CASE PRESENTATION: A 52-year-old Malay gentleman, with hepatitis C virus and HIV infection was admitted to the intensive care unit for severe lactic acidosis, with concurrent Escherichia coli bacteremia with multiorgan dysfunction. The patient was started on highly active antiretroviral therapy, which included tenofovir, 5 weeks before presentation. Antimicrobial therapy, continuous veno-venous hemofiltration, and other supportive treatments were instituted. However, the patient eventually succumbed to his illness.

METHODS: Between June 2015 and August 2016, 50 HIV-positive TGW were recruited in Lima, Peru. Multivariable logistic regression was used to identify factors associated with viral suppression (<200 copies/mL) among the TGW.

RESULTS: Among TGW, 85% achieved viral suppression. Approximately half (54%) reported anal sex with more than five partners in the past 6 months, 38% reported sex work, 68% had not disclosed their HIV status to one or more of their partners, and 38% reported condomless sex with their last partner. The prevalence of alcohol use disorders was high (54%), and 38% reported use of drugs in the past year. Moderate-to-severe drug use significantly reduced odds of achieving viral suppression (adjusted odds ratio 0.69; 95% confidence interval: 0.48-0.98).

METHODS: We did a cohort analysis of TB cases in SECOND-LINE. TB cases included any clinical or laboratory-confirmed diagnoses and/or commencement of treatment for TB after randomization. Baseline factors associated with TB were analyzed using Cox regression stratified by site.

RESULTS: TB cases occurred at sites in Argentina, India, Malaysia, Nigeria, South Africa, and Thailand, in a cohort of 355 of the 541 SECOND-LINE participants. Overall, 20 cases of TB occurred, an incidence rate of 3.4 per 100 person-years (95% CI: 2.1 to 5.1). Increased TB risk was associated with a low CD4+-cell count (≤200 cells/μL), high viral load (>200 copies/mL), low platelet count (<150 ×109/L), and low total serum cholesterol (≤4.5 mmol/L) at baseline. An increased risk of death was associated with TB, adjusted for CD4, platelets, and cholesterol. A low CD4+-cell count was significantly associated with incident TB, mortality, other AIDS diagnoses, and virologic failure.

DESIGN: A randomized, double-blind, placebo-controlled trial was conducted among incarcerated individuals with HIV and AUDs transitioning to the community from 2010 through 2016.

METHODS: Eligible participants (N = 100) were randomized 2:1 to receive 6 monthly injections of XR-NTX (n = 67) or placebo (n = 33) starting at release and continued for 6 months. The primary and secondary outcomes were the proportion that maintained or improved VS at <200 and <50 copies per milliliter from baseline to 6 months, respectively, using an intention-to-treat analysis.

RESULTS: Participants allocated to XR-NTX improved VS from baseline to 6 months for <200 copies per milliliter (48.0%-64.2%, P = 0.024) and for <50 copies per milliliter (31.0%-56.7%, P = 0.001), whereas the placebo group did not (<200 copies/mL: 64%-42.4%, P = 0.070; <50 copies/mL: 42.0%-30.3%, P = 0.292). XR-NTX participants were more likely to achieve VS than the placebo group at 6 months (<200 copies/mL: 64.2% vs. 42.4%; P = 0.041; <50 copies/mL: 56.7% vs. 30.3%; P = 0.015). XR-NTX independently predicted VS [<200 copies/mL: adjusted odds ratio (aOR) = 2.68, 95% confidence interval (CI) = 1.01 to 7.09, P = 0.047; <50 copies/mL: aOR = 4.54; 95% CI = 1.43 to 14.43, P = 0.009] as did receipt of ≥3 injections (<200 copies/mL: aOR = 3.26; 95% CI = 1.26 to 8.47, P = 0.010; <50 copies/mL: aOR = 6.34; 95% CI = 2.08 to 19.29, P = 0.001). Reductions in alcohol consumption (aOR = 1.43, 95% CI = 1.03 to 1.98, P = 0.033) and white race (aOR = 5.37, 95% CI = 1.08 to 27.72, P = 0.040) also predicted VS at <50 copies per milliliter.

DESIGN: A 4-site, prospective randomized double-blind, placebo-controlled trial was conducted among prison and jail inmates with HIV and OUD transitioning to the community from September 2010 through March 2016.

METHODS: Eligible participants (N = 93) were randomized 2:1 to receive 6 monthly injections of XR-NTX (n = 66) or placebo (n = 27) starting at release and observed for 6 months. The primary outcome was the proportion that maintained or improved VS (<50 copies/mL) from baseline to 6 months.

RESULTS: Participants allocated to XR-NTX significantly improved to VS (<50 copies/mL) from baseline (37.9%) to 6 months (60.6%) (P = 0.002), whereas the placebo group did not (55.6% at baseline to 40.7% at 6 months P = 0.294). There was, however, no statistical significant difference in VS levels at 6 months between XR-NTX (60.6%) vs. placebo (40.7%) (P = 0.087). After controlling for other factors, only allocation to XR-NTX (adjusted odds ratio = 2.90; 95% confidence interval = 1.04 to 8.14, P = 0.043) was associated with the primary outcome. Trajectories in VS from baseline to 6 months differed significantly (P = 0.017) between treatment groups, and the differences in the discordant values were significantly different as well (P = 0.041): the XR-NTX group was more likely than the placebo group to improve VS (30.3% vs. 18.5%), maintain VS (30.3% vs. 27.3), and less likely to lose VS (7.6% vs. 33.3%) by 6 months.

