Cost of implementing HIV pre-exposure prophylaxis at community-based clinics in Indonesia.

INTRODUCTION: Currently, Indonesia still has one of the highest rates of new HIV/AIDS infections among countries in Asia and the Pacific region. The WHO has recommended pre-exposure prophylaxis (PrEP) as an additional HIV epidemic prevention step, which has been applied globally and related to the reduction in the number of HIV cases. However, information on the cost of implementing PrEP is rarely available in developing countries, especially in Southeast Asia. Designing a cost-effective approach to scale up PrEP and to estimate the potential budget impact requires information on the cost of implementing PrEP. This study aims to estimate the cost of implementing PrEP at community-based clinics in Indonesia. METHODS: We collected healthcare and non-healthcare/client costs from nine community-based clinics in various cities/districts in Indonesia. The healthcare costs included data on resource utilisation and costs to deliver PrEP, divided into recurrent and capital costs using a discount rate of 3%. Non-healthcare costs included out-of-pocket costs (e.g., transportation, meals) and productivity loss by clients and accompanying person(s) in accessing PrEP. On average, we interviewed 27 clients/clinic. RESULTS: The annual cost of providing PrEP per client is US $365.03, 39% lower than the yearly cost of antiretroviral treatment (ART) per person (approximately US $600). Drugs and non-healthcare costs contribute approximately 67% of the cost. The cost of PrEP amounts to US $292,756.45/year, covering 802 clients. The non-healthcare cost per visit at all sites never reaches more than 10% of the average monthly household expenditure. CONCLUSIONS: The cost of providing PrEP per person is approximately US $365 and is 39% lower than the annual cost of ART per person. Lowering the cost of PrEP ARV drugs would reduce the cost. Scaling up PrEP should recognise this cost structure and strive to reach economies of scale as the intervention gains more clients while simultaneously controlling new HIV infections.

Acceptability of a pilot motivational interviewing intervention at public health facilities to improve the HIV treatment cascade among people who inject drugs in Indonesia.

BACKGROUND: HIV-positive people who inject drugs (PWID) experience challenges in initiating and adhering to antiretroviral treatment (ART). Counselling using motivational interviewing (MI) techniques may help them formulate individualised strategies, and execute actions to address these challenges collaboratively with their providers. We evaluated the acceptability of MI from a pilot implementation at three public health facilities in Indonesia. METHODS: Adapting the acceptability constructs developed by Sekhon (2017) we assessed the acceptability to HIV-positive PWID clients (n = 12) and providers (n = 10) in four synthesised constructs: motivation (attributes that inspire engagement); cost consideration (sacrifices made to engage in MI); learned understanding (mechanism of action); and outcomes (ability to effect change with engagement). We included all providers and clients who completed ≥ 2 MI encounters. Qualitative analysis with an interpretive paradigm was used to extract and categorise themes by these constructs. RESULTS: In motivation, clients valued the open communication style of MI, while providers appreciated its novelty in offering coherent structure with clear boundaries. In cost consideration, both groups faced a challenge in meeting MI encounters due to access or engagement in other health care areas. In learned understanding, clients understood that MI worked to identify problematic areas of life amenable to change to support long-term ART, with reconciliation in family life being the most targeted change. By contrast, providers preferred targeting tangible health outcomes to such behavioural proxies. In outcomes, clients were confident in their ability to develop behaviours to sustain ART uptakes, whereas providers doubted the outcome of MI on younger PWID or those with severe dependence. CONCLUSIONS: There is broad acceptability of MI in motivating engagement for both actors. Relative to providers, clients were more acceptable in its mechanism and had greater confidence to perform behaviours conducive to ART engagement. Design innovations to improve the acceptability of MI for both actors are needed.

The cost of providing hospital-based (early) antiretroviral treatment in Indonesia: what has changed in almost a decade?

