0
Global Medicine |

Changing Global Epidemiology of Pulmonary Manifestations of HIV/AIDS FREE TO VIEW

Mark W. Hull, MD, MHSc, FRCPC; Peter Phillips, MD, FRCPC; Julio S. G. Montaner, MD, FRCPC, FCCP
Author and Funding Information

*From the Canadian HIV Trials Network (Dr. Hull); Division of AIDS (Dr. Montaner), Faculty of Medicine, University of British Columbia; and Division of Infectious Diseases (Dr. Phillips), Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.

Correspondence to: Julio S. G. Montaner, MD, FCCP, Director, BC Centre for Excellence in HIV/AIDS 667, 1081 Burrard St, Vancouver BC, V6Z 1Y6, Canada; e-mail: 8527jmontaner@cfenet.ubc.ca


Dr. Hull has received honoraria for speaking engagements and/or consultancy meetings from the following: Merck Frosst and Pfizer. He has been a coinvestigator on grants supported in part by Wyeth Pharmaceuticals. Dr. Phillips has no conflict of interest to disclose. Dr. Julio Montaner has received grants from, served as an ad hoc advisor to, or spoke at various events sponsored by Abbott, Argos Therapeutics, Bioject Inc, Boehringer Ingelheim, BMS, Gilead Sciences, GlaxoSmithKline, Hoffmann-La Roche, Janssen-Ortho, Merck Frosst, Panacos, Pfizer, Schering, Serono Inc, TheraTechnologies, Tibotec (J&J), and Trimeris.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/misc/reprints.shtml).


Chest. 2008;134(6):1287-1298. doi:10.1378/chest.08-0364
Text Size: A A A
Published online

Tremendous advances have occurred in the care of patients with HIV/AIDS resulting from the advent of highly active antiretroviral therapy (HAART). This has led to differences in the presentations of HIV-related pulmonary disease. Infections such as bacterial pneumonias, particularly Streptococcus pneumoniae, remain commonplace, while opportunistic agents such as Pneumocystis jirovecii remain a concern in patients without adequate access to optimal medical care. The tuberculosis epidemic, once thought to be slowing, has been re-energized by the spread of HIV, particularly in sub-Saharan Africa. Unusual inflammatory responses due to a phenomenon of immune reconstitution, are now recognized as a consequence of HAART, with a reported incidence of IRIS in this setting ranges from 7 to 45% in retrospective reviews. Noninfectious pulmonary conditions such as chronic obstructive lung disease and pulmonary malignancies are gaining prominence as patients are accessing antiretroviral care and enjoying significantly extended survival.

Figures in this Article

It has been over a quarter century since reports of Pneumocystis pneumonia in previously healthy individuals heralded the onset of the AIDS epidemic and led to the identification of the HIV.13 There have since been large-scale shifts in the epidemiology of the epidemic, with the majority of incident cases now occurring in the developing world.4 In addition, there has been tremendous advancement in the management of HIV/AIDS in the developed world with the advent of highly active antiretroviral therapy (HAART).5,6 This has led to differences in presentations of HIV-related pulmonary disease across the globe. In the developed world, opportunistic infections are diminishing in frequency, and there is growing recognition of the importance of chronic obstructive lung disease and pulmonary neoplasms.7,8 In contrast, opportunistic infections remain frequent in other settings where there is limited access to HAART. Furthermore, the intersection of the HIV and tuberculosis epidemics has had devastating consequences, particularly in sub-Saharan Africa.9,10 More recently, with the increased use of HAART unusual manifestations of pulmonary disease have been recognized as a result of immune reconstitution syndromes.

Cases of HIV/AIDS increased rapidly in the developed world in the 1980s and peaked in the United States in 1992, before stabilizing in 1998. Subsequently there have been approximately 40,000 new cases diagnosed annually.11 There were approximately 2.1 million adults and children living with HIV in North America and Western Europe in 2007.4 This is in stark contrast to the global estimates of 33.2 million individuals infected worldwide (Fig 1). The majority of HIV-infected individuals reside in sub-Saharan Africa (22.5 million adults and children) and South/South-East Asia (4.0 million adults and children).4

Figure Jump LinkFigure 1 Global prevalence of HIV/AIDS, 2007. Reproduced with permission from the Joint United Nations Program on HIV/AIDS and World Health Organization.4Grahic Jump Location

The use of HAART has resulted in prolonged HIV virologic suppression, immune reconstitution, and dramatic reductions in rates of opportunistic infections, hospitalizations, and AIDS-related mortality in Europe and North America.1214 Similar benefits have now been confirmed in resource-limited settings where HAART programs have been implemented, such as in South Africa,15 Zambia,16 Uganda,17 and South-East Asia.18,19 Worldwide initiatives have led to large-scale HAART roll-out programs in sub-Saharan Africa, Asia, and Latin America (Fig 2). Approximately 2,120,000 individuals in sub-Saharan Africa were receiving antiretroviral therapy as of December 2007.20 Despite these advances, a full 70% of those in need of HAART in sub-Saharan Africa had not yet accessed therapy.20 To a large extent, access to HAART determines the regional incidence and spectrum of pulmonary diseases among HIV-infected persons.

Figure Jump LinkFigure 2 Global distribution of antiretroviral use, 2006. Reproduced with permission from the World Health Organization.112Grahic Jump Location

Evidence for pulmonary tissue-level effects of HIV is conflicting. Alveolar macrophages and dendritic cells within the lung are targets for HIV infection.21 Infection of human alveolar macrophages occurs preferentially via the CCR5 coreceptor.22 Alveolar macrophages become increasingly infected as HIV infection progresses.23In vitro data suggest that alveolar macrophage respiratory burst and response to interferon-γ does not differ between HIV-infected individuals and control subjects.24 In contrast, other studies25,26 have found decreases in phagocytosis of opportunistic infections such as Pneumocystis, and loss of fungistatic activity for Cryptococcus neoformans. Similarly decreased alveolar macrophage function in the setting of advanced HIV has been shown to further promote dissemination of Mycobacterium tuberculosis.27

HIV-infected individuals may also have increased infiltration of CD8+ T-lymphocytes within the interstitium and alveoli.28 Lymphocytic alveolitis falls within the spectrum of lymphocytic infiltrative disorders, most common of which is lymphocytic interstitial pneumonitis in children.29 Lymphocytic alveolitis is relatively common in HIV-infected adults, and can be seen in patients with no evidence of respiratory symptoms.30 The infiltration of CD8+ cytotoxic cells may represent an immune response to HIV-infected cells, and appears to correlate with high viral load burden within the lung.31

B-cell abnormalities may lead to altered production of Igs. BAL from asymptomatic patients with HIV demonstrated decreased concentration of IgG compared to uninfected control subjects in one study,32,33 but BAL Ig levels were not found to differ when patients were receiving antiretroviral therapy. Impaired local and systemic host defenses due to the effects of HIV replication on immune function serve to provide an explanation for the frequency of serious pulmonary infections in this population.

Bacterial Pneumonia

Bacterial pneumonias remain one of the most common causes of pulmonary infection, and a cause of considerable morbidity and mortality worldwide.34,35 Etiologically, Streptococcus pneumoniae predominates, followed by Haemophilus influenzae, in the developed and developing world settings.3638Staphylococcus aureus and Pseudomonas aeruginosa account for about 5% of cases each.37,39

Pre-HAART rates of pneumonia in the developed world were significantly higher than in uninfected individuals, and similar to rates seen in resource-limited settings. In a prospective study34 in North America, rates of pneumonia in HIV-infected individuals in the period between 1988 and 1990 were 5.5 per 100 person-years compared to 0.9 per 100 person-years in uninfected individuals. More recently, a large cohort40 of HIV-infected women found rates of 8.5 per 100 person-years compared to 0.7 per 100 person-years over the period 1993 to 2000. Risk of pneumonia was clearly associated with decreasing CD4 counts, and rates were as high as 10.8 per 100 person-years, and 17.9 per 100 person-years for patients with CD4 counts < 200 cells/μL.34,40 Rates of pneumonia were similarly high in a large cohort of HIV-infected miners in South Africa and even higher at 33 cases per 100 person-years in a cohort of postpartum women in Kenya.41,42 In both settings, risk of pneumonia increased as CD4 cell counts decreased to < 200 cells/μL.41,42

Bacteremia associated with S pneumoniae contributes significantly to morbidity in HIV-infected individuals worldwide. Rates of invasive pneumococcal disease have been seen to climb in parallel with the emerging HIV epidemic in the pre-HAART era in North America, and similarly in Africa (Table 1).4346

Table Graphic Jump Location
Table 1 Summary of Selected Studies of HIV and AIDS-Associated Invasive Pneumococcal Disease Rates*

*Unless otherwise specified, rates are for invasive pneumococcal disease (defined as isolation of S pneumoniae from a normally sterile site)

Impact of HIV-Related Interventions and HAART on Bacterial Pneumonia

Prior to the advent of HAART, interventions such as antimicrobial prophylaxis had been shown to decrease overall rates for bacterial pneumonias. Trimethoprim-sulfamethoxazole (TMP-SMX) use was associated with a 67% reduction in rates of pneumonia in a large US retrospective cohort study,39and similarly was found to be protective in the prospective US women's cohort (the HIV Epidemiologic Research Study).40 Of note, the protective effect of TMP-SMX was no longer detectable in another cohort study47 conducted during the HAART era, in which reductions in bacterial pneumonia rates were associated with antiretroviral use.

TMP-SMX prophylaxis has been shown to reduce morbidity and mortality in resource-limited settings on the African continent in the absence of HAART.48,49 Two randomized trials conducted in Cote D'Ivoire examined the impact of TMP-SMX on bacterial respiratory disease, one study48 conducted in patients with no major underlying comorbid illnesses, and the other study49 in patients with underlying tuberculosis. Only in patients without preexisting disease were rates of bacterial pneumonia specifically reduced in the TMP-SMX group (hazard ratio, 0.07; 95% confidence interval [CI], 0.01 to 0.56).48

The efficacy of the 23-valent pneumococcal polysaccharide vaccine is less clear.39 Studies39,50,51 in the developed world have suggested that pneumococcal vaccine may prevent invasive disease; however, a randomized clinical trial51 conducted in Uganda failed to confirm a protective effect. Nonetheless, the vaccine continues to be recommended, particularly for patients with higher CD4 cell counts.

