ResearchPad - hiv-clinical-manifestations https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Interventions to improve self-management of adults living with HIV on Antiretroviral Therapy: A systematic review]]> https://www.researchpad.co/article/elastic_article_7726 Since its initial recognition, HIV has been responsible for around 35 million deaths globally. The introduction of Antiretroviral Therapy has helped to reduce mortality from HIV. However, the resulting increased longevity has influenced the experience of people living with HIV, which now manifests as a chronic condition requiring effective self-management. This review aimed to identify and evaluate the effectiveness of interventions to improve self-management of adults living with HIV on Antiretroviral therapy.MethodsThe review included published experimental studies addressing interventions to improve self-management of adults living with HIV on Antiretroviral Therapy. Studies were included if they addressed two or more outcomes of self-management, as defined by the Theory of Individual and Family Self-Management. The search covered four databases and was limited to papers published in the English language from 2001 to March 30, 2019. The reference lists of included studies were further searched for additional studies. Two independent reviewers using the Joanna Briggs Institute Meta-Analysis of Statistics Assessment and Review Instrument (JBI SUMARI) assessed the methodological quality of the reviewed papers. Data extraction was undertaken using the JBI SUMARI standardized data extraction tool. As the included papers were not homogeneous, it was not possible to conduct a meta-analysis. A narrative synthesis was undertaken to synthesize the findings of the included studies.ResultsThe search identified 337 articles from which 10 experimental and 2 quasi-experimental studies were included. The total participant sample in the included studies was 1661 adults living with HIV. The overall evidence quality of the findings was considered moderate. Many of the studies included in this review comprised multi-component interventions to improve self-management. Skills training, in conjunction with other forms of interventions, particularly phone counseling, was commonly employed and generally effective in improving self-management outcomes. Counseling with a symptom management manual was another employed and effective intervention, followed by technology-assisted self-management interventions. The most common outcomes measured were maintaining medication adherence and quality of life, followed by symptom management, self-efficacy, coping, and social support.ConclusionsInterventions to improve self-management varied across studies. However, promising outcomes achieved in the majority of studies through interventions comprising a combination of skills training, phone counseling, counseling with symptom management manuals, and technology-assisted interventions. ]]> <![CDATA[‘We are the change’ - An innovative community-based response to address self-stigma: A pilot study focusing on people living with HIV in Zimbabwe]]> https://www.researchpad.co/article/5c6dca28d5eed0c48452a859

Introduction

Self-stigma–negative self-judgements resulting in shame, worthlessness and self-blame–may play a crucial role in emotional reactions and cause emotional distress among many people living with HIV and other chronic illnesses. Furthermore, self-stigma negatively impacts on self-agency, quality of life, adherence to treatment, and access to services. High levels of self-stigma have been reported across many countries, however few programmes or interventions exist to specifically tackle this phenomenon. This paper reports the findings of a pilot study carried out in Zimbabwe using a programme incorporating “Inquiry-Based Stress Reduction (IBSR): The Work of Byron Katie”–a guided form of self-inquiry which helps users to overcome negative thoughts and beliefs.

Objectives

The primary objective of this uncontrolled pilot study was to examine the potential role of the IBSR intervention in helping people living with HIV to overcome self-stigma and associated states.

Methods

23 people living with HIV (17 Female, 6 male, average age 41 years) were recruited from a local HIV support network, via open call for volunteers. All participants received the intervention, consisting of a 12-week facilitated programme using techniques derived from IBSR: The Work of Byron Katie. Qualitative and quantitative data were collected and analysed pre- and post-programme.

Results

After taking part in the intervention, participants reported significant improvements in factors including self-stigma (1-month follow-up vs baseline Z = 2.1, p = 0.039; 3-month follow-up vs baseline Z = 3.0, p = 0.003, n = 23, Wilcoxon Matched Pairs Signed Rank Test) and depression (1mo vs baseline Z = 3.7, p = <0.001; 3mo vs baseline Z = 3.3, p = 0.001). Qualitatively, participants reported improvements including lessened fears around disclosure of their HIV status, reduced feelings of life limitations due to HIV, and greater positive mentality. Improvements persisted at three-month follow-up.

Conclusion

With further development and larger comparative studies to confirm effects, the IBSR programme could become a novel tool to enable people living with HIV to support themselves in overcoming self-stigma.