17% of all people living with HIV in Indonesia who are in need of antiretroviral treatment (ART) actually receive the treatment. The cost of ART based on three CD4 cell count groups (e.g., 0-200, 201-350, >350 cells/mm3) in a main referral hospital in West Java, Indonesia, in 2011-2016 was compared to the results from a decade earlier in the same setting. Costs were estimated including resources used for opportunistic infection treatment, laboratory tests, and antiretroviral (ARV) drugs. For each group, we divided the costs into several periods: pre-ART, and every 6 months up to 24 months after onset of treatment. Before ART, costs were dominated by laboratory tests (>80%); ARV drugs were the main cost after treatment onset (>92%). Average cost of treatment per year was US$600 across all groups. Moreover, the patient cost to access ART (n = 49 patients) did not exceed 10% of their household monthly expenditures (i.e., 4%). The unit cost of providing ART per patient/year is half the cost under the previous treatment initiation guidelines. A lower ARV drug cost, more patients in higher CD4 cell-count groups, and lower viral load test cost characterize the current cost profile.

HIV self-testing for men who have sex with men: an implementation trial in Indonesia.

We investigated oral fluid testing (OFT) among men who have sex with men (MSM) to increase HIV testing in Bali, Indonesia. We distributed OFT in January-December 2018 to 813 MSM in Bali. Supervised testing was offered first, and unsupervised was only offered to an individual who declined supervised testing. Included participants were MSM who did not have a HIV test result in the last 6 months and declined referral to facility-based testing. Of 813 participants, 93% (765/813) chose supervised testing and 7% (57/813) unsupervised. The OFT result was reactive for 83 (10%), of whom 52/83 (63%) underwent confirmatory testing with 47/52 (90%) found HIV positive. Among confirmed positives, 43/47 (92%) were enrolled in HATI study cohort, of whom 39 (91%) started treatment. At six months follow up, 25/39 (64%) of those initiating treatment were still receiving it, and all had a suppressed viral load. There was an increase in the mean number of MSM tested for HIV by HATI study Bali sites per month, from 100 (95%CI: 85-112) before the intervention to 152 (95% CI: 130-172) during the intervention. Our findings show the potential utility of offering HIV oral fluid self-test kits to scale-up HIV testing in MSM.Trial registration: ClinicalTrials.gov identifier: NCT03429842.

Simplified clinical algorithm for immediate antiretroviral therapy initiation: The HATI [HIV awal (early) Test & Treat in Indonesia] implementation research in Indonesia.

Background & objectives: Although the World Health Organization recommends same day or rapid (< seven days) antiretroviral therapy (ART) initiation, delays in ART initiation remain common due to waiting for laboratory test results. This study employed a simplified clinical algorithm the HATI [HIV Awal (Early) Test & Treat Indonesia]-SAI (Simple ART Initiation) aimed to increase the proportion of ART uptake and decrease the time to ART initiation that can be used in various care settings. Methods: This study compared the percentage of ART uptake and retention, viral load (VL) suppression and time to ART initiation between the observation and intervention phases among newly diagnosed HIV patients from key populations. As part of the intervention, the newly diagnosed patients underwent screening using a simple form [consisting of data on age, height and weight (for body mass index calculation), questions on the presence of symptoms of HIV stages 1 and 2, tuberculosis, history of diabetes, hypertension and kidney disease], to determine eligibility for immediate ART initiation. Those who met the pre-defined criteria immediately received a combination of tenofovir lamivudine and efavirenz for two weeks. The baseline laboratory examination due to this was moved up to two weeks post ART. Factors significantly associated with ART uptake were also determined and their odds ratios were measured using logistic regression analysis. Results: A total of 2173 people newly diagnosed with HIV were recruited, with 1579 and 594 in the observation and intervention phases, respectively. In both phases, the majority were men who have sex with men, who were young (<30 yr old) and employed, with high levels of education. The intervention phase significantly increased the proportion of ART initiation [91%, 95% confidence interval (CI): 89-93% vs. 78%, 95% CI: 76-80%] but did not have any impact on the proportion of six months retention and VL suppression. The intervention also significantly decreased the time to ART initiation from median ± interquartile range: 9±20 days to 2±10 days. Interpretation & conclusions: The findings of this study suggest that the HATI-SAI intervention increased the uptake and decreased the time for immediate ART initiation. The HATI-SAI provides a simple and safe clinical approach that can readily be adopted in different settings without a costly investment in technology.

