Non-acquired Immunodeficiency Syndrome Research Articles

Impact of Tobacco Smoke in HIV Progression: a Major Risk Factor for the Development of NeuroAIDS and Associated of CNS Disorders.

With the advent of highly active and combination antiretroviral therapy have substantially increased the life expectancy of patients infected with human immunodeficiency virus (HIV). However, this has brought into sharp contrast the incidence of several 'Non-acquired immunodeficiency syndrome (AIDS) diseases such as NeuroAIDS which identifies a group of neurological disorders caused primarily by HIV-mediated damage to the central and peripheral nervous systems. Given the patients depleted immune condition, the use and abuse of drug and addictive substances such as tobacco smoking can further deteriorates their overall health and accelerate the progression and severity of the disease. In this review we detail the pathogenesis, progression and characteristics of HIV and the impact of tobacco smoking as a risk factor for the progression of the disease to NeuroAIDS. This is a poorly understood aspect of HIV-related complications that needs to be addressed. Review of theoretical approaches and knowledge synthesis. Tobacco smoking is highly prevalent in HIV patients when compared to the general population. The oxidative damage and inflammatory stress caused by chronic smoking on the cerebrovascular system have been well established. Considering that HIV patients have an impaired immune system and smokers per se are more susceptible to viral and bacterial inflammatory neuropathologies than non-smokers, it is conceivable that tobacco smoking as a risk factor for the progression of HIV into NeuroAIDS and related neurological impairments. Tobacco smoke (TS) may bring about a synergistic effect in the context of persistent inflammatory state and cerebrovascular damage which facilitate HIV infection and progression to NeuroAIDS when compared to non-smokers.

Oral Microbiome in HIV-Infected Women: Shifts in the Abundance of Pathogenic and Beneficial Bacteria Are Associated with Aging, HIV Load, CD4 Count, and Antiretroviral Therapy.

Human immunodeficiency virus (HIV)-associated nonacquired immunodeficiency syndrome (AIDS) conditions, such as cardiovascular disease, diabetes, osteoporosis, and dementia are more prevalent in older than in young adult HIV-infected subjects. Although the oral microbiome has been studied as a window into pathogenesis in aging populations, its relationship to HIV disease progression, opportunistic infections, and HIV-associated non-AIDS conditions is not well understood. We utilized 16S rDNA-based pyrosequencing to compare the salivary microbiome in three groups: (1) Chronically HIV-infected women >50 years of age (aging); (2) HIV-infected women <35 years of age (young adult); and (3) HIV-uninfected age-matched women. We also examined correlations between salivary dysbiosis, plasma HIV RNA, CD4+ T cell depletion, and opportunistic oral infections. In both aging and young adult women, HIV infection was associated with salivary dysbiosis characterized by increased abundance of Prevotella melaninogenica and Rothia mucilaginosa. Aging was associated with increased bacterial diversity in both uninfected and HIV-infected women. In HIV-infected women with oral coinfections, aging was also associated with reduced abundance of the common commensal Veillonella parvula. Patients taking antiretroviral therapy showed increased numbers of Neisseria and Haemophilus. High plasma HIV RNA levels correlated positively with the presence of Prevotella and Veillonella, and negatively with the abundance of potentially beneficial Streptococcus and Lactobacillus. Circulating CD4+ T cell numbers correlated positively with the abundance of Streptococcus and Lactobacillus. Our findings extend previous studies of the role of the microbiome in HIV pathogenesis, providing new evidence that HIV infection is associated with a shift toward an increased pathogenic footprint of the salivary microbiome. Taken together, the data suggest a complex relationship, worthy of additional study, between chronic dysbiosis in the oral cavity, aging, viral burden, CD4+ T cell depletion, and long-term antiretroviral therapy.

Eradication of hepatitis C virus and non-liver-related non-acquired immune deficiency syndrome-related events in human immunodeficiency virus/hepatitis C virus coinfection.