Multiple studies40,47,52,53 from sites within the United States and Europe have now demonstrated reduction in rates of bacterial pneumonia after introduction of HAART. The HIV Epidemiologic Research Study40 found that each month of HAART decreased risk of bacterial pneumonia by 10% in those not receiving TMP-SMX prophylaxis. Results from a single clinic cohort in Baltimore47 found that rates of bacterial pneumonia decreased from 22.7 cases per 100 person-years to 9.1 cases per 100 person-years following the introduction of HAART in 1997. Similar low rates of pneumonia in patients receiving HAART were noted in a cohort in France,54 where over a median follow-up period of 43 months, the incidence of bacterial pneumonia was only 0.8 per 100 person-years. Population-based surveillance of pneumococcal bacteremia in the United States and Spain found that the rates of disease dropped substantially after the introduction of HAART (Table 1),52,53 although rates remain higher than that of the general population. No studies from adult HAART programs in the developing world have yet looked specifically at bacterial pneumonia end points as a marker for response to HAART. A decrease in rates of pneumonia has been observed in a pediatric cohort initiating antiretroviral therapy in Cote D'Ivoire55; and given the overall responses to HAART noted in adults, it is likely that this will translate into improved morbidity due to bacterial pneumonia and invasive pneumococcal disease.

Pneumocystis jirovecii Pneumonia

P jirovecii pneumonia (PJP), previously known as Pneumocystis carinii pneumonia, was recognized as an important marker for immune dysfunction early in the HIV epidemic, and remains a major opportunistic infection. During the pre-HAART era in the developed world, PJP was the major AIDS-defining illness for a majority of HIV-infected individuals. The identification of a CD4 cell count of 200 cells/μL as a critical threshold for increased risk of PJP was a major landmark in the management of HIV/AIDS because it allowed formulation of guidelines for the use of specific PJP prophylaxis.56 Rates of PJP were high in the pre-HAART era, with an incidence of 20 cases per 100 person-years in those with CD4 cell counts < 200 cells/μL.56 The incidence of PJP declined markedly after the introduction of TMP-SMX prophylaxis, and further with the introduction of HAART. Rates in the United States decreased 3.4% per year during 1992 to 1995 and thereafter declined 21.5% per year from 1996 to 1998.57 Similarly, in the EuroSIDA cohort, the incidence declined from 4.9 cases per 100 person-years prior to the introduction of HAART, to a rate of 0.3 cases per 100 person-years in 1998.58 HAART-related immune reconstitution leads to long-term protection from PJP and, as such, long-term prophylaxis, both primary and secondary, can be safely discontinued if the CD4 cell count is > 200 cells/μL.5860 Despite these advances, PJP continues to be a common presenting illness in HIV-infected individuals. This reflects both incomplete adherence to HAART or prophylaxis guidelines by physicians and patients, and the large burden of undiagnosed HIV in patients not accessing medical care.61

With the possible exception of sub-Saharan Africa, PJP is a common opportunistic infection among untreated HIV-infected individuals globally. PJP was the second most common opportunistic infection seen annually in a surveillance program62 conducted between from 1993 to 2002 in Rio De Janiero, Brazil. Rates of PJP have climbed over a similar time period in a study63 conducted in Thailand, and PJP was the second most common AIDS defining illness in a Kuala Lumpur hospital.64 A study61 in Africa originally found low rates of PJP, with prevalence rates of 0 to 11% in differing geographic locales. The reasons for this remain unclear. More recent studies65,66 in Kenya and Uganda have found rates of 33 to 37% in patients undergoing bronchoscopy for acid-fast bacilli smear-negative pulmonary infiltrates. Exposure to TMP-SMX as PJP prophylaxis has been associated with the development of dihydropteroate synthase gene mutations in the developed world, and genotypic studies6769 of PJP from sub-Saharan regions have reported similar mutations in isolates from South Africa and Zimbabwe. Mutation rates remain low (13.3% of 30 isolates tested in Cape Town, South Africa) but may climb as use of TMP-SMX prophylaxis becomes commonplace. The presence of these mutations has been associated with decreased response to TMP-SMX therapy for PJP infection.67 Given limited diagnostic strategies in many resource-limited settings, emphasis must be placed on prophylaxis, and treatment algorithms must include PJP therapy when patients are acid-fast bacilli smear negative and have failed to respond to antibacterial therapy.

HIV has proven to be a key factor fueling the rampant expansion of the global tuberculosis epidemic. HIV is associated with significant increased risk of reactivation of latent tuberculosis and progression to active disease in recently acquired infections. Tuberculosis is now seen as the major pulmonary infection in HIV-infected patients in many centers.70 The twin epidemics have an epidemiologic epicenter in sub-Saharan Africa. In 2006, there were an estimated 9.2 million new cases of tuberculosis worldwide (Fig 3).70 The World Health Organization African Region accounted for 31% of these cases, and for 38% of the approximately 1.7 million deaths due to tuberculosis in 2006.70 Among the 15 countries with the highest tuberculosis incidence, 13 were from Africa. Overall globally, HIV accounted for 8% of all new cases; however, the World Health Orga-nization African Region accounts for 85% of these cases.70

Figure Jump LinkFigure 3 Global tuberculosis incidence rates, 2006. Reproduced with permission from the World Health Organization.70Grahic Jump Location

The clinical presentation, radiographic findings and utility of sputum-based diagnostic modalities may differ between HIV-infected and HIV-negative cases, and may differ in HIV-infected individuals as immune suppression progresses.71,72 These factors increase the complexity in management of coinfected patients. In particular, the difficulty establishing a diagnosis poses difficulties for the initiation of isoniazid therapy for latent infection (prophylaxis) for patients with prior tuberculosis exposure as determined by positive tuberculin skin testing.

Nonetheless, it must be recognized that two overarching features of management are clear: HIV-infected patients with tuberculosis have treatment responses to a standard 6-month course of antituberculosis therapy that mirror that of uninfected individuals; and that the introduction of antiretroviral therapy has played a significant role in improving mortality rates in coinfected patients.7375 In addition, initiation of HAART plays a major role in decreasing incidence of tuberculosis infection both in the developed world and in resource-limited settings (Table 2).7679

Table Graphic Jump Location
Table 2 Impact of HAART on Tuberculosis Incidence in the Developed World and Resource-Limited Settings

Current therapeutic guidelines recommend a standard approach to tuberculosis therapy in the setting of HIV infection.80,81 Due to the development of acquired rates of rifampin resistance, the use of daily or three-times-weekly treatment, as opposed to twice-weekly dosing schedules, is recommended, particularly in patients with CD4 cell counts < 100 cells/μL.80,81

Drug interactions between antiretroviral agents and rifampin-based regimens are a major determinant of possible HAART regimens. Drug interactions occur predominantly due to rifampin-related induction of the cytochrome P-450 isoenzyme 3A4. Use of rifampin leads to reductions in concentrations of the nonnucleoside reverse transcriptase inhibitors efavirenz and nevirapine.82,83 The reduction is greater for nevirapine, leading to a recommendation for the preferential use of efavirenz use in HAART regimens in coinfected patients receiving rifampin-based regimens.81 However, the widespread use of nevirapine as a component of standard HAART in resource-limited settings, and concerns regarding potential teratogenicity of efavirenz make this recommendation difficult to implement. Several small studies84,85 have evaluated the use of nevirapine-based regimens in the setting of rifampin therapy, and have found similar outcomes in terms of virologic control but a potential for increased side effects. Given the potential for development of HIV-drug resistance in patients exposed to suboptimal concentrations of antiretroviral regimens, further study is needed before this regimen can be widely recommended. The use of protease inhibitors (PIs) are contraindicated in patients receiving rifampin-based regimens due to profound decreases in plasma concentrations of PIs, and as such alternative rifamycins such as rifabutin are recommended in patients who require PI-based HAART. The use of rifabutin is limited by cost in the developing world.

In addition to drug interactions, complexities regarding concerns of overlapping toxicities, polypharmacy, and risks of immune reconstitution have led to debate regarding optimal timing for initiation of antiretroviral therapy in patients with tuberculosis. The risks of toxicities must be assessed with consideration of the risk of increased mortality if HAART is delayed. At present, recommendations derive from observational data.74,75 For patients with CD4 counts > 350 cells/μL, initiation of antiretroviral therapy may be deferred. In individuals with CD4 cell counts between 100 and 200 cells/μL, it may be best to delay HAART for 4 to 8 weeks until completion of the induction phase of tuberculosis treatment is completed.74 Little data exist for patients with significant immune dysfunction, but early initiation of HAART is recommended. Mathematical modeling supports early initiation of HAART unless rates of immune reconstitution-related mortality rates are high (> 4.6%).86 The high rate of observed AIDS events and death during the 8-week induction phase of antituberculous therapy among patients with CD4 counts < 100/μL argues for earlier initiation of HAART once there has been a clinical response to antituberculous therapy.75

Multidrug-resistant tuberculosis (MDR-TB), defined as TB resistant to at least isoniazid and rifampin, represents nearly 5% of global annual cases of tuberculosis.87 The report88 of extensively drug-resistant tuberculosis (XDR-TB) [MDR-TB resistant to fluoroquinolones and at least one second-line injectable agent] in rural South Africa has focused attention on HIV coinfection and tuberculosis drug resistance. In the study,88 the prevalence of XDR-TB was found to be 6% among 475 patients with culture-confirmed tuberculosis. All patients with XDR-TB tested for HIV were positive, and mortality rate was 98%, including all patients receiving concurrent HAART.88