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<![CDATA[Visual cues that predict intuitive risk perception in the case of HIV]]> https://www.researchpad.co/article/5c76fe53d5eed0c484e5b8b2

Field studies indicate that people may form impressions about potential partners’ HIV risk, yet lack insight into what underlies such intuitions. The present study examined which cues may give rise to the perception of riskiness. Towards this end, portrait pictures of persons that are representative of the kinds of images found on social media were evaluated by independent raters on two sets of data: First, sixty visible cues deemed relevant to person perception, and second, perceived HIV risk and trustworthiness, health, and attractiveness. Here, we report correlations between cues and perceived HIV risk, exposing cue-criterion associations that may be used to infer intuitively HIV risk. Second, we trained a multiple cue-based model to forecast perceived HIV risk through cross-validated predictive modelling. Trained models accurately predicted how ‘risky’ a person was perceived (r = 0.75) in a novel sample of portraits. Findings are discussed with respect to HIV risk stereotypes and implications regarding how to foster effective protective behaviors.

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<![CDATA[Anxiety symptoms and felt stigma among young people living with perinatally or behaviourally-acquired HIV in Ukraine: A cross-sectional survey]]> https://www.researchpad.co/article/5c536a29d5eed0c484a46fa8

Background

Ukraine has the second largest European HIV epidemic. This study aimed to describe stigma, demographic and social factors and their association with anxiety among perinatally and behaviourally-HIV-infected (PHIV; BHIV) young people in Kiev and Odessa.

Methods

104 PHIV and 100 BHIV young people aged 13–25 years completed a confidential tablet-based survey. Survey tools included the Hospital Anxiety and Depression Scale (HADS) (anxiety sub-scale scores of 8–10 indicating mild and ≥11 moderate/severe symptoms in last 7 days), Rosenberg Self-Esteem Scale (RSES) and HIV Stigma Scale (HSS) (short version, composite of disclosure, negative self-image and public attitudes sub-scales). Unadjusted Poisson regression models were fitted to explore factors associated with moderate/severe anxiety symptoms.

Results

PHIV and BHIV young people were of median age 15.5 [IQR 13.9–17.1] and 23.0 [21.0–24.3] years, having registered for HIV care a median 12.3 [10.3–14.4] and 0.9 [0.2–2.4] years previously; 97% (97/100) and 66% (65/99) respectively were on ART. Overall 43% (95%CI 36–50%) reported any and 13% (95%CI 9–19%) moderate/severe anxiety symptoms, with no difference by HIV acquisition mode (p = 0.405) or gender (p = 0.700). 42% (75/180) reported history of an emotional health problem for which they had not been referred/attended for care. Moderate/severe anxiety symptoms were associated with HIV-related stigma (prevalence ratio (PR) 1.24 95%CI 1.14–1.34 per HSS unit increase), lower self-esteem (PR 0.83 95%CI 0.78–0.90 per RSES point increase), CD4 ≤350 cells/mm3 (PR 2.29 95%CI 1.06–4.97), having no-one at home who knew the respondent’s HIV status (PR 9.15 95%CI 3.40–24.66 vs all know) and, among BHIV, less stable living situation (PR 6.83 95%CI 1.99–23.48 for ≥2 vs no home moves in last 3 years) and history of drug use (PR 4.65 95%CI 1.83–11.85).

Conclusions

Results indicated unmet need for psychosocial support. Further work is needed to explore strategies for mental health support, particularly around disclosure, self-esteem and stigma.

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<![CDATA[Trends and emerging directions in HIV risk and prevention research in the Philippines: A systematic review of the literature]]> https://www.researchpad.co/article/5c117b7dd5eed0c484699690

Background

The Philippines is experiencing one of the fastest growing epidemics globally. Evidence-based public health policies are needed. To describe the public health literature on HIV risk groups and prevention approaches in the Philippines, we reviewed published empirical studies with HIV-related outcomes.

Methods

Based on an a priori systematic review protocol, we searched PubMed, PsycINFO and CINAHL databases for quantitative studies conducted in the Philippines that reported on HIV risk groups factors and interventions to prevent HIV. The search included studies published as of April 2018.

Results

We identified 755 records, screened 699 unique titles and abstracts, and conducted full text review of 122 full reports of which 51 articles met inclusion criteria. The majority were cross-sectional studies describing HIV and STI prevalence and risk factors in samples recruited from the Philippines. Four HIV prevention programs conducted in the Philippines were identified, all of which reported improvements on HIV knowledge, attitudes, and behaviors. Overall, female sex workers (FSWs) constituted the primary study population, and few studies reported data from men who have sex with men (MSM), people who inject drugs (PWIDs), and youth. No studies reported on transgender populations. Most studies were focused on examining condom use-related outcomes and STI history, few had biomarkers for HIV, and none addressed biomedical HIV prevention strategies.

Conclusion

This review identifies an agenda for future HIV research that is needed to address the growing and shifting nature of the HIV epidemic in the Philippines.