"No good man will ever want me". How structural social inequality increases women's vulnerability to HIV transmission: a qualitative study from Bandung, Indonesia.

Understanding the pathways that expose women to HIV transmission are vital in improving HIV prevention, especially among a "hidden" group of women without pre-established known risk for HIV. We investigated the pathways which place certain women at greater risk for HIV in a qualitative exploratory study with theoretical sampling using an emergent theory study design in an urban setting in Indonesia. We conducted semi-structured interviews with 47 HIV-infected women, one focus group discussion with five young women who occassionally engage in sex work, participant observation at six sex work venues and two midwife clinics, and 11 informal interviews with midwives, nurses, and obstetricians. Our research found that many women not characterized as belonging to a "high-risk group" or "key population" were nevertheless at increased risk for HIV. A history of sexual abuse, premarital sex, divorce, or involvement in sex work, often precipitated by poverty coupled with discriminatory public health policies further heightened women's exposure to HIV. While reaching at-risk populations is a key strategy in HIV prevention, a novel and more tailored approach is needed to reach more hidden categories of women with less apparent risk behavior yet considerable risk for HIV infection.

Impact of strategic use of antiretroviral therapy intervention to the HIV continuum of care in 13 cities in Indonesia: an interrupted time series analysis.

BACKGROUND: In 2013 the Indonesian government introduced the strategic use of antiretroviral therapy (SUFA) initiative of expanding access to HIV test and treatment, to help achieve the UNAIDS 90-90-90 targets. However, there has been no comprehensive evaluation of the impact of this intervention in Indonesia. We conducted an interrupted time series (ITS) analysis across 6-years to assess its immediate and medium-term impact. METHODS: Monthly aggregated HIV data from all HIV care clinics for persons aged ≥ 15 years were collected from 13 pilot cities. The data period encompassed 3-years prior to SUFA (26 Dec 2010-25 Dec 2013) and 3-years post-SUFA (26 Dec 2013-25 Dec 2016). The ITS was performed using a multilevel negative binomial regression model to assess the immediate and trend changes in each stage of the HIV continuum of care. RESULTS: In the pre-SUFA period, the overall coverage in the respective risk populations for HIV tests, cases, enrolments, eligible cases and ARV initiation were 1.0%, 8.6%, 98.9%, 76.9% and 75.8% respectively. In the post-SUFA period coverage was 3%, 3.8%, 98.6%, 90.3% and 81.2% respectively-with a significant increase in the median number of HIV tests, HIV cases, those eligible for ARV treatment and treatment initiation (p < 0.05 for each). The ITS analysis demonstrated immediate increases in HIV tests (IRR = 1.41, 95% CI 1.25, 1.59; p < 0.001) and an immediate decrease in detected HIV cases per person tested (IRR = 0.77, 95% CI 0.69-0.86; p < 0.001) in the month following commencement of SUFA. There was also a 3% decline in the monthly trend for HIV tests performed (IRR = 0.97; 95% CI 0.97-0.98, p < 0.001), a 1% increase for detected cases (IRR = 1.01, 95% CI 1.0-1.02, p < 0.001), and a 1% decline for treatment initiation (IRR = 0.99,95% CI 0.99-1.0 p < 0.05). CONCLUSIONS: SUFA was associated with an immediate and sustained increase in the absolute number of HIV tests performed, detected HIV cases, and close to complete coverage of detected cases that were enrolled to care and defined as eligible for treatment. However, treatment initiation remained sub-optimal. The findings of this study provide valuable information on the real-world effect of accelerating ARV utilizing Treatment as Prevention for the full HIV continuum of care in limited resource countries.

Corrigendum to: A strengths-based analysis of social influences that enhance HIV testing among female sex workers in urban Indonesia.

