Associations between MICA and MICB Genetic Variants, Protein Levels, and Colorectal Cancer: Atherosclerosis Risk in Communities (ARIC).

BACKGROUND: The MHC class I chain-related protein A (MICA) and protein B (MICB) participate in tumor immunosurveillance and may be important in colorectal cancer, but have not been examined in colorectal cancer development. METHODS: sMICA and sMICB blood levels were measured by SomaScan in Visit 2 (1990-92, baseline) and Visit 3 (1993-95) samples in cancer-free participants in the Atherosclerosis Risk in Communities Study. We selected rs1051792, rs1063635, rs2516448, rs3763288, rs1131896, rs2596542, and rs2395029 that were located in or in the vicinity of MICA or MICB and were associated with cancer or autoimmune diseases in published studies. SNPs were genotyped by the Affymetrix Genome-Wide Human SNP Array. We applied linear and Cox proportional hazards regressions to examine the associations of preselected SNPs with sMICA and sMICB levels and colorectal cancer risk (236 colorectal cancers, 8,609 participants) and of sMICA and sMICB levels with colorectal cancer risk (312 colorectal cancers, 10,834 participants). In genetic analyses, estimates adjusted for ancestry markers were meta-analyzed. RESULTS: Rs1051792-A, rs1063635-A, rs2516448-C, rs3763288-A, rs2596542-T, and rs2395029-G were significantly associated with decreased sMICA levels. Rs2395029-G, in the vicinity of MICA and MICB, was also associated with increased sMICB levels. Rs2596542-T was significantly associated with decreased colorectal cancer risk. Lower sMICA levels were associated with lower colorectal cancer risk in males (HR = 0.68; 95% confidence interval, 0.49-0.96) but not in females (Pinteraction = 0.08). CONCLUSIONS: Rs2596542-T associated with lower sMICA levels was associated with decreased colorectal cancer risk. Lower sMICA levels were associated with lower colorectal cancer risk in males. IMPACT: These findings support an importance of immunosurveillance in colorectal cancer.

Pharmacy-Based Interventions to Increase Use of HIV Pre-exposure Prophylaxis in the United States: A Scoping Review.

HIV pre-exposure prophylaxis (PrEP) remains underutilized in the U.S. Since greater than 85% of PrEP prescriptions are filled at commercial pharmacies, pharmacists are uniquely positioned to increase PrEP use. This scoping review explores pharmacy-based initiatives to increase PrEP use. We searched PubMed, PsycINFO, CINAHL, and Scopus for peer-reviewed studies on pharmacist-led interventions to increase PrEP use or pharmacy-based PrEP initiatives. Forty-nine articles were included in this review. Overall, studies demonstrated that patients expressed strong support for pharmacist prescription of PrEP. Three intervention designs compared changes in PrEP initiation or knowledge pre- and post-intervention. Commentary/review studies recommended PrEP training for pharmacists, policy changes to support pharmacist screening for HIV and PrEP prescription, and telemedicine to increase prescriptions. Pharmacists could play key roles in improving PrEP use in the U.S. Studies that assess improvements in PrEP use after interventions such as PrEP prescription, PrEP-specific training, and adherence monitoring by pharmacists are needed.

Economic Burden Among Gay, Bisexual, and Other Men Who Have Sex With Men Living With HIV or Living Without HIV in the Multicenter AIDS Cohort Study.

BACKGROUND: With HIV now considered a chronic disease, economic burden for people living with HIV (LWH) may threaten long-term disease outcomes. We studied associations between economic burden (employment, income, insurance, and financial difficulty) and HIV status for gay, bisexual, and other men who have sex with men (GBMSM) and how economic burden relates to disease progression. SETTING: We analyzed data collected every 6 months through 2015 from GBMSM LWH and GBMSM living without HIV from 2 waves (2001-2003 cohort and 2010+ new recruit cohort) of the Multicenter AIDS Cohort Study. METHODS: Using generalized estimating equations, we first assessed the association between HIV status (exposure) and economic burden indicators since the last study visit (outcomes) of employment (working/student/retired versus not currently working), personal annual income of ≥$10,000, insurance (public/private versus none), and financial difficulty meeting basic expenses. Then among people LWH, we assessed the relationships between economic burden indicators (exposures), risk of progressive immune suppression (CD4 ≤500 cells/uL), and progression to AIDS (CD4 ≤200; outcomes). RESULTS: Of 1721 participants, 59.5% were LWH (n = 1024). GBMSM LWH were 12% less likely to be employed, 16% more likely to have health insurance, and 9% more likely to experience financial difficulty than GBMSM living without HIV. Among GBMSM LWH, employment was associated with a 6% and 32% lower likelihood of immune suppression or progression to AIDS, respectively, and the income was associated with a 15% lower likelihood of progression to AIDS. CONCLUSIONS: Interventions that stabilize employment, income, and offer insurance support may enrich GBMSM LWH's ability to prevent disease progression.

Cancer risk following lymphoid malignancies among HIV-infected people.