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<![CDATA[Long term effect of primary health care training on HIV testing: A quasi-experimental evaluation of the Sexual Health in Practice (SHIP) intervention]]> https://www.researchpad.co/article/5b6d94b4463d7e2f79286cbd

Background

To examine the effect of Sexual Health in Practice (SHIP) training for general practitioners (GPs) on HIV testing rates in Haringey, a deprived area of London, UK, with a population of over 250,000 and HIV prevalence of 0.7% (in 2014). SHIP is an educational intervention delivering peer-developed and peer-led face-to-face training to improve quality of sexual and reproductive health (SRH) care.

Methods

We carried out a quasi-experimental study of intervention effects across 52 GP practices (2008–2016). We used time variation in SHIP intervention exposure for effect estimation, controlling for practice and calendar month fixed effects in panel analysis. From 2008–2010, baseline data were collected, and in the subsequent six-year period, 78 GPs in Haringey (approximately 40% of all GPs) were SHIP trained. 46 Haringey practices (of 52) had at least one trained doctor. Outcome measures were monthly HIV tests and results by practice (obtained from the hospital laboratories).

Results

SHIP significantly increased HIV testing; for every GP trained, practice HIV testing rates increased by 16% (testing rate ratio (TRR) 1.16, 95% confidence interval (CI) 1.05–1.28, p value 0.004). This significant effect was demonstrated using an 8-year observation period, and was sustained over the post-intervention period. An average of 1.42% of HIV tests were positive.

Conclusion

SHIP training produces a significant and sustained increase in HIV testing for each GP trained. Compared with general population screening, HIV tests used in routine clinical care have a high probability of detecting a positive person. Unlike an RCT, this evaluation is a ‘real life’ measure of the effect that commissioners of SHIP could expect in comparable areas of the UK. The effectiveness of the SHIP training may be related to the programme components not included in interventions that did not demonstrate an effect, such as peer-led teaching, and use of approaches to communication and rapid risk assessment tailored to the setting.

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<![CDATA[The Semen Microbiome and Its Relationship with Local Immunology and Viral Load in HIV Infection]]> https://www.researchpad.co/article/5989da39ab0ee8fa60b87690

Semen is a major vector for HIV transmission, but the semen HIV RNA viral load (VL) only correlates moderately with the blood VL. Viral shedding can be enhanced by genital infections and associated inflammation, but it can also occur in the absence of classical pathogens. Thus, we hypothesized that a dysregulated semen microbiome correlates with local HIV shedding. We analyzed semen samples from 49 men who have sex with men (MSM), including 22 HIV-uninfected and 27 HIV-infected men, at baseline and after starting antiretroviral therapy (ART) using 16S rRNA gene-based pyrosequencing and quantitative PCR. We studied the relationship of semen bacteria with HIV infection, semen cytokine levels, and semen VL by linear regression, non-metric multidimensional scaling, and goodness-of-fit test. Streptococcus, Corynebacterium, and Staphylococcus were common semen bacteria, irrespective of HIV status. While Ureaplasma was the more abundant Mollicutes in HIV-uninfected men, Mycoplasma dominated after HIV infection. HIV infection was associated with decreased semen microbiome diversity and richness, which were restored after six months of ART. In HIV-infected men, semen bacterial load correlated with seven pro-inflammatory semen cytokines, including IL-6 (p = 0.024), TNF-α (p = 0.009), and IL-1b (p = 0.002). IL-1b in particular was associated with semen VL (r2 = 0.18, p = 0.02). Semen bacterial load was also directly linked to the semen HIV VL (r2 = 0.15, p = 0.02). HIV infection reshapes the relationship between semen bacteria and pro-inflammatory cytokines, and both are linked to semen VL, which supports a role of the semen microbiome in HIV sexual transmission.

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<![CDATA[T-Cell Phenotypes, Apoptosis and Inflammation in HIV+ Patients on Virologically Effective cART with Early Atherosclerosis]]> https://www.researchpad.co/article/5989da75ab0ee8fa60b96624

Objective

We investigated the potential relationship between T-cell phenotype, inflammation, endotoxemia, and atherosclerosis evaluated by carotid intima-media thickness (IMT) in a cohort of HIV-positive patients undergoing long-term virologically suppressive combination antiretroviral therapy (cART).

Design

We studied 163 patients receiving virologically suppressive cART.

Methods

We measured IMT (carotid ultrasound); CD4+/CD8+ T-cell activation (CD38, CD45R0), differentiation (CD127), apoptosis (CD95), and senescence (CD28, CD57) (flow cytometry); plasma sCD14, IL-6, TNF- α, sVCAM-1, hs-CRP, anti-CMV IgG (ELISA); LPS (LAL). The results were compared by Mann-Whitney, Kruskal-Wallis or Chi-square tests, and factors associated with IMT were evaluated by multivariable logistic regression.

