HIV-associated Risk Factors Research Articles

Clonal hematopoiesis in people with advanced HIV and associated inflammatory syndromes.

People with HIV (PWH) have a higher age-adjusted mortality due to chronic immune activation and age-related comorbidities. PWH also have higher rates of clonal hematopoiesis (CH) than age-matched non-HIV cohorts; however, risk factors influencing the development and expansion of CH in PWH remain incompletely explored. We investigated the relationship between CH, immune biomarkers, and HIV-associated risk factors (CD4+ and CD8+ T cells, nadir CD4+ count, opportunistic infections [OIs], and immune reconstitution inflammatory syndrome [IRIS]) in a diverse cohort of 197 PWH with median age of 42 years, using a 56-gene panel. Seventy-nine percent had a CD4+ nadir below 200 cells/μL, 58.9% had prior OIs, and 34.5% had a history of IRIS. The prevalence of CH was high (27.4%), even in younger individuals, and CD8+ T cells and nadir CD4+ counts strongly associated with CH after controlling for age. A history of IRIS was associated with CH in a subgroup analysis of patients 35 years of age and older. Inflammatory biomarkers were higher in CH carriers compared with noncarriers, supporting a dysregulated immune state. These findings suggest PWH with low nadir CD4+ and/or inflammatory complications may be at high risk of CH regardless of age and represent a high-risk group that could benefit from risk reduction and potentially targeted immunomodulation.

Lung cancer and HIV

BACKGROUND: People, living with HIV, have a greater chance of malignancies especially with the success of antiretroviral therapy, and non-AIDS-defining cancers have become the most common cause of death after AIDS and the most common of them is the lung cancer in developed countries.
 AIM: To research nosological characteristics of lung cancer in the context of HIV infection, HIV-associated risk factors during antiretroviral therapy and compare with global trends of this problem.
 MATERIALS AND METHODS: Retrospectively were analyzed the medical documentation of 98 patients with lung cancer and HIV-infection, who were in database and received specialized treatment in Saint Petersburg from 2008 to 2018 years.
 RESULTS: The population was dominated by patients of young (1844 years old) and middle (4559 years old) ages, 45.9% and 42.9%, respectively, and 11.2% of elderly patients (6074 years old), p 0.001, which satisfies the global data of earlier incidence of lung cancer in people living with HIV.
 Adenocarcinomas were more common histological subtype of lung cancer as in the general population (p 0.001).
 There was no static significance between high viral load and lung cancer, which can indicate the absence of a direct mechanism of HIV-carcinogenesis (90.8% of patients with low and medium viral load, p 0.001). Nevertheless, the prevalence of 4-stage of HIV infection among lung cancer patients (p 0.001) indicates a history of inflammatory diseases, including pulmonary diseases, as a result of induced immunosuppression due to CD8+-lymphocyte dysfunction and the formation of a micro-tumor environment, which can be a prognostic unfavorable factor in the occurrence of lung cancer in this group of patients , as well as indirect mechanism of viral carcinogenesis.
 The presence of elderly patients (11.2%, MAX71 years) indirectly indicates an increasing of period of life expectancy among this category of patients in Russia.
 CONCLUSION: The mechanisms of increased risk of lung cancer among HIV-infected people remain largely unclear and can be the area for active research. HIV-infected patients with lung cancer are younger than HIV-negative patients and have more advanced stages of cancer with a prevalence of adenocarcinoma type of cancer. The lung cancer prognosis of survival in HIV-infected people is much worse than that of persons without HIV-infection, but it is not fully known whether this is due to a more aggressive course of the disease, disparities in treatment, treatment resistance, or a greater risk and toxicity of therapy.

A baseline studies on the nutritional interplay between HIV drugs and kidney, liver and heart indices in patients receiving HIV treatment in North-Central Nigeria

