Opportunistic Illnesses and Other Comorbidities

Hopkins HIV Report 2006 May; 18(3):

Kelly Gebo, M.D., M.P.H. and Lucy Wilson M.D., Sc.M.
Johns Hopkins

The 13th CROI clearly reinforced the shift in HIV clinical practice from the management of opportunistic infections (OI) to the management of chronic HIV infection and its comorbidities. There were relatively few abstracts addressing OIs, although several were worth noting.

In an oral session using data from the Moore clinic database in Baltimore, Lau and colleagues demonstrated a decrease in HIV-related mortality in the current era of HAART [Lau B, et al., Conf Retrovir Opportunistic Infect 2006 Feb 5-8;13:abstract no. 29]. HIV-associated mortality decreased from 41 to 20 per 1000 person-years (PY) between 1997 and 2004, while non-AIDS mortality increased from 11 to 23 per 1000 PY in the same interval. Although all cause mortality was the same in injection drug users (IDUs) and non-IDUs during this interval, IDUs had much greater mortality due to non-AIDS related conditions than non-IDUs. Current analyses are ongoing to evaluate the primary causes of non-AIDS related deaths in this cohort.

Evaluation of 2,149 AIDS Clinical Trials Group (ACTG) patients by Smurzynski and colleagues revealed an increased risk of OIs in the first 24 weeks of HAART among individuals followed in the ACTG Longitudinal Linked Randomized Trials (AALRT) [Abstract 783]. At baseline, all patients were HAART naïve; however, 332 (15%) patients developed an OI during the study period. Interestingly, 52% of first OIs occurred within 24 weeks of starting HAART. Not surprisingly, the most common OIs were Pneumocystis jiroveci pneumonia (20%), disseminated Mycobacterium avium complex (MAC) (17%), esophageal candidiasis (17%), cytomegalovirus disease (7%), and tuberculosis (7%). They found that high viral loads, lower CD4 counts, increasing age and female gender (OR 1.6) were associated with increased risk of development of an OI within 6 months of starting HAART.

A study from the EuroSIDA cohort evaluated the incidence of OIs in patient groups having CD4 counts higher than would be expected (i.e. group 1, CD4 count >100 cells/mm³, risk for CMV disease, disseminated MAC or toxoplasmosis; group 2, CD4 count >200 cells/mm³, risk for Pneumocystis jiroveci pneumonia or esophageal candidiasis and group 3, CD4 >300 cells/mm³, risk for pulmonary TB) [Podlekareva D, et al. Conf Retrovir Opportunistic Infect 2006 Feb 5-8;13:abstract no. 783]. The incidence of OIs in these groups were low: 1.7, 3.8, and 1.3 per 1000 PY, respectively. IDU was the only risk factor for pulmonary TB. Being started on HAART and having an increase in CD4 count of 50% from baseline were associated with a lower risk of development of CMV disease, disseminated MAC, toxoplasmosis, and PCP.

Malignancies

Engels and associates linked AIDS and cancer registries in 11 US regions to assess AIDS-associated cancer risk from 1980-2002, comparing the pre-HAART, early HAART and current-HAART eras [Engels E, et al., Conf Retrovir Opportunistic Infect 2006 Feb 5-8;13:abstract no. 810]. The risk of both Kaposi’s sarcoma (KS) and Non-Hodgkins lymphoma (NHL) dropped in the early HAART era (RR 0.41 and 0.64, respectively), but then reached a plateau in the current HAART era. In contrast, cervical cancer risk remained low and was unchanged over the 3 times periods analyzed. This study suggests that HAART may have substantially contributed to the declines in KS and NHL but not cervical cancer. The residual incidence may be due to antiretroviral drug resistance or access to care issues affecting those with HIV/AIDS. Gingues and colleagues observed similar trends in the pre- and current HAART eras in a Canadian cohort [Gingues S, et al., Conf Retrovir Opportunistic Infect 2006 Feb 5-8;13:abstract no. 830]. They noted that KS and NHL cases predominated in those with declining CD4 cell counts or failing HAART. Consistent with Engel’s study, they noted a decline in mortality from KS and NHL.