Background: HIV prevalence among female sex workers in Indonesia remains high and large proportions of female sex workers have never been tested for HIV. International research highlights the importance of community-led strategies to increase HIV testing in this population. Little qualitative research has been conducted to address these issues in Indonesia or other Asia-Pacific countries. This paper documents social influences that enhance HIV testing among female sex workers in urban Indonesia. Methods: This was an interpretive qualitative study in Yogyakarta, Denpasar and Bandung. In total, 57 female sex workers participated in 11 focus group discussions, and four participated in individual semi-structured interviews. Deductive and inductive thematic analysis techniques were used to identify narratives of strengths pertaining to uptake of HIV testing. Results: Participants described supportive relationships with peers, community-based organisations and 'bosses'. Participants reported trusted networks with peers within which to share information about HIV testing and receive emotional support. Relationships with community outreach workers facilitated HIV testing through reminders, accompanied visits, and emotional/informational support. Community-based organisations worked with health services to facilitate mobile, community-based testing to overcome employment- and family-related constraints that inhibited women's clinic attendance. 'Bosses' employed a variety of practices to encourage HIV testing among their workers. Conclusions: Relationships, practices and action in community- and workplace-based settings outside formal health service spaces enhanced HIV testing among female sex workers. Community- or workplace-based HIV testing with outreach support from health services, peer-led HIV testing within existing social and work-based networks, and working with bosses to implement HIV prevention strategies can address low HIV testing rates in this key population.

A strengths-based analysis of social influences that enhance HIV testing among female sex workers in urban Indonesia.

Background HIV prevalence among female sex workers in Indonesia remains high and large proportions of female sex workers have never been tested for HIV. International research highlights the importance of community-led strategies to increase HIV testing in this population. Little qualitative research has been conducted to address these issues in Indonesia or other Asia-Pacific countries. This paper documents social influences that enhance HIV testing among female sex workers in urban Indonesia. METHODS: This was an interpretive qualitative study in Yogyakarta, Denpasar and Bandung. In total, 57 female sex workers participated in 11 focus group discussions, and four participated in individual semi-structured interviews. Deductive and inductive thematic analysis techniques were used to identify narratives of strengths pertaining to uptake of HIV testing. RESULTS: Participants described supportive relationships with peers, community-based organisations and 'bosses'. Participants reported trusted networks with peers within which to share information about HIV testing and receive emotional support. Relationships with community outreach workers facilitated HIV testing through reminders, accompanied visits, and emotional/informational support. Community-based organisations worked with health services to facilitate mobile, community-based testing to overcome employment- and family-related constraints that inhibited women's clinic attendance. 'Bosses' employed a variety of practices to encourage HIV testing among their workers. CONCLUSIONS: Relationships, practices and action in community- and workplace-based settings outside formal health service spaces enhanced HIV testing among female sex workers. Community- or workplace-based HIV testing with outreach support from health services, peer-led HIV testing within existing social and work-based networks, and working with bosses to implement HIV prevention strategies can address low HIV testing rates in this key population.

Translating international HIV treatment guidelines into local priorities in Indonesia.

OBJECTIVE: International guidelines recommend countries to expand antiretroviral therapy (ART) to all HIV-infected individuals and establish local-level priorities in relation to other treatment, prevention and mitigation interventions through fair processes. However, no practical guidance is provided for such priority-setting processes. Evidence-informed deliberative processes (EDPs) fill this gap and combine stakeholder deliberation to incorporate relevant social values with rational decision-making informed by evidence on these values. This study reports on the first-time implementation and evaluation of an EDP in HIV control, organised to support the AIDS Commission in West Java province, Indonesia, in the development of its strategic plan for 2014-2018. METHODS: Under the responsibility of the provincial AIDS Commission, an EDP was implemented to select priority interventions using six steps: (i) situational analysis; (ii) formation of a multistakeholder Consultation Panel; (iii) selection of criteria; (iv) identification and assessment of interventions' performance; (v) deliberation; and (vi) selection of funding and implementing institutions. An independent researcher conducted in-depth interviews (n = 21) with panel members to evaluate the process. RESULTS: The Consultation Panel included 23 stakeholders. They identified 50 interventions and these were evaluated against four criteria: impact on the epidemic, stigma reduction, cost-effectiveness and universal coverage. After a deliberative discussion, the Consultation Panel prioritised a combination of several treatment, prevention and mitigation interventions. CONCLUSION: The EDP improved both stakeholder involvement and the evidence base for the strategic planning process. EDPs fill an important gap which international guidelines and current tools for strategic planning in HIV control leave unaddressed.