Malnutrition is one of the major problems among those infected with HIV/AIDS receiving Antiretroviral Therapy (ART). Various studies have shown that HIV infection and malnutrition are intricately linked to each other. In the absence of proper nutrition and treatment, HIV infection can lead to malnutrition which in turn impairs the immune system there by progressing HIV to AIDS, conversely use of ART has been reported to have significant effect on people living with HIV. This study aims at assessing the nutritional interplay between HIV drugs and kidney, liver, and heart indices among subjects undergoing HIV treatment at medical out-patient department of Federal Medical Centers in North Central part of Nigeria. A hospital based cross-sectional study was conducted where 677 people living with HIV attending the ART clinic were selected using a systematic random sampling technique. Nutritional status among these people was assessed through anthropometry Body Mass Index (BMI) and were classified accordingly; Underweight (BMI < 18.5 kg/m2) and overweight/obesity (BMI > 23 kg/m2). Patients information’s including HIV associated risk factors, opportunistic infections, ART regimen, etc. were collected from the medical record department. Socio-demographic data were collected using structured questionnaire. Blood samples were collected to access kidney, liver and heart indices as well as levels of Vitamin D and trace elements such as Zinc and Selenium. Chi-square was used to test for a significant difference between sociodemographic characteristics and BMI, while ANOVA was used to compare the levels of kidney, liver and heart indices as well as vitamin D, Zn and Se based on BMI status at 95% C.I. Most of the study participants were overweight 201 (29.7%) and obese 211 (31.2%), a large number had a normal BMI 32.9%. The prevalence of underweight was found to be 42(6.2%). there was a significant increase in the level of some kidney, liver and cardiac indices in participants who were overweight and obese compared to those who were normal and underweights, these significant increase was observed in the levels of Na, K, Cl, HCo3, ALP, AST, ALT, Cholesterol, LDL and TG. There was a significant decrease in levels of Vitamin D, Zn and Se in participants who were underweight. Underweight, overweight and obesity are emerging problem among HIV patients on ART. Patients undergoing ART should be placed under strict nutritional monitoring and be subjected to nutritional supplementation to avert untimely death, also effort should be made to address the burden of malnutrition by addressing identified determinants.

Assessing risk factors for hypertension in young adults with perinatally acquired HIV infection: A case-control study.

Although the risk of AIDS-associated diseases has declined dramatically with combination antiretroviral therapy (cART), the incidence rates of chronic non-AIDS-associated diseases in perinatally HIV-infected adults have risen and have not been well characterized. Both traditional and HIV-associated risk factors have been found to contribute to hypertension in non-perinatally HIV-infected adults; whether these same factors contribute to hypertension in perinatally infected adults is not known. The purpose of this study was to determine the socio-demographic, clinical, virological and immunological factors associated with systemic hypertension among a cohort of perinatally HIV-infected adolescents and young adults. We conducted a case-control study among a population of adults aged 18-35years with perinatally acquired HIV infection receiving care at the University of Maryland Medical Center. Covariates assessed included traditional risk factors such as age, family history of hypertension, and smoking, as well as numerous HIV- and antiretroviral-associated covariates, including CD4 nadir. Approximately 31% of the cohort met criteria for hypertension. There were no significant differences in the odds of most traditional or HIV-associated risk factors among perinatally HIV-infected adults with hypertension compared with those with no diagnosis of hypertension. Exposure to lopinavir/ritonavir was associated with greater odds of not having hypertension, while a concurrent diagnosis of chronic kidney disease (CKD) was associated with greater odds of having hypertension. The results of this study suggest that most traditional and HIV-related risk factors do not appear to increase the odds of having hypertension in this cohort of individuals. The aetiology of hypertension in this population remains to be elucidated.

HIV Associated Risk Factors for Ischemic Stroke and Future Perspectives.

Although retroviral therapy (ART) has changed the HIV infection from a fatal event to a chronic disease, treated HIV patients demonstrate high prevalence of HIV associated comorbidities including cardio/cerebrovascular diseases. The incidence of stroke in HIV infected subjects is three times higher than that of uninfected controls. Several clinical and postmortem studies have documented the higher incidence of ischemic stroke in HIV infected patients. The etiology of stroke in HIV infected patients remains unknown; however, several factors such as coagulopathies, opportunistic infections, vascular abnormalities, atherosclerosis and diabetes can contribute to the pathogenesis of stroke. In addition, chronic administration of ART contributes to the increased risk of stroke in HIV infected patients. Concurrently, experimental studies in murine model of ischemic stroke demonstrated that HIV infection worsens stroke outcome, increases blood brain barrier permeability and increases neuroinflammation. Additionally, residual HIV viral proteins, such as Trans-Activator of Transcription, glycoprotein 120 and Negative regulatory factor, contribute to the pathogenesis. This review presents comprehensive information detailing the risk factors contributing to ischemic stroke in HIV infected patients. It also outlines experimental evidence demonstrating the impact of HIV infection on stroke outcomes, in addition to possible novel therapeutic approaches to improve these outcomes.