DISCUSSION: Twenty scientists from regions across the world developed this Expert Consensus Statement to address the use of HIV science by the criminal justice system. A detailed analysis of the best available scientific and medical research data on HIV transmission, treatment effectiveness and forensic phylogenetic evidence was performed and described so it may be better understood in criminal law contexts. Description of the possibility of HIV transmission was limited to acts most often at issue in criminal cases. The possibility of HIV transmission during a single, specific act was positioned along a continuum of risk, noting that the possibility of HIV transmission varies according to a range of intersecting factors including viral load, condom use, and other risk reduction practices. Current evidence suggests the possibility of HIV transmission during a single episode of sex, biting or spitting ranges from no possibility to low possibility. Further research considered the positive health impact of modern antiretroviral therapies that have improved the life expectancy of most people living with HIV to a point similar to their HIV-negative counterparts, transforming HIV infection into a chronic, manageable health condition. Lastly, consideration of the use of scientific evidence in court found that phylogenetic analysis alone cannot prove beyond reasonable doubt that one person infected another although it can be used to exonerate a defendant.

METHODS: HIV-positive patients enrolled in the TREAT Asia HIV Observational Database who had used second-line ART for ≥6 months were included. ART use and rates and predictors of second-line treatment failure were evaluated.

RESULTS: There were 302 eligible patients. Most were male (76.5%) and exposed to HIV via heterosexual contact (71.5%). Median age at second-line initiation was 39.2 years, median CD4 cell count was 146 cells per cubic millimeter, and median HIV viral load was 16,224 copies per milliliter. Patients started second-line ART before 2007 (n = 105), 2007-2010 (n = 147) and after 2010 (n = 50). Ritonavir-boosted lopinavir and atazanavir accounted for the majority of protease inhibitor use after 2006. Median follow-up time on second-line therapy was 2.3 years. The rates of treatment failure and mortality per 100 patient/years were 8.8 (95% confidence interval: 7.1 to 10.9) and 1.1 (95% confidence interval: 0.6 to 1.9), respectively. Older age, high baseline viral load, and use of a protease inhibitor other than lopinavir or atazanavir were associated with a significantly shorter time to second-line failure.

METHODS: The effect of geraniin on DENV-2 RNA synthesis in infected Vero cells was tested using quantitative RT-PCR. The in vivo efficacy of geraniin in inhibiting DENV-2 infection was then tested using BALB/c mice with geraniin administered at three different times. The differences in spleen to body weight ratio, DENV-2 RNA load and liver damage between the three treatment groups as compared to DENV-2 infected mice without geraniin administration were determined on day eight post-infection.

RESULTS: Quantitative RT-PCR confirmed the decrease in viral RNA synthesis of infected Vero cells when treated with geraniin. Geraniin seemed to provide a protective effect on infected BALB/c mice liver when given at 24 h pre- and 24 h post-infection as liver damage was observed to be very mild even though a significant reduction of DENV-2 RNA load in serum was not observed in these two treatment groups. However, when administered at 72 h post-infection, severe liver damage in the form of necrosis and haemorrhage had prevailed despite a substantial reduction of DENV-2 RNA load in serum.

SETTING: An Asian cohort in 16 pediatric HIV services across 6 countries.

METHODS: From 2005 to 2014, patients younger than 20 years who achieved virologic suppression and had subsequent viral load testing were included. Early virologic failure was defined as a HIV RNA ≥1000 copies per milliliter within 12 months of virologic suppression, and late virologic as a HIV RNA ≥1000 copies per milliliter after 12 months following virologic suppression. Characteristics at combination antiretroviral therapy initiation and virologic suppression were described, and a competing risk time-to-event analysis was used to determine cumulative incidence of virologic failure and factors at virologic suppression associated with early and late virologic failure.

RESULTS: Of 1105 included in the analysis, 182 (17.9%) experienced virologic failure. The median age at virologic suppression was 6.9 years, and the median time to virologic failure was 24.6 months after virologic suppression. The incidence rate for a first virologic failure event was 3.3 per 100 person-years. Factors at virologic suppression associated with late virologic failure included older age, mostly rural clinic setting, tuberculosis, protease inhibitor-based regimens, and early virologic failure. No risk factors were identified for early virologic failure.

SETTING: Asian regional cohort incorporating 16 pediatric HIV services across 6 countries.

METHODS: Data from PHIVA (aged 10-19 years) who received combination antiretroviral therapy 2007-2016 were used to analyze LTFU through (1) an International epidemiology Databases to Evaluate AIDS (IeDEA) method that determined LTFU as >90 days late for an estimated next scheduled appointment without returning to care and (2) the absence of patient-level data for >365 days before the last data transfer from clinic sites. Descriptive analyses and competing-risk survival and regression analyses were used to evaluate LTFU epidemiology and associated factors when analyzed using each method.

RESULTS: Of 3509 included PHIVA, 275 (7.8%) met IeDEA and 149 (4.3%) met 365-day absence LTFU criteria. Cumulative incidence of LTFU was 19.9% and 11.8% using IeDEA and 365-day absence criteria, respectively. Risk factors for LTFU across both criteria included the following: age at combination antiretroviral therapy initiation <5 years compared with age ≥5 years, rural clinic settings compared with urban clinic settings, and high viral loads compared with undetectable viral loads. Age 10-14 years compared with age 15-19 years was another risk factor identified using 365-day absence criteria but not IeDEA LTFU criteria.