Kirk and coworkers examined lung cancer mortality among the ALIVE IDU cohort in Baltimore [Kirk G, et al., Conf Retrovir Opportunistic Infect 2006 Feb 5-8;13:abstract no. 811]. They found that a history of smoking and age greater than 50 years were strongly associated with lung cancer death. Adjusting for other risk factors, including smoking, HIV seropositivity was a risk factor for lung cancer deaths (RR 3.04). Additionally, among those with HIV infection, recurrent pneumonia, defined as 2 or more hospitalizations, was also associated with lung cancer death (RR 1.99; 1.10-9.20), and explained a proportion of the HIV effect. CD4 cell count, viral load, and HAART usage were not associated with lung cancer mortality.

Patel and collaborators evaluated incidence rates of AIDS-defining and non-AIDS defining malignancies in HIV-infected and -uninfected persons using data from the HIV Outpatient Study (HOPS) and the Adults/Adolescent Spectrum of Disease Project (ASD) [Patel P, et al., Conf Retrovir Opportunistic Infect 2006 Feb 5-8;13:abstract no. 813]. They demonstrated significantly increased adjusted rates of the following cancers among HIV-infected patients: KS, NHL, Hodgkin’s lymphoma, melanoma, cervical cancer, anal cancer, liver cancer, testicular cancer, oropharyngeal cancer, and lung cancer. Among HIV-infected and -uninfected patients, similar rates of colorectal and renal cancer were reported. HIV-infected patients had significantly decreased rates of breast (RR 0.7) and prostate cancer (RR 0.3), which could be due to decreased rates of screening for these diseases.

The prevalence of anal dysplasia was high in several studies, suggesting the need for better screening and evaluation. Using data from an outpatient Spanish clinic, Sirera and associates demonstrated a high prevalence of abnormal anal cytology (43%); however, there was no difference in the rates among MSM (48%) and heterosexual men (32%) [Sirera G, et al., Conf Retrovir Opportunistic Infect 2006 Feb 5-8;13:abstract no. 806]. Multivariate logistic regression analysis revealed that those with a viral load >400 c/mL (AOR 3.5) or at least 5 episodes of receptive anal intercourse per lifetime (AOR 4.6) had a higher risk of abnormal anal cytology. Of note, CD4 cell count nadir, current CD4 cell count, use of HAART, previous STIs, tobacco, and alcohol were not associated with abnormal cytology. The prevalence of HPV infection was 78%, with all those with abnormal anal cytology having high-risk HPV types present.

Using data from men followed in an outpatient clinic in San Diego, Caperna and colleagues showed no change the in incidence rates of invasive anal cancer between pre-screening time period (1995-2001) and current screening period (2002-2005) [Caperna J, et al., Conf Retrovir Opportunistic Infect 2006 Feb 5-8;13:abstract no. 808]. This suggests the need to identify more effective screening for anal dysplasia as well as more standardized monitoring and treatment protocols. Of note, they did find the incidental presence of asymptomatic gonorrhea or Chlamydia (4.2%) to be higher than expected.

Other Infections

Burkey presented the results of a study that evaluated the incidence of methicillin-resistant Staphylococcus aureus (MRSA) in the Johns Hopkins Moore clinic in the period 2000-2003 [Burkey M, et al., Conf Retrovir Opportunistic Infect 2006 Feb 5-8;13:abstract no. 789]. The incidence of S. aureus bacteremia among this cohort was 19.1 events/1000 PY between 2000-03 and increased significantly during this interval. The proportion of all S. aureus cases that were due to MRSA increased from 24% in 2000 to 47% in 2003. Not surprisingly, IDU, end stage renal disease, greater viral load, and CD4 count <200 cells/mm³ were associated with increased odds of MRSA bacteremia in an adjusted multivariate analysis. This analysis suggests that use of vancomycin should be considered in HIV-infected patients who present with sepsis.

Overall, the 13th CROI revealed that OIs still occur, although less frequently than before. In addition, while overall mortality has decreased, non-AIDS related mortality remains a significant issue, particularly among IDUs. AIDS-related and non-AIDS-related malignancies remain a significant comorbidity in HIV infected patients. Managing concomitant drug and tobacco abuse, along with vigilant cancer screening are important in helping our HIV-infected patients reduce cancer risk.

2006-05-10
HHR-2006-05-03

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