Unique Aspects of the Care of HIV-Positive Latino Patients Living in the United States

Abstract

Latinos are disproportionately affected by HIV, with a higher risk of infection and a delayed presentation to care as compared to non-Hispanic whites. Over the last decade many Latinos, especially foreign-born migrants, have settled in regions of the country with historically low Latino representation. Therefore, clinicians who care for HIV-infected patients are likely to encounter Latino patients, regardless of their practice location. Providing optimal care to this population may be especially challenging for clinicians practicing in areas of newer Latino expansion, where culturally appropriate services may be sparse. In this article, we argue that an understanding of the HIV epidemic among Latinos requires an appreciation of the diversity and heterogeneity of the Latino population in the United States. We also review unique clinical aspects of HIV care among Latinos, including manifestation of co-infections with pathogens endemic in Latin America but rare in the United States.

Introduction

Latinos are the largest and fastest growing minority group in the United States, accounting for approximately 15% of the total population. They are also disproportionately affected by HIV, representing 19% of the HIV-positive population in 2005 [1•]. Latinos are not only at increased risk of infection, but also often have a delayed presentation to HIV care, with worse clinical outcomes than non-Hispanic whites. Rates of new infections are three times higher for Latino men and fivefold higher for Latina women than for their non-Hispanic white counterparts [1•]. Moreover, recent studies demonstrate lower survival among Latinos infected with HIV than non-Hispanic white populations [2]. Late diagnosis and unrecognized HIV infection appear to be important factors associated with disparities in health outcomes among Latinos. This review focuses on unique aspects of clinical care that may impact the quality of life and prognosis of Latinos infected with HIV living in the United States. Particular emphasis will be given to the heterogeneity of the Latino population, and how differences in specific subgroups may impact HIV presentation, diagnosis, care, and outcomes.

Heterogeneity of Latinos Living in the United States

The Latino population in the United States is highly heterogeneous, comprised of both US-born and foreign-born individuals. Mexican Americans comprise by far the largest proportion, at 66% in 2008. By comparison, Puerto Ricans, the next largest group, comprise only 9% of the population, followed by Central Americans (8.2%), Cuban Americans (3.5%), Dominican Americans (2.8%), and other groups with even lower representation [3]. Specific details about the health status of these groups tend to be “washed out” by the much larger Mexican American population in national statistics, but are important to consider as differences exist that can affect clinical care.

Late Presentation and Access to Care

Country of origin and US citizenship are associated with inequalities in access to health care that can have important implications for HIV. In 2006, 22% of all new HIV diagnoses among Latinos were reported in individuals born in Puerto Rico even though Puerto Ricans account only for 9% of the total Hispanic US population [1•]. This disparity may reflect a higher risk for HIV in this group, but may also reflect increased detection in Puerto Ricans (who are US citizens) compared to other populations with less access to health care. This suggestion is supported by the fact that Puerto Ricans actually have a lower risk for late HIV diagnosis than foreign-born Latinos. Approximately 40% of Puerto Ricans and other Latinos born in the United States have a late HIV diagnosis (defined as progression to AIDS within 1 year of diagnosis), compared to 55% and 58% of Latinos born in Mexico or Central America, respectively [1•]. Although federal funding for HIV testing is available for all US residents at public health clinics regardless of citizenship status, accessing these services requires some expertise navigating the health care system, and may be difficult for non-English speakers. In addition, undocumented immigrants may have suspicion or anxiety about visiting health centers for fear that information might be turned over to authorities.

In the last decade, there has been a significant change in the distribution of new Latino immigrants to the United States, with many recent migrants, particularly from Central America, settling in nontraditionally Latino areas, such as the Midwest and Mid-Atlantic, where access to culturally appropriate health care and other social services may be unavailable. This rapidly changing demographic often leads to a “lag time” between the arrival of new immigrant groups and the development of culturally and linguistically appropriate health care, social services, and outreach programs.

