Social and Structural Factors Associated with HIV Infection among Female Sex Workers Who Inject Drugs in the Mexico-US Border Region

BACKGROUND: FSWs who inject drugs (FSW-IDUs) can acquire HIV through high risk sexual and injection behaviors. We studied correlates of HIV infection among FSW-IDUs in northern Mexico, where sex work is quasi-legal and syringes can be legally obtained without a prescription. METHODS: FSW-IDUs>18 years old who reported injecting drugs and recent unprotected sex with clients in Tijuana and Ciudad Juarez underwent surveys and HIV/STI testing. Logistic regression identified correlates of HIV infection. RESULTS: Of 620 FSW-IDUs, prevalence of HIV, gonorrhea, Chlamydia, trichomonas, syphilis titers ≥1:8, or any of these infections was 5.3%, 4%, 13%, 35%, 10% and 72%, respectively. Compared to other FSW-IDUs, HIV-positive women were more likely to: have syphilis titers ≥1:8 (36% vs. 9%, p<0.001), often/always inject drugs with clients (55% vs. 32%, p = 0.01), and experience confiscation of syringes by police (49% vs. 28%, p = 0.02). Factors independently associated with HIV infection were syphilis titers ≥1:8, often/always injecting with clients and police confiscation of syringes. Women who obtained syringes from NEPs (needle exchange programs) within the last month had lower odds of HIV infection associated with active syphilis, but among non-NEP attenders, the odds of HIV infection associated with active syphilis was significantly elevated. CONCLUSIONS: Factors operating in both the micro-social environment (i.e., injecting drugs with clients) and policy environment (i.e., having syringes confiscated by police, attending NEPs) predominated as factors associated with risk of HIV infection, rather than individual-level risk behaviors. Interventions should target unjustified policing practices, clients' risk behaviors and HIV/STI prevention through NEPs

Formative Assessment of ARM-U: A Modular Intervention for Decreasing Risk Behaviors Among HIV-Positive and HIV-Negative Methamphetamine-Using MSM

BACKGROUND: Methamphetamine is a major contributor to HIV transmission among men who have sex with men (MSM). Recent studies show that up to one-third of methamphetamine-using MSM (MUMSM) inject the drug. We developed a behavioral intervention for MUMSM to decrease unprotected anal intercourse and increase awareness of parenteral HIV transmission risk. This 6-session (3 in-person, 3 by telephone) modular intervention was designed to be tailored to participants' HIV (+/-) and injection drug user ([IDU] yes/no) status. We present results of formative research used to evaluate the content and to assess feasibility and acceptability of this individual-level HIV risk-reduction intervention. SETTING: HIV research clinic in a high MSM and methamphetamine prevalence neighborhood. PROJECT: Avoiding Risks from Methamphetamine-Use (ARM-U) is a brief toolbox intervention that allows counselors to select modules that suit a client's individual risk profile and intervention needs employing motivational interviewing and cognitive behavioral theory. We evaluated the format and content of the intervention through focus groups and pre-testing of the entire intervention using volunteers from the target population stratified into four groups (HIV+/IDU, HIV-/IDU, HIV+/non-IDU, HIV-/non-IDU). Four individuals in each stratum were recruited to undergo the intervention and complete a satisfaction survey at the end of each in-person session. RESULTS: In total, 25 MUMSM attended one of five focus groups. Participants thought all proposed intervention topics were important and could aid in reducing sexual risk behaviors among MUMSM. However, the neurocognitive effects of methamphetamine were reported to be a barrier to practicing safer sex, condom use negotiation or HIV status disclosure. Fifteen (94%) of 16 participants completed all 6 sessions and the satisfaction survey. On average, participants felt the intervention was useful for MUMSM, made them contemplate and move toward behavior change, and would recommend the program to their peers. LESSONS LEARNED: Based on our formative research, we revised the ARM-U intervention to emphasize pre-planning to avoid combining methamphetamine use and sex or develop strategies to avoid sex risk following methamphetamine use. We also increased emphasis on referrals for care and other requested services. Future efficacy trials are needed to evaluate the intervention's ability to reduce HIV-associated risk behaviors

