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.
CONCLUSIONS: Between 12% and 20% of PHIVA were determined LTFU with treatment fatigue and rural treatment settings consistent risk factors. Better tracking of adolescents is required to provide a definitive understanding of LTFU and optimize evidence-based models of care.
METHODS: Regional Asian data (2001-2016) were analyzed to describe PHIVA who experienced ≥2 weeks of lamivudine or emtricitabine monotherapy or treatment interruption and trends in CD4 count and HIV viral load during and after episodes. Survival analyses were used for World Health Organization (WHO) stage III/IV clinical and immunologic event-free survival during monotherapy or treatment interruption, and a Poisson regression to determine factors associated with monotherapy or treatment interruption.
RESULTS: Of 3,448 PHIVA, 84 (2.4%) experienced 94 monotherapy episodes, and 147 (4.3%) experienced 174 treatment interruptions. Monotherapy was associated with older age, HIV RNA >400 copies/mL, younger age at ART initiation, and exposure to ≥2 combination ART regimens. Treatment interruption was associated with CD4 count <350 cells/μL, HIV RNA ≥1,000 copies/mL, ART adverse event, and commencing ART age ≥10 years compared with age <3 years. WHO clinical stage III/IV 1-year event-free survival was 96% and 85% for monotherapy and treatment interruption cohorts, respectively. WHO immunologic stage III/IV 1-year event-free survival was 52% for both cohorts. Those who experienced monotherapy or treatment interruption for more than 6 months had worse immunologic and virologic outcomes.
CONCLUSIONS: Until challenges of treatment adherence, engagement in care, and combination ART durability/tolerability are met, monotherapy and treatment interruption will lead to poor long-term outcomes.
METHODS: Based on existing frameworks for the EMTCT for each individual infection, an integrated framework that combines infection prevention procedures with routine antenatal care was constructed. Using decision tree analyses, population impacts, cost-effectiveness and the potential reduction in required resources of the integrated approach as a result of resource pooling and improvements in service coverage and coordination, were evaluated. The tool was assessed using simulated epidemiological data from Cambodia.
RESULTS: The current prevention programme for 370,000 Cambodian pregnant women was estimated at USD$2.3 ($2.0-$2.5) million per year, including the duration of pregnancy and up to 18 months after delivery. A model estimate of current MTCT rates in Cambodia was 6.6% (6.2-7.1%) for HIV, 14.1% (13.1-15.2%) for HBV and 9.4% (9.0-9.8%) for syphilis. Integrating HIV and syphilis prevention into the existing antenatal care framework will reduce the total time required to provide this integrated care by 19% for health care workers and by 32% for pregnant women, resulting in a net saving of $380,000 per year for the EMTCT programme. This integrated approach reduces HIV and HBV MTCT to 6.1% (5.7-6.5%) and 13.0% (12.1-14.0%), respectively, and substantially reduces syphilis MCTC to 4.6% (4.3-5.0%). Further introduction of either antiviral treatment for pregnant women with high viral load of HBV, or hepatitis B immunoglobulin (HBIG) to exposed newborns, will increase the total cost of EMTCT to $4.4 ($3.6-$5.2) million and $3.3 ($2.7-$4.0) million per year, respectively, but substantially reduce HBV MTCT to 3.5% (3.2-3.8%) and 5.0% (4.6-5.5%), respectively. Combining both antiviral and HBIG treatments will further reduce HBV MTCT to 3.4% (3.1-3.7%) at an increased total cost of EMTCT of $4.5 ($3.7-$5.4) million per year. All these HBV intervention scenarios are highly cost-effective ($64-$114 per disability-adjusted life years averted) when the life benefits of these prevention measures are considered.
CONCLUSIONS: The integrated approach, using antenatal, perinatal and postnatal care as a platform in Cambodia for triple EMTCT of HIV, HBV and syphilis, is highly cost-effective and efficient.
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).
CONCLUSION: Our findings highlight the need for integrated treatment for substance disorders in HIV care to increase the viral suppression rate among TGW in Lima, Peru.
METHODS: Data collected 2001 to 2016 from PHIVA 10-19 years of age within a regional Asian cohort were analyzed using competing risk time-to-event and Poisson regression analyses to describe the nature and incidence of morbidity events and hospitalizations and identify factors associated with disease-related, treatment-related and overall morbidity. Morbidity was defined according to World Health Organization clinical staging criteria and U.S. National Institutes of Health Division of AIDS criteria.
RESULTS: A total 3,448 PHIVA contributed 17,778 person-years. Median age at HIV diagnosis was 5.5 years, and ART initiation was 6.9 years. There were 2,562 morbidity events and 307 hospitalizations. Cumulative incidence for any morbidity was 51.7%, and hospitalization was 10.0%. Early adolescence was dominated by disease-related infectious morbidity, with a trend toward noninfectious and treatment-related morbidity in later adolescence. Higher overall morbidity rates were associated with a CD4 count <350 cells/µL, HIV viral load ≥10,000 copies/mL and experiencing prior morbidity at age <10 years. Lower overall morbidity rates were found for those 15-19 years of age compared with 10-14 years and those who initiated ART at age 5-9 years compared with <5 or ≥10 years.