Some Latinos may also not be aware of HIV as a disease for which they may be at risk. As an example, in a free public HIV counseling and testing outreach program in Baltimore, MD, Latino participants, who were predominantly foreign-born, were less likely to have been previously tested for HIV than non-Latinos (37% vs 77%). And among Latinos, low educational level was associated with never having been tested previously [4]. National data also show that Latinos less acculturated to the United States are less likely to undergo HIV testing, not only because of insufficient access to testing but also because of poor knowledge about the disease [5].

Cultural Concepts and Care

Cultural values can impact risk of HIV acquisition and affect care of some HIV-infected Latinos as well. For example, marianismo, a concept emphasizing a submissive role for women, can undermine women’s control of HIV risk by discouraging them from obtaining a sexual history from their partners, advocating for condom use, or learning more about safe sexual practices [6]. It can also make Latina women less comfortable making decisions about issues of HIV care when diagnosed. The concept of familismo, an emphasis on family solidarity and responsibility to family, can be beneficial when coping with chronic illness, but can also lead to isolation if HIV or certain behaviors (such as homosexuality) are associated with significant stigma [7]. Fatalismo, or the concept that one’s life is predestined, may impact self-advocacy for HIV testing and care [8]. Finally, machismo, a cultural concept of male expression of power, can be used by males to justify risky behaviors, such as having multiple sexual partners. Supporting this, multiple studies describe a high rate of men frequenting commercial sex workers (CSWs), particularly among recent immigrants. Approximately one third of migrant farm workers in Florida report visiting CSWs within a year, and between 28% and 68% of urban day laborers report sex with a CSW [9–11]. These practices put men at high risk of acquisition of HIV and other sexually transmitted infections, but also put their female partners at risk, who may, depending on their cultural beliefs, feel uncomfortable advocating for condoms to protect themselves.

Implications for the Clinician

An understanding of the heterogeneity of the Latino population in the United States has important implications for the clinician. Cultural sensitivity and good doctor–patient communication have been associated with improved clinical outcomes, though definitive studies in Latinos are lacking [12]. Spanish-speaking HIV-positive Latinos in particular have been found to have more problems paying for medical care and difficulty communicating with physicians than English-speaking Latinos [13]. Small studies in Latino communities have demonstrated that culturally and linguistically appropriate care significantly increase CD4 counts and decrease viral loads, largely through improved adherence [14]. Therefore, whenever possible, Spanish-speaking providers should be available in clinics serving Latino populations, but if not possible, translation services are a necessity.

Undocumented Latinos who may be fearful of authorities should be reassured that seeking medical care will not place them at risk for deportation. Until January 4, 2010, immigration law precluded admission and naturalization to the United States for HIV-infected individuals, which may have acted as a deterrent to early testing for non-citizen Latino immigrants fearful of jeopardizing future naturalization [15]. Therefore, common clinic procedures should be explained to minimize barriers to care. For example, patients should be reassured that security guards will not enquire about their immigration status, that their medical information is confidential, and that access to HIV care is not dependent on citizenship status.

Clinicians must be prepared to explain a new diagnosis of HIV in simple terminology, cognizant of the stigma associated with HIV among some Latino groups. Special attention should be paid to the needs of Latina women, particularly with regard to disclosure to their partners, which may place them at risk for domestic violence in a community where intimate partner violence is 54% higher than in the general population [16]. Similarly, clinicians must be aware of differences in definitions of sexuality, since more Latino men who have sex with men (MSM) may identify exclusively as heterosexual, and there remains a high social stigma around the acknowledgment of homosexual behavior. Peer support groups for HIV-infected Latinos may mitigate the isolation and stigma that is unfortunately associated with the diagnosis.

Latinos and Antiretroviral Therapy

Treatment with antiretroviral (ARV) therapy for Latinos should adhere to national guidelines, such as those published by the Department of Health and Human Services [17•]. As with all patients, ARV selection should be guided by the potency of the regimen, toxicity profile, and patient lifestyle and preference in order to maximize adherence. The late presentation of many Latinos, often with opportunistic infections (OIs), can complicate management, particularly during initial therapy due to the risk of immune reconstitution inflammatory syndrome, drug toxicity, and pharmacokinetic interactions. Furthermore, concurrent therapy for HIV and OIs often requires regimens with a high pill burden and complicated dosing schedule, which may compromise adherence. Unfortunately, data on outcomes of ARV therapy among Latinos are somewhat limited due to low representation of Latinos in clinical trials. In addition, participation in many studies is biased against non-English-speaking Latinos unless the research team has Spanish consent forms and bilingual study coordinators. In the following segment, we summarize the limited data available from clinical studies addressing the response of Latino HIV-infected individuals to ARVs.