Improving Diagnostic of Pulmonary Tuberculosis in HIV Patients by Bronchoscopy: A Cross Sectional Study.

BACKGROUND: diagnostic of pulmonary TB in HIV patients is a problem due to non specific clinical features, or radiological appearance. HIV patients with CD4≤200 cells/mL infected with M. tuberculosis have less capacity in containing M. tuberculosis, developing granulomas, casseous necrosis, or cavities. This condition is caused by weakend inflammatory which later reduced sputum production and may cause false negative result. This study aimed to assess differences in the positivity level of acid fast bacilli (AFB) and cultures of M. tuberculosis from non-bronchoscopic sputum (spontaneous and induced sputum) compared to bronchoscopic sputum (bronchoalveolar lavage) in HIV positive patients suspected pulmonary tuberculosis with CD4<200 cells/µL. METHODS: this cross sectional study was conducted in adult HIV patients treated in Hasan Sadikin Hospital with CD4≤200 cells/µL suspected with pulmonary tuberculosis by using paired comparative analytic test. All patients expelled sputum spontaneously or with sputum induction on the first day. On the next day, bronchoalveolar lavage (BAL) was performed. The two samples obtained from two methods were examined by AFB examination with staining Ziehl Neelsen (ZN) and cultured of M. tuberculosis on solid media Ogawa on all patients. Positivity, sensitivity and increased sensitivity of AFB and culture of M. tuberculosis in the non bronchoscopic and bronchoscopic groups were compared. RESULTS: there were differences in the positivity level of AFB with ZN staining between non-bronchoscopic and bronchoscopic groups which were 7/40 (17.5%) vs 20/40 (50.0%) (p<0.001). The differences between the cultures of non-bronchoscopic and bronchoscopic groups were 16/40 (40.0%) vs 23/40 (57.5%) (p=0.039). Bronchoscopic sputum increased the positivity level of the ZN AFB examination by 32.5% (from 17.5% to 50.0%) as well as on culture examination by 17.5% (from 40.0% to 57.5%). CONCLUSION: Bronchoalveolar lavage can improve the positivity level of smears and cultures in patients suspected of pulmonary TB in HIV patients with CD4<200 cells/µL.

HIV Patients Drop Out in Indonesia: Associated Factors and Potential Productivity Loss.

AIM: this study reported various factors associated with a higher probability of HIV patients drop out, and potential productivity loss due to HIV patients drop out. METHODS: we analyzed data of 658 HIV patients from a database in a main referral hospital in Bandung city, West Java, Indonesia from 2007 to 2013. First, we utilized probit regression analysis and included, among others, the following variables: patients' status (active or drop out), CD4 cell count, TB and opportunistic infection (OI), work status, sex, history of injecting drugs, and support from family and peers. Second, we used the drop out data from our database and CD 4 cell count decline rate from another study to estimate the productivity loss due to HIV patients drop out. RESULTS: lower CD4 cell count was associated with a higher probability of drop out. Support from family/peers, living with family, and diagnosed with TB were associated with lower probability of drop out. The productivity loss at national level due to treatment drop out (consequently, due to CD4 cell count decline) can reach US$365 million (using average wage). CONCLUSION: first, as lower CD 4 cell count was associated with higher probability of drop out, we recommend (to optimize) early ARV initiation at a higher CD 4 cell count, involving scaling up HIV service at the community level. Second, family/peer support should be further emphasized to further ensure treatment success. Third, dropping out from ART will result in a relatively large productivity loss.

Costs of HIV/AIDS treatment in Indonesia by time of treatment and stage of disease.