The data regarding links between HIV and MDR-TB are conflicting. Although HIV infection is associated with institutional outbreaks of MDR-TB (usually linked to poor infection control practices and delays in diagnosis), population-based assessments of determinants of MDR-TB have not confirmed a clear association with HIV.89 HIV infection has been associated with acquired resistance to rifamycins, possibly due to inadequate dosing schedules, co-use of other medications, and decreased drug absorption related to malabsorption.90,91 Coinfected patients with MDR-TB face increasingly complex management issues related to drug interactions and overlapping toxicities, and have been shown to have higher mortality compared to HIV-negative patients with MDR-TB.89,92

Reconstitution of a functional immune system due to the suppression of HIV replication by HAART has led to unusual clinical presentations with features of an exaggerated inflammatory response to newly recognized antigens. This phenomenon has been named immune reconstitution inflammatory syndrome (IRIS). Proposed criteria include documented viral load decreases in addition to new or worsening symptoms of an infectious or inflammatory condition after initiation of HAART.93 Currently the severity of the inflammatory syndrome is thought to be due to the interactions between the degree of immune recovery, previously unrecognized (subclinical or residual) antigenic burden, and possible host genetic factors.94 Pulmonary manifestations of IRIS have been well described with both P jirovecii infection and M tuberculosis. IRIS in the setting of tuberculosis can present either as a paradoxical worsening of tuberculosis symptoms in otherwise clinically improving patients who initiate antiretroviral therapy some time after tuberculosis therapy, or as an unmasking of unrecognized tuberculosis when antiretrovirals are initiated.95,96 However, at least in developed countries, most of the reported cases of tuberculosis-IRIS have been observed among patients whose tuberculosis diagnosis preceded the initiation of HAART.97. The reported incidence of IRIS in this setting ranges from 7 to 45% in retrospective reviews.95,96 Clinical manifestations include increased respiratory symptoms, fever, and lymphadenopathy. Worsening of radiologic findings is common, with increasing infiltrates, lymphadenopathy, or pleural effusions.98 IRIS occurs usually within 6 to 8 weeks after initiation of HAART, and has been associated with lower CD4 cell counts at time of initiation, higher viral loads at baseline, and shorter duration of TB therapy before HAART initiation.9597 In addition, degree of CD4 cell count or HIV viral response has also been identified as a risk factor. Despite worsening symptoms, mortality is low. Mycobacterium avium complex IRIS includes a pulmonary-thoracic presentation in 29% of cases. Aside from constitutional symptoms, cough or wheeze (93%) and dyspnea (47%) are the most frequent respiratory symptoms. The imaging and bronchoscopy findings most often include mediastinal and/or hilar lymphadenopathy, endobronchial nodular lesions, cavities, pleural-based lesions, or pulmonary infiltrates.99 Clinical management usually includes therapy with nonsteroidal anti-inflammatories or corticosteroids, and HAART is continued unless life-threatening features are present.94

HIV-infected patients in the developed world have higher rates of smoking than the general population. Almost 75% of patients report a smoking history, and 40 to 50% are current smokers.100,101 Smoking history, in conjunction with pulmonary effects of prior opportunistic lung infections and drug use-related lung damage, combine to place patients with HIV at risk for development of emphysema, airway disease, and COPD.101 Furthermore, there is growing evidence that HIV itself may be a risk factor for the development of COPD. In a study102 of HIV-infected patients and control subjects matched for age and smoking history, 15% of HIV-infected patients were found to have evidence of emphysema on CT scan compared to 2% of control subjects. Similarly, in a study7 of 1,014 patients with HIV infection and 713 control subjects, COPD was determined by patient self-report or International Classification of Diseases, Ninth Revision diagnostic codes. After adjustment for age, smoking history, and other confounders, HIV-infected individuals were 50 to 60% more likely to have COPD than the HIV-negative comparators.7 In the latter study, use of HAART did not appear to be statistically associated with protection from development of COPD in multivariate modeling (odds ratio, 0.77; 95% CI, 0.46 to 1.32, for International Classification of Diseases, Ninth Revision codes for COPD), although total numbers of patients receiving HAART was small.7 The mechanisms by which HIV contributes to COPD are not fully understood, and the long-terms effects of HAART on COPD development are not yet known. These warrant further prospective evaluation.

The management of COPD in the setting of HIV infection follows the same principles as in other patient populations.101 However, it is now clear that there is a significant drug interaction between commonly used inhaled corticosteroids, and the PI ritonavir (even when used at low, “boosting” doses). This has proven clinically problematic, as current HAART guidelines favor the use of ritonavir boosting when PI-based HAART is used. Under normal circumstances, the inhaled or nasal corticosteroids such as fluticasone propionate, beclamethasone and budesonide have little systemic absorption due to clearance by the CYP3A4 enzyme system. Fluticasone in particular is highly lipophilic, has a greater volume of distribution, and has a longer elimination half-life.103 The inhibition of the CYP3A4 system by ritonavir is thought to increase corticosteroid bioavailability and lead to the subsequent inhibition of the hypothalamic-pituitary-adrenal axis. There are numerous case reports104106 documenting the development of iatrogenic Cushing syndrome due to exogenous glucocorticoid excess due to the interaction of ritonavir and inhaled or nasal corticosteroid. The patients described presented with clinical features of Cushing syndrome and documented evidence of adrenal suppression based on basal cortisol values and abnormal adrenocorticotrophic hormone stimulation tests. A pharmacokinetic study104 in healthy volunteers receiving low-dose ritonavir (200 mg/d) and fluticasone nasal spray have confirmed a significant increase in the area under the curve for fluticasone and a decrease in plasma cortisol area under the curve within 7 days. The manufacturer (Abbott Laboratories; North Chicago, IL) currently recommends against co-administration of these agents at present.

The advent of effective antiretroviral therapy has served to decrease rates of AIDS-defining malignancies such as Kaposi sarcoma and non-Hodgkin lymphoma.107 These vascular and lymphoid malignancies have well-described pulmonary manifestations.108 In contrast, as people with HIV are living longer due to the impact of HAART, rates of non–AIDS-defining malignancies are climbing.8,109,110 An analysis of an HIV-positive cohort in England found rates of 6.7 per 10,000 person-years after HAART, compared to 0.8 per 10,000 person-years before HAART. Compared to the general population, the relative risk (RR) was 8.93 (95% CI, 4.92 to 19.98).8 Similarly, a cohort study109 in France found that rates of lung cancer were twofold higher in the post-HAART era, with higher increased risk in injection drug users (standardized incident ratio, 4.70; 95% CI, 2.83 to 7.34) and in women (standardized incident ratio, 6.59; 95 CI, 3.4 to 11.5). This increased risk in women was believed to be in keeping with trends in the general French population.109 In addition, confounders such as smoking have made interpretation of these data difficult. Data from a large cohort111 of injection drug users in the United States showed that rates of lung cancer deaths had increased in the post-HAART era (mortality rate ratio, 4.7; 95% CI, 1.7 to 16), and that after adjustment for smoking (which was comprehensively recorded within the cohort), HIV was associated with increased lung cancer risk (hazard ratio, 3.6; 95% CI, 1.6 to 7.9). Postulated mechanisms include possible direct oncogenic effects of HIV, genetic instability due to HIV integration leading to increased susceptibility for carcinogens such as tobacco, or possible decreased immune surveillance for malignant cells.110,111 Prognosis appears to be worse than in the general population, and further work evaluating treatment in the setting of HIV may be required.

Pulmonary manifestations of HIV disease differ globally due to differences in current availability of effective HAART programs. In resource-limited settings, AIDS-related infectious complications such as P carinii pneumonia and pulmonary tuberculosis still predominate. In comparison, in patients accessing HAART, further attention to long-term consequences of both HIV and antiretroviral therapy is warranted, where an emphasis on COPD and neoplasms is necessary.

CI

confidence interval

HAART

highly active antiretroviral therapy

IRIS

immune reconstitution inflammatory syndrome

MDR-TB

multidrug-resistant tuberculosis

PI

protease inhibitor

PJP

Pneumocystis jirovecii pneumonia

RR

relative risk

TMP-SMX

trimethoprim-sulfamethoxazole

XDR-TB

extensively drug resistant tuberculosis

Pneumocystis pneumonia–Los Angeles. MMWR Morb Mortal Wkly Rep. 1981; 65 30:250-252. [PubMed]
 
Barre-Sinoussi F, Chermann JC, Rey F, et al. Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). Science. 1983; 520 220:868-871. [PubMed] [CrossRef]
 
Gallo RC, Sarin PS, Gelmann EP, et al. Isolation of human T-cell leukemia virus in acquired immune deficiency syndrome (AIDS). Science. 1983;220:865-867. [PubMed]
 
UNAIDS/WHO AIDS epidemic update.Accessed June 23, 2008 Available at:http://data.unaids.org/pub/EPISlides/2007/2007_epiupdate_en.pdf.
 
