Characterizing Network-Based HIV Testing Interventions to Guide HIV Testing and Contact Tracing at STI Clinics in Lilongwe, Malawi.

BACKGROUND: Understanding heterogeneity across patients in effectiveness of network-based HIV testing interventions may optimize testing and contact tracing strategies, expediting linkage to therapy or prevention for contacts of persons with HIV (PWH). SETTING: We analyzed data from a randomized controlled trial of a combination intervention comprising acute HIV testing, contract partner notification (cPN), and social contact referral conducted among PWH at 2 STI clinics in Lilongwe, Malawi, between 2015 and 2019. METHODS: We used binomial regression to estimate the effect of the combination intervention vs. passive PN (pPN) on having any (1) contact, (2) newly HIV-diagnosed contact, and (3) HIV-negative contact present to the clinic, overall and by referring participant characteristics. We repeated analyses comparing cPN alone with pPN. RESULTS: The combination intervention effect on having any presenting contact was greater among referring women than men [prevalence difference (PD): 0.17 vs. 0.10] and among previously vs. newly HIV-diagnosed referring persons (PD: 0.20 vs. 0.11). Differences by sex and HIV diagnosis status were similar in cPN vs. pPN analyses. There were no notable differences in the intervention effect on newly HIV-diagnosed referrals by referring participant characteristics. Intervention impact on having HIV-negative presenting contacts was greater among younger vs. older referring persons and among those with >1 vs. ≤1 recent sex partner. Effect differences by age were similar for cPN vs. pPN. CONCLUSION: Our intervention package may be particularly efficacious in eliciting referrals from women and previously diagnosed persons. When the combination intervention is infeasible, cPN alone may be beneficial for these populations.

Depression, Alcohol Use, and Sexual Behaviors by HIV Infection Stage and Diagnosis Timing Among STI Clinic Patients in Lilongwe, Malawi.

Understanding depression, alcohol use, and sexual behaviors according to HIV infection stage and diagnosis timing is important for HIV prevention efforts. We enrolled persons with recent infection and diagnosis (i.e., acute HIV infection (AHI) (n = 92) persons newly diagnosed seropositive (n = 360)) and persons previously diagnosed with HIV (n = 190) into a randomized controlled trial in Lilongwe, Malawi (N = 641) and estimated the prevalence of probable depression (Patient Health Questionnaire-9 ≥ 5), hazardous alcohol use (Alcohol Use Disorder Identification Test-C: men ≥ 4; women ≥ 3), and sexual behaviors (transactional sex, condomless sex). Compared with previously diagnosed participants, participants newly seropositive and those with AHI reported a higher proportion of probable depression (7%, 27%, 38%; AHI/Previous: Table Probability: 0.02, p < 0.01; AHI/New: Table Probability: <0.01, p < 0.01), hazardous alcohol use (8%, 18%, 29%; AHI/Previous and AHI/New: Table Probability: <0.01, p < 0.01), and transactional sex (5%, 14%, 20%; AHI/Previous: Table Probability: <0.01, p < 0.01; AHI/New: Table Probability: 0.06, p = 0.24), respectively. HIV prevention services addressing mental health and alcohol misuse may be particularly beneficial for persons with recent HIV infection and or diagnosis.

Intended and unintended consequences: Changes in opioid prescribing practices for postsurgical, acute, and chronic pain indications following two policies in North Carolina, 2012-2018 - Controlled and single-series interrupted time series analyses.

BACKGROUND: The potential misapplication of current opioid prescribing policies remains understudied and may have substantial adverse implications for patient safety. METHODS: We used autoregressive integrated moving average models to assess level and trend changes in monthly 1) prescribing rates, 2) days' supply, and 3) daily morphine milligram equivalents (MME) of incident opioid prescriptions relative to 1) a state medical board initiative to reduce high-dose and -volume opioid prescribing and 2) legislation to limit initial opioid prescriptions for acute and postsurgical pain. We examined outcomes by pain indication overall and by cancer history, using prescribing patterns for benzodiazepines to control for temporal trends. We used large private health insurance claims data to include North Carolina residents, aged 18-64, insured at any point between January 2012 and August 2018. RESULTS: After the medical board initiative, prescribing patterns for chronic pain patients did not change; conversely, acute and postsurgical pain patients experienced immediate declines in daily MME. Post-legislation prescription rates did not decline for those with acute, postsurgical, and non-cancer pain, but instead declined among cancer patients with chronic pain. Chronic pain patients experienced the largest days' supply declines post-legislation, instead of acute and postsurgical pain patients. CONCLUSIONS: We found mixed evidence on the potential impact of two opioid prescribing policies, with some observed declines in a group not intended to be impacted by the policy. This study provides evidence of the need for clearer opioid prescribing policies to ensure impacts on intended populations and avoid unintended consequences.

