Client and provider preferences for HIV care: Implications for implementing differentiated service delivery in Thailand.

INTRODUCTION: Differentiated service delivery (DSD) for antiretroviral therapy (ART) maintenance embodies the client-centred approach to tailor services to support people living with HIV in adhering to treatment and achieving viral suppression. We aimed to assess the preferences for HIV care and attitudes towards DSD for ART maintenance among ART clients and providers at healthcare facilities in Thailand. METHODS: A cross-sectional study using self-administered questionnaires was conducted in September-November 2018 at five healthcare facilities in four high HIV burden provinces in Thailand. Eligible participants who were ART clients aged ≥18 years and ART providers were recruited by consecutive sampling. Descriptive statistics were used to summarize demographic characteristics, preferences for HIV services and expectations and concerns towards DSD for ART maintenance. RESULTS: Five hundred clients and 52 providers completed the questionnaires. Their median ages (interquartile range; IQR) were 38.6 (29.8 to 45.5) and 37.3 (27.3 to 45.1); 48.5% and 78.9% were females, 16.8% and 1.9% were men who have sex with men, and 2.4% and 7.7% were transgender women, respectively. Most clients and providers agreed that ART maintenance tasks, including ART refill, viral load testing, HIV/sexually transmitted infection monitoring, and psychosocial support should be provided at ART clinics (85.2% to 90.8% vs. 76.9% to 84.6%), by physicians (77.0% to 94.6% vs. 71.2% to 100.0%), every three months (26.7% to 40.8% vs. 17.3% to 55.8%) or six months (33.0% to 56.7% vs. 28.9% to 80.8%). Clients agreed that DSD would encourage their autonomy (84.9%) and empower responsibility for their health (87.7%). Some clients and providers disagreed that DSD would lead to poor ART retention (54.0% vs. 40.4%), increased loss to follow-up (52.5% vs. 42.3%), and delayed detection of treatment failure (48.3% vs. 44.2%), whereas 31.4% to 50.0% of providers were unsure about these expectations and concerns. CONCLUSIONS: Physician-led, facility-based clinical consultation visit spacing in combination with multi-month ART refill was identified as one promising DSD model in Thailand. However, low preference for decentralization and task shifting may prove challenging to implement other models, especially since many providers were unsure about DSD benefits. This calls for local implementation studies to prove feasibility and governmental and social support to legitimize and normalize DSD in order to gain acceptance among clients and providers.

Long term renal function in Asian HIV-1 infected adults receiving tenofovir disoproxil fumarate without protease inhibitors.

OBJECTIVES: The risk of kidney dysfunction on the WHO recommended first line regimens containing tenofovir disoproxil fumarate (TDF) without protease inhibitors (PI) remains unclear in Asian patients, especially those with low body weight. METHODS: Using data collected in a multicenter clinical trial in Thailand and proportional hazard regression models, we compared the risk of a >25% estimated glomerular filtration rate (eGFR) reduction in HIV naïve patients initiating TDF or zidovudine (AZT) containing non-PI regimen. RESULTS: Of 640 patients included in the analysis, 461 (72%) received a TDF-containing regimen for a median 6.7 years and 179 (28%) an AZT-containing regimen for 6.5 years. The risk of a >25% eGFR reduction was not associated with treatment (HR 1.11, 95% CI 0.84-1.47, P = 0.46). In multivariate analysis, the risk of >25% eGFR reduction form baseline was associated with body weight at baseline (HR 2.12, 95% CI 1.48-3.02 for <48 kg patients and HR 1.64, 95% CI 1.20-2.25 for 48-59.9 kg patients, compared to those with >60 kg, P < 0.001) and hypertension (HR 4.03, 95% CI 2.0-8.0, P < 0.001). The effect of baseline weight on >25% eGFR reduction did not significantly vary with treatment (P = 0.27). CONCLUSIONS: The risk of eGFR reduction was not higher on TDF- versus AZT-based non-PI regimens. Although the risk of eGFR reduction was greater for patients of lower body weight, this risk was not significantly increased by TDF.

New-Onset Diabetes and Antiretroviral Treatments in HIV-Infected Adults in Thailand.