Hammer SM, Squires KE, Hughes MD, et al. A controlled trial of two nucleoside analogues plus indinavir in persons with human immunodeficiency virus infection and CD4 cell counts of 200 per cubic millimeter or less: AIDS Clinical Trials Group 320 Study Team. N Engl J Med. 1997;337:725-733. [PubMed]
 
Montaner JS, Reiss P, Cooper D, et al. A randomized, double-blind trial comparing combinations of nevirapine, didanosine, and zidovudine for HIV-infected patients: the INCAS Trial: Italy, the Netherlands, Canada and Australia Study. JAMA. 1998;279:930-937. [PubMed]
 
Crothers K, Butt AA, Gibert CL, et al. Increased COPD among HIV-positive compared to HIV-negative veterans. Chest. 2006;130:1326-1333. [PubMed]
 
Bower M, Powles T, Nelson M, et al. HIV-related lung cancer in the era of highly active antiretroviral therapy. Aids. 2003;17:371-375. [PubMed]
 
Dye C, Scheele S, Dolin P, et al. Consensus statement: global burden of tuberculosis: estimated incidence, prevalence, and mortality by country; WHO Global Surveillance and Monitoring Project. JAMA. 1999;282:677-686. [PubMed]
 
Corbett EL, Steketee RW, ter Kuile FO, et al. HIV-1/AIDS and the control of other infectious diseases in Africa. Lancet. 2002;359:2177-2187. [PubMed]
 
Centers for Disease Control and Prevention HIV/AIDS surveillance report, 2005. 2005; Atlanta, GA US Department of Health and Human Services
 
Palella FJ Jr, Delaney KM, Moorman AC, et al. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection: HIV Outpatient Study Investigators. N Engl J Med. 1998;338:853-860. [PubMed]
 
Hogg RS, Heath KV, Yip B, et al. Improved survival among HIV-infected individuals following initiation of antiretroviral therapy. JAMA. 1998;279:450-454. [PubMed]
 
Mocroft A, Ledergerber B, Katlama C, et al. Decline in the AIDS and death rates in the EuroSIDA study: an observational study. Lancet. 2003;362:22-29. [PubMed]
 
Coetzee D, Hildebrand K, Boulle A, et al. Outcomes after two years of providing antiretroviral treatment in Khayelitsha, South Africa. Aids. 2004;18:887-895. [PubMed]
 
Stringer JS, Zulu I, Levy J, et al. Rapid scale-up of antiretroviral therapy at primary care sites in Zambia: feasibility and early outcomes. JAMA. 2006;296:782-793. [PubMed]
 
Weidle PJ, Malamba S, Mwebaze R, et al. Assessment of a pilot antiretroviral drug therapy programme in Uganda: patients' response, survival, and drug resistance. Lancet. 2002;360:34-40. [PubMed]
 
Madec Y, Laureillard D, Pinoges L, et al. Response to highly active antiretroviral therapy among severely immuno-compromised HIV-infected patients in Cambodia. Aids. 2007;21:351-359. [PubMed]
 
Zhou J, Kumarasamy N, Ditangco R, et al. The TREAT Asia HIV Observational Database: baseline and retrospective data. J Acquir Immune Defic Syndr. 2005;38:174-179. [PubMed]
 
World Health Organization Towards universal access: scaling up priority HIV/AIDS interventions in the health sector; progress report 2008.Accessed June 23 2008 Available at:http://www.who.int/hiv/pub/towards_universal_access_report_2008.pdf.
 
Beck JM. The immunocompromised host: HIV infection. Proc Am Thorac Soc. 2005;2:423-427. [PubMed]
 
Park IW, Koziel H, Hatch W, et al. CD4 receptor-dependent entry of human immunodeficiency virus type-1 env-pseudotypes into CCR5-, CCR3-, and CXCR4-expressing human alveolar macrophages is preferentially mediated by the CCR5 coreceptor. Am J Respir Cell Mol Biol. 1999;20:864-871. [PubMed]
 
Sierra-Madero JG, Toossi Z, Hom DL, et al. Relationship between load of virus in alveolar macrophages from human immunodeficiency virus type 1-infected persons, production of cytokines, and clinical status. J Infect Dis. 1994;169:18-27. [PubMed]
 
Murray HW, Gellene RA, Libby DM, et al. Activation of tissue macrophages from AIDS patients:in vitroresponse of AIDS alveolar macrophages to lymphokines and interferon-γ. J Immunol. 1985;135:2374-2377. [PubMed]
 
Koziel H, Eichbaum Q, Kruskal BA, et al. Reduced binding and phagocytosis ofPneumocystis cariniiby alveolar macrophages from persons infected with HIV-1 correlates with mannose receptor downregulation. J Clin Invest. 1998;102:1332-1344. [PubMed]
 
Ieong MH, Reardon CC, Levitz SM, et al. Human immunodeficiency virus type 1 infection of alveolar macrophages impairs their innate fungicidal activity. Am J Respir Crit Care Med. 2000;162:966-970. [PubMed]
 
Bonecini-Almeida Mda G, Werneck-Barroso E, Carvalho PB, et al. Functional activity of alveolar and peripheral cells in patients with human acquired immunodeficiency syndrome and pulmonary tuberculosis. Cell Immunol. 1998;190:112-120. [PubMed]
 
Semenzato G, Agostini C. HIV-related interstitial lung disease. Curr Opin Pulm Med. 1995;1:383-391. [PubMed]
 
Das S, Miller RF. Lymphocytic interstitial pneumonitis in HIV infected adults. Sex Transm Infect. 2003;79:88-93. [PubMed]
 
Guillon JM, Autran B, Denis M, et al. Human immunodeficiency virus-related lymphocytic alveolitis. Chest. 1988;94:1264-1270. [PubMed]
 
Twigg HL, Soliman DM, Day RB, et al. Lymphocytic alveolitis, bronchoalveolar lavage viral load, and outcome in human immunodeficiency virus infection. Am J Respir Crit Care Med. 1999;159:1439-1444. [PubMed]
 
Twigg HL III, Spain BA, Soliman DM, et al. Impaired IgG production in the lungs of HIV-infected individuals. Cell Immunol. 1996;170:127-133. [PubMed]
 
Fahy RJ, Diaz PT, Hart J, et al. BAL and serum IgG levels in healthy asymptomatic HIV-infected patients. Chest. 2001;119:196-203. [PubMed]
 
Hirschtick RE, Glassroth J, Jordan MC, et al. Bacterial pneumonia in persons infected with the human immunodeficiency virus: Pulmonary Complications of HIV Infection Study Group. N Engl J Med. 1995;333:845-851. [PubMed]
 
Mayaud C, Parrot A, Cadranel J. Pyogenic bacterial lower respiratory tract infection in human immunodeficiency virus-infected patients. Eur Respir J Suppl. 2002;36:28s-39s. [PubMed]
 
Park DR, Sherbin VL, Goodman MS, et al. The etiology of community-acquired pneumonia at an urban public hospital: influence of human immunodeficiency virus infection and initial severity of illness. J Infect Dis. 2001;184:268-277. [PubMed]
 
Rimland D, Navin TR, Lennox JL, et al. Prospective study of etiologic agents of community-acquired pneumonia in patients with HIV infection. Aids. 2002;16:85-95. [PubMed]
 
Scott JA, Hall AJ, Muyodi C, et al. Aetiology, outcome, and risk factors for mortality among adults with acute pneumonia in Kenya. Lancet. 2000;355:1225-1230. [PubMed]
 
Feikin DR, Feldman C, Schuchat A, et al. Global strategies to prevent bacterial pneumonia in adults with HIV disease. Lancet Infect Dis. 2004;4:445-455. [PubMed]
 
Kohli R, Lo Y, Homel P, et al. Bacterial pneumonia, HIV therapy, and disease progression among HIV-infected women in the HIV epidemiologic research (HER) study. Clin Infect Dis. 2006;43:90-98. [PubMed]
 
Corbett EL, Churchyard GJ, Charalambos S, et al. Morbidity and mortality in South African gold miners: impact of untreated disease due to human immunodeficiency virus. Clin Infect Dis. 2002;34:1251-1258. [PubMed]
 
Walson JL, Brown ER, Otieno PA, et al. Morbidity among HIV-1-infected mothers in Kenya: prevalence and correlates of illness during 2-year postpartum follow-up. J Acquir Immune Defic Syndr. 2007;46:208-215. [PubMed]
 
Plouffe JF, Breiman RF, Facklam RR. Bacteremia withStreptococcus pneumoniae: implications for therapy and prevention; Franklin County Pneumonia Study Group. JAMA. 1996;275:194-198. [PubMed]
 
Nuorti JP, Butler JC, Gelling L, et al. Epidemiologic relation between HIV and invasive pneumococcal disease in San Francisco County, California. Ann Intern Med. 2000;132:182-190. [PubMed]
 
Gilks CF, Ojoo SA, Ojoo JC, et al. Invasive pneumococcal disease in a cohort of predominantly HIV-1 infected female sex-workers in Nairobi, Kenya. Lancet. 1996;347:718-723. [PubMed]
 
Jones N, Huebner R, Khoosal M, et al. The impact of HIV on Streptococcus pneumoniae bacteraemia in a South African population. Aids. 1998;12:2177-2184. [PubMed]
 
Sullivan JH, Moore RD, Keruly JC, et al. Effect of antiretroviral therapy on the incidence of bacterial pneumonia in patients with advanced HIV infection. Am J Respir Crit Care Med Jul. 2000;162:64-67
 
Anglaret X, Chene G, Attia A, et al. Early chemoprophylaxis with trimethoprim-sulphamethoxazole for HIV-1-infected adults in Abidjan, Cote d'Ivoire: a randomised trial: Cotrimo-CI Study Group. Lancet. 1999;353:1463-1468. [PubMed]
 
Wiktor SZ, Sassan-Morokro M, Grant AD, et al. Efficacy of trimethoprim-sulphamethoxazole prophylaxis to decrease morbidity and mortality in HIV-1-infected patients with tuberculosis in Abidjan, Cote d'Ivoire: a randomised controlled trial. Lancet. 1999;353:1469-1475. [PubMed]
 
Dworkin MS, Ward JW, Hanson DL, et al. Pneumococcal disease among human immunodeficiency virus-infected persons: incidence, risk factors, and impact of vaccination. Clin Infect Dis. 2001;32:794-800. [PubMed]
 
French N, Nakiyingi J, Carpenter LM, et al. 23-valent pneumococcal polysaccharide vaccine in HIV-1-infected Ugandan adults: double-blind, randomised and placebo controlled trial. Lancet. 2000;355:2106-2111. [PubMed]
 
Heffernan RT, Barrett NL, Gallagher KM, et al. Declining incidence of invasiveStreptococcus pneumoniaeinfections among persons with AIDS in an era of highly active antiretroviral therapy, 1995–2000. J Infect Dis. 2005;191:2038-2045. [PubMed]
 
Grau I, Pallares R, Tubau F, et al. Epidemiologic changes in bacteremic pneumococcal disease in patients with human immunodeficiency virus in the era of highly active antiretroviral therapy. Arch Intern Med. 2005;165:1533-1540. [PubMed]
 
Le Moing V, Rabaud C, Journot V, et al. Incidence and risk factors of bacterial pneumonia requiring hospitalization in HIV-infected patients started on a protease inhibitor-containing regimen. HIV Med. 2006;7:261-267. [PubMed]
 