BACKGROUND: We report an economic analysis of Human Immunodeficiency Virus (HIV) care and treatment in Indonesia to assess the options and limitations of costs reduction, improving access, and scaling up services. METHODS: We calculated the cost of providing HIV care and treatment in a main referral hospital in West Java, Indonesia from 2008 to 2010, differentiated by initiation of treatment at different CD4 cell count levels (0-50, 50-100, 100-150, 150-200, and >200 cells/mm(3)); time of treatment; HIV care and opportunistic infections cost components; and the costs of patients for seeking and undergoing care. DISCUSSION: Before antiretroviral treatment (ART) initiation, costs were dominated by laboratory tests (>65 %), and after initiation, by antiretroviral drugs (≥60 %). Average treatment costs per patient decreased with time on treatment (e.g. from US$580 per patient in the first 6 month to US$473 per patient in months 19-24 for those with CD4 cell counts under 50 cells/mm(3)). Higher CD4 cell counts at initiation resulted in lower laboratory and opportunistic infection treatment costs. Transportation cost dominated the costs of patients for seeking and undergoing care (>40 %). CONCLUSIONS: Costs of providing ART are highest during the early phase of treatment. Costs reductions can potentially be realized by early treatment initiation and applying alternative laboratory tests with caution. Scaling up ART at the community level in certain high prevalence settings may improve early uptake, adherence, and reduce transportation costs.

Risk Factors Associated with Unsuppressed Viral Load in People Living with HIV Receiving Antiretroviral Treatment in Jawa Barat, Indonesia.

Introduction: The success rate of antiretroviral therapy (ART) was sufficiently high globally that by 2030, Human Immunodeficiency Virus (HIV) infection would no longer become a significant health issue. The evaluation of the success rate of ART in Indonesia is still fairly low, with estimates that 6.1% of the total population living with HIV. This is affected by treatment failure and limitations of viral load (VL) testing. We investigated the risk factors for failure of VL suppression in HIV patients on ART. Methods: An institution-based cross-sectional study was conducted among 1203 subjects, medical records of adult HIV patients in Jawa Barat, who followed the Viral Load Months Program from the government in 2020. Data were taken using total sampling technique and analyzed with multivariate logistic regression model using SPSS version 21 software. Results: Of the 1203 subjects, 5.2% had unsuppressed VL and 94.8% had suppressed VL. The results showed that a nevirapine-based regimen was the main factor increasing unsuppressed risk (Prevalence Odds Ratio (POR) 3.75 (95% CI: 1.41-9.99, p-value 0.008)). The other factors are ART duration <5 years (POR 2.46; 95% CI: 1.22-4.97, p-value 0.012), WHO clinical stage III-IV (POR 2.30; 95% CI: 1.30-4.08, p-value 0.004), and loss to follow-up history (POR 2.28, 95% CI: 1.03-5.07). Meanwhile, the zidovudine-based regimen reduced the risk of failure (POR 0.34 (95% CI: 0.12-0.96)). Conclusion: Several factors could contribute to unsuppressed VL in HIV patients receiving ART, which warrants further investigations.

The Association Between Oral Mucosal Lesions and Oral Health-Related Quality of Life Using the Validated Indonesian Version of OHIP-14 Among People Living with HIV/AIDS.

Background: Oral mucosal lesions in human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) patients, posing a concern for healthcare professionals, impact their oral health-related quality of life (OHRQoL). This study aimed to evaluate the association between oral mucosal lesions and OHRQoL as measured by the validated Indonesian version of the oral health impact profile-14 questionnaire (OHIP-14) among people living with HIV/AIDS (PLWHA). Methods: A cross-sectional study was conducted at the Central Referral Hospital in West Java, Indonesia. The validity of OHIP-14 was evaluated in 30 PLWHA using inter-item corrected correlation, while reliability was assessed through Cronbach's alpha and kappa coefficient agreement. Subsequently, a consecutive sample of 110 PLWHA self-completed the validated Indonesian version of OHIP-14 and underwent an oral examination. The association between oral mucosal lesions and OHRQoL was analyzed using the chi-squared test. Results: The validity test of the OHIP-14 questionnaire produced a rcount > 0.189, meaning that all question items were valid and could be used to describe OHRQoL. The reliability test of the OHIP-14 questionnaire produced a Cronbach's alpha value of 0.960 (> 0.7), which means that overall, the OHIP-14 questionnaire is reliable and feasible to be used to assess OHRQoL. Among the 110 enrolled participants, 61.8% were female and 38.2% were male, with the mean age 23.5 years old, the majority of them (59.1%) had been taking antiretrovirals (ARV), and (81.5%) had good QoL. There was a statistically significant relationship between oral lesions and quality of life (p<0.05), particularly acute pseudomembranous candidiasis, angular cheilitis, recurrent intraoral herpes, and Stevens-Johnson syndrome. Conclusion: This study indicated a significant association between oral mucosal lesions and OHRQoL in PLWHA. The successfully validated Indonesian version of the OHIP-14 questionnaire serves as a reliable and effective tool for assessing OHRQoL among PLWHA.