CONCLUSIONS: Half of our PHIVA cohort experienced a morbidity event, with a trend from disease-related infectious events to treatment-related and noninfectious events as PHIVA age. ART initiation to prevent immune system damage, optimize virologic control and minimize childhood morbidity are key to limiting adolescent morbidity.
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.
CONCLUSIONS: Around 1 in 5 experienced virologic failure in our cohort after achieving virologic suppression. Targeted interventions to manage complex treatment scenarios, including adolescents, tuberculosis coinfection, and those with poor virologic control are required.
METHODS: Adults living with HIV enrolled in a regional observational cohort in Asia who had initiated combination antiretroviral therapy (cART) were included in the analysis. Factors associated with new TB diagnoses after cohort entry and survival after cART initiation were analysed using Cox regression, stratified by site.
RESULTS: A total of 7355 patients from 12 countries enrolled into the cohort between 2003 and 2016 were included in the study. There were 368 reported cases of TB after cohort entry with an incidence rate of 0.99 per 100 person-years (/100 pys). Multivariate analyses adjusted for viral load (VL), CD4 count, body mass index (BMI) and cART duration showed that CTX reduced the hazard for new TB infection by 28% (HR 0.72, 95% CI l 0.56, 0.93). Mortality after cART initiation was 0.85/100 pys, with a median follow-up time of 4.63 years. Predictors of survival included age, female sex, hepatitis C co-infection, TB diagnosis, HIV VL, CD4 count and BMI.
CONCLUSIONS: CTX was associated with a reduction in the hazard for new TB infection but did not impact survival in our Asian cohort. The potential preventive effect of CTX against TB during periods of severe immunosuppression should be further explored.
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.
CONCLUSIONS: Geraniin was found to be effective in reducing DENV-2 RNA load when administered at 72 h post-infection while earlier administration could prevent severe liver damage caused by DENV-2 infection. These results provide evidence that geraniin is a potential candidate for the development of anti-dengue drug.
Methods: An observational study was conducted among 3935 patients presenting with acute upper respiratory illnesses in the ambulatory settings between 2012 and 2014.
Results: The VP4/VP2 gene was genotyped from all 976 RV-positive specimens, where the predominance of RV-A (49%) was observed, followed by RV-C (38%) and RV-B (13%). A significant regression in median nasopharyngeal viral load (VL) (P < .001) was observed, from 883 viral copies/µL at 1-2 days after symptom onset to 312 viral copies/µL at 3-4 days and 158 viral copies/µL at 5-7 days, before declining to 35 viral copies/µL at ≥8 days. In comparison with RV-A (median VL, 217 copies/µL) and RV-B (median VL, 275 copies/µL), RV-C-infected subjects produced higher VL (505 copies/µL; P < .001). Importantly, higher RV VL (median, 348 copies/µL) was associated with more severe respiratory symptoms (Total Symptom Severity Score ≥17, P = .017). A total of 83 phylogenetic-based transmission clusters were identified in the population. It was observed that the relative humidity was the strongest environmental predictor of RV seasonality in the tropical climate.
Conclusions: Our findings underline the role of VL in increasing disease severity attributed to RV-C infection, and unravel the factors that fuel the population transmission dynamics of RV.
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.
CONCLUSIONS: The application of up-to-date scientific evidence in criminal cases has the potential to limit unjust prosecutions and convictions. The authors recommend that caution be exercised when considering prosecution, and encourage governments and those working in legal and judicial systems to pay close attention to the significant advances in HIV science that have occurred over the last three decades to ensure current scientific knowledge informs application of the law in cases related to HIV.
METHODS: To create a retrospective cohort of all adults with HIV released from jails and prisons in Connecticut, USA (2007-14), we linked administrative custody and pharmacy databases with mandatory HIV/AIDS surveillance monitoring and case management data. We examined time to LTC (defined as first viral load measurement after release) and viral suppression at LTC. We used generalised estimating equations to show predictors of LTC within 14 days and 30 days of release.
FINDINGS: Among 3302 incarceration periods for 1350 individuals between 2007 and 2014, 672 (21%) of 3181 periods had LTC within 14 days of release, 1042 (34%) of 3064 had LTC within 30 days of release, and 301 (29%) of 1042 had detectable viral loads at LTC. Factors positively associated with LTC within 14 days of release are intermediate (31-364 days) incarceration duration (adjusted odds ratio 1·52; 95% CI 1·19-1·95), and transitional case management (1·65; 1·36-1·99), receipt of antiretroviral therapy during incarceration (1·39; 1·11-1·74), and two or more medical comorbidities (1·86; 1·48-2·36). Reincarceration (0·70; 0·56-0·88) and conditional release (0·62; 0·50-0·78) were negatively associated with LTC within 14 days. Hispanic ethnicity, bonded release, and psychiatric comorbidity were also associated with LTC within 30 days but reincarceration was not.
INTERPRETATION: LTC after release is suboptimal but improves when inmates' medical, psychiatric, and case management needs are identified and addressed before release. People who are rapidly cycling through jail facilities are particularly vulnerable to missed linkage opportunities. The use of integrated programmes to align justice and health-care goals has great potential to improve long-term HIV treatment outcomes.
FUNDING: US National Institutes of Health.