Fassinou P, Elenga N, Rouet F, et al. Highly active antiretroviral therapies among HIV-1-infected children in Abidjan, Cote d'Ivoire. Aids. 2004;18:1905-1913. [PubMed]
 
Phair J, Munoz A, Detels R, et al. The risk ofPneumocystis cariniipneumonia among men infected with human immunodeficiency virus type 1: multicenter AIDS Cohort Study Group. N Engl J Med. 1990;322:161-165. [PubMed]
 
Kaplan JE, Hanson D, Dworkin MS, et al. Epidemiology of human immunodeficiency virus-associated opportunistic infections in the United States in the era of highly active antiretroviral therapy. Clin Infect Dis. 2000;30suppl 1:S5-S14. [PubMed]
 
Weverling GJ, Mocroft A, Ledergerber B, et al. Discontinuation ofPneumocystis cariniipneumonia prophylaxis after start of highly active antiretroviral therapy in HIV-1 infection: EuroSIDA Study Group. Lancet. 1999;353:1293-1298. [PubMed]
 
Ledergerber B, Mocroft A, Reiss P, et al. Discontinuation of secondary prophylaxis againstPneumocystis cariniipneumonia in patients with HIV infection who have a response to antiretroviral therapy: eight European study groups. N Engl J Med. 2001;344:168-174. [PubMed]
 
Lopez Bernaldo de Quiros JC, Miro JM, Pena JM, et al. A randomized trial of the discontinuation of primary and secondary prophylaxis againstPneumocystis cariniipneumonia after highly active antiretroviral therapy in patients with HIV infection: Grupo de Estudio del SIDA 04/98. N Engl J Med. 2001;344:159-167. [PubMed]
 
Morris A, Lundgren JD, Masur H, et al. Current epidemiology of Pneumocystis pneumonia. Emerg Infect Dis. 2004;10:1713-1720. [PubMed]
 
Soares EC, Saraceni V, Lauria Lde M, et al. Tuberculosis as a disease defining acquired immunodeficiency syndrome: ten years of surveillance in Rio de Janeiro, Brazil. J Bras Pneumol. 2006;32:444-448. [PubMed]
 
Sritangratanakul S, Nuchprayoon S, Nuchprayoon I. Pneumocystis pneumonia: an update. J Med Assoc Thai. 2004;87suppl 2:S309-S317. [PubMed]
 
Nissapatorn V, Lee C, Fatt QK, et al. AIDS-related opportunistic infections in Hospital Kuala Lumpur. Jpn J Infect Dis. 2003;56:187-192. [PubMed]
 
Chakaya JM, Bii C, Ng‘ang’a L, et al. Pneumocystis cariniipneumonia in HIV/AIDS patients at an urban district hospital in Kenya. East Afr Med J. 2003;80:30-35. [PubMed]
 
Worodria W, Okot-Nwang M, Yoo SD, et al. Causes of lower respiratory infection in HIV-infected Ugandan adults who are sputum AFB smear-negative. Int J Tuberc Lung Dis. 2003;7:117-123. [PubMed]
 
Kazanjian P, Armstrong W, Hossler PA, et al. Pneumocystis cariniimutations are associated with duration of sulfa or sulfone prophylaxis exposure in AIDS patients. J Infect Dis. 2000;182:551-557. [PubMed]
 
Zar HJ, Alvarez-Martinez MJ, Harrison A, et al. Prevalence of dihydropteroate synthase mutants in HIV-infected South African children withPneumocystis jirovecipneumonia. Clin Infect Dis. 2004;39:1047-1051. [PubMed]
 
Miller RF, Lindley AR, Ambrose HE, et al. Genotypes ofPneumocystis jiroveciisolates obtained in Harare, Zimbabwe, and London, United Kingdom. Antimicrob Agents Chemother. 2003;47:3979-3981. [PubMed]
 
Worlh Health Organization Global tuberculosis control 2008: surveillance, planning, financing.Accessed June 23 2008 Available at:http://www.who.int/tb/publications/global_report/2008/pdf/fullreport.pdf.
 
Aaron L, Saadoun D, Calatroni I, et al. Tuberculosis in HIV-infected patients: a comprehensive review. Clin Microbiol Infect. 2004;10:388-398. [PubMed]
 
Corbett EL, Marston B, Churchyard GJ, et al. Tuberculosis in sub-Saharan Africa: opportunities, challenges, and change in the era of antiretroviral treatment. Lancet. 2006;367:926-937. [PubMed]
 
El-Sadr WM, Perlman DC, Denning E, et al. A review of efficacy studies of 6-month short-course therapy for tuberculosis among patients infected with human immunodeficiency virus: differences in study outcomes. Clin Infect Dis. 2001;32:623-632. [PubMed]
 
Dean GL, Edwards SG, Ives NJ, et al. Treatment of tuberculosis in HIV-infected persons in the era of highly active antiretroviral therapy. Aids. 2002;16:75-83. [PubMed]
 
Dheda K, Lampe FC, Johnson MA, et al. Outcome of HIV-associated tuberculosis in the era of highly active antiretroviral therapy. J Infect Dis. 2004;190:1670-1676. [PubMed]
 
Muga R, Ferreros I, Langohr K, et al. Changes in the incidence of tuberculosis in a cohort of HIV-seroconverters before and after the introduction of HAART. Aids. 2007;21:2521-2527. [PubMed]
 
Kirk O, Gatell JM, Mocroft A, et al. Infections withMycobacterium tuberculosisandMycobacterium aviumamong HIV-infected patients after the introduction of highly active antiretroviral therapy: EuroSIDA Study Group JD. Am J Respir Crit Care Med. 2000;162:865-872. [PubMed]
 
Lawn SD, Myer L, Bekker LG, et al. Burden of tuberculosis in an antiretroviral treatment programme in sub-Saharan Africa: impact on treatment outcomes and implications for tuberculosis control. Aids. 2006;20:1605-1612. [PubMed]
 
Santoro-Lopes G, de Pinho AM, Harrison LH, et al. Reduced risk of tuberculosis among Brazilian patients with advanced human immunodeficiency virus infection treated with highly active antiretroviral therapy. Clin Infect Dis. 2002;34:543-546. [PubMed]
 
Treatment of tuberculosis. MMWR Recomm Rep. 2003;52RR-11:1-77
 
Pozniak AL, Miller RF, Lipman MC, et al. BHIVA treatment guidelines for tuberculosis (TB)/HIV infection 2005. HIV Med. 2005;6 suppl 2:62-83
 
Lopez-Cortes LF, Ruiz-Valderas R, Viciana P, et al. Pharmacokinetic interactions between efavirenz and rifampicin in HIV-infected patients with tuberculosis. Clin Pharmacokinet. 2002;41:681-690. [PubMed]
 
Cohen K, van Cutsem G, Boulle A, et al. Effect of rifampicin-based antitubercular therapy on nevirapine plasma concentrations in South African adults with HIV-associated tuberculosis. J Antimicrob Chemother. 2008;61:389-393. [PubMed]
 
Oliva J, Moreno S, Sanz J, et al. Co-administration of rifampin and nevirapine in HIV-infected patients with tuberculosis. Aids. 2003;17:637-638. [PubMed]
 
van Oosterhout JJ, Kumwenda JJ, Beadsworth M, et al. Nevirapine-based antiretroviral therapy started early in the course of tuberculosis treatment in adult Malawians. Antivir Ther. 2007;12:515-521. [PubMed]
 
Schiffer JT, Sterling TR. Timing of antiretroviral therapy initiation in tuberculosis patients with AIDS: a decision analysis. J Acquir Immune Defic Syndr. 2007;44:229-234. [PubMed]
 
Zignol M, Hosseini MS, Wright A, et al. Global incidence of multidrug-resistant tuberculosis. J Infect Dis. 2006;194:479-485. [PubMed]
 
Gandhi NR, Moll A, Sturm AW, et al. Extensively drug-resistant tuberculosis as a cause of death in patients co-infected with tuberculosis and HIV in a rural area of South Africa. Lancet. 2006;368:1575-1580. [PubMed]
 
Wells CD, Cegielski JP, Nelson LJ, et al. HIV infection and multidrug-resistant tuberculosis: the perfect storm. J Infect Dis. 2007;196suppl 1:S86-S107. [PubMed]
 
Ridzon R, Whitney CG, McKenna MT, et al. Risk factors for rifampin mono-resistant tuberculosis. Am J Respir Crit Care Med. 1998;157:1881-1884. [PubMed]
 
Vernon A, Burman W, Benator D, et al. Acquired rifamycin monoresistance in patients with HIV-related tuberculosis treated with once-weekly rifapentine and isoniazid: Tuberculosis Trials Consortium. Lancet. 1999;353:1843-1847. [PubMed]
 
Park MM, Davis AL, Schluger NW, et al. Outcome of MDR-TB patients, 1983–1993: prolonged survival with appropriate therapy. Am J Respir Crit Care Med. 1996;153:317-324. [PubMed]
 
Robertson J, Meier M, Wall J, et al. Immune reconstitution syndrome in HIV: validating a case definition and identifying clinical predictors in persons initiating antiretroviral therapy. Clin Infect Dis. 2006;42:1639-1646. [PubMed]
 
French MA, Price P, Stone SF. Immune restoration disease after antiretroviral therapy. Aids. 2004;18:1615-1627. [PubMed]
 
McIlleron H, Meintjes G, Burman WJ, et al. Complications of antiretroviral therapy in patients with tuberculosis: drug interactions, toxicity, and immune reconstitution inflammatory syndrome. J Infect Dis. 2007;196suppl 1:S63-S75. [PubMed]
 
Murdoch DM, Venter WD, Van Rie A, et al. Immune reconstitution inflammatory syndrome (IRIS): review of common infectious manifestations and treatment options. AIDS Res Ther. 2007;4:9. [PubMed]
 
Lawn SD, Bekker LG, Miller RF. Immune reconstitution disease associated with mycobacterial infections in HIV-infected individuals receiving antiretrovirals. Lancet Infect Dis. 2005;5:361-373. [PubMed]
 
