ratio is
maintained
▪ Irreversible lower airway obstruction and exercise limitations are the
predominant features
▪ Mosaic attenuation, extent of bronchiectasis, history of pulmonary tuberculosis or
previous lower respiratory tract infection and cough for more than 1 month were
associated with lower lung function
▪ Ongoing effects of HIV-related pulmonary damage are suggested as the principal
driving factors over the HIV-associated legacy effects (including previous
infections, nadir CD4 cell count)

43. Basic summary of impact of
chronic HIV infection
on lung health
o Despite ART, HIV is associated with significant
respiratory symptoms and functional impairment
o Understanding the pathogenesis may be the key,
as new treatment strategies may emerge

44. Lung protective measures
in CLHIV
o Early initiation of ART and monitor adherence
o Vaccination and prophylaxis against prevalent OIs
o Prompt management of intercurrent respiratory illness
o Extended surveillance and counselling
National AIDS Control Organization (2021). National Guidelines for HIV Care and Treatment,
2021. New Delhi: NACO, Ministry of Health and Family Welfare, Government of India.

45. 45
IDENTIFICATION OF INFANTS AT RISK OF HIV
INFECTION
• Low risk infants:
- Infants born to mothers with suppressed plasma viral loads (<1000 copies/ml)
assessed any time after 32 weeks of pregnancy up to delivery
• High risk infants:
- Infants born to HIV-positive mother not on ART
- Maternal viral load not done after 32 weeks of pregnancy
- Maternal plasma viral load not suppressed after 32 weeks of pregnancy
- Mother newly identified HIV positive within 6 weeks of delivery

46. 46
CPT PROPHYLAXIS AGAINST PCP IN CHILDREN
When to Start
Cotrimoxazole?
When to Discontinue CPT prophylaxis?
All HIV-exposed
infants/children
From 6 weeks of age (or at
first encounter with health
services)
HIV infection has been reliably excluded by a
negative antibody test at 18 months, regardless of
ART initiation
All HIV-infected
infants and children up to
5 years of age
Regardless of WHO stage
or
CD4 counts
At 5 years of age, when clinical or immunological
indicators confirm restoration of the immune
system for more than 6 months i.e., in a child >5
years of age with a WHO T-stage 1 or 2 and CD4
count of >350 cells/ mm3 on two occasions not
less than 6 months apart
All HIV-infected
children >5 years of age
WHO Stage 3 and 4
regardless of CD4 cell count
or
CD4 <350 cells/mm3
regardless of WHO staging
When clinical or immunological indicators
confirm restoration of the immune system for
more than 6 months i.e., in a child >5 years of age
with a WHO stage 1 or 2 and CD4 count of >350
cells/mm3 on two occasions not less than 6
months apart
As secondary prophylaxis After completion of
treatment for PCP
<5 years of age: do not stop
>5 years of age: with a WHO stage 1 or 2 and
CD4 count of >350 cells/mm3 on two occasions
not less than 6 months apar
Guidelines on co-trimoxazole
prophylaxis for HIV-related
infections among children,
adolescents and adults:
recommendations for a public
health approach. Geneva:
World Health Organization;
2006

47. 47
IPT IN CLHIV
• < 12 months: Infants living with HIV who are in contact with a person with TB
and who are unlikely to have TB disease on an appropriate clinical evaluation or
according to national guidelines should receive TB preventive treatment
• ≥ 12 months: Children living with HIV who are considered unlikely to have TB
disease on an appropriate clinical evaluation or according to national guidelines
should be offered TB preventive treatment as part of a comprehensive package
of HIV prevention and care if they live in a setting with high TB transmission,
regardless of contact with TB
• All children living with HIV who have successfully completed treatment for TB
disease may receive TB preventive treatment.
Zar HJ, Cotton MF, Strauss S,
Karpakis J, Hussey G, Schaaf
HS, et al. Effect of isoniazid
prophylaxis on mortality and
incidence of tuberculosis in
children with HIV:
randomised controlled trial.
BMJ. 2007;334:136.

48. Basic summary of lung
protective measures in
CLHIV
o Marked effect of ART on the reduction of the
incidence of PTB (60%) and PCP (30%)
o Vaccination remain still the most effective
strategy to reduce recurrence of pneumoniae

49. Recent developments
49
▪ Once weekly Azithromycin in CLHIV with CLD
Reduction in acute respiratory exacerbations but didn’t reverse lung function or growth impairment
▪ PD-1 inhibitors
Reversing immune exhaustion and downregulation of HIV-specific immune responses
▪ Fecal microbiota transplantation
Decrease immune activation and improve the persistent inflammatory state
▪ Statin therapy
Reduction in circulatory inflammatory markers
Ferrand RA, McHugh G,
Rehman AM, Mujuru H,
Simms V, Majonga ED, et
al. Effect of Once-Weekly
Azithromycin vs Placebo in
Children With HIV-
Associated Chronic Lung
Disease: The BREATHE
Randomized Clinical Trial.
JAMA Netw Open.
2020;3:e2028484

50. Conclusion
50
▪ The spectrum of lung disease in children living with HIV is gradually
changing in relation to the availability of better healthcare resources
▪ While control over the disease is achieved with ART but it may not allow the
lungs to be free of infection
▪ Future studies are invited to assess the effect of ongoing infection on the
development of chronic lung disease in children
▪ Incorporation of pulmonary function tests in the regular monitoring schedule
can help to understand the evolving burden of CLD on lung health

51. THANK YOU