Cancer and HIV infection: any association?

PURPOSE: Morbidity and mortality related to neoplasia are increasing in HIV-infected patients. CURRENT KNOWLEDGE AND KEY-POINTS: The incidence of AIDS opportunistic infections dramatically decreased since the introduction of highly active antiretroviral therapy (HAART). Among AIDS-cancers, the incidences of Kaposi sarcoma and of cerebral lymphoma decreased in a same way than AIDS infections but the incidences of systemic non-Hodgkin lymphoma and of cervical cancer decreased less than the others and remain higher than in the general population. This suggests that other factors than the quantitative immune reconstitution could be implicated. The most recent and large studies have also shown a 1.7 to 3 fold increased risk of developing non-AIDS cancers in HIV-infected patients when compared to the general population without significant impact of HAART on incidence curves. These malignancies include Hodgkin disease, lung, anal, head and neck cancers, hemopathies, and conjunctival cancers. PERSPECTIVES: Epidemiologic survey will help to define priorities in terms of prevention and screening in this specific population and to evaluate interventions which should be systematically proposed (alcohol and tobacco cessation programs, viral coinfection). The own roles of HIV itself and of antiretrovirals as prooncogenic factors need to be assessed.     

The HIV infection and immune activation: ‘To fight and burn’

Immune activation, a normal immune reaction to pathogens, is now recognized as a major driving force of the CD4 T-cell depletion and immune disorders caused by HIV. By contrast, the natural hosts of its ancestor virus, simian immunodeficiency virus, have adapted to this virus by blocking immune activation and remaining healthy. This review will focus on evidence demonstrating how immune activation associated with HIV infection exhausts immune defenses to HIV as well as the immune system, thus leading to immunosenescence and immunodeficiency, and how treatment can disrupt this vicious and ultimately fatal circle.     

HIV and chronic obstructive pulmonary disease: is it worse and why?

Smoking-related diseases, such as chronic obstructive pulmonary disease (COPD), are of particular concern in the HIV-infected population. Smoking rates are high in this population, and long-term exposure to cigarette smoke in the setting of HIV infection may increase the number of complications seen. Before the era of combination antiretroviral therapy, HIV-infected persons were noted to have an accelerated form of COPD, with significant emphysematous disease seen in individuals less than 40 years old. Unlike many of the AIDS-defining opportunistic infections, HIV-associated COPD may be more common in the current era of HIV because it is frequently reported in patients without a history of AIDS-related pulmonary complications and because many aging HIV-infected individuals have had a longer exposure to smoking and HIV. In this review, we document the epidemiology of HIV-associated COPD before and after the institution of combination antiretroviral therapy, review data suggesting that COPD is accelerated in those with HIV, and discuss possible mechanisms of HIV-associated COPD, including an increased susceptibility to chronic, latent infections; an aberrant inflammatory response; altered oxidant-antioxidant balance; increased apoptosis associated with HIV; and the effects of antiretroviral therapy.     

Opt-out HIV testing in prison: informed and voluntary?

HIV testing in prison settings has been identified as an important mechanism to detect cases among high-risk, underserved populations. Several public health organizations recommend that testing across health-care settings, including prisons, be delivered in an opt-out manner. However, implementation of opt-out testing within prisons may pose challenges in delivering testing that is informed and understood to be voluntary. In a large state prison system with a policy of voluntary opt-out HIV testing, we randomly sampled adult prisoners in each of seven intake prisons within two weeks after their opportunity to be HIV tested. We surveyed prisoners' perception of HIV testing as voluntary or mandatory and used multivariable statistical models to identify factors associated with their perception. We also linked survey responses to lab records to determine if prisoners' test status (tested or not) matched their desired and perceived test status. Thirty-eight percent (359/936) perceived testing as voluntary. The perception that testing was mandatory was positively associated with age less than 25 years (adjusted relative risk [aRR]: 1.45, 95% confidence interval [CI]: 1.24, 1.71) and preference that testing be mandatory (aRR: 1.81, 95% CI: 1.41, 2.31) but negatively associated with entry into one of the intake prisons (aRR: 0.41 95% CI: 0.27, 0.63). Eighty-nine percent of prisoners wanted to be tested, 85% were tested according to their wishes, and 82% correctly understood whether or not they were tested. Most prisoners wanted to be HIV tested and were aware that they had been tested, but less than 40% understood testing to be voluntary. Prisoners' understanding of the voluntary nature of testing varied by intake prison and by a few individual-level factors. Testing procedures should ensure that opt-out testing is informed and understood to be voluntary by prisoners and other vulnerable populations.     

HIV and dialysis: is it a real risk?

The need to expound this work was born of the necessity to confront all the organisational difficulties that present themselves with the arrival of a HIV+ patient for dialysis in our centre. On such occasions, in fact, we were unable to find a protocol, guidelines or a text that could help us in a complete and adequate way, to resolve the doubts, the fears and the practical, ethical and legal problems that we suddenly had to face.     

Coexistent sarcoidosis and HIV infection: an immunological paradox?

The CD4 lymphocyte plays a pivotal role in both sarcoidosis and HIV infection. Caring for a patient with both conditions represents a diagnostic and therapeutic challenge. We describe a patient, previously diagnosed with sarcoidosis, who subsequently contracted HIV infection. Manifestations of sarcoidosis were clinically silent until highly active anti-retroviral therapy was instituted. Her condition improved with the institution of corticosteroids. The diagnostic and therapeutic dilemmas encountered in patients with both conditions will be discussed including a complete review of the literature.     

HIV and HCV Coinfection: Where Are We in 2010?