Fishman JE, Saraf-Lavi E, Narita M, et al. Pulmonary tuberculosis in AIDS patients: transient chest radiographic worsening after initiation of antiretroviral therapy. AJR Am J Roentgenol. 2000;174:43-49. [PubMed]
 
Phillips P, Bonner S, Gataric N, et al. Nontuberculous mycobacterial immune reconstitution syndrome in HIV-infected patients: spectrum of disease and long-term follow-up. Clin Infect Dis. 2005;41:1483-1497. [PubMed]
 
Niaura R, Shadel WG, Morrow K, et al. Human immunodeficiency virus infection, AIDS, and smoking cessation: the time is now. Clin Infect Dis. 2000;31:808-812. [PubMed]
 
Crothers K. Chronic obstructive pulmonary disease in patients who have HIV infection. Clin Chest Med Sep. 2007;28:575-587
 
Diaz PT, King MA, Pacht ER, et al. Increased susceptibility to pulmonary emphysema among HIV-seropositive smokers. Ann Intern Med. 2000;132:369-372. [PubMed]
 
Mollmann H, Wagner M, Meibohm B, et al. Pharmacokinetic and pharmacodynamic evaluation of fluticasone propionate after inhaled administration. Eur J Clin Pharmacol. 1998;53:459-467. [PubMed]
 
Samaras K, Pett S, Gowers A, et al. Iatrogenic Cushing's syndrome with osteoporosis and secondary adrenal failure in human immunodeficiency virus-infected patients receiving inhaled corticosteroids and ritonavir-boosted protease inhibitors: six cases. J Clin Endocrinol Metab. 2005;90:4394-4398. [PubMed]
 
Hillebrand-Haverkort ME, Prummel MF, ten Veen JH. Ritonavir-induced Cushing's syndrome in a patient treated with nasal fluticasone [letter]. Aids. 1999;13:1803. [PubMed]
 
Rouanet I, Peyriere H, Mauboussin JM, et al. Cushing's syndrome in a patient treated by ritonavir/lopinavir and inhaled fluticasone. HIV Med. 2003;4:149-150. [PubMed]
 
Clifford GM, Polesel J, Rickenbach M, et al. Cancer risk in the Swiss HIV Cohort Study: associations with immunodeficiency, smoking, and highly active antiretroviral therapy. J Natl Cancer Inst. 2005;97:425-432. [PubMed]
 
Grubb JR, Moorman AC, Baker RK, et al. The changing spectrum of pulmonary disease in patients with HIV infection on antiretroviral therapy. Aids. 2006;20:1095-1107. [PubMed]
 
Herida M, Mary-Krause M, Kaphan R, et al. Incidence of non-AIDS-defining cancers before and during the highly active antiretroviral therapy era in a cohort of human immunodeficiency virus-infected patients. J Clin Oncol. 2003;21:3447-3453. [PubMed]
 
Cadranel J, Garfield D, Lavole A, et al. Lung cancer in HIV infected patients: facts, questions and challenges. Thorax. 2006;61:1000-1008. [PubMed]
 
Kirk GD, Merlo C, O'Driscoll P, et al. HIV infection is associated with an increased risk for lung cancer, independent of smoking. Clin Infect Dis. 2007;45:103-110. [PubMed]
 
Toward universal access: how WHO is working with countries to scale up HIV prevention. 2007; Geneva, Switzerland World Health Organization
 

Figures

Figure Jump LinkFigure 1 Global prevalence of HIV/AIDS, 2007. Reproduced with permission from the Joint United Nations Program on HIV/AIDS and World Health Organization.4Grahic Jump Location
Figure Jump LinkFigure 2 Global distribution of antiretroviral use, 2006. Reproduced with permission from the World Health Organization.112Grahic Jump Location
Figure Jump LinkFigure 3 Global tuberculosis incidence rates, 2006. Reproduced with permission from the World Health Organization.70Grahic Jump Location

Tables

Table Graphic Jump Location
Table 1 Summary of Selected Studies of HIV and AIDS-Associated Invasive Pneumococcal Disease Rates*

*Unless otherwise specified, rates are for invasive pneumococcal disease (defined as isolation of S pneumoniae from a normally sterile site)

Table Graphic Jump Location
Table 2 Impact of HAART on Tuberculosis Incidence in the Developed World and Resource-Limited Settings

References

Pneumocystis pneumonia–Los Angeles. MMWR Morb Mortal Wkly Rep. 1981; 65 30:250-252. [PubMed]
 
Barre-Sinoussi F, Chermann JC, Rey F, et al. Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). Science. 1983; 520 220:868-871. [PubMed] [CrossRef]
 
Gallo RC, Sarin PS, Gelmann EP, et al. Isolation of human T-cell leukemia virus in acquired immune deficiency syndrome (AIDS). Science. 1983;220:865-867. [PubMed]
 
UNAIDS/WHO AIDS epidemic update.Accessed June 23, 2008 Available at:http://data.unaids.org/pub/EPISlides/2007/2007_epiupdate_en.pdf.
 
Hammer SM, Squires KE, Hughes MD, et al. A controlled trial of two nucleoside analogues plus indinavir in persons with human immunodeficiency virus infection and CD4 cell counts of 200 per cubic millimeter or less: AIDS Clinical Trials Group 320 Study Team. N Engl J Med. 1997;337:725-733. [PubMed]
 
Montaner JS, Reiss P, Cooper D, et al. A randomized, double-blind trial comparing combinations of nevirapine, didanosine, and zidovudine for HIV-infected patients: the INCAS Trial: Italy, the Netherlands, Canada and Australia Study. JAMA. 1998;279:930-937. [PubMed]
 
Crothers K, Butt AA, Gibert CL, et al. Increased COPD among HIV-positive compared to HIV-negative veterans. Chest. 2006;130:1326-1333. [PubMed]
 
Bower M, Powles T, Nelson M, et al. HIV-related lung cancer in the era of highly active antiretroviral therapy. Aids. 2003;17:371-375. [PubMed]
 
Dye C, Scheele S, Dolin P, et al. Consensus statement: global burden of tuberculosis: estimated incidence, prevalence, and mortality by country; WHO Global Surveillance and Monitoring Project. JAMA. 1999;282:677-686. [PubMed]
 
Corbett EL, Steketee RW, ter Kuile FO, et al. HIV-1/AIDS and the control of other infectious diseases in Africa. Lancet. 2002;359:2177-2187. [PubMed]
 
Centers for Disease Control and Prevention HIV/AIDS surveillance report, 2005. 2005; Atlanta, GA US Department of Health and Human Services
 
Palella FJ Jr, Delaney KM, Moorman AC, et al. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection: HIV Outpatient Study Investigators. N Engl J Med. 1998;338:853-860. [PubMed]
 
Hogg RS, Heath KV, Yip B, et al. Improved survival among HIV-infected individuals following initiation of antiretroviral therapy. JAMA. 1998;279:450-454. [PubMed]
 
Mocroft A, Ledergerber B, Katlama C, et al. Decline in the AIDS and death rates in the EuroSIDA study: an observational study. Lancet. 2003;362:22-29. [PubMed]
 
Coetzee D, Hildebrand K, Boulle A, et al. Outcomes after two years of providing antiretroviral treatment in Khayelitsha, South Africa. Aids. 2004;18:887-895. [PubMed]
 
Stringer JS, Zulu I, Levy J, et al. Rapid scale-up of antiretroviral therapy at primary care sites in Zambia: feasibility and early outcomes. JAMA. 2006;296:782-793. [PubMed]
 
Weidle PJ, Malamba S, Mwebaze R, et al. Assessment of a pilot antiretroviral drug therapy programme in Uganda: patients' response, survival, and drug resistance. Lancet. 2002;360:34-40. [PubMed]
 
Madec Y, Laureillard D, Pinoges L, et al. Response to highly active antiretroviral therapy among severely immuno-compromised HIV-infected patients in Cambodia. Aids. 2007;21:351-359. [PubMed]
 
Zhou J, Kumarasamy N, Ditangco R, et al. The TREAT Asia HIV Observational Database: baseline and retrospective data. J Acquir Immune Defic Syndr. 2005;38:174-179. [PubMed]
 
World Health Organization Towards universal access: scaling up priority HIV/AIDS interventions in the health sector; progress report 2008.Accessed June 23 2008 Available at:http://www.who.int/hiv/pub/towards_universal_access_report_2008.pdf.
 
Beck JM. The immunocompromised host: HIV infection. Proc Am Thorac Soc. 2005;2:423-427. [PubMed]
 
Park IW, Koziel H, Hatch W, et al. CD4 receptor-dependent entry of human immunodeficiency virus type-1 env-pseudotypes into CCR5-, CCR3-, and CXCR4-expressing human alveolar macrophages is preferentially mediated by the CCR5 coreceptor. Am J Respir Cell Mol Biol. 1999;20:864-871. [PubMed]
 
Sierra-Madero JG, Toossi Z, Hom DL, et al. Relationship between load of virus in alveolar macrophages from human immunodeficiency virus type 1-infected persons, production of cytokines, and clinical status. J Infect Dis. 1994;169:18-27. [PubMed]
 
Murray HW, Gellene RA, Libby DM, et al. Activation of tissue macrophages from AIDS patients:in vitroresponse of AIDS alveolar macrophages to lymphokines and interferon-γ. J Immunol. 1985;135:2374-2377. [PubMed]
 
Koziel H, Eichbaum Q, Kruskal BA, et al. Reduced binding and phagocytosis ofPneumocystis cariniiby alveolar macrophages from persons infected with HIV-1 correlates with mannose receptor downregulation. J Clin Invest. 1998;102:1332-1344. [PubMed]
 
Ieong MH, Reardon CC, Levitz SM, et al. Human immunodeficiency virus type 1 infection of alveolar macrophages impairs their innate fungicidal activity. Am J Respir Crit Care Med. 2000;162:966-970. [PubMed]
 
Bonecini-Almeida Mda G, Werneck-Barroso E, Carvalho PB, et al. Functional activity of alveolar and peripheral cells in patients with human acquired immunodeficiency syndrome and pulmonary tuberculosis. Cell Immunol. 1998;190:112-120. [PubMed]
 