Association of Opioid Dose Reduction With Opioid Overdose and Opioid Use Disorder Among Patients Receiving High-Dose, Long-term Opioid Therapy in North Carolina.

Importance: Rapid reduction or discontinuation of long-term opioid therapy may increase risk of opioid overdose or opioid use disorder (OUD). Current guidelines for chronic pain management caution against rapid dose reduction but are based on limited evidence. Objective: To characterize the association between rapid reduction or abrupt discontinuation of opioid therapy (vs maintained or gradual reduction) and incidence of opioid overdose and OUD among patients prescribed high-dose, long-term opioid therapy (HDLTOT). Design, Setting, and Participants: This retrospective cohort study was conducted among patients aged 18 to 64 years who were prescribed HDLTOT (≥90 daily morphine milligram equivalents for ≥90% of 90 days) from January 2006 to September 2018, with follow-up up to 4 years after cohort entry. Claims data were drawn from a large private health insurer in North Carolina and analyzed from March 1, 2006, to September 30, 2018. Exposures: Time-varying exposure of rapid dose reduction or discontinuation (>10% dose reduction/week) vs maintenance, increase, or gradual reduction or discontinuation. Main Outcomes and Measures: The main outcome was incident opioid overdose (fatal or nonfatal) or diagnosed OUD. Inverse probability-weighted cumulative incidence of outcomes were estimated using the cumulative incidence function and hazard ratios (HRs) using marginal structural Fine-Gray models as a function of rapid dose tapering or discontinuation (vs gradual reduction or discontinuation or maintained or increased), accounting for competing risks. Results: A total of 19 443 patients (median [IQR] age, 49 [41-55] years; 10 073 [51.8%] men) who received HDLTOT were identified. Rapid reduction or discontinuation was associated with higher risk of fatal and nonfatal overdoses compared with gradual reduction after the first year (year 1: HR, 1.43; 95% CI, 0.94-2.18; years 2-4: HR, 1.95; 95% CI, 1.31-2.90). There was no association between rapid reduction or discontinuation and diagnosed OUD through 2 years of follow-up; however, the hazard of incident OUD among patients exposed to rapid tapering or discontinuation was greater 25 to 48 months after the start of follow-up (HR, 1.28; 95% CI, 1.01-1.63). Conclusions and Relevance: In this cohort study, rapid dose reduction or discontinuation was associated with increased risk of opioid overdose and OUD during long-term follow-up. These findings reinforce prior concerns about safety of rapid dose reductions for patients receiving HDLTOT and highlight the need for caution when reducing opioid doses.

Association Between Statewide Opioid Prescribing Interventions and Opioid Prescribing Patterns in North Carolina, 2006-2018.

OBJECTIVE: To examine the impact of three sequential statewide policy and legislative interventions on opioid prescribing practices among privately insured individuals in North Carolina. METHODS: An interrupted time series approach was used to examine level and trajectory changes of new and prevalent opioid prescription rates, days' supply, and daily morphine milligram equivalents before and after implementation of a 1) prescription drug monitoring program, 2) state medical board initiative, and 3) legislative action. Analyses were conducted using individual-level claims data from a large private health insurance provider serving North Carolina residents, ages 18-64 years, from January 2006 to August 2018. RESULTS: Rates of new and prevalent prescription opioid patients were relatively unaffected by the prescription monitoring program but sharply declined in the months immediately following both medical board (-3.7 new and -19.3 prevalent patients per 10,000 person months) and legislative (-14.1 new and -26.7 prevalent patients) actions. Among all opioid prescriptions, days' supply steadily increased on average over the study period but declined after legislative action (-1.5 days' supply per year). CONCLUSIONS: The voluntary prescription drug monitoring program launched in 2010 only marginally affected opioid prescribing patterns on its own, but its redeployment as an investigative and clinical tool in multifaceted public policy approaches by the state medical board and legislature later in the decade plausibly contributed to notable declines in prescription rates and days' supply. This study lends new emphasis to the importance of enforcement mechanisms for state and national policies seeking to reverse this critical public health crisis.

A randomized controlled trial evaluating combination detection of HIV in Malawian sexually transmitted infections clinics.

