The Impact of Combination Antiretroviral Therapy and its Interruption on Anxiety, Stress, Depression and Quality of Life in Thai Patients

OBJECTIVE: Investigation on anxiety, stress, depression, and quality of life (QoL) within STACCATO, a randomised trial of two treatment strategies: CD4 guided scheduled treatment interruption (STI) compared to continuous treatment (CT). PARTICIPANTS: Thai patients with HIV-infection enrolled in the STACCATO trial. METHODS: Anxiety, depression assessed by the questionnaires Hospital Anxiety and Depression Scale (HADS) and DASS, stress assessed by the Depression Anxiety Stress Scale (DASS), and QoL evaluated by the HIV Medical Outcome Study (MOS-HIV) questionnaires. Answers to questionnaires were evaluated at 4 time-points: baseline, 24 weeks, 48 weeks and at the end of STACCATO. RESULTS: A total of 251 patients answered the HADS/DASS and 241 answered the MOS-HIV of the 379 Thai patients enrolled into STACCATO (66.2 and 63.6% respectively). At baseline 16.3% and 7.2% of patients reported anxiety and depression using HADS scale. Using the DASS scale, 35.1% reported mild to moderate and 9.6% reported severe anxiety; 8.8% reported mild to moderate and 2.0% reported severe depression; 42.6% reported mild to moderate and 4.8% reported severe stress. We showed a significant improvement of the MHS across time (p=0.001), but no difference between arms (p=0.17). The summarized physical health status score (PHS) did not change during the trial (p=0.15) nor between arm (p=0.45). There was no change of MHS or PHS in the STI arm, taking into account the number of STI cycle (p=0.30 and 0.57) but MHS significant increased across time-points (p=0.007). CONCLUSION: Antiretroviral therapy improved mental health and QOL, irrespective of the treatment strategy

Implementation and assessment of a prevention with positives intervention among people living with HIV at five hospitals in Thailand.

BACKGROUND:We implemented a hospital-based prevention with positives (PwP) intervention among people living with HIV (PLHIV) that included HIV transmission risk screening, short HIV prevention messages, family planning, HIV disclosure counseling, and partner HIV testing at five hospitals in Thailand. We assessed changes in sexual risk behaviors among PLHIV who received the PwP services at the hospitals. METHODS:From January 2008-March 2009, we systematically selected a subset of PLHIV receiving care at the five hospitals to offer participation in the PwP intervention. We collected demographic, risk behavior, and laboratory data using a standardized questionnaire. We analyzed data from PLHIV who completed at least four visits, using generalized estimating equations to identify baseline participant characteristics that were associated with adopting sexual practices less likely to be associated with HIV transmission during follow-up. RESULTS:A total of 830 PLHIV were interviewed and 756 (91.1%) completed four visits. The median age of these 756 participants was 37 years, 400 (52.9%) were women, and 475 (62.8%) had a steady partner. At baseline, 353 (74.3%) of the steady partners had been tested for HIV and 132 (37.4%) had tested negative. Among the 756 PLHIV, 427 (56.5%) reported having sex in the 3 months before enrollment and 413 (54.6%) in the 3 months before the fourth visit. The proportion reporting having vaginal or anal sex without a condom decreased from 20.8% at baseline to 5.1% at the fourth visit (p<0.001). Factors associated (p<0.05) with abstinence or 100% condom use at follow-up visits included: completing ≥ two visits, being diagnosed with HIV for longer than 3 months, and receiving HIV prevention messages from a doctor (versus a nurse or counselor). CONCLUSION:Safe sex behaviors increased among PLHIV receiving PwP services, suggesting that expansion of hospital-based PwP services may reduce the number of new HIV infections in Thailand