Adherence

As with any internally diverse group, it is difficult to generalize about adherence among Latinos. A recent study of 1,102 men with HIV (of whom 151 were Latino) found that Latinos were 2.16 times more likely than whites not to report 100% adherence [18]. This study notably did not control for language preference, which may impact doctor–patient communication. Another recent study of 5,887 patients showed a higher rate of missed medications among Latinos in the 48 hours prior to the visit [19]. However, anecdotal reports (including our own experiences, discussed later), particularly in specific subgroup populations, describe excellent adherence. One should note that the studies mentioned above all relied on self-report of adherence, rather than on clinically based outcomes. In fact, a recent retrospective cohort study of 4,686 HIV-infected patients at a large integrated health care system did find a significant difference in adherence between Latinos and whites (65.2% vs 70.1%) but did not find a difference for clinical outcomes of AIDS diagnosis or death [20].

As in other populations, substance abuse, mental illness, homelessness, and financial distress can negatively impact adherence among Latinos, and confound many of the previously discussed adherence studies. Transient populations with irregular work hours (eg, day laborers, migrant workers) may have difficulty with scheduled appointments, adhering to complex medication regimens, or obtaining refills or new prescriptions. Additionally, Latinos have high rates of alcoholism and depression, which can worsen adherence. A recent national survey reported symptoms diagnostic of dysthymia in 50% of Latino women with HIV, and while studies directly examining alcoholism and medication adherence among Latinos are lacking, heavy alcohol and stimulant use was recently described in 23% of Latinos in a nationwide survey of 3513 HIV-infected patients (though this was lower than the sample of white patients) [21, 22].

More established populations, especially in urban areas with access to Spanish-language clinics and transportation, generally have better adherence to therapy. Culturally appropriate care with bilingual and bicultural staff has been shown to improve adherence significantly, as discussed previously [14]. In our experience, urban foreign-born Latinos, largely from Mexico and Central America, demonstrate excellent adherence when offered care in clinics with appropriate Spanish language resources and adherence aids. In general, these patients have negligible rates of intravenous drug use (though alcohol abuse is common) and tend to have a submissive interaction with the clinician, often following directions without questioning. This often reflects roles established in more paternalistic health care systems outside the United States, and seems to promote adherence, though physicians must work hard to foster relationships that will allow patients to express their concerns.

Selection of ARV therapy should take into account the lifestyle and adherence of the patients. Efforts should be made to assess and address issues that may impact adherence prior to initiation of therapy, such as ensuring medication coverage, facilitating transport to the clinic, and treating active mental health issues or substance addictions. It is important to remember, however, that many Latino patients present in late stages of HIV, and initiation of ARV therapy should not be unduly delayed because of adherence concerns. For patients who are unlikely to reach 100% adherence, agents with high barriers to resistance and good kinetic profiles are preferable [23]. Although protease inhibitors (PIs) are usually preferred over nonnucleoside reverse transcriptase inhibitors (NNRTIs) in patients with adherence issues, other factors, such as the availability of refrigeration (especially for migrant workers), must be considered and may influence the choice of drug.

Genetic Determinants of ARV Response in Latinos

Recent data show that genetic polymorphisms can explain some racial differences in drug metabolism, toxicity, and efficacy. For example, the HLA-B*5701 allele has been strongly associated with abacavir hypersensitivity in whites. Presence of this allele is estimated at 4% in the Latino population (as compared to 8% of whites). However, in a study of 100 patients, which included 10 Latinos, and a separate case-control study of 526 HIV-1-infected adults and 515 controls with 71 Latinos, only 20% to 22% of Latinos with a history of abacavir hypersensitivity had an HLA-B*5701 allele [24, 25]. This finding could be partially explained by misclassification of clinically defined abacavir hypersensitivity, but does appear to be consistent with reports of non-HLA-B*5701-associated hypersensitivity in other non-white populations.