Results

Of 163 patients, 112 demonstrated normal IMT (nIMT), whereas 51 (31.3%) had pathological IMT (pIMT: ≥1 mm). Of the patients with pIMT, 22 demonstrated an increased IMT (iIMT), and 29 were shown to have plaques. These patient groups had comparable nadir and current CD4+, VLs and total length of time on cART. Despite similar proportions of CD38-expressing CD8+ cells (p = .95), pIMT patients exhibited higher activated memory CD8+CD38+CD45R0+ cells (p = .038) and apoptotic CD4+CD95+ (p = .01) and CD8+CD95+ cells (p = .003). In comparison to nIMT patients, iIMT patients tended to have lower numbers of early differentiated CD28+CD57− memory CD4+ (p = .048) and CD28–CD57−CD8+ cells (p = .006), both of which are associated with a higher proliferative potential. Despite no differences in plasma LPS levels, pIMT patients showed significantly higher circulating levels of sCD14 than did nIMT patients (p = .046). No differences in anti-CMV IgG was shown. Although circulating levels of sCD14 seemed to be associated with a risk of ATS in an unadjusted analysis, this effect was lost after adjusting for classical cardiovascular predictors.

Conclusions

Despite the provision of full viral suppression by cART, a hyperactivated, pro-apoptotic T-cell profile characterizes HIV-infected patients with early vascular damage, for whom the potential contribution of subclinical endotoxemia and anti-CMV immunity should be investigated further.

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<![CDATA[Validating a Shortened Depression Scale (10 Item CES-D) among HIV-Positive People in British Columbia, Canada]]> https://www.researchpad.co/article/5989da5aab0ee8fa60b8fbdf

Objective

To establish the reliability and validity of a shortened (10-item) depression scale used among HIV-positive patients enrolled in the Drug Treatment Program in British Columbia, Canada.

Methods

The 10-item CES-D (Center for Epidemiologic Studies Depression Scale) was examined among 563 participants who initiated antiretroviral therapy (ART) between August 1, 1996 and June 30, 2002. Internal consistency of the scale was measured by Cronbach’s alpha. Using the original CES-D 20 as primary criteria, comparisons were made using the Kappa statistic. Predictive accuracy of CES-D 10 was assessed by calculating sensitivity, specificity, positive predictive values and negative predictive values. Factor analysis was also performed to determine if the CES-D 10 contained the same factors of positive and negative affect found in the original development of the CES-D.

Results

The correlation between the original and the shortened scale is very high (Spearman correlation coefficient  = 0.97 (P<0.001). Internal consistency reliability coefficients of the CES-D 10 were satisfactory (Cronbach α = 0.88). The CES-D 10 showed comparable accuracy to the original CES-D 20 in classifying participants with depressive symptoms (Kappa = 0.82, P<0.001). Sensitivity of CES-D 10 was 91%; specificity was 92%; and positive predictive value was 92%. Factor analysis demonstrates that CES-D 10 contains the same underlying factors of positive and negative affect found in the original development of the CES-D 20.

Conclusion

The 10-item CES-D is a comparable tool to measure depressive symptoms among HIV-positive research participants.

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<![CDATA[New Emerging Recombinant HIV-1 Strains and Close Transmission Linkage of HIV-1 Strains in the Chinese MSM Population Indicate a New Epidemic Risk]]> https://www.researchpad.co/article/5989da10ab0ee8fa60b795ac

In recent years, the population of men who have sex with men (MSM) have become the most significant increasing group of HIV-1 transmission in China. To identify new recombinant strains and transmission patterns of HIV-1 in Chinese MSM population, a cross-sectional investigation of MSM in Anhui Province (in south-eastern China) was performed in 2011. The diagnosed AIDS case rate, CD4 T-cell counts, HIV subtypes, and origin of the recombinant strains were investigated in 138 collected samples. The phylogenetic and bootscan analyses demonstrated that, apart from three previously reported circulating strains (CRF07_BC, CRF01_AE, subtype B), various recombinant strains among subtype B, subtype C, CRF01_AE, and CRF07_BC were simultaneously identified in Chinese MSM for the first time. The introducing time of B subtype in Chinese MSM populations was estimated in 1985, CRF01_AE in 2000, and CRF07_BC in 2003; the latter two account for more than 85% of MSM infections. Notably, in comparison with B subtype infections in Anhui MSM, CRF01_AE, with the highest prevalence rate, may accelerate AIDS progression. Over half of patients (56%) infected with new recombinant strains infection are diagnosed as progression into AIDS. Both Bayes and phylogenetic analyses indicated that there was active HIV transmission among MSM nationwide, which may facilitate the transmission of the new 01B recombinant strains in MSM. In conclusion, new recombinant strains and active transmission were identified in the Chinese MSM population, which may lead to a new alarming HIV pandemic in this population due to the increased pathogenesis of the newly emerging strains.