Polydrug Use among IDUs in Tijuana, Mexico: Correlates of Methamphetamine Use and Route of Administration by Gender

Tijuana is situated on the Mexico–USA border adjacent to San Diego, CA, on a major drug trafficking route. Increased methamphetamine trafficking in recent years has created a local consumption market. We examined factors associated with methamphetamine use and routes of administration by gender among injection drug users (IDUs). From 2006–2007, IDUs ≥18 years old in Tijuana were recruited using respondent-driven sampling, interviewed, and tested for HIV, syphilis, and TB. Logistic regression was used to assess associations with methamphetamine use (past 6 months), stratified by gender. Among 1,056 participants, methamphetamine use was more commonly reported among females compared to males (80% vs. 68%, p < 0.01), particularly, methamphetamine smoking (57% vs. 34%; p < 0.01). Among females (N = 158), being aged >35 years (AOR, 0.2; 95% CI, 0.1–0.6) was associated with methamphetamine use. Among males (N = 898), being aged >35 years (AOR, 0.5; 95% CI, 0.3–0.6), homeless (AOR, 1.4 (0.9–2.2)), and ever reporting sex with another male (MSM; AOR, 1.9; 95% CI, 1.4–2.7) were associated with methamphetamine use. Among males, a history of MSM was associated with injection, while sex trade and >2 casual sex partners were associated with multiple routes of administration. HIV was higher among both males and females reporting injection as the only route of methamphetamine administration. Methamphetamine use is highly prevalent among IDUs in Tijuana, especially among females. Routes of administration differed by gender and subgroup which has important implications for tailoring harm reduction interventions and drug abuse treatment

Oncogenic BRAF, unrestrained by TGFβ-receptor signalling, drives right-sided colonic tumorigenesis.

Right-sided (proximal) colorectal cancer (CRC) has a poor prognosis and a distinct mutational profile, characterized by oncogenic BRAF mutations and aberrations in mismatch repair and TGFβ signalling. Here, we describe a mouse model of right-sided colon cancer driven by oncogenic BRAF and loss of epithelial TGFβ-receptor signalling. The proximal colonic tumours that develop in this model exhibit a foetal-like progenitor phenotype (Ly6a/Sca1+) and, importantly, lack expression of Lgr5 and its associated intestinal stem cell signature. These features are recapitulated in human BRAF-mutant, right-sided CRCs and represent fundamental differences between left- and right-sided disease. Microbial-driven inflammation supports the initiation and progression of these tumours with foetal-like characteristics, consistent with their predilection for the microbe-rich right colon and their antibiotic sensitivity. While MAPK-pathway activating mutations drive this foetal-like signature via ERK-dependent activation of the transcriptional coactivator YAP, the same foetal-like transcriptional programs are also initiated by inflammation in a MAPK-independent manner. Importantly, in both contexts, epithelial TGFβ-receptor signalling is instrumental in suppressing the tumorigenic potential of these foetal-like progenitor cells

HIV-1 subtype A infection in a community of intravenous drug users in Pakistan

BACKGROUND: Data on the subtypes of HIV in a population help in predicting the potential foci of epidemic, tracking the routes of infection and following the patterns of the virus' genetic divergence. Globally, the most prevalent HIV infection is the HIV-1 subtype C. In Asia, predominant subtypes of HIV-1 are B, C, and CRF-01AE. During the last few years, HIV prevalence in Pakistan has taken the form of a concentrated epidemic in at least two high risk groups, namely, Intravenous Drug Users (IDUs) and Male Sex Workers (MSWs). Factors that have facilitated the proliferation of HIV infection include transmission through a large number of repatriates and needle-sharing intravenous drug users, unscreened blood transfusions, and sexual illiteracy. The HIV subtypes infecting Pakistani populations have not been explored to date. In this study, we analyzed HIV-1 subtypes from in a high-risk community of IDUs in Karachi, the largest city of Pakistan. METHODS: Samples were collected from 34 IDUs after their informed consent. In addition, the study subjects were administered a questionnaire regarding their sexual behavior and travel history. For HIV analysis, DNA was extracted from the samples and analyzed for HIV types and subtypes using subtype-specific primers in a nested polymerase chain reaction (PCR). The results from this PCR were further confirmed using the Heteroduplex Mobility Assay (HMA). RESULTS: We found HIV-1 subtype A in all the 34 samples analyzed. A few of the study subjects were found to have a history of travel and stay in the United Arab Emirates. The same subjects also admitted to having contact with commercial sex workers during their stay abroad. CONCLUSION: Our study therefore shows clade A HIV-1 to be prevalent among the IDUs in Karachi. As the prevalence of HIV in Pakistan continues to rise, more work needs to be done to track the infection, and to analyze the strains of HIV spreading through the country