Supersensitive Viral Load Assay in Predicting CD4-Guided Treatment Failure

In HIV patients who discontinue highly active antiretroviral therapy (HAART), the degree of HIV RNA suppression at the time of treatment interruption may predict success of re-treatment after the interruption (STI). A case-control substudy of the Staccato trial in Thailand included CD4-guided STI subjects with HIV RNA > 50 copies /ml (virological failure cases, n=11) and HIV RNA < 50 copies/ml (controls, n=22) after 12-24 weeks of HAART re-treatment following a median of 2 STI cycles. Controls were matched for age, gender and pre-ART CD4 count. HIV RNA with 5 copies/ml detection limit was determined on pre-virological failure samples. HIV RNA increased in cases compared to controls with each successive STI cycle (p-trend across time-points 0.004). The last HIV RNA below 50 copies/ml was significantly higher among cases compared to controls (p=.004). Measuring HIV RNA below 50 copies/ml may be useful in predicting virological failure to STI

A newly designed economizer to improve waste heat recovery: A case study in a pasteurized milk plant

noAn economizer is normally employed to perform heat recovery from hot exhaust gases to cold fluid. In this work, a newly designed economizer is devised to achieve high heat recovery in a pasteurized milk plant. In the economizer, the hot exhaust gas is divided into two channels flowing up on the left and right sides. After that, it is moving down passing over aligned banks of tubes, which water is flowing inside, in a triple passes fashion. Moreover, three dimensional (3D) models with heat transfer including fluid dynamic have been developed, validated by actual plant data and used to evaluate the performance of the economizer. Simulation results indicate that the newly designed economizer can recover the heat loss of 38% and can achieve the cost saving of 13%

A prospective study of efficacy and safety of once-daily saquinavir/ritonavir plus two nucleoside reverse transcriptase inhibitors in treatment-naive Thai patients

OBJECTIVE: To assess the efficacy and safety of first-line treatment with once-daily saquinavir/ritonavir with two nucleoside reverse transcriptase inhibitors (NRTIs), as induction therapy before enrollment in a randomized trial of structured treatment interruption strategies. DESIGN: Two-hundred antiretroviral-naive patients with CD4+ cell counts between 200-350 at screening were enrolled in this open-label 24week study. METHODS: Patients were followed up every 8 weeks for CD4+ cells, HIV RNA, and clinical and laboratory toxicities. RESULTS: Two-hundred patients were enrolled with median baseline CD4+ cell count of 267 cells/microl and HIV RNA 50 118 (4.7 log10) copies/mi. After 24 weeks of treatment, 191 of 200 (96%) patients had below 400 copies/ml HIV RNA, with 177/200 (89%) below 50 copies/ml (intent to treat, missing equals failure method), with a median rise in CD4+ cell count of 122 cells/microl. There was no significant correlation between the minimum concentration of saquinavir and HIV RNA reductions at week 8 (P = 0.957) or absolute HIV RNA at week 24 (P = 0.77). CONCLUSION: First-line highly active antiretroviral therapy (HAART) with once-daily saquinavir/ritonavir plus two NRTIs showed strong antiviral efficacy over 24 weeks, and should be evaluated in larger prospective randomized clinical trials

Absence of resistance mutations in antiretroviral-naive patients treated with ritonavir-boosted saquinavir

BACKGROUND: There are few data on the selection of resistance by ritonavir-boosted saquinavir (SQV/r), particularly in antiretroviral (ARV)-naive patients. OBJECTIVE: To assess the incidence of virological failure and evolution of resistance in ARV-naive individuals receiving SQV/r in the induction phase of the Staccato trial. METHODS: ARV-naive subjects (n = 272) received SQV/r 1,600/100 mg once daily with two nucleoside reverse transcriptase inhibitors (NRTIs) for at least 24 weeks. Patients were defined as having virological failure (VF) when there were two consecutive HIV-1 RNA measurements > 500 copies/ml after week 12. Viral genotypes (reverse transcriptase [RT] and protease [PRO]) were determined at baseline in all patients and as close as possible to the time of initial failure in patients experiencing VF. RESULTS: VF was observed in 9/272 patients receiving SQV/r 1,600/100 mg once daily with two NRTIs (3.3%) and occurred 19-48 weeks after treatment initiation. Eight of these patients were evaluable at failure. No major PRO mutations were detected, but 2/8 displayed single new minor PRO substitutions (M36I, L10I) at VF that were known or suspected not to have been present at baseline; both these substitutions exist as natural polymorphisms. A third patient displayed a single new RT mutation (M184I). CONCLUSIONS: SQV/r plus two NRTIs (1,600/100 mg once daily) is an effective initial treatment option for ARV-naive patients, resulting in a low rate of viral rebound (3.3%). Furthermore, no major protease mutations were detected following VF, suggesting that future treatment options are preserved