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<![CDATA[Longitudinal Changes of Peripheral Blood DC Subsets and Regulatory T Cells in Chinese Chronic HIV-1-Infected Patients during Antiretroviral Therapy]]> https://www.researchpad.co/article/5989db12ab0ee8fa60bcc587

It has been emphasized that chronic generalized immune dysfunction is the leading event in the pathogenesis of HIV infection, in which the contribution of dendritic cells (DCs) and regulatory T cells (Tregs) should not be underestimated. In current study, we assessed the longitudinal changes of peripheral blood DC subsets and Tregs in chronically asymptomatic treatment-naive HIV-1-infected patients during 60 weeks of antiretroviral therapy (ART), and compared with those in healthy controls and long term non-progressors (LTNPs). Blood samples were collected at week 0, 4, 12, 24, 48 and 60 of treatment to measure the counts of DC subsets and Tregs by flow cytometry and IFN-a plasma levels by ELISA. The counts of myeloid dendritic cells (mDCs) increased during ART, reaching similar levels to healthy controls at week 60 post ART but still lower than those of LTNPs. In HIV-1-infected patients, the mDCs counts were directly correlated with CD4 counts during ART. Changes in mDCs at week 8 were positively correlated with the changes in CD4 counts at week 60 post ART. However, the counts and function of plasmacytoid dendritic cells (pDCs) remained relatively stable during ART, and similar to those in healthy controls and LTNPs. The percentage of Tregs increased before ART and normalized after ART. Importantly, we found pDCs counts were associated with percentage of Tregs during ART, which may help in understanding of the role of these cells in HIV infection.

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<![CDATA[Similar Evolution of Cellular HIV-1 DNA Level in Darunavir/Ritonavir Monotherapy versus Triple Therapy in MONOI –ANRS136 Trial over 96 Weeks]]> https://www.researchpad.co/article/5989db44ab0ee8fa60bd8034

Background

A higher proportion of intermittent viremia (to have a HIV-1 RNA viral load>50 copies/mL not confirmed) was reported in the boosted protease inhibitor monotherapy arm in some studies including MONOI trial, and that could have an impact on the replenishment of the HIV-1 DNA reservoirs. The HIV-1 DNA level is an interesting marker which reflects the size of cellular HIV reservoir. Our objectives were to study the impact of 96 weeks of Darunavir/ritonavir monotherapy versus a triple standard combination on the HIV-1 blood reservoir and factors associated with HIV-1 plasma DNA at baseline in MONOI trial sub-study.

Methodology/Principal Findings

This sub-study is focused on 160 patients (79 patients in monotherapy arm and 81 in tritherapy arm) for whom blood cells were available both at baseline and at week 96 (W96). Baseline HIV-1 plasma DNA was associated with CD4 nadir, pre therapeutic HIV-1 RNA viral load and baseline HIV-1 RNA measured by ultrasensitive assay. A similar median delta HIV-DNA was observed between D0 and W96 in both arms; 0.35 log copies/106 leucocytes in monotherapy arm versus 0.51 log copies/106 leucocytes in tritherapy arm.

Conclusion/Significance

Despite a higher proportion of intermittent viremia in monotherapy arm, a similar evolution of cellular HIV-1 DNA level was observed between mono and triple therapy arm.

Trial Registration

ClinicalTrials. gov NCT00421551 <NCT00421551>

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<![CDATA[Poor Clinical Outcomes for HIV Infected Children on Antiretroviral Therapy in Rural Mozambique: Need for Program Quality Improvement and Community Engagement]]> https://www.researchpad.co/article/5989da75ab0ee8fa60b96447

Introduction

Residents of Zambézia Province, Mozambique live from rural subsistence farming and fishing. The 2009 provincial HIV prevalence for adults 15–49 years was 12.6%, higher among women (15.3%) than men (8.9%). We reviewed clinical data to assess outcomes for HIV-infected children on combination antiretroviral therapy (cART) in a highly resource-limited setting.

Methods

We studied rates of 2-year mortality and loss to follow-up (LTFU) for children <15 years of age initiating cART between June 2006–July 2011 in 10 rural districts. National guidelines define LTFU as >60 days following last-scheduled medication pickup. Kaplan-Meier estimates to compute mortality assumed non-informative censoring. Cumulative LTFU incidence calculations treated death as a competing risk.