The epidemics of hepatitis C virus (HCV) and HIV are major causes of morbidity and mortality worldwide; the 33 million individuals who are coinfected with HCV and HIV face an increased risk of complications and death from liver disease in light of the accelerated progression of hepatitis C to fibrosis and cirrhosis in HIV coinfection. The mechanisms by which HIV accelerates the progression of HCV are thought to be related to alterations in the immunologic milieu, which collectively act to promote fibrogenesis. The progression of liver disease is in large part related to immunodeficiency, and, as with monoinfected individuals, optimal management of HIV infection with HAART may be important for prevention of hepatic morbidity. Treatment of HCV with pegylated interferon and ribavirin should be considered in eligible coinfected persons. Clinical trials in this population demonstrate sustained virologic response rates ranging from 17% to 35% in genotypes 1 and 4 and 44% to 73% in genotypes 2 and 3. However, given these limited response rates and high rates of intolerability, the impending introduction of directly acting antivirals against HCV holds particular promise for interruption of the insidious natural history of liver disease in HIV coinfected persons.     

Alcohol Consumption and HIV Disease Progression: Are They Related?

BACKGROUND: The relationship between alcohol consumption and HIV disease progression has received limited attention in the era of highly active antiretroviral therapy (HAART). METHODS: We assessed CD4 cell count, HIV RNA levels, and alcohol consumption in the past month, defined as none, moderate, and at risk, in 349 HIV-infected people with a history of alcohol problems. We investigated the relationship between alcohol consumption and HIV disease markers CD4 cell count and HIV RNA level, stratified by HAART use, using multivariable regression. RESULTS: No significant differences in CD4 cell count or HIV RNA level were found across the categories of alcohol consumption for patients who were not receiving HAART. However, among patients who were receiving HAART, log HIV RNA levels were significantly higher in those with moderate (2.17 copies/ml) and at-risk (2.73 copies/ml) alcohol use compared with none (1.73 copies/ml; p = 0.006). CD4 cell counts in those with moderate (368 cells/microl) and at-risk (360 cells/microl) alcohol use were lower than for subjects who reported none (426 cells/microl; p = 0.07). CONCLUSION: Among patients who have a history of alcohol problems and are receiving antiretroviral treatment, alcohol consumption was associated with higher HIV RNA levels and lower CD4 counts. No comparable association was found for similar patients who were not receiving HAART. Addressing alcohol use in HIV-infected patients, especially those who are receiving HAART, may have a substantial impact on HIV disease progression.     

HIV infection in women: Do sex and gender matter?

At least half of all HIV infections occur in women. Most women are of childbearing potential; therefore, issues encompassing reproduction and mother-to-child transmission are critical in the management of this population. The efficacy of antiretroviral therapy (ART) is similar in men and women, although rates of adverse events or toxicity may be higher in women, which, in turn, may be related to higher antiretroviral drug levels documented in pharmacokinetic studies. A substantial proportion of women may not derive the benefit of highly active ART because nonsuppressive regimens are commonly used, especially in resource-limited settings, to decrease mother-to-child transmission. The likely emergence of resistant virus can have long-term sequelae for the mother, child, and other exposed individuals. Additional studies are needed of sex/gender-related issues including antiretroviral toxicities, pharmacokinetic profiles of approved and novel agents, ART strategies during pregnancy to minimize HIV resistance, and determination of optimal antiretroviral regimens for women.     

Audit of HIV testing: who, why and when?

The risk factors, referral pattern and presence/absence of genital tract symptoms and/or sexually transmitted infections (STIs) in 189 patients having HIV counselling and/or testing at genitourinary medicine (GUM) clinics are reviewed. Eighty per cent were concerned about heterosexual transmission, 9.5% men who have sex with men (MSM) and 4.8% intravenous drug users (IDUs). Heterosexuals and first-time GUM attenders were more likely to have sought prior advice from their general practitioner (GP). The majority were asymptomatic for genital tract infections, but 83% accepted an STI screen, with 44 STIs being diagnosed. Only one individual who had attended primarily for HIV screening was found to have an STI. About half of individuals presented within the window period, and of those stating that they wished to proceed with deferred testing, half subsequently failed to return, resulting in wasted health adviser appointments.     

Syphilis and HIV co-infection: when is lumbar puncture indicated?

The rate of syphilis/HIV co-infection amongst men who have sex with men (MSM) in large urban regions ranges from 20 to 70%. Concurrent HIV infection can alter the clinical presentation of syphilis, the response to treatment, and complicate the diagnosis and clinical course of neurosyphilis. Therefore whether to perform a lumbar puncture (LP) on every co-infected patient in order to diagnose neurosyphilis is controversial. Current clinical guidelines specify the indications for LP, but fall short of recommending LP in certain clinical situations such as early syphilis without neurological involvement. This article reviews the current literature on the relative utility and indications for LP in syphilis/HIV co-infected patients and new research in this area.     

Coinfection with HTLV-I and HIV: increase in HTLV-I-related outcomes but not accelerated HIV disease progression?

Human T-lymphotropic virus type I (HTLV-I) and HTLV-II have been postulated to accelerate disease progression in patients coinfected with HIV. However, recent evidence suggests that HTLV-II has no effect on HIV disease progression. In addition, it has recently been reported that HIV viral load was not increased in subjects coinfected with HTLV-I, suggesting that the biologic basis for the hypothesis does not exist. Several recent studies in Brazil, however, suggest that coinfection with HTLV-I and HIV has substantial medical consequences. For example, coinfection was associated with a higher CD4 lymphocytes count following adjustment for HIV viral load or HIV clinical stage. In addition, coinfected subjects have a high prevalence of clinical significant myelopathy. The effect of other putative viruses as cofactors in HIV disease progression is also discussed.