Semenzato G, Agostini C. HIV-related interstitial lung disease. Curr Opin Pulm Med. 1995;1:383-391. [PubMed]
 
Das S, Miller RF. Lymphocytic interstitial pneumonitis in HIV infected adults. Sex Transm Infect. 2003;79:88-93. [PubMed]
 
Guillon JM, Autran B, Denis M, et al. Human immunodeficiency virus-related lymphocytic alveolitis. Chest. 1988;94:1264-1270. [PubMed]
 
Twigg HL, Soliman DM, Day RB, et al. Lymphocytic alveolitis, bronchoalveolar lavage viral load, and outcome in human immunodeficiency virus infection. Am J Respir Crit Care Med. 1999;159:1439-1444. [PubMed]
 
Twigg HL III, Spain BA, Soliman DM, et al. Impaired IgG production in the lungs of HIV-infected individuals. Cell Immunol. 1996;170:127-133. [PubMed]
 
Fahy RJ, Diaz PT, Hart J, et al. BAL and serum IgG levels in healthy asymptomatic HIV-infected patients. Chest. 2001;119:196-203. [PubMed]
 
Hirschtick RE, Glassroth J, Jordan MC, et al. Bacterial pneumonia in persons infected with the human immunodeficiency virus: Pulmonary Complications of HIV Infection Study Group. N Engl J Med. 1995;333:845-851. [PubMed]
 
Mayaud C, Parrot A, Cadranel J. Pyogenic bacterial lower respiratory tract infection in human immunodeficiency virus-infected patients. Eur Respir J Suppl. 2002;36:28s-39s. [PubMed]
 
Park DR, Sherbin VL, Goodman MS, et al. The etiology of community-acquired pneumonia at an urban public hospital: influence of human immunodeficiency virus infection and initial severity of illness. J Infect Dis. 2001;184:268-277. [PubMed]
 
Rimland D, Navin TR, Lennox JL, et al. Prospective study of etiologic agents of community-acquired pneumonia in patients with HIV infection. Aids. 2002;16:85-95. [PubMed]
 
Scott JA, Hall AJ, Muyodi C, et al. Aetiology, outcome, and risk factors for mortality among adults with acute pneumonia in Kenya. Lancet. 2000;355:1225-1230. [PubMed]
 
Feikin DR, Feldman C, Schuchat A, et al. Global strategies to prevent bacterial pneumonia in adults with HIV disease. Lancet Infect Dis. 2004;4:445-455. [PubMed]
 
Kohli R, Lo Y, Homel P, et al. Bacterial pneumonia, HIV therapy, and disease progression among HIV-infected women in the HIV epidemiologic research (HER) study. Clin Infect Dis. 2006;43:90-98. [PubMed]
 
Corbett EL, Churchyard GJ, Charalambos S, et al. Morbidity and mortality in South African gold miners: impact of untreated disease due to human immunodeficiency virus. Clin Infect Dis. 2002;34:1251-1258. [PubMed]
 
Walson JL, Brown ER, Otieno PA, et al. Morbidity among HIV-1-infected mothers in Kenya: prevalence and correlates of illness during 2-year postpartum follow-up. J Acquir Immune Defic Syndr. 2007;46:208-215. [PubMed]
 
Plouffe JF, Breiman RF, Facklam RR. Bacteremia withStreptococcus pneumoniae: implications for therapy and prevention; Franklin County Pneumonia Study Group. JAMA. 1996;275:194-198. [PubMed]
 
Nuorti JP, Butler JC, Gelling L, et al. Epidemiologic relation between HIV and invasive pneumococcal disease in San Francisco County, California. Ann Intern Med. 2000;132:182-190. [PubMed]
 
Gilks CF, Ojoo SA, Ojoo JC, et al. Invasive pneumococcal disease in a cohort of predominantly HIV-1 infected female sex-workers in Nairobi, Kenya. Lancet. 1996;347:718-723. [PubMed]
 
Jones N, Huebner R, Khoosal M, et al. The impact of HIV on Streptococcus pneumoniae bacteraemia in a South African population. Aids. 1998;12:2177-2184. [PubMed]
 
Sullivan JH, Moore RD, Keruly JC, et al. Effect of antiretroviral therapy on the incidence of bacterial pneumonia in patients with advanced HIV infection. Am J Respir Crit Care Med Jul. 2000;162:64-67
 
Anglaret X, Chene G, Attia A, et al. Early chemoprophylaxis with trimethoprim-sulphamethoxazole for HIV-1-infected adults in Abidjan, Cote d'Ivoire: a randomised trial: Cotrimo-CI Study Group. Lancet. 1999;353:1463-1468. [PubMed]
 
Wiktor SZ, Sassan-Morokro M, Grant AD, et al. Efficacy of trimethoprim-sulphamethoxazole prophylaxis to decrease morbidity and mortality in HIV-1-infected patients with tuberculosis in Abidjan, Cote d'Ivoire: a randomised controlled trial. Lancet. 1999;353:1469-1475. [PubMed]
 
Dworkin MS, Ward JW, Hanson DL, et al. Pneumococcal disease among human immunodeficiency virus-infected persons: incidence, risk factors, and impact of vaccination. Clin Infect Dis. 2001;32:794-800. [PubMed]
 
French N, Nakiyingi J, Carpenter LM, et al. 23-valent pneumococcal polysaccharide vaccine in HIV-1-infected Ugandan adults: double-blind, randomised and placebo controlled trial. Lancet. 2000;355:2106-2111. [PubMed]
 
Heffernan RT, Barrett NL, Gallagher KM, et al. Declining incidence of invasiveStreptococcus pneumoniaeinfections among persons with AIDS in an era of highly active antiretroviral therapy, 1995–2000. J Infect Dis. 2005;191:2038-2045. [PubMed]
 
Grau I, Pallares R, Tubau F, et al. Epidemiologic changes in bacteremic pneumococcal disease in patients with human immunodeficiency virus in the era of highly active antiretroviral therapy. Arch Intern Med. 2005;165:1533-1540. [PubMed]
 
Le Moing V, Rabaud C, Journot V, et al. Incidence and risk factors of bacterial pneumonia requiring hospitalization in HIV-infected patients started on a protease inhibitor-containing regimen. HIV Med. 2006;7:261-267. [PubMed]
 
Fassinou P, Elenga N, Rouet F, et al. Highly active antiretroviral therapies among HIV-1-infected children in Abidjan, Cote d'Ivoire. Aids. 2004;18:1905-1913. [PubMed]
 
Phair J, Munoz A, Detels R, et al. The risk ofPneumocystis cariniipneumonia among men infected with human immunodeficiency virus type 1: multicenter AIDS Cohort Study Group. N Engl J Med. 1990;322:161-165. [PubMed]
 
Kaplan JE, Hanson D, Dworkin MS, et al. Epidemiology of human immunodeficiency virus-associated opportunistic infections in the United States in the era of highly active antiretroviral therapy. Clin Infect Dis. 2000;30suppl 1:S5-S14. [PubMed]
 
Weverling GJ, Mocroft A, Ledergerber B, et al. Discontinuation ofPneumocystis cariniipneumonia prophylaxis after start of highly active antiretroviral therapy in HIV-1 infection: EuroSIDA Study Group. Lancet. 1999;353:1293-1298. [PubMed]
 
Ledergerber B, Mocroft A, Reiss P, et al. Discontinuation of secondary prophylaxis againstPneumocystis cariniipneumonia in patients with HIV infection who have a response to antiretroviral therapy: eight European study groups. N Engl J Med. 2001;344:168-174. [PubMed]
 
Lopez Bernaldo de Quiros JC, Miro JM, Pena JM, et al. A randomized trial of the discontinuation of primary and secondary prophylaxis againstPneumocystis cariniipneumonia after highly active antiretroviral therapy in patients with HIV infection: Grupo de Estudio del SIDA 04/98. N Engl J Med. 2001;344:159-167. [PubMed]
 
Morris A, Lundgren JD, Masur H, et al. Current epidemiology of Pneumocystis pneumonia. Emerg Infect Dis. 2004;10:1713-1720. [PubMed]
 
Soares EC, Saraceni V, Lauria Lde M, et al. Tuberculosis as a disease defining acquired immunodeficiency syndrome: ten years of surveillance in Rio de Janeiro, Brazil. J Bras Pneumol. 2006;32:444-448. [PubMed]
 
Sritangratanakul S, Nuchprayoon S, Nuchprayoon I. Pneumocystis pneumonia: an update. J Med Assoc Thai. 2004;87suppl 2:S309-S317. [PubMed]
 
Nissapatorn V, Lee C, Fatt QK, et al. AIDS-related opportunistic infections in Hospital Kuala Lumpur. Jpn J Infect Dis. 2003;56:187-192. [PubMed]
 
Chakaya JM, Bii C, Ng‘ang’a L, et al. Pneumocystis cariniipneumonia in HIV/AIDS patients at an urban district hospital in Kenya. East Afr Med J. 2003;80:30-35. [PubMed]
 
Worodria W, Okot-Nwang M, Yoo SD, et al. Causes of lower respiratory infection in HIV-infected Ugandan adults who are sputum AFB smear-negative. Int J Tuberc Lung Dis. 2003;7:117-123. [PubMed]
 
Kazanjian P, Armstrong W, Hossler PA, et al. Pneumocystis cariniimutations are associated with duration of sulfa or sulfone prophylaxis exposure in AIDS patients. J Infect Dis. 2000;182:551-557. [PubMed]
 
Zar HJ, Alvarez-Martinez MJ, Harrison A, et al. Prevalence of dihydropteroate synthase mutants in HIV-infected South African children withPneumocystis jirovecipneumonia. Clin Infect Dis. 2004;39:1047-1051. [PubMed]
 
Miller RF, Lindley AR, Ambrose HE, et al. Genotypes ofPneumocystis jiroveciisolates obtained in Harare, Zimbabwe, and London, United Kingdom. Antimicrob Agents Chemother. 2003;47:3979-3981. [PubMed]
 
Worlh Health Organization Global tuberculosis control 2008: surveillance, planning, financing.Accessed June 23 2008 Available at:http://www.who.int/tb/publications/global_report/2008/pdf/fullreport.pdf.
 