Results

Of 753 children, 29.0% (95% CI: 24.5, 33.2) were confirmed dead by 2 years and 39.0% (95% CI: 34.8, 42.9) were LTFU with unknown clinical outcomes. The cohort mortality rate was 8.4% (95% CI: 6.3, 10.4) after 90 days on cART and 19.2% (95% CI: 16.0, 22.3) after 365 days. Higher hemoglobin at cART initiation was associated with being alive and on cART at 2 years (alive: 9.3 g/dL vs. dead or LTFU: 8.3–8.4 g/dL, p<0.01). Cotrimoxazole use within 90 days of ART initiation was associated with improved 2-year outcomes Treatment was initiated late (WHO stage III/IV) among 48% of the children with WHO stage recorded in their records. Marked heterogeneity in outcomes by district was noted (p<0.001).

Conclusions

We found poor clinical and programmatic outcomes among children taking cART in rural Mozambique. Expanded testing, early infant diagnosis, counseling/support services, case finding, and outreach are insufficiently implemented. Our quality improvement efforts seek to better link pregnancy and HIV services, expand coverage and timeliness of infant diagnosis and treatment, and increase follow-up and adherence.

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<![CDATA[Modeling HIV/AIDS Drug Price Determinants in Brazil: Is Generic Competition a Myth?]]> https://www.researchpad.co/article/5989db0aab0ee8fa60bc9f9f

Background

Brazil became the first developing country to guarantee free and universal access to HIV/AIDS treatment, with antiretroviral drugs (ARVs) being delivered to nearly 190,000 patients. The analysis of ARV price evolution and market dynamics in Brazil can help anticipate issues soon to afflict other developing countries, as the 2010 revision of the World Health Organization guidelines shifts demand towards more expensive treatments, and, at the same time, current evolution of international legislation and trade agreements on intellectual property rights may reduce availability of generic drugs for HIV care.

Methods and Findings

Our analyses are based on effective prices paid for ARV procurement in Brazil between 1996 and 2009. Data panel structure was exploited to gather ex-ante and ex-post information and address various sources of statistical bias. In-difference estimation offered in-depth information on ARV market characteristics which significantly influence prices. Although overall ARV prices follow a declining trend, changing characteristics in the generic segment help explain recent increase in generic ARV prices. Our results show that generic suppliers are more likely to respond to factors influencing demand size and market competition, while originator suppliers tend to set prices strategically to offset compulsory licensing threats and generic competition.

Significance

In order to guarantee the long term sustainability of access to antiretroviral treatment, our findings highlight the importance of preserving and stimulating generic market dynamics to sustain developing countries' bargaining power in price negotiations undertaken with originator companies.

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<![CDATA[Increased Prevalence of Albuminuria in HIV-Infected Adults with Diabetes]]> https://www.researchpad.co/article/5989da76ab0ee8fa60b96bc9

Objective

HIV and type 2 diabetes are known risk factors for albuminuria, but no previous reports have characterized albuminuria in HIV-infected patients with diabetes.

Research Design and Methods

We performed a cross-sectional study including 73 HIV-infected adults with type 2 diabetes, 82 HIV-infected non-diabetics, and 61 diabetic control subjects without HIV. Serum creatinine >1.5 mg/dL was exclusionary. Albuminuria was defined as urinary albumin/creatinine ratio >30 mg/g.

Results

The prevalence of albuminuria was significantly increased among HIV-infected diabetics (34% vs. 13% of HIV non-diabetic vs. 16% diabetic control, p = 0.005). HIV status and diabetes remained significant predictors of albuminuria after adjusting for age, race, BMI, and blood pressure. Albumin/creatinine ratio correlated significantly with HIV viral load (r = 0.28, p = 0.0005) and HIV-infected subjects with albuminuria had significantly greater cumulative exposure to abacavir (p = 0.01). In an adjusted multivariate regression analysis of HIV-infected subjects, the diagnosis of diabetes (p = 0.003), higher HIV viral load (p = 0.03) and cumulative exposure to abacavir (p = 0.0009) were significant independent predictors of albuminuria.

Conclusions

HIV and diabetes appear to have additive effects on albuminuria which is also independently associated with increased exposure to abacavir and HIV viral load. Future research on the persistence, progression and management of albuminuria in this unique at-risk population is needed.