Accuracy of Anti-SARS-CoV-2 Antibody in Comparison with Surrogate Viral Neutralization Test in Persons Living with HIV, Systemic Lupus Erythematosus, and Chronic Kidney Disease.

The presence of the anti-SARS-CoV-2-RBD antibody (anti-RBD) prevents severe COVID-19. We aimed to determine the accuracy of a point-of-care anti-RBD testing implemented in persons living with HIV (PLWH), systemic lupus erythematosus (SLE), and chronic kidney disease (CKD). We enrolled 182 non-comorbid subjects and 335 comorbid subjects (PLWH, SLE, CKD) to test the anti-RBD assay compared to the surrogate viral neutralization test (sVNT) as the reference test. We performed linear correlation analysis between anti-RBD and sVNT, along with an ROC analysis to ascertain the anti-RBD cutoff at 30%, 60%, and 90% inhibition of sVNT, to calculate accuracy. The correlations between anti-RBD and sVNT among all groups were excellent, with R = 0.7903, R = 0.7843, and R = 0.8153 among the non-comorbid, SLE, and CKD groups, respectively, and with significantly higher correlation among the PLWH group (R = 0.8877; p-value = 0.0072) compared to the non-comorbid group. The accuracy of the anti-RBD test among the PLWH and CKD groups was similar to that among the non-comorbid group but showed lower sensitivity in the SLE group (p = 0.000014). The specificity of the test remained high in all groups. In conclusion, the anti-RBD test had excellent correlation with the sVNT. The persistently high specificity in all groups suggests that this test can be reliably utilized to detect the presence of low neutralization capacity, prompting additional vaccination.

Identification of cytokine signatures in HIV­infected individuals with and without Mycobacterium tuberculosis co­infection.

Individuals with human immunodeficiency virus (HIV) infection are susceptible to immune system dysregulation, particularly during co-infection with Mycobacterium tuberculosis (MTB). Although there is an association between cytokine profiles and HIV-MTB co-infection, little is known about the cytokine-related host immune response mechanism to HIV-MTB co-infection. Therefore, the present study aimed to analyze expression of cytokines IL-17A, IFN-γ, TNF, IL-2, IL-10, IL-6 and IL-4 in individuals with HIV-MTB co-infection. A total of 30 patients with HIV and 40 with HIV-MTB co-infection were recruited into the present study, including those with active (A) (n=19) and latent (L)TB (n=21). HIV infection status was established based on national HIV guideline (Pedoman Nasional Pelayanan Kedokteran Tatalaksana HIV). ATB was confirmed using a positive acid-fast bacillus staining and culture of sputum; LTB status was established using IFN-γ release assay. Furthermore, the levels of cytokines IL-17A, IFN-γ, TNF, IL-10, IL-6, IL-4 and IL-2 were measured using flow cytometric bead array and CD4 cell count was performed by PIMA™ CD4 assay. IFN-γ, TNF, IL-10, IL-6 and IL-2 were able to significantly differentiate patients with HIV-ATB from those with HIV-LTB. Furthermore, in the patient subgroup with CD4 count <350 cells/µl, IFN-γ, IL-10 and IL-6 were able to differentiate between patients with HIV-ATB and HIV alone, as well as between patients with HIV-ATB and HIV-LTB. Based on these findings, the cytokine profiles are likely to be distinct between individuals with HIV infection with A- and LTB. Furthermore, the expression of CD4-positive T cells may influence the immune response in the body under HIV-MTB co-infection.

Virological failure and drug resistance during first line anti-retroviral treatment in Indonesia.

