Emulating a trial of joint dynamic strategies: An application to monitoring and treatment of HIV-positive individuals.

Decisions about when to start or switch a therapy often depend on the frequency with which individuals are monitored or tested. For example, the optimal time to switch antiretroviral therapy depends on the frequency with which HIV-positive individuals have HIV RNA measured. This paper describes an approach to use observational data for the comparison of joint monitoring and treatment strategies and applies the method to a clinically relevant question in HIV research: when can monitoring frequency be decreased and when should individuals switch from a first-line treatment regimen to a new regimen? We outline the target trial that would compare the dynamic strategies of interest and then describe how to emulate it using data from HIV-positive individuals included in the HIV-CAUSAL Collaboration and the Centers for AIDS Research Network of Integrated Clinical Systems. When, as in our example, few individuals follow the dynamic strategies of interest over long periods of follow-up, we describe how to leverage an additional assumption: no direct effect of monitoring on the outcome of interest. We compare our results with and without the "no direct effect" assumption. We found little differences on survival and AIDS-free survival between strategies where monitoring frequency was decreased at a CD4 threshold of 350 cells/µl compared with 500 cells/µl and where treatment was switched at an HIV-RNA threshold of 1000 copies/ml compared with 200 copies/ml. The "no direct effect" assumption resulted in efficiency improvements for the risk difference estimates ranging from an 7- to 53-fold increase in the effective sample size.

Interaction Patterns of Men Who Have Sex With Men on a Geosocial Networking Mobile App in Seven United States Metropolitan Areas: Observational Study.

BACKGROUND: The structure of the sexual networks and partnership characteristics of young black men who have sex with men (MSM) may be contributing to their high risk of contracting HIV in the United States. Assortative mixing, which refers to the tendency of individuals to have partners from one's own group, has been proposed as a potential explanation for disparities. OBJECTIVE: The objective of this study was to identify the age- and race-related search patterns of users of a diverse geosocial networking mobile app in seven metropolitan areas in the United States to understand the disparities in sexually transmitted infection and HIV risk in MSM communities. METHODS: Data were collected on user behavior between November 2015 and May 2016. Data pertaining to behavior on the app were collected for men who had searched for partners with at least one search parameter narrowed from defaults or used the app to send at least one private chat message and used the app at least once during the study period. Newman assortativity coefficient (R) was calculated from the study data to understand assortativity patterns of men by race. Pearson correlation coefficient was used to assess assortativity patterns by age. Heat maps were used to visualize the relationship between searcher's and candidate's characteristics by age band, race, or age band and race. RESULTS: From November 2015 through May 2016, there were 2,989,737 searches in all seven metropolitan areas among 122,417 searchers. Assortativity by age was important for looking at the profiles of candidates with correlation coefficients ranging from 0.284 (Birmingham) to 0.523 (San Francisco). Men tended to look at the profiles of candidates that matched their race in a highly assortative manner with R ranging from 0.310 (Birmingham) to 0.566 (Los Angeles). For the initiation of chats, race appeared to be slightly assortative for some groups with R ranging from 0.023 (Birmingham) to 0.305 (Los Angeles). Asian searchers were most assortative in initiating chats with Asian candidates in Boston, Los Angeles, New York, and San Francisco. In Birmingham and Tampa, searchers from all races tended to initiate chats with black candidates. CONCLUSIONS: Our results indicate that the age preferences of MSM are relatively consistent across cities, that is, younger MSM are more likely to be chatted with and have their profiles viewed compared with older MSM, but the patterns of racial mixing are more variable. Although some generalizations can be made regarding Web-based behaviors across all cities, city-specific usage patterns and trends should be analyzed to create targeted and localized interventions that may make the most difference in the lives of MSM in these areas.

Possible mitochondrial dysfunction and its association with antiretroviral therapy use in children perinatally infected with HIV.