INTRODUCTION: HIV diagnosis is the necessary first step towards HIV care initiation, yet many persons living with HIV (PLWH) remain undiagnosed. Employing multiple HIV testing strategies in tandem could increase HIV detection and promote linkage to care. We aimed to assess an intervention to improve HIV detection within socio-sexual networks of PLWH in two sexually transmitted infections (STI) clinics in Lilongwe, Malawi. METHODS: We conducted a randomized controlled trial to evaluate an intervention combining acute HIV infection (AHI) screening, contract partner notification and social contact referral versus the Malawian standard of care: serial rapid serological HIV tests and passive partner referral. Enrolment occurred between 2015 and 2019. HIV-seropositive persons (two positive rapid tests) were randomized to the trial arms and HIV-seronegative (one negative rapid test) and -serodiscordant (one positive test followed by a negative confirmatory test) persons were screened for AHI with HIV RNA testing. Those found to have AHI were offered enrolment into the intervention arm. Our primary outcome of interest was the number of new HIV diagnoses made per index participant within participants' sexual and social networks. We also calculated total persons, sexual partners and PLWH (including those previously diagnosed) referred per index participant. RESULTS: A total of 1230 HIV-seropositive persons were randomized to the control arm, and 561 to the intervention arm. Another 12,713 HIV-seronegative or -serodiscordant persons underwent AHI screening, resulting in 136 AHI cases, of whom 94 enrolled into the intervention arm. The intervention increased the number of new HIV diagnoses made per index participant versus the control (ratio: 1.9; 95% confidence interval (CI): 1.2 to 3.1). The intervention also increased the numbers of persons (ratio: 2.5; 95% CI: 2.0 to 3.2), sexual partners (ratio: 1.7; 95% CI: 1.4 to 2.0) and PLWH (ratio: 2.3; 95% CI: 1.7 to 3.2) referred per index participant. CONCLUSIONS: Combining three distinct HIV testing and referral strategies increased the detection of previously undiagnosed HIV infections within the socio-sexual networks of PLWH seeking STI care. Combination HIV detection strategies that leverage AHI screening and socio-sexual contact networks offer a novel and efficacious approach to increasing HIV status awareness.

Use of Antiretroviral Therapy During Pregnancy and Adverse Birth Outcomes Among Women Living With HIV-1 in Low- and Middle-Income Countries: A Systematic Review.

BACKGROUND: Worldwide, nearly 18 million women of reproductive age are living with HIV-1. Although increased access to antiretroviral therapy (ART) during pregnancy has significantly reduced HIV-1 mother-to-child transmission (MTCT), a similarly robust reduction in preterm birth (PTB) and low birthweight (LBW) among infants born to women living with HIV has not been observed. This study was designed to identify associations between classes of ART regimens and risk of PTB or LBW. SETTING: Low- and middle-income countries. METHODS: We conducted a systematic review of randomized and observational studies that assessed the effect of ART regimen on the risk of PTB (≤37 completed weeks of gestation) or LBW (<2500 g at birth) among pregnant women in low- and middle-income countries living with HIV-1. We searched Medline, COCHRANE, Web of Science, SCOPUS, and CPCI-S for included studies. RESULTS: When compared to monotherapy, both nonnucleoside reverse transcriptase inhibitor- and protease inhibitor-based regimens had a consistent, harmful association with LBW. There is mixed evidence suggesting both potential harm and potential benefit for most other regimens on risk of LBW and PTB, and the harmful or protective effects of certain regimens varies depending on the drug backbone. CONCLUSIONS: Although the benefits of ART during pregnancy for prevention of MTCT are undisputed, this systematic review indicates that ART regimens vary substantially in their association with LBW and PTB. Although challenging, optimization of ART regimens could simultaneously promote maternal health, prevent MTCT, and also minimize risks of PTB and LBW.

Large Cluster of Neisseria meningitidis Urethritis in Columbus, Ohio, 2015.