346. Factors Associated with Hypertension in Young Adults with Perinatally-Acquired HIV Infection: a Case–Control Study

BackgroundThe incidence of systemic hypertension (HTN) among perinatally-HIV-infected (PHIV) patients appears to increase as they enter adulthood. Among non-perinatally HIV-infected adults both traditional and HIV-associated risk factors have been found to contribute to HTN. Whether these same factors contribute to HTN in PHIV is unknown. The purpose of this study was to determine the socio-demographic, clinical, virologic, and immunologic factors associated with HTN among a cohort of PHIV adolescents and young adults, aged ≥18 years.MethodsWe conducted a case–control study among a population of 160 PHIV adults with and without HTN who were receiving care at the University of Maryland and aged 18–35 years as of December 31, 2017. Covariates assessed included traditional risk factors such as age, family history of HTN, and smoking, as well as HIV- and antiretroviral-associated covariates.ResultsWe identified 49 HTN cases (30.6%) and 111 (69.4%) controls. There were no significant differences in the odds of most traditional (age, gender, race, family history of HTN, tobacco, alcohol, and/or other drug use) or HIV-associated (CD4 nadir <100 cells/mm3, individual ART exposure, ART interruption) risk factors among PHIV adults with HTN compared with those with no diagnosis of HTN. Cases had lower odds of a history of treatment with lopinavir/ritonavir (LPV/r). Cases had 3.7 (95% CI 1.11, 12.56) times the odds of a prior diagnosis of chronic kidney disease (CKD) compared with controls after controlling for CD4 nadir and ARV treatment history.ConclusionThe results of this study suggest that most traditional and HIV-related risk factors do not appear to increase the odds of having HTN in this PHIV cohort. However, HTN among PHIV may be driven in part by CKD, and a focus on the prevention and early management of CKD in this group may be necessary to prevent the development of HTN. Additionally, there may be as yet unidentified risk factors for HTN among PHIV which require further exploration. Given the large and growing population of PHIV entering adulthood worldwide, it is imperative to explore risk factors for and effects of HTN in large, diverse PHIV populations.Disclosures All authors: No reported disclosures.

Exploring HIV-related stigma among HIV-infected men who have sex with men in Beijing, China: a correlation study

ABSTRACTHuman immunodeficiency virus (HIV)-related stigma among HIV-infected men who have sex with men (MSM) has been associated with adverse health outcomes, including poor adherence to antiretroviral therapy and care, and increased participation in behaviors linked to higher rates of HIV transmission. In China, the incidence of HIV is growing more rapidly among MSM than among other subgroups. This study characterizes and quantifies HIV stigma among HIV-infected MSM in Beijing, China, which arguably may be driving this epidemic. A cross-sectional survey study was performed among 266 HIV-positive MSM in Beijing, China, in 2014. The Berger HIV Stigma Scale was used to measure levels of HIV-related stigma. Participants additionally answered questions regarding socio-demographic characteristics and HIV-associated risk factors; previously validated Mandarin-language scales assessed depression, coping style, and social support networks. Multivariable linear regression models were used to identify variables significantly associated with HIV stigma. The mean overall HIV stigma score among the study population was 112.78 ± 18.11 (score range: 40–160). Higher HIV stigma scores were positively associated with depression (β = 7.99, 95% CI:3.69, 12.29, p < .001) and negative coping skills (β = 0.64, 95% CI:0.21,1.08, p < .01), and was negatively associated with disclosed HIV status (β = −6.45, 95%CI:−11.80, −1.11, p < .05), and availability of social support networks (β = −0.12, 95%CI:−0.22, −0.02, p < .05). Other variables such as poor self-rated health status and presence of opportunistic infections were positively associated with individual dimensions of HIV-related stigma. The results of this study can inform the development of culturally sensitive interventions to reduce HIV-related stigma among MSM with HIV in China, with the overarching goal of reducing HIV transmission in this vulnerable population.

Incidence and progression of coronary artery calcium in HIV-infected and HIV-uninfected men.