Another polymorphism that has gained attention recently is the CYP2B6 isoform of cytochrome P450, which has been associated with variable rates of metabolism of NNRTIs, particularly efavirenz. Small studies have suggested that Latinos and blacks have higher serum efavirenz levels and are at higher risk of neurotoxicity than non-Hispanic whites due to differences in their CYP2B6 polymorphisms. These studies have been limited by the small number of Latinos, and therefore estimates of the prevalence of CYP2B6 polymorphisms in the Latino population are broad [26, 27]. While currently not applied in clinical practice, an increased understanding of such genetic polymorphisms may in the future affect optimal drug choice decisions for individual patients.

Adverse Drug Reactions

There are scarce data regarding ARV toxicity among Latinos. A recent analysis of the FIRST study, which included 225 Latino participants, did not show a difference in class 4 adverse reactions between Latinos and whites [28]. However, as previously mentioned, findings in Latino participants of clinical trials may not be generalizable to specific Latino subgroups. In the section below, we outline a few studies that have evaluated drug toxicity among Latinos, but clearly further investigation in this area is warranted.

Dysglycemia and Insulin Resistance

Latinos have a high risk of diabetes compared to non-Hispanic whites, and a higher rate of death from diabetes (33.3 per 100,000) than the general population (24.6 per 100,000) [29•]. Therefore, there has been concern that the risk of metabolic syndrome associated with some ARVs may be higher in Latinos. A recent small study provided some data, finding that Latinos had the most unfavorable metabolic changes after ARV initiation, with significant increases in glucose from baseline (11.23 mg/dL for Latinos vs 1.81 mg/dL for whites), insulin resistance (1.18 vs 0.36), and the greatest level of fat redistribution [30]. While it is difficult to generalize from this single study with only 41 Latino participants, many of whom received antiquated drugs such as stavudine and nelfinavir, the metabolic effect of ARVs on HIV-infected Latinos deserves further evaluation, given the high rates of insulin resistance and diabetes among Latinos and therefore comorbid diabetes and HIV.

Plasma Lipid Levels

The pathophysiology of dyslipidemia associated with ARVs is multifactorial, and includes specific drug effects, insulin resistance, and host genetic factors. A recent study correlating ARV-associated changes in lipid profiles with race/ethnicity and genetic polymorphisms found that African Americans had the highest increase in lipid levels following initiation of a PI, but there was no statistical difference in change in lipid profile between Latinos and non-Hispanic whites. Interestingly, a subset of Latino patients was found to have non-wild-type apoC-III variant alleles that were protective against hyperlipidemia. Patients with these mutations were found to have lower triglycerides than patients with wild-type genotypes [31]. The clinical significance of this finding is yet to be determined. PIs as a class are associated with a rise in serum lipid levels, and the difference in the rise seen in Latinos was modest and nonsignificant.

Neuropathy

Peripheral neuropathy is a common side effect of ARVs, particularly associated with some agents such as stavudine and didanosine (the so-called “d-drugs”). There is some evidence suggesting that ethnic or cultural differences may influence the severity of pain associated with neuropathy. In a longitudinal study of 109 participants with advanced AIDS, there was no difference between development of distal sensory polyneuropathy, but there was a trend toward reporting of higher pain scores by Latinos, which could be associated with either differences in severity of neuropathy or cultural perceptions of pain. This study had important limitations, such as differences in the baseline characteristics of the different ethnic/racial groups, with more Latino intravenous drug users and a larger proportion of Latinos receiving “d-drugs” [32]. It is of questionable relevance today when few “d-drugs” remain in therapeutic use.

Co-infections

As previously mentioned, HIV-infected Latinos tend to present late to care, often symptomatic with an OI. Foreign-born Latinos with HIV are at risk for OIs endemic in their countries of origin. While the list is long and diverse, we will review here the key diseases that the clinician should keep in mind when treating this population (summarized in Table 1).