We assessed non‐liver‐related non–acquired immunodeficiency syndrome (AIDS)‐related (NLR‐NAR) events and mortality in a cohort of human immunodeficiency virus (HIV)/hepatitis C virus (HCV)–coinfected patients treated with interferon (IFN) and ribavirin (RBV), between 2000 and 2008. The censoring date was May 31, 2014. Cox regression analysis was performed to assess the adjusted hazard rate (HR) of overall death in responders and nonresponders. Fine and Gray regression analysis was conducted to determine the adjusted subhazard rate (sHR) of NLR deaths and NLR‐NAR events considering death as the competing risk. The NLR‐NAR events analyzed included diabetes mellitus, chronic renal failure, cardiovascular events, NLR‐NAR cancer, bone events, and non‐AIDS‐related infections. The variables for adjustment were age, sex, past AIDS, HIV transmission category, nadir CD4+ T‐cell count, antiretroviral therapy, HIV RNA, liver fibrosis, HCV genotype, and exposure to specific anti‐HIV drugs. Of the 1,625 patients included, 592 (36%) had a sustained viral response (SVR). After a median 5‐year follow‐up, SVR was found to be associated with a significant decrease in the hazard of diabetes mellitus (sHR, 0.57; 95% confidence interval [CI], 0.35‐0.93; P = 0.024) and decline in the hazard of chronic renal failure close to the threshold of significance (sHR, 0.43; 95% CI, 0.17‐1.09; P = 0.075). Conclusion: Our data suggest that eradication of HCV in coinfected patients is associated not only with a reduction in the frequency of death, HIV progression, and liver‐related events, but also with a reduced hazard of diabetes mellitus and possibly of chronic renal failure. These findings argue for the prescription of HCV therapy in coinfected patients regardless of fibrosis stage. (Hepatology 2017;66:344–356).

Gut epithelial barrier dysfunction in human immunodeficiency virus-hepatitis C virus coinfected patients: Influence on innate and acquired immunity.

Even in cases where viral replication has been controlled by antiretroviral therapy for long periods of time, human immunodeficiency virus (HIV)-infected patients have several non-acquired immunodeficiency syndrome (AIDS) related co-morbidities, including liver disease, cardiovascular disease and neurocognitive decline, which have a clear impact on survival. It has been considered that persistent innate and acquired immune activation contributes to the pathogenesis of these non-AIDS related diseases. Immune activation has been related with several conditions, remarkably with the bacterial translocation related with the intestinal barrier damage by the HIV or by hepatitis C virus (HCV)-related liver cirrhosis. Consequently, increased morbidity and mortality must be expected in HIV-HCV coinfected patients. Disrupted gut barrier lead to an increased passage of microbial products and to an activation of the mucosal immune system and secretion of inflammatory mediators, which in turn might increase barrier dysfunction. In the present review, the intestinal barrier structure, measures of intestinal barrier dysfunction and the modifications of them in HIV monoinfection and in HIV-HCV coinfection will be considered. Both pathogenesis and the consequences for the progression of liver disease secondary to gut microbial fragment leakage and immune activation will be assessed.

Low testosterone is associated with poor health status in men with human immunodeficiency virus infection: a retrospective study.

Men with human immunodeficiency virus (HIV) infection are often hypogonadal and develop several HIV-associated non-acquired immunodeficiency syndrome (AIDS) (HANA) conditions that impair overall health status. No studies explored the relationship between health status and serum testosterone (T) in HIV-infected men. This study aims to investigate the association between total serum T and HANA, multimorbidity, and frailty in a large cohort of 1359 HIV-infected men and to explore the relationship between patients' overall health status and serum T. Among biochemical and hormonal measurement performed the main are serum total T, free triiodothyronine (fT3), and luteinizing hormone. Other outcome measurements include anthropometry, assessment of comorbidities and disabilities, overall health status defined as the number of HANA and by the 38-item multimorbidity frailty index, anthropometry, and bone mineral density. The cumulative relative risk of comorbidities is increased in HIV-infected men with hypogonadism (p < 0.001) and hypogonadism is associated with several comorbidities. The prevalence of hypogonadism increases progressively with the increase of the number of comorbidities. Frailty index is inversely related to serum total T (age-adjusted r = 0.298, r(2) = 0.089, p < 0.0001). Serum fT3 levels are significantly lower in hypogonadal than eugonadal men (p = 0.022). This suggests that low serum T could be considered a sensitive marker of frailty and poor health status and that the latter might induce hypogonadism. The more HIV-infected men are frail the more they are hypogonadal. This suggests that hypogonadism might be a naturally occurring condition in unhealthy HIV-infected men and raises concern about the safety of T treatment. In conclusion, low serum T is associated with multimorbidity, HANA, and frailty in HIV-infected men and this association seems to be bidirectional. Given the wide attitude to offer T treatment to HIV-infected men, caution is needed when prescribing T to HIV-infected male patients, especially if the patient is unhealthy or frail.

