Man Po Lee

Introduction: Incident syphilis leads to changes in plasma HIV-1 RNA and CD4 + T-cell level in people with HIV (PWH) with viraemia. Its effect in PWH on suppressive antiretroviral therapy (ART) is less clear. Methods: PWH on suppressive ART (plasma HIV-1 RNA < 50copies/mL) followed at the Queen Elizabeth Hospital, Hong Kong, China were regularly screened for syphilis. Their plasma HIV-1 RNA, CD4 + and CD8 + T-cell, and total lymphocyte levels before syphilis, during syphilis, and after successful treatment were compared. Results: Between 2005 and 2020, 288 syphilis episodes from 180 individuals were identified; 287 episodes were related to male, with a median age of 41 at diagnosis; 221 (77%) were syphilis re-infection. The rates of plasma HIV-1 suppression were statistically unchanged across the time-points (97% pre-syphilis, 98% during syphilis, and 99% post-treatment). Total lymphocyte, CD4+ and CD8+ T-cell levels decreased during incident syphilis (p<0.01), and rebounded post-treatment (p<0.01). VDRL titre was associated with declines in CD4+ T-cell (p=0.045), CD8+ T-cell (p=0.004), and total lymphocyte levels (p=0.021). Pre-syphilis CD4/CD8 ratio was associated with increases in CD8+ T-cell (p=0.001) and total lymphocyte levels (p=0.046) during syphilis. Syphilis re-infection was associated with an increase in total lymphocyte level (p=0.037). In the multivariable analysis, only pre-syphilis CD4/CD8 ratio was independently associated with increases in CD8+ T-cell (p=0.014) and total lymphocyte levels (p=0.039) during syphilis. Conclusions: Among virally-suppressed PWH, total lymphocyte, CD4+, and CD8+ T-cell levels declined during incident syphilis but rebounded post-treatment. The status of plasma HIV suppression was unaffected by syphilis.

INTRODUCTION: Data on HIV treatment outcomes in people who inject drugs (PWID) in the Asia‐Pacific are sparse despite the high burden of drug use. We assessed immunological and virological responses, AIDS‐defining events and mortality among PWID receiving antiretroviral therapy (ART).METHODS: We investigated HIV treatment outcomes among people who acquired HIV via injecting drug use in the TREAT Asia HIV Observational Database (TAHOD) between January 2003 and March 2019. Trends in CD4 count and viral suppression (VS, HIV viral load <1000 copies/mL) were assessed. Factors associated with mean CD4 changes were analysed using repeated measures linear regression, and combined AIDS event and mortality were analysed using survival analysis.RESULTS: Of 622 PWID from 12 countries in the Asia‐Pacific, 93% were male and the median age at ART initiation was 31 years (IQR, 28 to 34). The median pre‐ART CD4 count was 71 cells/µL. CD4 counts increased over time, with a mean difference of 401 (95% CI, 372 to 457) cells/µL at year‐10 (n = 78). Higher follow‐up HIV viral load and pre‐ART CD4 counts were associated with smaller increases in CD4 counts. Among 361 PWID with ≥1 viral load after six months on ART, proportions with VS were 82%, 88% and 93% at 2‐, 5‐ and 10‐years following ART initiation. There were 52 new AIDS‐defining events and 50 deaths during 3347 person‐years of follow‐up (PYS) (incidence 3.05/100 PYS, 95% CI, 2.51 to 3.70). Previous AIDS or TB diagnosis, lower current CD4 count and adherence <95% were associated with combined new AIDS‐defining event and death.CONCLUSIONS: Despite improved outcomes over time, our findings highlight the need for rapid ART initiation and adherence support among PWID within Asian settings.

HIV-associated neurocognitive disorder (HAND) remains prevalent in the era of combination antiretroviral therapy (cART). The prevalence of HAND in Hong Kong is not known. Between 2013 and 2015, 98 treatment-naïve HIV-1-infected individuals were referred to and screened by the AIDS Clinical Service, Queen Elizabeth Hospital with (1) the International HIV Dementia Scale (IHDS), a screening tool that targets moderate to severe HAND, (2) the Montreal Cognitive Assessment (MoCA), a frequently used cognitive screening test and (3) the Patient Health Questionnare-9 (PHQ-9), a 9-item questionnaire that evaluates depression symptoms. Within the study period, 57 of them completed the second set of IHDS and MoCA at 6 months after baseline assessment. Most participants were male (94%), with a median age of 31 years. At baseline, 38 (39%) and 25 (26%) of them scored below the IHDS (≤10) and MoCA (25/26) cut-offs respectively. Poor IHDS performers also scored lower on MoCA (p = 0.039) but the correlation between IHDS and MoCA performance was weak (r = 0.29, p = 0.004). Up to a third of poor IHDS performers (13/38) showed moderate depression (PHQ-9 > 9). In the multivariable analysis, a lower education level (p = 0.088), a history of prior psychiatric illness (p = 0.091) and the presence of moderate depression (p = 0.079) tended to be significantly associated with poor IHDS performance. At follow-up, 54 out of 57 were on cART, of which 46 (85%) had achieved viral suppression. Their blood CD4+ T-lymphocytes and IHDS scores were higher at follow-up compared to baseline values (both p < 0.001) but their MoCA performance was similar at both assessments. Of note, 17 participants in this subgroup scored below the IHDS cut-off at both assessments. Poor IHDS performance, and likely cognitive impairment, was frequently observed in treatment-naïve HIV-infected individuals in our locality. A considerable proportion continued to score below the IHDS cut-off at 6 months after cART. Depression was frequently observed in this vulnerable population and was associated with poor IHDS performance.