The aim of this article is to determine whether HIV-infected (HIV+) men have either higher incidence or more rapid progression of coronary artery calcium (CAC) compared with HIV-uninfected (HIV-) controls. Prospective observational study. Multicenter study in four US academic research centers: University of Pittsburgh, Johns Hopkins University, University of California Los Angeles, and Northwestern University. Eight hundred and twenty-five men (541 HIV+ and 284 HIV-) enrolled in the cardiovascular substudy of the Multicenter AIDS Cohort Study who underwent serial cardiac computed tomography (CT) imaging during a mean follow-up of 5 years (range, 2-8 years). Incidence and progression of CAC assessed by cardiac CT. During follow-up, 21% of HIV+ men developed incident CAC compared with 16% of HIV- men. This association persisted after adjustment for traditional and HIV-associated risk factors: hazard ratio 1.64 (1.13-3.14). However, there was no association between HIV serostatus and CAC progression among men with CAC present at baseline. Current smoking and increased insulin resistance, both modifiable risk factors, were independently associated with increased incidence of CAC. No evidence supporting an elevated risk for either CAC progression or incidence was found for either dyslipidemia or long-term usage of antiretroviral therapy. In this large study of HIV+ and HIV- men who underwent serial cardiac CT scan imaging, HIV+ men were at significantly higher risk for development of CAC: hazard ratio 1.64 (1.13-3.14). In addition, two important and modifiable risk factors were identified for increased incidence of CAC. Taken together, these findings underscore the potential importance for smoking cessation and interventions to improve insulin resistance among HIV+ men.

Time trends for risk of severe age-related diseases in individuals with and without HIV infection in Denmark: a nationwide population-based cohort study

Whether the reported high risk of age-related diseases in HIV-infected people is caused by biological ageing or HIV-associated risk factors such as chronic immune activation and low-grade inflammation is unknown. We assessed time trends in age-standardised and relative risks of nine serious age-related diseases in a nationwide cohort study of HIV-infected individuals and population controls. We identified all HIV-infected individuals in the Danish HIV Cohort Study who had received HIV care in Denmark between Jan 1, 1995, and June 1, 2014. Population controls were identified from the Danish Civil Registration System and individually matched in a ratio of nine to one to the HIV-infected individuals for year of birth, sex, and date of study inclusion. Individuals were included in the study if they had a Danish personal identification number, were aged 16 years or older, and were living in Denmark at the time of study inclusion. Data for study outcomes were obtained from the Danish National Hospital Registry and the Danish National Registry of Causes of Death and were cardiovascular diseases (myocardial infarction and stroke), cancers (virus associated, smoking related, and other), severe neurocognitive disease, chronic kidney disease, chronic liver disease, and osteoporotic fractures. We calculated excess and age-standardised incidence rates and adjusted incidence rate ratios of outcomes for time after HIV diagnosis, highly active antiretroviral therapy (ART) initiation, and calendar time. The regression analyses were adjusted for age, sex, calendar time, and origin. We identified 5897 HIV-infected individuals and 53,073 population controls; median age was 36·8 years (IQR 30·6-44·4), and 76% were men in both cohorts. Dependent on disease, the HIV cohort had 55,050-57,631 person-years of follow-up and the population controls had 638,204-659,237 person-years of follow-up. Compared with the population controls, people with HIV had high excess and relative risk of all age-related diseases except other cancers. Overall, the age-standardised and relative risks of cardiovascular diseases, cancers, and severe neurocognitive disease did not increase substantially with time after HIV diagnosis or ART initiation. Except for chronic kidney diseases, the age-standardised and relative risks of age-related diseases did not increase with calendar time. Severe age-related diseases are highly prevalent in people with HIV, and continued attention and strategies for risk reduction are needed. The findings from our study do not suggest that accelerated ageing is a major problem in the HIV-infected population. Preben og Anna Simonsens Fond, Novo Nordisk Foundation, Danish AIDS Foundation, Augustinus Foundation, and Odense University Hospitals Frie Fonds Midler.

HIV Among Women in the District of Columbia: An Evolving Epidemic?