Impact of clinical and therapeutic factors on incident cardiovascular and cerebrovascular events in a population-based cohort of HIV-infected and non-HIV-infected adults.

Cardiovascular and cerebrovascular (CVD) events/diseases are a common cause of non-acquired immunodeficiency syndrome (AIDS)-related mortality in the aging human immunodeficiency virus (HIV)-infected population. The incidence rate and clinical correlates of CVD in people living with HIV/AIDS compared to the general population warrants further investigation. HIV/AIDS is associated with increased risk CVD compared to general population. CVD events in a matched cohort of HIV-infected and non-HIV-infected adults, ≥18 years old, served through the South Carolina Medicaid program during 1994 to 2011 were examined using time-dependent proportional hazards regression and marginal structural modeling. A retrospective cohort of 13,632 adults was followed longitudinally for an average of 51 months. The adjusted hazard ratio (aHR) of incident CVD events was higher among HIV-infected individuals exposed to combination antiretroviral therapy (cART) (aHR = 1.15) compared to the non-HIV-infected group, but did not differ from the subgroup of cART-naïve HIV-infected adults. A higher aHR of incident CVD was associated with comorbid hypertension (aHR = 2.18), diabetes (aHR = 1.38), obesity (aHR = 1.30), tobacco use (aHR = 1.47), and hepatitis C coinfection (aHR = 1.32), and older age (aHR = 1.26), but with a lower risk among females (aHR = 0.86). A higher risk of incident CVD events was also apparent in HIV-infected individuals with exposure to both protease inhibitors (adjusted risk ratio [aRR] = 1.99) and non-nucleoside reverse transcriptase inhibitors (aRR = 2.19) compared to those with no exposure. Sustained viral load suppression was associated with a lower risk of incident CVD events (aRR = 0.74). After adjusting for traditional risk factors and sociodemographic differences, there is higher risk of incident cardiovascular events among HIV-infected individuals exposed to combined antiretroviral medications compared to the general population.

The prevalence of opportunistic infections and malignancies in autopsied patients with human immunodeficiency virus infection in Japan.

BackgroundOpportunistic infections and malignancies such as malignant lymphoma and Kaposi sarcoma are significant complications of human immunodeficiency virus (HIV) infection. However, following the introduction of antiretroviral therapy in Japan in 1997, the incidence of clinical complications has decreased. In the present study, autopsy cases of HIV infection in Japan were retrospectively investigated to reveal the prevalence of opportunistic infections and malignancies.MethodsA total of 225 autopsy cases of HIV infection identified at 4 Japanese hospitals from 1985–2012 were retrospectively reviewed. Clinical data were collected from patient medical records.ResultsMean CD4 counts of patients were 77.0 cells/μL in patients who received any antiretroviral therapy during their lives (ART (+) patients) and 39.6 cells/μL in naïve patients (ART (−) patients). Cytomegalovirus infection (142 cases, 63.1%) and pneumocystis pneumonia (66 cases, 29.3%) were the most frequent opportunistic infections, and their prevalence was significantly lower in ART (+) patients than ART (−) patients. Non-Hodgkin lymphoma and Kaposi sarcoma were observed in 30.1% and 16.2% of ART (−) patients, and 37.9% and 15.2% of ART (+) patients, respectively. Malignant lymphoma was the most frequent cause of death, followed by cytomegalovirus infection regardless of ART. Non-acquired immunodeficiency syndrome (AIDS)-defining cancers such as liver and lung cancer caused death more frequently in ART (+) patients (9.1%) than in ART (−) patients (1.5%; P = 0.026).ConclusionsThe prevalence of infectious diseases and malignancies were revealed in autopsy cases of HIV infection in Japan. The prevalence of cytomegalovirus infection and pneumocystis pneumonia at autopsy were lower in ART (+) patients than ART (−) patients. Higher prevalence of non-AIDS defining malignancies among ART (+) patients than ART (−) patients suggests that onsets of various opportunistic infections and malignancies should be carefully monitored regardless of whether the patient is receiving ART.

