The HIV/AIDS epidemic, now in its 4th decade, has seen major shifts in epidemiology leading to an aging population increasingly susceptible to cancer. The advent of effective combination antiretroviral therapies (cART) associated with immune system reconstitution and improved HIV care has dramatically improved the life expectancy of infected persons. By the end of 2012, an estimated 35.3 million people worldwide were living with HIV infection [1].

In developed nations, HIV infection, once considered a death sentence, is now a chronic and treatable comorbidity in many persons living otherwise normal and healthy lives, even decades after infection. The improved survival of infected persons with a declining incidence of new infections [1] has resulted in an aging HIV population. In high-income countries, nearly a third of adults living with HIV are over age 50 [2]. As a result of the changing demographics, cancer diagnoses are frequent, diagnosed in up to 40 % of persons with HIV infection [3]. Furthermore, malignancy has become an important cause of death of persons with HIV infection, noted as a cause of 28 % of deaths in one French study [4]. And as cancer is a disease of aging, it should not be a surprise that cancer will continue to be a major concern in this population. This chapter will review the current epidemiology and clinical considerations and treatment for HIV-associated malignancies as it pertains to LGBT populations.

In addition to the aging of HIV infected persons, major shifts in the demographics of HIV infection have also been observed since HIV emerged in the 1980s. HIV infection, initially seen almost exclusively in gay men and intravenous drug users (IDU), is no longer considered a gay men’s disease, as high-risk heterosexual transmission has increased and women now make up over 50 % of the worldwide HIV population. In the United States, women comprise over 25 % of the nearly 900,000 people living with diagnosed HIV infection [5].

The primary behavioral routes of HIV acquisition remain IDU and sexual intercourse. Although IDU accounted for only 8 % of estimated incident HIV infections in 2011 [5], it is one of the higher risks of HIV acquisition, estimated at 63 in 10,000 exposures. Regarding sexual transmission of HIV, receptive anal intercourse is associated with much higher risk (138/10,000) than receptive vaginal intercourse (8/10,000). The risk of HIV acquisition with insertive anal or vaginal intercourse is also lower, at 11 and 4 in 10,000 exposures, respectively [6]. In 2012, the FDA approved Truvada® (tenofovir/emtricitabine) for pre-exposure prophylaxis (PrEP) of HIV-negative adults with ongoing sexual activity with a partner who is HIV infected or who engages in high-risk behaviors [7].

Although great efforts in the prevention of sexual transmitted diseases have historically focused on gay men, the need to address this important health issue in the broader LGBT community has become increasingly important. An estimated 64 % of all newly diagnosed HIV infections in the United States in 2009 were in men who have sex with men (MSM) [8], a term which includes not only gay- and bisexual-identified men but also MSM who identify as heterosexual, and which does not adequately describe specific sexual practices and even less accurately accounts for transgender persons. Aging with HIV infection is a particular concern in the LGBT older adult community. Approximately 9 % of LGBT persons aged 50 or older have HIV infection, with most occurring in gay or bisexual men [9]. Other LGBT populations, including lesbian and transgender persons, have had considerably less research focus.

HIV infection has continued to disproportionately affect minority populations. The Centers for Disease Control and Prevention (CDC) has estimated that among newly infected MSM in 2006, 46 % were white, 35 % were black and 19 % were Hispanic. Among women, high-risk sexual contact accounted for 80 % of new HIV transmissions [10], and also disproportionately affects racial minorities.

Cancers in HIV infection are generally classified in the literature as being AIDS defining or non-AIDS-defining. Since 1993, the CDC definition of AIDS has included three specific malignancies associated with immunosuppression: non-Hodgkin lymphoma (NHL), Kaposi sarcoma (KS) and invasive cervical cancer [11]. Under this definition, persons with HIV infection diagnosed with one of these malignancies had AIDS, regardless of other measures of immunosuppression, including low CD4+ T-cell subset or prior opportunistic infection. These malignancies (particularly NHL and KS) are generally associated with advanced immunosuppression and are termed AIDS-defining cancers (ADCs). In contrast, other malignancies are termed non-AIDS defining cancers (NADCs).

Early in the course of the HIV epidemic where antiretroviral therapy was either not available or of limited efficacy, the vast majority of malignancies in the setting of HIV infection were ADCs. These malignancies were often the presenting symptom of patients with advanced HIV infection and were associated with dismal prognoses.

The widespread availability of combination antiretroviral therapy (cART) regimens, generally considered post-1996 with the protease inhibitors, has led to effective, at least partial reconstitution of patient immune systems resulting in marked declines in ADC incidence [12], particularly for NHL and KS. Although persons with HIV infection remain at marked risk for ADCs, cART improves immunologic, virologic and clinical outcomes [13]. The Swiss HIV Cohort Study included 9429 patients with 54,715 person-years of follow-up and evaluated cancers in the pre- (1985–1996), early- (1997–2001) and late- (2002–2006) cART periods; as compared to the non-HIV infected population, the incidence of ADCs in the HIV-infected population progressively declined over these periods (Standardized Incidence Ratios [SIRs] of 136, 27.7, and 14.7, respectively) [14]. Data from United States AIDS and cancer registries have also noted declines in incidence of KS and NHL in the cART era [15].

Conversely, the improved survival among persons with HIV infection in the cART era has led to an aging HIV population, resulting in increased prevalence of NADCs to the extent that the number of NADCs diagnosed each year in the US now exceeds those of ADCs [16]. Some studies, including the Swiss HIV Cohort Study, have noted increased incidence of NADCs, which have been stable over the study intervals (SIRs of 2.3, 2.7, and 2.2, respectively) [14]. Although NHL remains the most common malignancy in persons with HIV infection, cancers of the lung, liver, and head and neck, anus as well as Hodgkin lymphoma, all NADCs, are being seen more frequently in this aging population. Moreover, these NADCs are seen in excess in HIV populations in several cohort studies, ­suggesting ­increased risk. Furthermore, many of these malignancies are diagnosed at an early age, on average a decade and a half earlier than the general population. As a result of the shifting cancer epidemiology, the distinction/classification of ADCs and NADCs has become blurred and in several ways outdated, though the terms remain in widespread use [17].