The virological response and development of drug resistance during first-line anti-retroviral treatment (ART) were studied in Indonesia where the majority of patients infected with HIV have a history of injecting drug use, which is often linked with lower treatment adherence and development of drug-resistance. As many as 575 patients starting ART between September 2007 and March 2010 in Hasan Sadikin Hospital Bandung were followed prospectively. Clinical and laboratory monitoring was performed every 6 months. Plasma samples with HIV-RNA ≥ 400 copies/ml were examined for drug resistance mutations. Most patients were male (72.3%), 59.7% had a history of injecting drug use, and the median CD4+ cells count before start of ART was 35 cells/mm(3) (IQR 10-104). From 438 HIV patients with HIV-RNA measurements, 40 (9.1%) subjects had HIV-RNA ≥ 400 copies/ml after 24 weeks (median follow-up 16 (IQR 8-25) months). Of these failing patients 16 (47%) subjects had drug resistance mutations, predominantly M184V (35.3%), Y181C (23.5%), K103N (11.7%), and TAMs (11.7%). A history of treatment discontinuation ≥ 1 month, reported by 5.3% (23) of patients, was strongly associated with virological failure (adjusted OR 12.64, 95% CI 4.51-35.41); and a history of injecting drug use was not (OR 0.75, 95% CI 0.38-1.46). This is the largest and most systematic evaluation of virological response to first line ART in Indonesia. Patients in this cohort responded well to first line ART, with low rates of virological failure and drug resistance. A history of injecting drug use should not be a reason to withhold ART in this setting.

Mutation patterns of integrase gene affect antiretroviral resistance in various non-B subtypes of human immunodeficiency virus Type-1 and their implications for patients' therapy.

Although primary integrase strand transfer inhibitor resistance mutations are currently uncommon, the increasing use of integrase strand transfer inhibitor as a key component of the first, second and third-line antiretroviral regimens suggests that the prevalence of integrase drug resistance mutations will likely increase. The rise of several polymorphic mutations and natural polymorphisms also affects the level of susceptibility of human immunodeficiency virus (HIV) type-1 to integrase strand transfer inhibitor. The considerable variability among the various subtypes of human immunodeficiency virus type-1 may contribute to differences in integrase mutations associated with integrase strand transfer inhibitors. Notably, non-B subtypes of HIV type-1 (HIV-1) are the predominant cause of human immunodeficiency virus infection worldwide. The presence of diverse integrase drug resistance mutations can have significant implications on the administration of integrase strand transfer inhibitor-based antiretroviral therapy to patients with human immunodeficiency virus infection.

Detection of Human Herpesviruses in Sera and Saliva of Asymptomatic HIV-Infected Individuals Using Multiplex RT-PCR DNA Microarray.

Human herpesviruses (HHVs) are frequently linked to an increased risk of acquiring human immunodeficiency virus (HIV), and vice versa. This study aimed to detect human herpesvirus (HHV) members in the sera and saliva of asymptomatic HIV-infected individuals. Paired saliva and serum samples were obtained from 30 asymptomatic HIV-infected individuals. HHVs were detected with a multiplex reverse transcription-polymerase chain reaction (RT-PCR) DNA microarray Clart®Entherpex kit. A total of 30 subjects were enrolled: 23 (76.67%) men and 7 (23.33%) women. The present study showed that at least one or more HHV members were detected in the saliva and sera of all (100%) of the subjects. In the saliva, we detected herpes simplex virus 1 (HSV-1) 6.67%, herpes simplex virus 2 (HSV-2) 6.67%, Epstein-Barr virus (EBV) 86.67%, cytomegalovirus (CMV) 63.33%, HHV-6 (40%), and HHV-7 (83.33%). In the sera, HSV-2 (20%), EBV (30%), CMV (40%), HHV-6 (0%), and HHV-7 (76.67%) were found, but not HSV-1. VZV and HHV-8 were not detected in either the saliva or sera. EBV and HHV6 were significantly more prevalent in the saliva than they were in the sera of asymptomatic HIV-infected individuals (p < 0.05). However, no significant differences were found in the prevalence of HSV-1, EBV, CMV, HHV-6, and HHV-7 in the saliva and sera of asymptomatic HIV-infected individuals (p > 0.05). In conclusion, the multiplex RT-PCR DNA microarray can serve as a valuable diagnostic tool that can be used as a screening tool or a first-line test for HHVs infections.