Aaron L, Saadoun D, Calatroni I, et al. Tuberculosis in HIV-infected patients: a comprehensive review. Clin Microbiol Infect. 2004;10:388-398. [PubMed]
 
Corbett EL, Marston B, Churchyard GJ, et al. Tuberculosis in sub-Saharan Africa: opportunities, challenges, and change in the era of antiretroviral treatment. Lancet. 2006;367:926-937. [PubMed]
 
El-Sadr WM, Perlman DC, Denning E, et al. A review of efficacy studies of 6-month short-course therapy for tuberculosis among patients infected with human immunodeficiency virus: differences in study outcomes. Clin Infect Dis. 2001;32:623-632. [PubMed]
 
Dean GL, Edwards SG, Ives NJ, et al. Treatment of tuberculosis in HIV-infected persons in the era of highly active antiretroviral therapy. Aids. 2002;16:75-83. [PubMed]
 
Dheda K, Lampe FC, Johnson MA, et al. Outcome of HIV-associated tuberculosis in the era of highly active antiretroviral therapy. J Infect Dis. 2004;190:1670-1676. [PubMed]
 
Muga R, Ferreros I, Langohr K, et al. Changes in the incidence of tuberculosis in a cohort of HIV-seroconverters before and after the introduction of HAART. Aids. 2007;21:2521-2527. [PubMed]
 
Kirk O, Gatell JM, Mocroft A, et al. Infections withMycobacterium tuberculosisandMycobacterium aviumamong HIV-infected patients after the introduction of highly active antiretroviral therapy: EuroSIDA Study Group JD. Am J Respir Crit Care Med. 2000;162:865-872. [PubMed]
 
Lawn SD, Myer L, Bekker LG, et al. Burden of tuberculosis in an antiretroviral treatment programme in sub-Saharan Africa: impact on treatment outcomes and implications for tuberculosis control. Aids. 2006;20:1605-1612. [PubMed]
 
Santoro-Lopes G, de Pinho AM, Harrison LH, et al. Reduced risk of tuberculosis among Brazilian patients with advanced human immunodeficiency virus infection treated with highly active antiretroviral therapy. Clin Infect Dis. 2002;34:543-546. [PubMed]
 
Treatment of tuberculosis. MMWR Recomm Rep. 2003;52RR-11:1-77
 
Pozniak AL, Miller RF, Lipman MC, et al. BHIVA treatment guidelines for tuberculosis (TB)/HIV infection 2005. HIV Med. 2005;6 suppl 2:62-83
 
Lopez-Cortes LF, Ruiz-Valderas R, Viciana P, et al. Pharmacokinetic interactions between efavirenz and rifampicin in HIV-infected patients with tuberculosis. Clin Pharmacokinet. 2002;41:681-690. [PubMed]
 
Cohen K, van Cutsem G, Boulle A, et al. Effect of rifampicin-based antitubercular therapy on nevirapine plasma concentrations in South African adults with HIV-associated tuberculosis. J Antimicrob Chemother. 2008;61:389-393. [PubMed]
 
Oliva J, Moreno S, Sanz J, et al. Co-administration of rifampin and nevirapine in HIV-infected patients with tuberculosis. Aids. 2003;17:637-638. [PubMed]
 
van Oosterhout JJ, Kumwenda JJ, Beadsworth M, et al. Nevirapine-based antiretroviral therapy started early in the course of tuberculosis treatment in adult Malawians. Antivir Ther. 2007;12:515-521. [PubMed]
 
Schiffer JT, Sterling TR. Timing of antiretroviral therapy initiation in tuberculosis patients with AIDS: a decision analysis. J Acquir Immune Defic Syndr. 2007;44:229-234. [PubMed]
 
Zignol M, Hosseini MS, Wright A, et al. Global incidence of multidrug-resistant tuberculosis. J Infect Dis. 2006;194:479-485. [PubMed]
 
Gandhi NR, Moll A, Sturm AW, et al. Extensively drug-resistant tuberculosis as a cause of death in patients co-infected with tuberculosis and HIV in a rural area of South Africa. Lancet. 2006;368:1575-1580. [PubMed]
 
Wells CD, Cegielski JP, Nelson LJ, et al. HIV infection and multidrug-resistant tuberculosis: the perfect storm. J Infect Dis. 2007;196suppl 1:S86-S107. [PubMed]
 
Ridzon R, Whitney CG, McKenna MT, et al. Risk factors for rifampin mono-resistant tuberculosis. Am J Respir Crit Care Med. 1998;157:1881-1884. [PubMed]
 
Vernon A, Burman W, Benator D, et al. Acquired rifamycin monoresistance in patients with HIV-related tuberculosis treated with once-weekly rifapentine and isoniazid: Tuberculosis Trials Consortium. Lancet. 1999;353:1843-1847. [PubMed]
 
Park MM, Davis AL, Schluger NW, et al. Outcome of MDR-TB patients, 1983–1993: prolonged survival with appropriate therapy. Am J Respir Crit Care Med. 1996;153:317-324. [PubMed]
 
Robertson J, Meier M, Wall J, et al. Immune reconstitution syndrome in HIV: validating a case definition and identifying clinical predictors in persons initiating antiretroviral therapy. Clin Infect Dis. 2006;42:1639-1646. [PubMed]
 
French MA, Price P, Stone SF. Immune restoration disease after antiretroviral therapy. Aids. 2004;18:1615-1627. [PubMed]
 
McIlleron H, Meintjes G, Burman WJ, et al. Complications of antiretroviral therapy in patients with tuberculosis: drug interactions, toxicity, and immune reconstitution inflammatory syndrome. J Infect Dis. 2007;196suppl 1:S63-S75. [PubMed]
 
Murdoch DM, Venter WD, Van Rie A, et al. Immune reconstitution inflammatory syndrome (IRIS): review of common infectious manifestations and treatment options. AIDS Res Ther. 2007;4:9. [PubMed]
 
Lawn SD, Bekker LG, Miller RF. Immune reconstitution disease associated with mycobacterial infections in HIV-infected individuals receiving antiretrovirals. Lancet Infect Dis. 2005;5:361-373. [PubMed]
 
Fishman JE, Saraf-Lavi E, Narita M, et al. Pulmonary tuberculosis in AIDS patients: transient chest radiographic worsening after initiation of antiretroviral therapy. AJR Am J Roentgenol. 2000;174:43-49. [PubMed]
 
Phillips P, Bonner S, Gataric N, et al. Nontuberculous mycobacterial immune reconstitution syndrome in HIV-infected patients: spectrum of disease and long-term follow-up. Clin Infect Dis. 2005;41:1483-1497. [PubMed]
 
Niaura R, Shadel WG, Morrow K, et al. Human immunodeficiency virus infection, AIDS, and smoking cessation: the time is now. Clin Infect Dis. 2000;31:808-812. [PubMed]
 
Crothers K. Chronic obstructive pulmonary disease in patients who have HIV infection. Clin Chest Med Sep. 2007;28:575-587
 
Diaz PT, King MA, Pacht ER, et al. Increased susceptibility to pulmonary emphysema among HIV-seropositive smokers. Ann Intern Med. 2000;132:369-372. [PubMed]
 
Mollmann H, Wagner M, Meibohm B, et al. Pharmacokinetic and pharmacodynamic evaluation of fluticasone propionate after inhaled administration. Eur J Clin Pharmacol. 1998;53:459-467. [PubMed]
 
Samaras K, Pett S, Gowers A, et al. Iatrogenic Cushing's syndrome with osteoporosis and secondary adrenal failure in human immunodeficiency virus-infected patients receiving inhaled corticosteroids and ritonavir-boosted protease inhibitors: six cases. J Clin Endocrinol Metab. 2005;90:4394-4398. [PubMed]
 
Hillebrand-Haverkort ME, Prummel MF, ten Veen JH. Ritonavir-induced Cushing's syndrome in a patient treated with nasal fluticasone [letter]. Aids. 1999;13:1803. [PubMed]
 
Rouanet I, Peyriere H, Mauboussin JM, et al. Cushing's syndrome in a patient treated by ritonavir/lopinavir and inhaled fluticasone. HIV Med. 2003;4:149-150. [PubMed]
 
Clifford GM, Polesel J, Rickenbach M, et al. Cancer risk in the Swiss HIV Cohort Study: associations with immunodeficiency, smoking, and highly active antiretroviral therapy. J Natl Cancer Inst. 2005;97:425-432. [PubMed]
 
Grubb JR, Moorman AC, Baker RK, et al. The changing spectrum of pulmonary disease in patients with HIV infection on antiretroviral therapy. Aids. 2006;20:1095-1107. [PubMed]
 
Herida M, Mary-Krause M, Kaphan R, et al. Incidence of non-AIDS-defining cancers before and during the highly active antiretroviral therapy era in a cohort of human immunodeficiency virus-infected patients. J Clin Oncol. 2003;21:3447-3453. [PubMed]
 
Cadranel J, Garfield D, Lavole A, et al. Lung cancer in HIV infected patients: facts, questions and challenges. Thorax. 2006;61:1000-1008. [PubMed]
 
Kirk GD, Merlo C, O'Driscoll P, et al. HIV infection is associated with an increased risk for lung cancer, independent of smoking. Clin Infect Dis. 2007;45:103-110. [PubMed]
 
Toward universal access: how WHO is working with countries to scale up HIV prevention. 2007; Geneva, Switzerland World Health Organization
 
NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging & repositioning the boxes below.

CHEST Journal Articles
CHEST Collections
PubMed Articles
Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol 2013;62(25 Suppl):D34-41.
Guidelines
Personality disorders in patients with HIV/AIDS.
New York State Department of Health | 7/20/2006
  • CHEST Journal
    Print ISSN: 0012-3692
    Online ISSN: 1931-3543