Table 1 Co-infections that are uncommon in the United States but should be considered in HIV-1-infected foreign-born Latinos

Bacterial Co-infections

Mycobacterium Tuberculosis

Tuberculosis, though occurring in the native-born US population, is much more prevalent in other parts of the world, including Latin America. According to US Centers for Disease Control and Prevention (CDC) data, Latinos accounted for 26% of all cases of tuberculosis in the United States and 23% of cases in HIV-infected individuals in 2005 [33]. In border states with high Latino populations, the vast majority of HIV/tuberculosis co-infection occurs among Latinos. A report from southern California found that in 2009, 80% of HIV/tuberculosis cases occurred among Latinos [34]. Given this incidence, early tuberculosis screening with the tuberculin skin test, ideally before ARV initiation, with aggressive workup of concerning symptoms is recommended in all Latino immigrants with HIV.

Mycobacterium leprae

Leprosy remains a common diagnosis in many parts of Latin America today. HIV is not associated with worsened clinical presentation of leprosy [35]. However, initiation of ARVs has been strongly associated with activation of subclinical M. leprae infection and exacerbation of existing lesions in several case series and retrospective studies [36]. Clinicians should be aware of this association when evaluating cutaneous lesions in HIV-infected patients from Latin America, particularly in those recently initiating antiretroviral therapy. Treatment often involves rifampin, and the clinician must be aware of potential drug interactions with ARVs.

Rhodococcus equi

Though a rare condition, Rhodococcus equi generally presents similarly to tuberculosis and is associated with a high mortality rate among patients with HIV and AIDS (20%-25% and 50%-55%, respectively, as compared with 11% of immunocompetent patients) [37]. There have been a few case reports of Rhodococcus infection from Latin America, mostly from Chile. It is a rare condition, but given that many Latinos in the United States have immigrated from more agrarian societies, it should not be forgotten in the differential for tuberculosis. Diagnosis is usually made through culture of appropriate involved fluid.

Syphilis

Syphilis remains widespread in the United States today, particularly among MSM populations. Among ethnic groups, black Americans continue to have the highest rates of syphilis, at 11 per 100,000, though Latinos still have rates more than double that of the white population (2.1 per 100,000 vs 0.7 per 100,000 for whites) [38]. There have been several recent reports of syphilis outbreaks associated with Latino communities: among male clients of female sex workers in Tijuana, Mexico; among patients at a Baltimore, MD public sexually transmitted disease clinic; and among Latino immigrants in Decatur, AL, many of whom frequented CSWs [39–41]. Taken in sum, these outbreaks emphasize the importance of regular sexually transmitted infection testing of Latino patients with HIV and aggressive contact tracing to control outbreaks quickly.

Viruses

Human T-lymphocyte Virus 1

Although uncommon in the United States, human T-lymphocyte virus 1 (HTLV-1) is a retrovirus found in multiple Latin American countries including Perú, Colombia, northern Brazil, Argentina, Central America, and the Caribbean [42]. Transmission is often vertical, though it can be sexually transmitted. HTLV-1 is usually asymptomatic but can cause severe disease, including adult T-cell leukemia/lymphoma and tropical spastic paraparesis/HTLV-1-associated myelopathy and uveitis, and HIV/HTLV-1 co-infection has been associated with an increased risk of these complications in small studies [43]. HTLV-1 can be associated with significant increases in the CD4 cell count without immunologic benefit. The effects of co-infection have not been adequately studied, and conflicting reports exist as to whether co-infection affects mortality [44]. HTLV-1 co-infection should be considered in HIV-infected patients who present with OIs despite elevated CD4 counts. Diagnosis is usually made by serology, which can be obtained through the CDC laboratories.