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<![CDATA[Naturally-Acquired Influenza-Specific CD4+ T-Cell Proliferative Responses Are Impaired in HIV-Infected African Adults]]> https://www.researchpad.co/article/5989daa8ab0ee8fa60ba875b

Background

Seasonal influenza has been associated with greater morbidity and mortality in AIDS patients. Highly-active antiretroviral therapy (HAART) has led to some reduction in influenza-related complications but the nature of naturally-acquired T-cell immunity to influenza virus in an African setting, and how this changes with immune reconstitution following HAART is unknown. We measured influenza-specific CD4+ T-cell immunity in unimmunized HIV-infected Malawian adults and then investigated immune reconstitution following HAART.

Methods

Peripheral blood mononuclear cells were isolated from HIV-infected and HIV-uninfected Malawian adults. CFSE proliferation and CD154 expression flow cytometry-based assays were used to measure influenza-specific CD4+ T-cell immunity.

Results

We found lower naturally-acquired proliferative influenza-specific CD4+ T-cell responses in AIDS patients that was also present in asymptomatic HIV-infected adults with relatively high CD4 counts (>350 cells/µl). Influenza-specific CD4+ T-cell immune reconstitution in HIV-infected patients on HAART for 12 months was poor despite a marked reduction in viral load and an increase in CD4 count. This poor immune reconstitution was characterised by a low influenza-specific proliferative CD4+ T-cell response and reduced proportions of CD154-expressing influenza-specific CD4+ T-cells in peripheral blood.

Conclusion

Our data suggest that asymptomatic HIV-infected adults may also be at risk of influenza-related complications and that HAART alone may not circumvent this risk in AIDS patients. This study highlights the need to identify possible interventions early in HIV infection to reduce the risk of influenza and to intensify influenza surveillance in these susceptible African populations.

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<![CDATA[Discontinuation of Pneumocystis jirovecii Pneumonia Prophylaxis with CD4 Count <200 Cells/µL and Virologic Suppression: A Systematic Review]]> https://www.researchpad.co/article/5989da02ab0ee8fa60b746a9

Background

HIV viral load (VL) is currently not part of the criteria for Pneumocystis jirovecii pneumonia (PCP) prophylaxis discontinuation, but suppression of plasma viremia with antiretroviral therapy may allow for discontinuation of PCP prophylaxis even with CD4 count <200 cells/µL.

Methods

A systematic review was performed to determine the incidence of PCP in HIV-infected individuals with CD4 count <200 cells/µL and fully suppressed VL on antiretroviral therapy but not receiving PCP prophylaxis.

Results

Four articles examined individuals who discontinued PCP prophylaxis with CD4 count <200 cells/µL in the context of fully suppressed VL on antiretroviral therapy. The overall incidence of PCP was 0.48 cases per 100 person-years (PY) (95% confidence interval (CI) (0.06–0.89). This was lower than the incidence of PCP in untreated HIV infection (5.30 cases/100 PY, 95% CI 4.1–6.8) and lower than the incidence in persons with CD4 count <200 cells/µL, before the availability of highly active antiretroviral therapy (HAART), who continued prophylaxis (4.85/100 PY, 95% CI 0.92–8.78). In one study in which individuals were stratified according to CD4 count <200 cells/µL, there was a greater risk of PCP with CD4 count ≤100 cells/µL compared to 101–200 cells/µL.

Conclusion

Primary PCP prophylaxis may be safely discontinued in HIV-infected individuals with CD4 count between 101–200 cells/µL provided the VL is fully suppressed on antiretroviral therapy. However, there are inadequate data available to make this recommendation when the CD4 count is ≤100 cells/µL. A revision of guidelines on primary PCP prophylaxis to include consideration of the VL is merited.

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<![CDATA[Maternal CD4+ Cell Count Decline after Interruption of Antiretroviral Prophylaxis for the Prevention of Mother-to-Child Transmission of HIV]]> https://www.researchpad.co/article/5989da83ab0ee8fa60b9b7a3

Background

We evaluated maternal CD4+ cell count (CD4+) decline after PMTCT prophylaxis in a multi-country HIV care program.

Methods

Analysis was restricted to antiretroviral therapy (ART)-naive, HIV-infected pregnant women with CD4+ ≥250 cells/mm3 at enrollment. Single-dose nevirapine (sd-NVP) or short-course antiretroviral prophylaxis (sc-ARVp) with zidovudine (AZT) or AZT + lamivudine (3TC) was initiated in 11 programs while 2 programs offered triple-drug antiretroviral prophylaxis (tARVp) (AZT+3TC+ NVP or nelfinavir). All regimens were stopped at delivery. CD4+ decline was defined as proportion of women who declined to CD4+ <350 cells/mm3 or <200 cells/mm3 at 24 months. Weibull regression was used for multivariable analysis.