Abacavir and rilpivirine are alternative antiretroviral drugs for treatment-naïve HIV-infected patients. However, both drugs are only recommended for the patients who have pre-treatment HIV RNA 350 cells/mm3 (OR 3.9 vs. 2000 cells/mm3 (OR 1.7 vs. 25 yielded the sensitivity of 46.7%, specificity of 79.1%, positive predictive value of 67.7%, and negative predictive value of 61.2% for prediction of pre-treatment HIV RNA <100,000 copies/mL among derivation patients. A model prediction for pre-treatment HIV RNA <100,000 copies/mL produced an area under the ROC curve of 0.70. A larger sample size for prediction model development as well as for model validation is warranted.

Introduction: Over time, there has been a substantial improvement in antiretroviral treatment (ART) programs, including expansion of services and increased patient engagement. We describe time trends in, and factors associated with, loss to follow-up (LTFU) in HIV-positive patients receiving ART in Asia. Methods: Analysis included HIV-positive adults initiating ART in 2003–2013 at 7 ART programs in Asia. Patients LTFU had not attended the clinic for ≥180 days, had not died, or transferred to another clinic. Patients were censored at recent clinic visit, follow-up to January 2014. We used cumulative incidence to compare LTFU and mortality between years of ART initiation. Factors associated with LTFU were evaluated using a competing risks regression model, adjusted for clinical site. Results: A total of 8305 patients were included. There were 743 patients LTFU and 352 deaths over 26,217 person-years (pys), a crude LTFU, and mortality rate of 2.83 (2.64–3.05) per 100 pys and 1.34 (1.21–1.49) per 100 pys, respectively. At 24 months, the cumulative LTFU incidence increased from 4.3% (2.9%–6.1%) in 2003–05 to 8.1% (7.1%–9.2%) in 2006–09 and then decreased to 6.7% (5.9%–7.5%) in 2010–13. Concurrently, the cumulative mortality incidence decreased from 6.2% (4.5%–8.2%) in 2003–05 to 3.3% (2.8%–3.9%) in 2010–13. The risk of LTFU reduced in 2010–13 compared with 2006–09 (adjusted subhazard ratio = 0.73, 0.69–0.99). Conclusions: LTFU rates in HIV-positive patients receiving ART in our clinical sites have varied by the year of ART initiation, with rates declining in recent years whereas mortality rates have remained stable. Further increases in site-level resources are likely to contribute to additional reductions in LTFU for patients initiating in subsequent years.

Antiretroviral treatment (ART) guidelines have changed over the past decade, recommending earlier initiation and more tolerable regimens. The study objective was to examine the CD4 response to ART, depending on the year of ART initiation, in HIV-positive patients in the Asia-Pacific. We included HIV-positive adult patients who initiated ART between 2003 and 2013 in our regional cohort from eight urban referral centres in seven countries within Asia. We used mixed-effects linear regression models to evaluate differences in CD4 response by year of ART initiation during 36 months of follow-up, adjusted a priori for other covariates. Overall, 16,962 patients were included. Patients initiating in 2006–9 and 2010–13 had an estimated mean CD4 cell count increase of 8 and 15 cells/µl, respectively, at any given time during the 36-month follow-up, compared to those in 2003–5. The median CD4 cell count at ART initiation also increased from 96 cells/µl in 2003–5 to 173 cells/µl in 2010–13. Our results suggest that the CD4 response to ART is modestly higher for those initiating ART in more recent years. Moreover, fewer patients are presenting with lower absolute CD4 cell counts over time. This is likely to reduce their risk of opportunistic infections and future non-AIDS defining cancers.

The scale-up of antiretroviral therapy (ART) has led to a substantial change in the clinical population of HIV-positive patients receiving care. We describe the temporal trends in the demographic and clinical characteristics of HIV-positive patients initiating ART in 2003–13 within an Asian regional cohort. All HIV-positive adult patients that initiated ART between 2003 and 2013 were included. We summarized ART regimen use, age, CD4 cell count, HIV viral load, and HIV-related laboratory monitoring rates during follow-up by calendar year. A total of 16 962 patients were included in the analysis. Patients in active follow-up increased from 695 patients at four sites in 2003 to 11,137 patients at eight sites in 2013. The proportion of patients receiving their second or third ART regimen increased over time (5% in 2003 to 29% in 2013) along with patients aged ≥50 years (8% in 2003 to 18% in 2013). Concurrently, CD4 monitoring has remained stable in recent years, whereas HIV viral load monitoring, although varied among the sites, is increasing. There have been substantial changes in the clinical and demographic characteristics of HIV-positive patients receiving ART in Asia. HIV programmes will need to anticipate the clinical care needs for their aging populations, expanded viral load monitoring, and, the eventual increase in second and third ART regimens that will lead to higher costs and more complex drug procurement needs.