The changing landscape of HIV‐related lung disease: Non‐AIDS lung malignancy as a player in the field

See article, page 339

Clinical Outcomes of AIDS-related Burkitt Lymphoma: A Multi-institution Retrospective Survey in Japan

Acquired immunodeficiency syndrome-related non-Hodgkin lymphoma is treated similarly to non-acquired immunodeficiency syndrome lymphoma, but it is not clear whether highly intensive regimens are beneficial for acquired immunodeficiency syndrome-related Burkitt lymphoma. We conducted a multicenter retrospective survey to clarify the clinical outcomes of acquired immunodeficiency syndrome-related Burkitt lymphoma in the combined antiretroviral therapy era in Japan. We retrospectively analyzed the outcome of 33 patients with acquired immunodeficiency syndrome-related Burkitt lymphoma, who were diagnosed at five regional hospitals for human immunodeficiency virus/acquired immunodeficiency syndrome in Japan between January 2002 and December 2010. The median follow-up period was 20.0 months (range 0.5-92.7 months). Six (18.2%) patients were treated with cyclophosphamide, vincristine, doxorubicin, high-dose methotrexate, ifosphamide, etoposide and high-dose cytarabine, and 23 (69.7%) patients were treated with hyperfractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone, high-dose methotrexate and high-dose cytarabine. The overall response rate for all patients was 78.8%, with a complete response rate of 72.7%. The two-year overall survival rate was 68.1%. There was no significant difference in overall survival between chemotherapeutic regimens with rituximab (n = 20) and without rituximab (n = 13) (P = 0.49). The two-year overall survival rate was 66.7% for patients receiving cyclophosphamide, vincristine, doxorubicin, dexamethasone, etoposide, ifosfamide and cytarabine, and was 72.6% for patients receiving cyclophosphamide, vincristine, doxorubicin, dexamethasone, methotrexate and cytarabine (P = 0.72). There was one treatment-related death. Highly intensive chemotherapy would bring a high remission rate and prolonged overall survival for patients with acquired immunodeficiency syndrome-related Burkitt lymphoma.

Pharmacotherapy in cancer patients with HIV/AIDS.

Antiretroviral therapy (ART) has significantly reduced morbidity and increased life expectancy of individuals infected with human immunodeficiency virus (HIV). Consequently, non-acquired immunodeficiency syndrome (AIDS)-defining malignancies are increasing in frequency, which necessitates the concurrent use of antineoplastics and ART. Although drug interactions are a major concern when combining these agents, there is currently limited guidance on dose adjustments required to maintain safe and efficacious drug exposure.

Changing characteristics and risk factors of patients with and without incident HCV infection among HIV-infected individuals

Chronic hepatitis C virus (HCV) infection has become a leading cause of non-acquired immunodeficiency syndrome (AIDS)-related morbidity and mortality for human immunodeficiency virus (HIV)-infected persons in the highly active antiretroviral therapy (HAART) era. Despite injection drug use (IDU) remaining the main route of HCV infection, recent reports indicate outbreaks of acute HCV infection among HIV-infected men who have sex with men (MSM) and sexually transmitted infections in the absence of IDU. We conducted a retrospective observational study of behavioural and demographic factors of patients with and without incident HCV infection among HIV-infected individuals followed at the AIDS Clinic of the Infectious Disease Department of the University of Ancona from 1989 to 2011. Overall, 440 patients were considered; a total of 145 patients had initial positive HCV antibody test results (HCV+); a total of 295 patients had initial negative HCV antibody test results (HCV-). In the latter population, 14 seroconverted to HCV antibody (neoHCV), with an overall incidence of 0.59 per 100 person-years. While IDU was the principal risk factor of HCV+, the main route of transmission of incident HCV infection was sexual transmission. The HCV- group was significantly older than the other two groups and showed a significantly lower CD4 count at HIV diagnosis than neoHCV. Being Italian and having a low level of education were significantly more represented in HCV+. Younger age at HIV infection, IDU and additional risk factors other than sexual transmission significantly affected the probability of being HCV+. The cumulative probability of developing HCV infection in the HCV- group was calculated to be 6% at 15 years. The epidemiology of the newly acquired HCV in HIV+ persons is changing. Therefore, a frequent and constant counselling about HCV infection is desirable and a periodical screening test is mandatory.