Fanconi anemia genes are highly expressed in primitive CD34(+ )hematopoietic cells

BACKGROUND: Fanconi anemia (FA) is a complex recessive genetic disease characterized by progressive bone marrow failure (BM) and a predisposition to cancer. We have previously shown using the Fancc mouse model that the progressive BM failure results from a hematopoietic stem cell defect suggesting that function of the FA genes may reside in primitive hematopoietic stem cells. METHODS: Since genes involved in stem cell differentiation and/or maintenance are usually regulated at the transcription level, we used a semiquantitative RT-PCR method to evaluate FA gene transcript levels in purified hematopoietic stem cells. RESULTS: We show that most FA genes are highly expressed in primitive CD34-positive and negative cells compared to lower levels in more differentiated cells. However, in CD34(- )stem cells the Fancc gene was found to be expressed at low levels while Fancg was undetectable in this population. Furthermore, Fancg expression is significantly decreased in Fancc -/- stem cells as compared to wild-type cells while the cancer susceptibility genes Brca1 and Fancd1/Brac2 are upregulated in Fancc-/- hematopoietic cells. CONCLUSIONS: These results suggest that FA genes are regulated at the mRNA level, that increased Fancc expression in LTS-CD34(+ )cells correlates with a role at the CD34(+ )differentiation stage and that lack of Fancc affects the expression of other FA gene, more specifically Fancg and Fancd1/Brca2, through an unknown mechanism

Correlates of Obsessive–Compulsive Disorder in a Sample of HIV-Positive, Methamphetamine-using Men Who have Sex with Men

Substance use has been identified as a risk factor for elevated levels of obsessive–compulsive disorder (OCD). This study examined methamphetamine use and sexual risk behaviors as correlates of OCD in a sample of 245 HIV-positive men having sex with men (MSM) in San Diego, CA. In a logistic regression analysis, OCD was associated with greater frequency of methamphetamine use, more depressive symptoms, seeking out risky venues and risky sexual partners when “high” on methamphetamine, and reporting fewer sex acts in the past 2 months. These data suggest the need for increased awareness and understanding of the role that OCD may play in the drug use behaviors and risky sexual practices of methamphetamine users

HIV Disclosure, Condom Use, and Awareness of HIV Infection Among HIV-Positive, Heterosexual Drug Injectors in St. Petersburg, Russian Federation

We examined the prevalence of HIV disclosure to sexual partners by HIV-positive drug injectors (IDUs) in St. Petersburg, Russia and compared the magnitude and direction of associations of condom use with awareness of one’s HIV infection and disclosure to partners. Among 157 HIV-infected participants, awareness of infection at time of last intercourse was associated with condom use with partners perceived to be HIV-negative (aOR 6.68, 95% CI 1.60–27.88). Among the 70 participants aware of their infection prior to enrolment, disclosure to potentially uninfected sexual partners was independently and negatively associated with condom use (aOR 0.13, 95% CI 0.02–0.66). Disclosure was independently associated with having injected ≥9 years (aOR 6.04, 95% CI 1.53–23.77) and partnership with another IDU (aOR 3.61, 95% CI 1.44–9.06) or HIV-seropositive (aOR 45.12, 95% CI 2.79–730.46). Scaling up HIV testing services and interventions that increase the likelihood of individuals receiving their test results is recommended