The epidemiology of HIV in urban centers of the United States such as the District of Columbia (DC) is dynamic with rates of new HIV and AIDS diagnoses as well as risk factors elevated. Correlates of HIV among heterosexual women extend beyond traditional, individual risk factors to structural factors. The purpose of this study was to compare proportions of HIV and correlates of HIV among women participating in National HIV behavioral surveillance (NHBS) system in 2006-7 (NHBS Cycle 1) and 2010 (NHBS Cycle 2). Analysis of 677 female participants at elevated risk for HIV revealed high prevalence of individual-level HIV-associated risk factors (e.g., sexual behavior) and socio-structural associated risk factors (e.g., homelessness, incarceration, lack of health insurance). While a greater proportion of women were HIV-infected in Cycle 2, after controlling for the distribution of demographic characteristics to adjust for a change in eligibility criteria, the pooled sample did not reveal a significantly increased proportion of HIV-infected women in Cycle 2. Homelessness and condom use were associated with greater relative odds of HIV after adjustment for confounders, and non-injection drug use was associated with reduced odds. Findings inform our understanding of the continuing HIV epidemic in DC and support development of effective interventions to slow the epidemic among women in DC and similar urban centers.

Osteoporosis and HIV

Osteoporosis poses a significant public health issue, causing significant morbidity and mortality. It is a disease of bone that leads to an increased fracture risk through a reduction in the bone mineral density (BMD), disruption of bone microarchitecture, and alteration of the amount and variety of non-collagenous proteins in bone. The treatment aims of this condition are to prevent fractures and maintain the quality of life of the aging adult. Approximately three million people in the UK have osteoporosis, and every year more than 230,000 fractures occur because of it. One in two women and one in five men over the age of 50 will have a fracture mainly as a result of the condition, and therefore, osteoporotic fractures are of great importance to patient and clinician. As the HIV-infected population continues to live longer, due to the advent of highly active anti-retroviral therapy (HAART), osteopenia and osteoporosis are becoming more common metabolic complications in the aging adult with HIV [1]. Certain lifestyle and hormonal factors, which increase the risk of disordered bone metabolism, are prevalent in HIV-infected patients. These include physical inactivity, suboptimal intake of calcium and Vitamin D, cigarette smoking, alcohol and opiate use, depression, and low testosterone levels. HAART itself may be associated with decreased BMD [2–5]. Although prevalence estimates of low BMD vary considerably, most studies indicate an increased risk in HIVinfected individuals. In a meta-analysis by Brown et al. [2], 20 cross-sectional studies were reviewed and it was demonstrated that 67 % of 884 HIV patients had reduced BMD and 15 % fulfilled the diagnostic criteria for osteoporosis. Similar findings were noted by Cazanave et al. [3] in a cross-sectional survey of 492 HIV patients within the Aquitaine cohort, which involved analysis of BMD of total body, lumbar spine, and femoral neck regions. Cazanave et al. reported osteopenia in 55 % of men and 51 % of women, along with osteoporosis in 34 and 8 %, respectively. Variations between sexes are being explained by age differences and cigarette use. More recent publications by Mallon [4] and Calmy et al. [5] report similar correlations between low BMD and HIV positive status among Irish and Australian patients, respectively. Low BMD among patients with HIV infection is usually multifactorial, since weight loss, malnutrition, malabsorption (leading to vitamin D deficiency), and hypogonadism may be present. HIV infection itself may cause chronic T cell activation and increased production of proinflammatory cytokines that enhance osteoclast activity [6]. Traditional risk factors for bone loss such as female gender, low body mass index (BMI), physical inactivity, steroid use, advanced age, duration of menopause, smoking, and injection drug use may act in concert with HIV-associated risk factors. In addition, the importance of the status of reproductive function was highlighted by a study of 84 normal-weight, HIV-infected women, which reported reduced bone density among women with oligomenorrhea or elevated follicle-stimulating hormone (FSH) levels compared to women with normal menses. Studies have been conducted to determine the effects of HAART and individual anti-retroviral agents or medication classes on bone loss in HIV-infected patients. In a metaanalysis of ten studies comparing HAART-naive (n = 202) with HAART-treated (n = 824) patients, there was a 2.5M. B. O’Connor (&) Department of Rheumatology, South Infirmary Victoria University Hospital, Old Blackrock Road, Cork, Ireland e-mail: mortimeroconnor@gmail.com

Parallel Rapid HIV Testing in Pregnant Women at Tijuana General Hospital, Baja California, Mexico