Non-AIDS-related Kaposi's sarcoma: A single-institution experience

To evaluate the outcomes and potential prognostic factors in patients with non-acquired immunodeficiency syndrome (AIDS)-related Kaposi's sarcoma (KS). Patients with histologically proven non-AIDS-related KS treated with systemic chemotherapy were included in this retrospective analysis. In some cases, the human herpes virus 8 status was assessed by immunohistochemistry. The patients were staged according to the Mediterranean KS staging system. A multivariable model was constructed using a forward stepwise selection procedure. A P value < 0.05 was considered statistically significant, and all tests were two-sided. Thirty-two cases were included in this analysis. The average age at diagnosis was 70 years, with a male/female ratio of approximately 2:1. Eighty-four percent of the cases had classic KS. All patients received systemic chemotherapy containing one of the following agents: vinca alkaloid, taxane, and pegylated liposomal doxorubicin. Ten patients (31.5%) experienced a partial response, and a complete response was achieved in four patients (12.4%) and stable disease in sixteen cases (50%). Two patients (6.2%) were refractory to the systemic treatment. The median progression-free survival (PFS) was 11.7 mo, whereas the median overall survival was 28.5 mo. At multivariate analysis, the presence of nodular lesions (vs macular lesions only) was significantly related to a lower PFS (hazard ratio: 3.09; 95%CI: 1.18-8.13, P = 0.0133). Non-AIDS-related KS appears mostly limited to the skin and is well-responsive to systemic therapies. Our data show that nodular lesions may be associated with a shorter PFS in patients receiving chemotherapy.

All-cause mortality in hospitalized HIV-infected patients at an acute tertiary care hospital with a comprehensive outpatient HIV care program in New York City in the era of highly active antiretroviral therapy (HAART)

The overall mortality rate among human immunodeficiency virus (HIV)-infected patients has significantly declined in the era of highly active antiretroviral therapy (HAART). However, little is known about the causes of death for HIV-infected patients who are hospitalized in acute care hospitals. A retrospective chart review of hospitalized HIV-infected patients from 2004 to 2008 was undertaken. Among 9,101 hospitalized HIV-infected patients, 237 deaths were identified, with an overall mortality rate of 237/9,101 (2.6 %). The mortality rate did not differ from year to year (2-3 %). Charts for 208 patients were available for review and were analyzed. The following medians were noted: age 49 years, CD4+ T cell count 137 cells/μL, HIV viral load (VL) log10 3.93, length of stay 16 days. The proportion of men were 71.6 %, African Americans (AAs) were 62.5 %, and HAART use was 52.4 %, with an overall good adherence rate of only 17.3 %. The major causes of death were non-acquired immunodeficiency syndrome (AIDS)-related illness (81.7 %, 170/208): sepsis (34.6 %, 72/208), non-recurrent bacterial pneumonia (19.7 %, 41/208), cardiac disease (5.8 %, 12/208), liver disease (4.3 %, 9/208), and non-AIDS-related malignancy (4.3 %, 9/208). The major causes of death due to AIDS-related illness (18.3 %, 38/208) were: Pneumocystis jirovecii pneumonia (4.8 %, 10/208) and AIDS-related encephalopathy, including progressive multifocal leukoencephalopathy/cryptococcal meningitis/cerebral toxoplasmosis (3.4 %, 7/208). Mortality due to AIDS-related illnesses was associated with younger age (median age 44 vs. 50 years, p = 0.001), female sex (44.7 vs. 24.7 %, p = 0.013), and lower CD4+ T cell counts (median 10 vs. 66, p = 0.001). The mortality rate in our hospitalized HIV-infected patients remained low. Non-AIDS-related illnesses were the major causes of death, with sepsis being the most common. Low CD4+ T cell count and female sex were associated with deaths due to AIDS-related illness. Poor adherence to HAART was also noted in those patients to whom treatment was offered in the outpatient setting. Further prospective studies are needed in order to better define the epidemiology and outcomes for hospitalized HIV-infected patients in the era of HAART.

Presentation and Outcome Amongst Older Singaporeans Living with Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome (HIV/AIDS): Does Age Alone Drive Excess Mortality?