Background: Neisseria meningitidis (Nm) is a Gram-negative diplococcus that normally colonizes the nasopharynx and rarely infects the urogenital tract. On Gram stain of urethral exudates, Nm can be misidentified as the more common sexually transmitted pathogen Neisseria gonorrhoeae. Methods: In response to a large increase in cases of Nm urethritis identified among men presenting for screening at a sexually transmitted disease clinic in Columbus, Ohio, we investigated the epidemiologic characteristics of men with Nm urethritis and the molecular and phylogenetic characteristics of their Nm isolates. The study was conducted between 1 January and 18 November 2015. Results: Seventy-five Nm urethritis cases were confirmed by biochemical and polymerase chain reaction testing. Men with Nm urethritis were a median age of 31 years (interquartile range [IQR] = 24-38) and had a median of 2 sex partners in the last 3 months (IQR = 1-3). Nm cases were predominantly black (81%) and heterosexual (99%). Most had urethral discharge (91%), reported oral sex with a female in the last 12 months (96%), and were treated with a ceftriaxone-based regimen (95%). A minority (15%) also had urethral chlamydia coinfection. All urethral Nm isolates were nongroupable, ST-11 clonal complex (cc11), ET-15, and clustered together phylogenetically. Urethral Nm isolates were similar by fine typing (PorA P1.5-1,10-8, PorB 2-2, FetA F3-6), except 2, which had different PorB types (2-78 and 2-52). Conclusions: Between January and November 2015, 75 urethritis cases due to a distinct Nm clade occurred among primarily black, heterosexual men in Columbus, Ohio. Future urogenital Nm infection studies should focus on pathogenesis and modes of sexual transmission.

Notes from the Field: Increase in Neisseria meningitidis-Associated Urethritis Among Men at Two Sentinel Clinics - Columbus, Ohio, and Oakland County, Michigan, 2015.

Neisseria meningitidis (Nm) urogenital infections, although less common than infections caused by Neisseria gonorrhoeae (Ng), have been associated with urethritis, cervicitis, proctitis, and pelvic inflammatory disease. Nm can appear similar to Ng on Gram stain analysis (gram-negative intracellular diplococci) (1-5). Because Nm colonizes the nasopharynx, men who receive oral sex (fellatio) can acquire urethral Nm infections (1,3,5). This report describes an increase in Nm-associated urethritis in men attending sexual health clinics in Columbus, Ohio, and Oakland County, Michigan.

High levels of self-reported prescription opioid use by HIV-positive individuals.

Prescription medication use (other than antiretroviral therapy (ART)) is highly prevalent among people living with HIV. Prescription medications may be used medically or non-medically: non-medical use includes using more medication than prescribed, using medication prescribed to someone else, or using medication for a purpose other than its prescribed use. During 12 weeks in 2014-2015, we characterized medical and non-medical prescription medication use among HIV-positive patients attending an academic medical center (n = 149) and a community clinic (n = 105). Separately for the past year and the past month, these 254 participants self-reported their use of prescription opioids, sedatives, stimulants, anti-anxiety medications, antipsychotic medications, and erectile dysfunction medications. Respondents were largely male (91%), aged 40 or older (61%), identified as gay or bisexual (79%), and were men who have sex with men (85%). ART use was nearly universal (95%). Nearly half (43%) of participants reported medical use of prescription opioids; 11% of the opioid use was reported as non-medical use. Anti-anxiety medication use was also frequent, and differed by site: 41% of community-clinic responders reported medical use of anti-anxiety medications compared to 23% of hospital clinic respondents who reported medical use. Prescription sedative use was also approximately twice as high among community-clinic participants, with medical use reported by 43% of respondents and non-medical use by 12%; in comparison, at the hospital clinic, sedative use was reported by 18% (medical) and 7% (non-medical) of participants. Stimulant use was rare in both sites. No demographic characteristic was significantly associated with medical or non-medical use of any prescription medication. The current focus of many studies on only non-medical prescription medication use not only underestimates the widespread exposure of HIV-positive individuals to these drugs, but may also underestimate potential adverse effects of prescription medications in this population.

Lubricant Use and Rectal Chlamydial and Gonococcal Infections Among Men Who Engage in Receptive Anal Intercourse.

BACKGROUND: Use of lubricants during anal intercourse is very common among men who have sex with men. However, few studies have evaluated associations between specific lubricants and rectal sexually transmitted infections (STIs). METHODS: Between July 2012 and October 2013, we conducted a cross-sectional study of men who have sex with men recruited from an urban, public sexual health clinic. In a self-administered survey, participants identified the lubricants used and frequency of lubricant use in the previous three months. Among men reporting any receptive anal intercourse (RAI) in the previous 3 months, we used multivariable binomial regression models to analyze associations between recent use of 9 specific lubricants and prevalent rectal chlamydia, rectal gonorrhea, and either rectal infection. RESULTS: Twenty-five percent of the 146 participants had rectal chlamydial infection and 21% had rectal gonococcal infection; 37% had either (chlamydial or gonococcal) infection. Three-quarters reported always or almost always using lubricant during recent receptive anal intercourse. After adjustment for age, race, human immunodeficiency virus status, and condom use, Gun Oil (adjusted prevalence ratio [aPR], 1.99; 95% confidence interval [CI], 1.04-3.80) and Slick (aPR, 3.55; 95% CI, 1.38-9.12) were significantly associated with prevalent gonococcal infection. No lubricants were significantly associated with prevalent rectal chlamydia, but in analyses of either rectal infection, precum (aPR, 1.68; 95% CI, 1.06-2.66), Vaseline (aPR, 1.70; 95% CI, 1.10-2.64), and baby oil (aPR, 2.26; 95% CI, 1.43-3.57) were all significantly associated with prevalent rectal infection. CONCLUSIONS: Several lubricants were significantly associated with increased prevalence of rectal STI. Longitudinal studies are needed to examine any causal relationship between specific lubricants and STI acquisition.