BACKGROUND: Use of several antiretrovirals (ARVs) has been shown to be associated with a higher risk of diabetes in HIV-infected adults. We estimated the incidence of new-onset diabetes and assessed the association between individual ARVs and ARV combinations, and diabetes in a large cohort in Thailand. METHODS: We selected all HIV-1-infected, nondiabetic, antiretroviral-naive adults enrolled in the Program for HIV Prevention and Treatment cohort (NCT00433030) between January 2000 and December 2011. Diabetes was defined as confirmed fasting plasma glucose ≥ 126 mg/dL or random plasma glucose ≥ 2 00 mg/dL. Incidence was the number of cases divided by the total number of person-years of follow-up. Association between ARVs and ARV combinations, and new-onset diabetes was assessed using Cox proportional hazards models. RESULTS: Overall, 1594 HIV-infected patients (76% female) were included. Median age at antiretroviral therapy initiation was 32.5 years. The incidence rate of diabetes was 5.0 per 1000 person-years of follow-up (95% confidence interval: 3.8 to 6.6) (53 cases). In analyses adjusted for potential confounders, exposure to stavudine + didanosine [adjusted hazard ratio (aHR) = 3.9; P = 0.001] and cumulative exposure ≥ 1 year to zidovudine (aHR = 2.3 vs. no exposure; P = 0.009) were associated with a higher risk of diabetes. Conversely, cumulative exposure ≥ 1 year to tenofovir (aHR = 0.4 vs. no exposure; P = 0.02) and emtricitabine (aHR = 0.4 vs. no exposure; P = 0.03) were associated with a lower risk. CONCLUSIONS: The incidence of diabetes in this predominantly female, young, lean population was relatively low. Although stavudine and didanosine have now been phased out in most antiretroviral therapy programs, our analysis suggests a higher risk of diabetes with zidovudine, frequently prescribed today in resource-limited settings.

Switching HIV treatment in adults based on CD4 count versus viral load monitoring: a randomized, non-inferiority trial in Thailand.

BACKGROUND: Viral load (VL) is recommended for monitoring the response to highly active antiretroviral therapy (HAART) but is not routinely available in most low- and middle-income countries. The purpose of the study was to determine whether a CD4-based monitoring and switching strategy would provide a similar clinical outcome compared to the standard VL-based strategy in Thailand. METHODS AND FINDINGS: The Programs for HIV Prevention and Treatment (PHPT-3) non-inferiority randomized clinical trial compared a treatment switching strategy based on CD4-only (CD4) monitoring versus viral-load (VL). Consenting participants were antiretroviral-naïve HIV-infected adults (CD4 count 50-250/mm(3)) initiating non-nucleotide reverse transcriptase inhibitor (NNRTI)-based therapy. Randomization, stratified by site (21 public hospitals), was performed centrally after enrollment. Clinicians were unaware of the VL values of patients randomized to the CD4 arm. Participants switched to second-line combination with confirmed CD4 decline >30% from peak (within 200 cells from baseline) in the CD4 arm, or confirmed VL >400 copies/ml in the VL arm. Primary endpoint was clinical failure at 3 years, defined as death, new AIDS-defining event, or CD4 <50 cells/mm(3). The 3-year Kaplan-Meier cumulative risks of clinical failure were compared for non-inferiority with a margin of 7.4%. In the intent to treat analysis, data were censored at the date of death or at last visit. The secondary endpoints were difference in future-drug-option (FDO) score, a measure of resistance profiles, virologic and immunologic responses, and the safety and tolerance of HAART. 716 participants were randomized, 356 to VL monitoring and 360 to CD4 monitoring. At 3 years, 319 participants (90%) in VL and 326 (91%) in CD4 were alive and on follow-up. The cumulative risk of clinical failure was 8.0% (95% CI 5.6-11.4) in VL versus 7.4% (5.1-10.7) in CD4, and the upper-limit of the one-sided 95% CI of the difference was 3.4%, meeting the pre-determined non-inferiority criterion. Probability of switch for study criteria was 5.2% (3.2-8.4) in VL versus 7.5% (5.0-11.1) in CD4 (p=0.097). Median time from treatment initiation to switch was 11.7 months (7.7-19.4) in VL and 24.7 months (15.9-35.0) in CD4 (p=0.001). The median duration of viremia >400 copies/ml at switch was 7.2 months (5.8-8.0) in VL versus 15.8 months (8.5-20.4) in CD4 (p=0.002). FDO scores were not significantly different at time of switch. No adverse events related to the monitoring strategy were reported. CONCLUSIONS: The 3-year rates of clinical failure and loss of treatment options did not differ between strategies although the longer-term consequences of CD4 monitoring would need to be investigated. These results provide reassurance to treatment programs currently based on CD4 monitoring as VL measurement becomes more affordable and feasible in resource-limited settings. TRIAL REGISTRATION: ClinicalTrials.govNCT00162682 Please see later in the article for the Editors' Summary.