There is little detailed information on human immunodeficiency virus (HIV) amongst older adults in Singapore. A retrospective study of 121 consecutive referrals of patients presenting for HIV care was conducted. Demographic, clinical and laboratory variables were collected. A prognostic model derived from the North American Veterans' Affairs Cohort Study (VACS) was used to estimate prognosis. The median age at presentation was 43 (range, 18 to 76). Thirty-eight patients (31%) were aged 50 or older and 106 patients (88%) were male. Older patients were more likely to be of Chinese ethnicity (P = 0.035), married (P = 0.0001), unemployed or retired (P = 0.0001), and to have acquired their infection heterosexually (P = 0.0002). The majority of patients in both groups were symptomatic at presentation. Eighty-one (67%) had CD4 counts less than 200 at baseline with no observable differences in HIV ribonucleic acid (RNA) or clinical stage based on age. Non-Acquired Immunodeficiency Syndrome (AIDS) morbidity was observed more frequently amongst older patients. The estimated prognosis of patients differed significantly based on age. Using the VACS Index and comparing younger patients with those aged 50 and above, mean 5 year mortality estimates were 25% and 50% respectively (P <0.001). A trend towards earlier antiretroviral therapy was noted amongst older patients (P = 0.067) driven mainly by fewer financial difficulties reported as barriers to treatment. Older patients form a high proportion of newly diagnosed HIV/AIDS cases and present with more non-AIDS morbidity. This confers a poor prognosis despite comparable findings with younger patients in terms of clinical stage, AIDS-defining illness, CD4 count and HIV viral load.

Pulmonary cryptococcosis in non-AIDS patients

ObjectiveTo investigate the clinical features, management, and prognosis of pulmonary cryptococcosis in non-acquired immunodeficiency syndrome (AIDS) patients. Method24 cases of pulmonary cryptococcosis with accurate pathological diagnosis were retrospectively studied. Results15 male patients and nine female patients were diagnosed at the first affiliated hospital of Sun Yat-sen University from November 1999 to November 2011. The mean age at the time of diagnosis was 44.2±11.3 years (range: 24 to 65 years). Among these patients, 13 had other comorbidities. 15 were symptomatic and the other nine were asymptomatic. The most common presenting symptoms were cough, chest tightness, expectoration, and fever. None had concurrent cryptococcal meningitis. The most frequent radiologic abnormalities on chest computed tomography (CT) scans were solitary or multiple pulmonary nodules, and masses or consolidations, and most lesions were located in the lower lobes. All patients had biopsies for the accurate diagnosis. Among the 24 patients, nine patients underwent surgical resections (eight had pneumonectomy via thoracotomy and one had a pneumonectomy via thoracoscopy). Five of the patients who underwent surgery also received antifungal drug therapy (fluconazole) for one to three months after the surgery. The other 15 only received antifungal drug therapy (fluconazole or voriconazole) for three to six months (five patients are still on therapy). The follow-up observation of 19 patients who had already finished their treatments lasted from two to 11 years, and there was no relapse, dissemination, or death in any of these patients. ConclusionNon-AIDS patients with pulmonary cryptococcosis have a good prognosis with appropriate management.

Retrospective analysis of relationship between radiological features and prognoses of pneumocystis pneumonia in non-AIDS immunocompromised patients

To elucidate the relationship between the radiological features and prognoses of pneumocystis pneumonia (PCP) in non-acquired immunodeficiency syndrome (non-AIDS) immunocompromised patients. Retrospective analyses were performed for the radiological features and prognoses of 36 non-AIDS immunocompromised PCP patients hospitalized at Peking University First Hospital from April 2006 to April 2010. There were 24 males and 12 females with an average age of (51.7 ± 18.9) years. All patients underwent chest photographic examinations and chest computed tomography (CT) was performed on 29 of them. The overall case fatality rate (CFR) of 36 patients was 33.3% (12/36). At the start of anti-PCP treatment, there were normal chest radiography (n = 7), bilateral diffuse infiltration (n = 21), bilateral diffuse consolidation (n = 8), aerothorax, mediastinal emphysema or pneumohypoderma (n = 6) and numbers of deceased patients (n = 0, 8, 5 and 5 respectively). The CFRs of the patients with normal chest radiography and aerothorax, mediastinal emphysema or pneumohypoderma were both statistically significant as compared with the overall rate (P < 0.05). At the start of anti-PCP treatment, there were bilateral diffuse ground glass opacities (GGO) (n = 29), "mosaic sign" (n = 19), air bronchogram (n = 19), pulmonary consolidation (n = 17), bilateral pleural effusion (n = 7), thickened lobular septa (n = 6), cystic lesions (n = 5), aerothorax, mediastinal emphysema or pneumohypoderma (n = 4) and numbers of deceased patients (n = 8, 5, 5, 5, 2, 2, 2 and 4 respectively). The CFRs of the patients with aerothorax, mediastinal emphysema or pneumohypoderma were statistically significant as compared with the overall rate (P < 0.05). The major radiological features of PCP in non-AIDS immunocompromised patients are bilateral diffuse infiltration. And bilateral diffuse GGO on chest CT scans are usually accompanied with "mosaic" sign, air bronchogram or pulmonary consolidation. The prognoses are excellent for the patients with normal chest radiograph and poor for those with aerothorax, mediastinal emphysema or pneumohypoderma.