OBJECTIVE(S): HIV-infected people have increased cancer risk. Lymphoma survivors have an increased risk of certain second primary cancers in the general population, but second cancer risk among HIV-infected people is poorly understood. Herein, we characterized the risk of cancers following lymphoid malignancies among HIV-infected people. DESIGN: Population-based linkage of HIV and cancer registries. METHODS: We used data from the US HIV/AIDS Cancer Match Study (1996-2015) and evaluated the risk of first nonlymphoid malignancy in Cox regression models, with first lymphoid malignancy diagnosis as a time-dependent variable. RESULTS: Among 531 460 HIV-infected people included in our study, 6513 first lymphoid and 18 944 first nonlymphoid malignancies were diagnosed. Risk of nonlymphoid cancer following a lymphoid malignancy was increased overall [adjusted hazard ratio (aHR) = 2.7; 95% confidence interval (CI) = 2.3--3.2], and specifically for cancers of the oral cavity (aHR = 2.6; 95% CI = 1.2-5.5), colon (2.4; 1.1-5.0), rectum (3.6; 1.9-6.7), anus (3.6; 2.5-5.1), liver (2.0; 1.2-3.5), lung (1.6; 1.1-2.4), vagina/vulva (6.1; 2.3-16.3), and central nervous system (5.0; 1.6-15.6), Kaposi sarcoma (4.6; 3.4-6.2), and myeloid malignancies (9.7; 6.1-15.4). After additional adjustment for prior AIDS diagnosis and time since HIV diagnosis, aHRs were attenuated overall (aHR = 1.7; 95% CI = 1.5-2.0) and remained significant for cancers of the rectum, anus, and vagina/vulva, Kaposi sarcoma, and myeloid malignancies. CONCLUSION: HIV-infected people with lymphoid malignancies have an increased risk of subsequent non-lymphoid cancers. As risks remained significant after adjustment for time since HIV diagnosis and prior AIDS diagnosis, it suggests that immunosuppression may explain some, but not all, of these risks.

Correlates of Patient Retention in HIV Care and Treatment Programs in Nigeria.

BACKGROUND: Long-term retention is a crucial component of HIV care because treatment success can only be measured among retained patients. Understanding determinants of retention will inform retention strategies. We evaluated the correlates of retention in a large HIV program in Nigeria. METHODS: We reviewed quality of care data for 5320 randomly selected HIV-positive adults aged ≥15 years enrolled in 37 treatment facilities in Nigeria between 2005 and 2009. Retention was described as having one or more clinic visits in the one year (2010) review period. Patient-related correlates of retention were determined using logistic regression. RESULTS: 144 patients exited the program through deaths or transferrals. Of the 5176 with no documented exits, 3231 (62.4%) were retained (65.6% female; median age: 35.6 years). 2938 (75.8%) patients on ART, and 286 (23.4%) pre-ART patients were retained. Being on ART (OR=10.3, p<0.001), Age 30-60 years (30 - 45 years: OR=1.36, p<0.001 and >45 - 60 years: OR=1.47, p<0.001) compared to patients <30 years; Female gender (OR=1.18, p=0.006), baseline CD4 cell count (100-350 cells/mm(3): OR=1.24, p=0.006) vs <100 cells/mm(3) and lower WHO stage at baseline (WHO Stage IV, III, II: OR=0.50,0.51,0.77 respectively) vs Stage I were associated with retention. Among patients on ART, recent ART initiation 2008-09 (OR=1.73, p<0.001) vs 2005-07, being on ART for >6 months (p<0.001) vs <6 month and initiating ART on non-Stavudine based regimen (p<0.001) were also associated with retention. CONCLUSION: 3 out of 4 pre-ART patients and 1-in-4 ART patients were not retained in 37 HIV treatment facilities in Nigeria. These findings provide insight that enables HIV programs integrate retention strategies at all stages of the HIV care continuum.

Update on HIV-1 acquired and transmitted drug resistance in Africa.

The last ten years have witnessed a significant scale-up and access to antiretroviral therapy in Africa, which has improved patient quality of life and survival. One major challenge associated with increased access to antiretroviral therapy is the development of antiretroviral resistance due to inconsistent drug supply and/or poor patient adherence. We review the current state of both acquired and transmitted drug resistance in Africa over the past ten years (2001-2011) to identify drug resistance associated with the different drug regimens used on the continent and to help guide affordable strategies for drug resistance surveillance. A total of 161 references (153 articles, six reports and two conference abstracts) were reviewed. Antiretroviral resistance data was available for 40 of 53 African countries. A total of 5,541 adult patients from 99 studies in Africa were included in this analysis. The pooled prevalence of drug resistance mutations in Africa was 10.6%, and Central Africa had the highest prevalence of 54.9%. The highest prevalence of nucleoside reverse transcriptase inhibitor mutations was in the west (55.3%) and central (54.8%) areas; nonnucleoside reverse transcriptase inhibitor mutations were highest in East Africa (57.0%) and protease inhibitors mutations highest in Southern Africa (16.3%). The major nucleoside reverse transcriptase inhibitor mutation in all four African regions was M184V. Major nonnucleoside reverse transcriptase inhibitor as well as protease inhibitor mutations varied by region. The prevalence of drug resistance has remained low in several African countries although the emergence of drug resistance mutations varied across countries. Continued surveillance of antiretroviral therapy resistance remains crucial in gauging the effectiveness of country antiretroviral therapy programs and strategizing on effective and affordable strategies for successful treatment.