BACKGROUND: Mitochondrial dysfunction has been associated with both human immunodeficiency virus (HIV) infection and exposure to antiretroviral therapy. Mitochondrial dysfunction has not been widely studied in HIV-infected children. We estimated the incidence of clinically defined mitochondrial dysfunction among children with perinatal HIV infection. METHODS: Children with perinatal HIV infection enrolled in a prospective cohort study (Pediatric AIDS Clinical Trials Group protocols 219 and 219C) from 1993 through 2004 were included. Two clinical case definitions of mitochondrial dysfunction, the Enquête Périnatale Française criteria and the Mitochondrial Disease Classification criteria, were used to classify signs and symptoms that were consistent with possible mitochondrial dysfunction. Adjusted odds ratios of the associations between single and dual nucleoside reverse-transcriptase inhibitor use and possible mitochondrial dysfunction were estimated using logistic regression. RESULTS: Overall, 982 (33.5%) of 2931 children met 1 or both case definitions of possible mitochondrial dysfunction. Mortality was highest among the 96 children who met both case definitions (20%). After adjusting for confounders, there was a higher risk of possible mitochondrial dysfunction among children who received stavudine regardless of exposure to other medications (odds ratio, 3.44 [95% confidence interval, 1.91-6.20]) or who received stavudine-didanosine combination therapy (odds ratio, 2.23 [95% confidence interval, 1.19-4.21]). Exposure to lamivudine and to lamivudine-stavudine were also associated with an increased risk of mitochondrial dysfunction. CONCLUSIONS: Receipt of nucleoside reverse-transcriptase inhibitors, especially stavudine and lamivudine, was associated with possible mitochondrial dysfunction in children with perinatal HIV infection. Further studies are warranted to elucidate potential mechanisms of nucleoside reverse-transcriptase inhibitor toxicities.

Using Social Media and Technology to Communicate in Pediatric HIV Research: Qualitative Study With Young Adults Living With or Exposed to Perinatal HIV.

BACKGROUND: As young adults living with perinatal HIV (PHIV) or perinatal HIV exposure but uninfected (PHEU) grow older and manage the challenges and competing demands of young adulthood, new approaches are needed to facilitate their retention in longitudinal research and clinical care beyond in-person clinic visits. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the novel virus that causes coronavirus disease (COVID-19), emerged in the United States in January 2020 and has underscored this need; studies are adapting to remote communication with and data collection from participants. However, there are limited data on communication preferences among young adults who are living with PHIV or PHEU. OBJECTIVE: The objectives of this qualitative study were to describe participants' perceptions and use of social media and technology in their personal lives and in the context of participating in longitudinal pediatric HIV research and to describe the implications of the use of technology and social media for communication and retention purposes within a longitudinal pediatric study about HIV. METHODS: We conducted 6 focus group discussions with 31 young adults living with PHIV and 13 in-depth interviews with 6 young adults living with PHIV and 7 living with PHEU. We asked about their preferences for the use of social media and digital technology in the Adolescent Master Protocol, a US-based longitudinal cohort study of youth affected by HIV. RESULTS: Participants' willingness to use social media platforms, telephone calls, SMS text messages, and video calls within the context of HIV research varied due to fears of HIV stigma and inadvertent disclosure. However, trusting relationships with clinical staff positively impacted their willingness to use these platforms. CONCLUSIONS: Our findings offer insight into how pediatric studies and clinics can communicate with participants as they age, even as new technologies and social media platforms emerge and replace old ones. For optimal retention, pediatric clinical staff should consider communication approaches offering flexible and tailored options for young adults participating in HIV research.

Meta-analysis: increased mortality associated with hepatitis C in HIV-infected persons is unrelated to HIV disease progression.

BACKGROUND: It is unclear whether coinfection with hepatitis C virus (HCV) increases mortality in patients with human immunodeficiency virus (HIV) infection during the era of highly active antiretroviral therapy (HAART). With use of a meta-analysis, we estimated the effect of HCV infection on HIV disease progression and overall mortality in the pre-HAART and HAART eras. METHOD: The PubMed and EMBASE databases were searched for studies published through 30 April 2008. Additional studies were identified from cited references. Studies reporting disease progression or mortality among HCV-HIV coinfected patients were selected. Cross-sectional studies, studies without HCV-negative control subjects, and studies involving children and/or patients who had undergone liver transplantation were excluded. Two authors reviewed articles and extracted data on the demographic characteristics of study populations and risk estimates. Meta-regression was used to explore heterogeneity. RESULTS: Ten studies from the pre-HAART era and 27 studies from the HAART era were selected. In the pre-HAART era, the risk ratio for overall mortality among patients with HCV-HIV coinfection, compared with that among patients with HIV infection alone, was 0.68 (95% confidence interval [CI], 0.53-0.87). In the HAART era, the risk ratio was 1.12 (95% CI, 0.82-1.51) for AIDS-defining events and 1.35 (95% CI, 1.11-1.63) for overall mortality among coinfected patients, compared with that among patients with HIV monoinfection. CONCLUSIONS: HCV coinfection did not increase mortality among patients with HIV infection before the introduction of HAART. In contrast, in the HAART era, HCV coinfection, compared with HIV infection alone, increases the risk of mortality, but not the risk of AIDS-defining events. Future studies should determine whether successful treatment of HCV infection could reduce this excess risk of mortality in coinfected patients.