Long-term efficacy and safety of first-line therapy with once-daily saquinavir/ritonavir

BACKGROUND: The aim of this study was to assess the long-term efficacy and safety of first-line treatment with once-daily saquinavir/ritonavir plus two nucleoside reverse transcriptase inhibitors (NRTIs). METHODS: A total of 272 antiretroviral-naive patients with a CD4+ T-cell count of 200-350 cells/mm3 were treated with two NRTIs and saquinavir/ritonavir 1,600/100 mg per day for 400 copies/ml, with a median HIV RNA decline of -2.89 (IQR 3.31--2.37) log10 copies/ml (P > 0.001) and a median rise in CD4+ T-cell count of 192 (IQR 117-317) cells (P > 0.001). At weeks 24, 48, 72 and 96, 249/272 (91.5%), 157/164 (95.7%), 113/126 (89.7%) and 84/90 (93.3%) had HIV RNA > 400 copies/ml, respectively; at the same time points, 83.8%, 92.7%, 85.7% and 85.6% had HIV RNA > 50 copies/ml. Drug-related adverse events were reported in 6.30%. Significant rises in total cholesterol, triglyceride, low-density lipoprotein and high-density lipoprotein were seen. CONCLUSION: First-line highly active antiretroviral therapy with once-daily saquinavir/ritonavir plus two NRTIs showed strong antiviral efficacy

Neurocognitive impairment in patients randomized to second-line lopinavir/ritonavir-based antiretroviral therapy vs. lopinavir/ritonavir monotherapy.

We compared rates of neurocognitive impairment (NCI) among 93 Thai adults failing non-nucleoside reverse transcriptase inhibitor (NNRTI)-based combination antiretroviral therapy (cART) before and after switching to lopinavir/ritonavir monotherapy (mLPV/r) vs. tenofovir/lamivudine/LPV/r (TDF/3TC/LPV/r). Participants completed the Color Trails 1 and 2, Digit Symbol, and Grooved Pegboard at weeks 0, 24, and 48. We calculated z-scores using normative data from 451 healthy HIV-negative Thais. We defined NCI as performance of &lt;-1 SD on ≥2 tests. The Thai depression inventory was used to capture depressive symptoms. Lumbar puncture was optional at week 0 and 48. At baseline, median (IQR) age was 36.9 (32.8-40.5) years, and 46 % had primary school education or lower. The median CD4 count was 196 (107-292) cells/mm(3), and plasma HIV RNA was 4.1 (3.6-4.5) log(10) copies/ml. Almost all (97 %) had circulating recombinant CRF01_AE. At baseline, 20 (47 %) of the mLPV/r vs. 22 (44 %) of TDF/3TC/LPV/r arms met NCI criteria (p = 0.89). The frequency of NCI at week 48 was 30 vs. 32 % (p = 0.85) with 6 vs. 7 % (p = 0.85) developing NCI in the mLPV/r vs. TDF/3TC/LPV/r arms, respectively. Having NCI at baseline and lower education each predicted NCI at week 48. Depression scores at week 48 did not differ between arms (p = 0.47). Cerebrospinal fluid HIV RNA of &lt;50 copies/ml at 48 weeks was observed in five out of seven in mLPV/r vs. three out of four in TDF/3TC/LPV/r arm. The rates of NCI and depression did not differ among cases failing NNRTI-based cART who received mLPV/r compared to LPV/r triple therapy

Flowchart of the Prevention with Positives (PwP) program for people living with HIV (PLHIV) in Thai hospitals.

<p>*Short prevention messages are provided to all PLHIV at routine clinical visits, covering all strategies in the initial visit and specific patient-centered strategies at follow-up visits. **High-risk/complicated case defined as people who inject drugs who report sharing needles, people who report sex without a condom, and people who have a history of STIs.</p