Beyond Anal Sex: Sexual Practices of Men Who have Sex with Men and Associations with HIV and Other Sexually Transmitted Infections.

INTRODUCTION: Unprotected anal intercourse is often used as a single indicator of risky behavior in men who have sex with men (MSM), yet MSM engage in a variety of behaviors that have unknown associations with sexually transmitted infection (STI) and HIV. AIM: To assess the prevalence of a wide range of sexual behaviors and their associations with prevalent STI and HIV. METHODS: We used a standardized, self-administered survey to collect behavioral data for this cross-sectional study of 235 MSM seeking care in a public clinic for sexually transmitted diseases. MEAN OUTCOME MEASURES: Using modified Poisson regression, we generated unadjusted and adjusted prevalence ratios (PRs) to characterize associations between recent participation in each behavior and prevalent STI and HIV. RESULTS: Participants' median age was 26 years. One third (35%) were positive for STI. STI prevalence was significantly associated with using sex slings (adjusted PR [aPR] = 2.35), felching (aPR = 2.22), group sex (aPR = 1.86), fisting (aPR = 1.78), anonymous sex (aPR = 1.51), and sex toys (aPR = 1.46). HIV prevalence was 17% and was significantly associated with fisting (aPR = 4.75), felching (aPR = 4.22), enemas (aPR = 3.65), and group sex (aPR = 1.92). CONCLUSION: Multiple behaviors were significantly associated with prevalent STI and HIV in adjusted analyses. To provide a more comprehensive understanding of sexual risk in MSM, prospective studies are needed to examine whether these behaviors are causally associated with HIV and STI acquisition.

Altered Monocyte and Endothelial Cell Adhesion Molecule Expression Is Linked to Vascular Inflammation in Human Immunodeficiency Virus Infection.

BACKGROUND: Human immunodeficiency virus (HIV)-infected individuals have increased risk for vascular thrombosis, potentially driven by interactions between activated leukocytes and the endothelium. METHODS: Monocyte subsets (CD14+CD16-, CD14+CD16+, CD14DimCD16+) from HIV negative (HIV-) and antiretroviral therapy-treated HIV positive (HIV+) participants (N = 19 and 49) were analyzed by flow cytometry for adhesion molecule expression (lymphocyte function-associated antigen 1 [LFA-1], macrophage-1 antigen [Mac-1], CD11c/CD18, very late antigen [VLA]-4) and the fractalkine receptor (CX3CR1); these receptors recognize ligands (intercellular adhesion molecules [ICAMs], vascular cell adhesion molecule [VCAM]-1, fractalkine) on activated endothelial cells (ECs) and promote vascular migration. Plasma markers of monocyte (soluble [s]CD14, sCD163) and EC (VCAM-1, ICAM-1,2, fractalkine) activation and systemic (tumor necrosis factor receptor [TNFR-I], TNFR-II) and vascular (lipoprotein-associated phospholipase A2 [Lp-PLA2]) inflammation were measured by enzyme-linked immunosorbent assay. RESULTS: Proportions of CD16+ monocyte subsets were increased in HIV+ participants. Among all monocyte subsets, levels of LFA-1 were increased and CX3CR1 levels were decreased in HIV+ participants (P < .01). Levels of sCD163, sCD14, fractalkine, ICAM-1, VCAM-1, TNFR-II, and Lp-PLA2 were also increased in HIV+ participants (P < .05), and levels of sCD14, TNFR-I, and TNFR-II were directly related to ICAM-1 and VCAM-1 levels in HIV+ participants. Expression of CX3CR1 on monocyte subsets was inversely related to plasma Lp-PLA2 (P < .05 for all). CONCLUSIONS: Increased proportions of CD16+ monocytes, cells with altered adhesion molecule expression, combined with elevated levels of their ligands, may promote vascular inflammation in HIV infection.