Blood lead levels and neurodevelopmental function in perinatally HIV-exposed, uninfected children in a US-based longitudinal cohort study.

BACKGROUND: While children's exposure to environmental lead in the U.S. has decreased, areas of elevated levels remain. Because lead exposure is a risk factor for developmental delays, it should be considered when studying neurodevelopmental effects of in-utero antiretroviral medication (ARV) exposure in the growing population of perinatally HIV-exposed, uninfected children (PHEU). We compared blood lead levels (BPb) in PHEU children enrolled in the Surveillance Monitoring of ART Toxicities (SMARTT) Study to U.S. children, assessed associations with neurodevelopment, and explored whether associations between in-utero ARV and neurodevelopment are modified by BPb. METHODS: Prevalence of elevated BPb (≥5 µg/dL) at ages 1-2 years was calculated by year and race/ethnicity and compared to that for children in the National Health and Nutrition Examination Survey (NHANES 2002-2010). Associations between elevated BPb and neurodevelopment at 1 and 3 years were assessed. Associations between ARVs (tenofovir disopropil fumarate [TDF]; atazanavir) and neurodevelopment were evaluated within BPb level (≥5 vs. <5 µg/dL). RESULTS: Mean BPb in SMARTT decreased from 5.9 to 2.7 µg/dL between 1998-2014; prevalence of elevated BPb decreased from 50% to 4%. Both were consistently higher than in NHANES. Elevated BPb was associated with cognitive delay at age 3 (adjusted odds ratio: 1.64; 95% CI: 0.95, 2.90). At age 1, TDF was associated with delay only among those with elevated BPb. CONCLUSIONS: PHEU children more often had elevated BPb than the general U.S. pediatric population. Exposure to environmental lead is one of several factors that may place these children at higher risk for neurodevelopmental delay.

Video as an effective method to deliver pretest information for rapid human immunodeficiency testing.

OBJECTIVES: Video-based delivery of human immunodeficiency virus (HIV) pretest information might assist in streamlining HIV screening and testing efforts in the emergency department (ED). The objectives of this study were to determine if the video "Do you know about rapid HIV testing?" is an acceptable alternative to an in-person information session on rapid HIV pretest information, in regard to comprehension of rapid HIV pretest fundamentals, and to identify patients who might have difficulties in comprehending pretest information. METHODS: This was a noninferiority trial of 574 participants in an ED opt-in rapid HIV screening program who were randomly assigned to receive identical pretest information from either an animated and live-action 9.5-minute video or an in-person information session. Pretest information comprehension was assessed using a questionnaire. The video would be accepted as not inferior to the in-person information session if the 95% confidence interval (CI) of the difference (Delta) in mean scores on the questionnaire between the two information groups was less than a 10% decrease in the in-person information session arm's mean score. Linear regression models were constructed to identify patients with lower mean scores based upon study arm assignment, demographic characteristics, and history of prior HIV testing. RESULTS: The questionnaire mean scores were 20.1 (95% CI = 19.7 to 20.5) for the video arm and 20.8 (95% CI = 20.4 to 21.2) for the in-person information session arm. The difference in mean scores compared to the mean score for the in-person information session met the noninferiority criterion for this investigation (Delta = 0.68; 95% CI = 0.18 to 1.26). In a multivariable linear regression model, Blacks/African Americans, Hispanics, and those with Medicare and Medicaid insurance exhibited slightly lower mean scores, regardless of the pretest information delivery format. There was a strong relationship between fewer years of formal education and lower mean scores on the questionnaire. Age, gender, type of insurance, partner/marital status, and history of prior HIV testing were not predictive of scores on the questionnaire. CONCLUSIONS: In terms of patient comprehension of rapid HIV pretest information fundamentals, the video was an acceptable substitute to pretest information delivered by an HIV test counselor. Both the video and the in-person information session were less effective in providing pretest information for patients with fewer years of formal education.