Association between detection of HIV-1 DNA resistance mutations by a sensitive assay at initiation of antiretroviral therapy and virologic failure.

BACKGROUND: Antiretroviral therapy (ART) has become more available throughout the developing world during the past 5 years. The World Health Organization recommends nonnucleoside reverse-transcriptase inhibitor-based regimens as initial ART. However, their efficacy may be compromised by resistance mutations selected by single-dose nevirapine (sdNVP) used to prevent mother-to-child transmission of human immunodeficiency virus (HIV)-1. There is no simple and efficient method to detect such mutations at the initiation of ART. METHODS: One hundred eighty-one women who were participating in a clinical trial to prevent mother-to-child transmission and who started NVP-ART after they had received sdNVP or a placebo were included in the study. One hundred copies of each patient's HIV-1 DNA were tested for NVP-resistance point-mutations (K103N, Y181C, and G190A) with a sensitive oligonucleotide ligation assay that was able to detect mutants even at low concentrations (> or = 5% of the viral population). Virologic failure was defined as confirmed plasma HIV-1 RNA >50 copies/mL after 6 to 18 months of NVP-ART. RESULTS: At initiation of NVP-ART, resistance mutations were identified in 38 (26%) of 148 participants given sdNVP (K103N in 19 [13%], Y181C in 8 [5%], G190A in 28 [19%], and > or = 2 mutations in 15 [10%]), at a median 9.3 months after receipt of sdNVP. The risk of virologic failure was 0.62 (95% confidence interval [CI], 0.46-0.77) in women with > or = 1% resistance mutation, compared with a risk of 0.25 (95% CI, 0.17-0.35) in those without detectable resistance mutations (P < .001). Failure was independently associated with resistance, an interval of <6 months between sdNVP and NVP-ART initiation, and a viral load higher than the median at NVP-ART initiation. CONCLUSIONS: Access to simple and inexpensive assays to detect low concentrations of NVP-resistant HIV-1 DNA before the initiation of ART could help improve the outcome of first-line ART.

Effects of long-term use of HAART on oral health status of HIV-infected subjects.

BACKGROUND: The aim of this study was to determine the effects of long-term use of highly active antiretroviral therapy (HAART) on oral health status of HIV-infected subjects. METHODS: Oral examination and measurement of saliva flow rate of both unstimulated and wax-stimulated whole saliva were performed in HIV-infected subjects with and without HAART, and in non-HIV individuals. The following data were recorded; duration and risk of HIV infection, type and duration of HAART, CD4 cell count, viral load, presence of orofacial pain, oral dryness, oral burning sensation, oral lesions, cervical caries, and periodontal pocket. Multiple logistic regression analysis was performed to determine the effects of long-term use of HAART on oral health status of HIV-infected subjects. RESULTS: One hundred and fifty-seven HIV-infected subjects - 99 on HAART (age range 23-57 years, mean 39 years) and 58 not on HAART (age range 20-59 years, mean 34 years) - and 50 non-HIV controls (age range 19-59 years, mean 36 years) were enrolled. The most common HAART regimen was 2 NRTI + 2 NNRTI. HIV-infected subjects without HAART showed greater risks of having orofacial pain, oral dryness, oral lesions, and periodontal pockets than those with short-term HAART (P < 0.01). The subjects with long-term HAART were found to have a greater risk of having oral lesions than those with short-term HAART (P < 0.05). The unstimulated and stimulated salivary flow rates of the subjects with HAART were significantly lower than in those without HAART (P < 0.05). CONCLUSION: We conclude that long-term HAART has adverse effects on oral health status of HIV-infected subjects.