Parasites

HIV-infected patients often develop an eosinophilia associated with HIV infection itself, allergic reaction to medications, or, less commonly, from adrenal insufficiency. In Latino immigrants, eosinophilia may also indicate a parasitic infection. The presence of intestinal parasites can be evaluated with three examinations of the stool for ova and parasites. If the history, physical examination, and stool evaluation are not revealing, the patient should also be evaluated for systemic parasitic infections such as Strongyloides, Schistosoma, and filariasis. Strongyloides is particularly concerning in immunosuppressed individuals, due to the risk of hyperinfection syndrome, though steroids and HTLV-1 are more important risk factors than HIV. Other parasitic infections of significance in HIV-infected individuals from Latin American include toxoplasmosis, which is common and often severe, and neurocysticercosis. Although neurocysticercosis is not specifically associated with HIV, it must be remembered in the differential diagnosis of brain lesions in individuals from Latin America. Also of note, leishmaniasis has been associated with a more rapid progression of HIV disease, while HIV infection increases the risk of developing visceral leishmaniasis by 100-fold to 2,320-fold, and reduces the likelihood of therapeutic response [45]. Lastly, American trypanosomiasis (Chagas disease), though rare, bears mention as coinfection has been associated with higher parasitemia, more frequent reactivation, and higher mortality [46].

Fungi

Histoplasmosis

Histoplasmosis is endemic in Central America and in HIV-infected individuals has a similar presentation to tuberculosis. In immunocompetent individuals, it is often asymptomatic, or minimally symptomatic. In contrast, patients with defective T-cell immunity are at high risk of Histoplasma reactivation and progressive disseminated histoplasmosis (PDH). Most present with fever, weight loss, and other constitutional symptoms. Pulmonary symptoms with radiographic abnormalities are present in 50% to 60% of cases. Less common manifestations include septic shock, central nervous system disease, and acute respiratory distress syndrome [47]. Fortunately, the urinary histoplasma antigen is a highly sensitive test that can facilitate diagnosis. Histoplasma serologies are generally not useful, since a large proportion of Central Americans have been exposed to H. capsulatum. Treatment of PDH with itraconazole can be challenging due to the multiple drug interactions with ARVs, particularly NNRTIs, and clinicians will need to monitor itraconazole drug levels or change regimens if feasible [48].

Coccidioidomycosis

Coccidioidomycosis represents another endemic mycosis found largely in the southwest United States and central Mexico. In a recent retrospective analysis, severity of coccidioidomycosis in HIV-infected patients, not surprisingly, was found to be inversely associated with control of HIV [49]. This inverse relationship between control of HIV disease and severity of infection is important to note in the context of Latinos’ tendency to present with late HIV infection. Presentation with severe coccidioidomycosis should prompt the clinician to consider testing for HIV. Coccidioides infection can be diagnosed by culture or microscopy.

Other Fungi

Cryptococcosis and P. jiroveci are infections seen commonly in HIV-infected patients with low CD4 counts. Though not specific to Latinos, the tendency of Latinos toward presenting later to care makes these co-infections relatively common in this population. Blastomycosis is a fungal infection seen throughout the southern and Midwestern United States, while paracoccidiomycosis is endemic to many parts of Latin America and common in Brazil. Neither is generally associated with HIV disease, though when occurring in patients with low CD4 counts, both often present with a more disseminated course.

Conclusions

Latinos, at approximately 47.8 million people, comprise the largest and fastest growing minority group in the United States today. With the population expansion, Latinos are constantly moving into new regions of the country. HIV-positive Latinos in the United States today face many challenges, including a tendency to present late to care and a higher mortality rate than HIV-positive non-Hispanic whites. These disparities not only carry a high cost to individual patients but also to society. Late diagnosis of HIV is associated with elevated health care costs, and unrecognized HIV infection increases HIV transmissibility in the community. The CDC has recently issued a series of recommendations on the epidemic and prevention of HIV in the community, which will hopefully result in improved access to culturally appropriate evidence-based prevention strategies and increased support for linkage of HIV-infected Latinos into quality health care [50••]. As public health interventions improve access to universal HIV testing, infectious disease and primary care clinicians are likely to encounter HIV-infected Latino patients in their practice. An appreciation for some of the unique risk factors, cultural norms, treatment decisions, and OIs is essential to provide optimal care to this vulnerable population.