The objectives of this study were to evaluate the performance of parallel rapid HIV testing and the presence of HIV-associated risk factors in pregnant women with unknown HIV status in Baja California, Mexico. Pregnant women attending the delivery unit or the prenatal clinic at Tijuana General Hospital had blood drawn for parallel rapid HIV testing with Determine™ HIV-1/2 and Uni-Gold™ Recombigen(®) HIV. The parallel rapid HIV test performance was compared to the enzyme immunoassay (EIA) and western blot. From September 2007 to July 2008, 1,383 (94%) of 1,464 women in labor and 1,992 (96%) of 2,075 women in prenatal care were enrolled. The HIV seroprevalence among women screened during labor (19/1,383, 1.37%, 95% CI: 0.85-2.18%) was significantly higher compared to those seeking prenatal care (5/1,992, 0.25%, 95% CI: 0.09-0.62%; p<0.001). Of 25 pregnant women testing positive by parallel rapid HIV testing 24 had a positive confirmatory western blot and one (0.03%) was confirmed as false positive. Additionally, two (0.06%) women had parallel rapid HIV discordant testing results; both tested negative by western blot. All women who tested negative by rapid testing had negative results on pooled EIA antibody testing. The overall sensitivity, specificity, and positive and negative predictive values of parallel rapid HIV testing were 100%, 99.9%, 96%, and 100%, respectively. These findings document a very high acceptance rate and an excellent performance of the parallel rapid HIV testing strategy during pregnancy.

Exploring the Venue’s Role in Risky Sexual Behavior Among Gay and Bisexual Men: An Event-Level Analysis from a National Online Survey in the U.S.

Venue-based characteristics (e.g., alcohol in bars, anonymous chat online, dark/quiet spaces in bathhouses) can impact how men who have sex with men (MSM) negotiate sex and HIV-associated risk behavior. We sought to determine the association between HIV-associated risk factors and the venues where MSM met their most recent new (first-time) male sex partner, using data from a 2004 to 2005 national online anonymous survey of MSM in the U.S. (n=2,865). Most men (62%) met their partner through the Internet. Among those reporting anal sex during their last encounter (n=1,550), half had not used a condom. In multivariate modeling, and among men reporting anal sex during their last encounter, venue where partner was met was not significantly associated with unprotected anal intercourse (UAI). Nevertheless, venue was related to other factors that contextualized men's sexual encounters. For example, HIV status disclosure was lowest among men who met their most recent partner in a park, outdoors, or other public place and highest among men who met their most recent partner online. Alcohol use prior to/during the last sexual encounter was highest among men who met their most recent partner in a bathhouse or a bar/club/party/event. These data suggest it is possible to reach men online who seek sex in many different venues, thus potentially broadening the impact of prevention messages delivered in virtual environments. Although not associated with UAI, venues are connected to social-behavioral facets of corresponding sexual encounters, and may be important arenas for differential HIV and STI education, treatment, and prevention.

HIV-associated risk factors among young Canadian Aboriginal and non-Aboriginal men who have sex with men.

Young Aboriginal men face marginalization distinct in cause but similar in pattern to those seen among men who have sex with men (MSM) and may be at increased risk for HIV infection. We compared sociodemographic characteristics and risk taking behaviours associated with HIV infection among MSM of Aboriginal and non-Aboriginal descent. Data for this comparison were gathered from baseline questionnaires completed by participants in a cohort study of young MSM. Data collection included: demographic characteristics such as age, length of time residing in the Vancouver region, housing, employment, income and income sources; mental health and personal support; instances of forced sex and sex trade participation and; sexual practices with regular and casual male sex partners. Data were available for 57 Aboriginal and 624 non-Aboriginal MSM. Aboriginal MSM were significantly less likely to be employed, more likely to live in unstable housing, to have incomes of <$10,000 and to receive income assistance than non-Aboriginals (all P<0.01). Aboriginals also had higher depression scores (P<0.01), were more likely to report non-consensual sex (P=0.03), sexual abuse during childhood (P=0.04) and having been paid for sex (P<0.01). In the past year they were no more likely to have had sex with a male partner they knew to be HIV positive, to have had more than 50 male partners or to have unprotected anal insertive or receptive intercourse with their male partners (all P>0.05). Our data indicate that among MSM, Aboriginal men are at increased risk of antecedent risk factors for HIV infection including sexual abuse, poverty, poor mental health and involvement in the sex trade.