BRF1 accelerates prostate tumourigenesis and perturbs immune infiltration

BRF1 is a rate-limiting factor for RNA Polymerase III-mediated transcription and is elevated in numerous cancers. Here, we report that elevated levels of BRF1 associate with poor prognosis in human prostate cancer. In vitro studies in human prostate cancer cell lines demonstrated that transient overexpression of BRF1 increased cell proliferation whereas the transient downregulation of BRF1 reduced proliferation and mediated cell cycle arrest. Consistent with our clinical observations, BRF1 overexpression in a Pten-deficient mouse (Pten BRF1 ) prostate cancer model accelerated prostate carcinogenesis and shortened survival. In Pten BRF1 tumours, immune and inflammatory processes were altered, with reduced tumoral infiltration of neutrophils and CD4 positive T cells, which can be explained by decreased levels of complement factor D (CFD) and C7 components of the complement cascade, an innate immune pathway that influences the adaptive immune response. We tested if the secretome was involved in BRF1-driven tumorigenesis. Unbiased proteomic analysis on BRF1-overexpresing PC3 cells confirmed reduced levels of CFD in the secretome, implicating the complement system in prostate carcinogenesis. We further identify that expression of C7 significantly correlates with expression of CD4 and has the potential to alter clinical outcome in human prostate cancer, where low levels of C7 associate with poorer prognosis

Incidence of HIV and hepatitis C virus among people who inject drugs, and associations with age and sex or gender: a global systematic review and meta-analysis

Background: Measuring the incidence of HIV and hepatitis C virus (HCV) infection among people who inject drugs (PWID) is key to track progress towards elimination. We aimed to summarise global data on HIV and primary HCV incidence among PWID and associations with age and sex or gender. Methods: In this systematic review and meta-analysis, we updated an existing database of HIV and HCV incidence studies among PWID by searching MEDLINE, Embase, and PsycINFO, capturing studies published between Jan 1, 2000, and Dec 12, 2022, with no language or study design restrictions. We contacted authors of identified studies for unpublished or updated data. We included studies that estimated incidence by longitudinally re-testing people at risk of infection or by using assays for recent infection. We pooled incidence and relative risk (RR; young [generally defined as ≤25 years] vs older PWID; women vs men) estimates using random-effects meta-analysis and assessed risk of bias with a modified Newcastle–Ottawa scale. This study is registered with PROSPERO, CRD42020220884. Findings: Our updated search identified 9493 publications, of which 211 were eligible for full-text review. An additional 377 full-text records from our existing database and five records identified through cross-referencing were assessed. Including 28 unpublished records, 125 records met the inclusion criteria. We identified 64 estimates of HIV incidence (30 from high-income countries [HICs] and 34 from low-income or middle-income countries [LMICs]) and 66 estimates of HCV incidence (52 from HICs and 14 from LMICs). 41 (64%) of 64 HIV and 42 (64%) of 66 HCV estimates were from single cities rather than being multi-city or nationwide. Estimates were measured over 1987–2021 for HIV and 1992–2021 for HCV. Pooled HIV incidence was 1·7 per 100 person-years (95% CI 1·3–2·3; I2=98·4%) and pooled HCV incidence was 12·1 per 100 person-years (10·0–14·6; I2=97·2%). Young PWID had a greater risk of HIV (RR 1·5, 95% CI 1·2–1·8; I2=66·9%) and HCV (1·5, 1·3–1·8; I2=70·6%) acquisition than older PWID. Women had a greater risk of HIV (RR 1·4, 95% CI 1·1–1·6; I2=55·3%) and HCV (1·2, 1·1–1·3; I2=43·3%) acquisition than men. For both HIV and HCV, the median risk-of-bias score was 6 (IQR 6–7), indicating moderate risk. Interpretation: Although sparse, available HIV and HCV incidence estimates offer insights into global levels of HIV and HCV transmission among PWID. Intensified efforts are needed to keep track of the HIV and HCV epidemics among PWID and to expand access to age-appropriate and gender-appropriate prevention services that serve young PWID and women who inject drugs. Funding: Canadian Institutes of Health Research, Fonds de recherche du Québec–Santé, Canadian Network on Hepatitis C, UK National Institute for Health and Care Research, and WHO