Long‐term follow‐up of patients with HIV‐related diffuse large B‐cell lymphomas treated in a phase II study with rituximab and CHOP

Long‐term follow‐up of patients with <scp>HIV</scp>‐related diffuse large <scp>B</scp>‐cell lymphomas treated in a phase <scp>II</scp> study with rituximab and <scp>CHOP</scp>

Human immunodeficiency virus‐associated lung cancer in the era of highly active antiretroviral therapy

Lung cancer is the leading cause of death among non-acquired immunodeficiency syndrome (AIDS)-defining malignancies. Because highly active antiretroviral therapy (HAART) has improved the survival of patients with human immunodeficiency virus (HIV), the authors evaluated lung cancer outcomes in the HAART era. HIV-positive patients who were diagnosed with lung cancer at the authors' institution during the HAART era (1995-2008) were analyzed. Patient charts were reviewed for clinical and laboratory data. The CD4 count at diagnosis was treated as a continuous variable and subcategorized into distinct variables with 3 cutoff points (50 cells/mL, 200 cells/mL, and 500 cells/mL). Pearson correlation coefficients were estimated for each covariate studied. Survival was determined by using the Kaplan-Meier method. Of 80 patients, 73 had nonsmall cell lung cancer. Baseline characteristics were as follows: median patient age, 52 years; male, 80%; African Americans, 84%; injection drug users, 25%; smokers, 100%; and previous exposure to antiretroviral agents, 55%. At the time of cancer diagnosis, the mean CD4 count was 304 cells/mL, and the mean viral load was 82,420 copies/mL. The latency between HIV diagnosis and lung cancer diagnosis was significantly shorter among women (4.1 years vs 7.7 years; P = .02), and 71% of patients received anticancer therapy. The 1-year and 3-year survival rates for stage IIIB/IV were 25% and 0%, respectively. Grade 3/4 toxicities occurred in 60% of patients who received chemoradiation versus 36% of patients who received chemotherapy. Cancer-related survival was better for patients with CD4 counts >200 cells/mL (P = .0298) and >500 cells/mL (P = .0076). The latency from diagnosis of HIV to lung cancer was significantly shorter for women. Although outcomes for patients with lung cancer who have HIV remain poor, a high CD4 count was associated with improved lung cancer-related survival.

Cytological diagnosis of typical carcinoid on bronchoscopic brush smears in an HIV-positive patient

We report a case of typical carcinoid of the lung in a 60-year-old human immunodeficiency virus (HIV)-positive man diagnosed on brush cytology smears. Bronchial carcinoids are rare tumors, accounting for 1% to 2% of all lung tumors. Although the exact incidence in HIV-infected individuals is not known, the paucity of their documentation in the literature indicates that they may be equally rare. Cytological diagnosis on brush smears is rarely documented as the tumor is covered with mucosa and cellular yield is often not good. In this case, bronchial brushings showed distinctive cytological features of typical carcinoid. The awareness of its characteristic cytological features and differential diagnosis is required for an accurate diagnosis. Clinical awareness that non–acquired immunodeficiency syndrome (AIDS)-defining cancers can also occur in HIV-infected individuals in the context of the prolonged survival in the antiretroviral era is equally important. This case emphasizes the clinical importance of a broad differential diagnosis for lung lesions in HIV-positive patients.

Lung Cancer in HIV-Positive Patients

Malignancies account for more than a third of all deaths in human immunodeficiency virus (HIV)-positive patients. Although acquired immunodeficiency syndrome-related mortality is decreasing with the introduction of effective antiretroviral therapy, the incidence of lung cancer in patients with HIV remains high. Lung cancer has now become the leading cause of mortality among the nonacquired immunodeficiency syndrome defining malignancies. Within the HIV population, the incidence of lung cancer is estimated to be approximately 2 to 4 times that of the general population. Often these patients present with advanced disease (stage III or IV) at a younger age and have an inferior overall survival, when compared with non-HIV patients. Development of lung cancer in patients with HIV has been linked to various factors including immunosuppression, CD4 count, viral load, and smoking. This article reviews the impact of HIV on the incidence, risk factors, clinical presentation, and treatment of lung cancer.