Findings

A total of 1,393 women with enrollment CD4+ ≥250 cells/mm3 initiated tARVp (172; 12%) or sc-ARVp (532; 38%) during pregnancy or received intrapartum sd-NVP (689; 50%). At enrollment, maternal median age was 27 years (interquartile range (IQR) 23–30), median CD4+ was 469 cells/mm3 (IQR: 363–613). At 24 months post-delivery, the cumulative probability of CD4+ decline to <200 cells/mm3 was 12% (95% CI: 10–14). Among a subgroup of 903 women with CD4+ ≥400 cells at enrollment, the 24 month cumulative probability of decline to CD4+ <350 cells/mm3 was 28%; (95% CI: 25–32). Lower antepartum CD4+ was associated with higher probability of CD4+ decline to <350 cells/mm3: 46% (CD4+400–499 cells/mm3) vs. 19% (CD4+ ≥500 cells/mm3). After adjusting for age, enrollment CD4+ and WHO stage, women who received tARVp or sd-NVP were twice as likely to experience CD4+ decline to <350 cells/mm3 within 24 months than women receiving sc-ARVp (adjusted hazard ratio: 2.2; 95% CI: 1.5–3.2, p<0.0001).

Conclusion

Decline in CD4+ cell count to ART eligibility thresholds by 24 months postpartum was common among women receiving PMTCT prophylaxis during pregnancy and/or delivery.

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<![CDATA[Increased Risk of Fragility Fractures among HIV Infected Compared to Uninfected Male Veterans]]> https://www.researchpad.co/article/5989dae6ab0ee8fa60bbd82a

Background

HIV infection has been associated with an increased risk of fragility fracture. We explored whether or not this increased risk persisted in HIV infected and uninfected men when controlling for traditional fragility fracture risk factors.

Methodology/Principal Findings

Cox regression models were used to assess the association of HIV infection with the risk for incident hip, vertebral, or upper arm fracture in male Veterans enrolled in the Veterans Aging Cohort Study Virtual Cohort (VACS-VC). We calculated adjusted hazard ratios comparing HIV status and controlling for demographics and other established risk factors. The sample consisted of 119,318 men, 33% of whom were HIV infected (34% aged 50 years or older at baseline, and 55% black or Hispanic). Median body mass index (BMI) was lower in HIV infected compared with uninfected men (25 vs. 28 kg/m2; p<0.0001). Unadjusted risk for fracture was higher among HIV infected compared with uninfected men [HR: 1.32 (95% CI: 1.20, 1.47)]. After adjusting for demographics, comorbid disease, smoking and alcohol abuse, HIV infection remained associated with an increased fracture risk [HR: 1.24 (95% CI: 1.11, 1.39)]. However, adjusting for BMI attenuated this association [HR: 1.10 (95% CI: 0.97, 1.25)]. The only HIV-specific factor associated with fragility fracture was current protease inhibitor use [HR: 1.41 (95% CI: 1.16, 1.70)].

Conclusions/Significance

HIV infection is associated with fragility fracture risk. This risk is attenuated by BMI.

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<![CDATA[Systemic Immune Activation in HIV Infection Is Associated with Decreased MDC Responsiveness to TLR Ligand and Inability to Activate Naive CD4 T-Cells]]> https://www.researchpad.co/article/5989da1bab0ee8fa60b7cb97

Background

HIV infection is characterized by ineffective anti-viral T-cell responses and impaired dendritic cell (DC) functions, including response to Toll-Like Receptor (TLR) ligands. Because TLR responsiveness may affect a host's response to virus, we examined TLR ligand induced Myeloid and Plasmacytoid DC (MDC and PDC) activation of naïve T-cells in HIV+ subjects.

Methods

Freshly purified MDC and PDC obtained from HIV+ subjects and healthy controls were cultured in the presence and absence of TLR ligands (poly I∶C or R-848). We evaluated indices of maturation/activation (CD83, CD86, and HLA-DR expression), cytokine secretion (IFN-alpha and IL-6), and ability to activate allogeneic naïve CD4 T-cells to secrete IFN-gamma and IL-2.

Results

MDC from HIV+ subjects had increased spontaneous IL-6 production and increased CD83 and CD86 expression when compared to MDC of controls. MDC IL-6 expression was associated with plasma HIV level. At the same time, poly I∶C induced HLA-DR up-regulation on MDC was reduced in HIV+ persons when compared to controls. The latter finding was associated with impaired ability of MDC from HIV+ subjects to activate allogeneic naïve CD4 T-cells. PDC from HIV+ persons had increased spontaneous and TLR ligand induced IL-6 expression, and increased HLA-DR expression at baseline. The latter was associated with an intact ability of HIV PDC to activate allogeneic naïve CD4 T-cells.

Conclusion

These results have implications for the ability of the HIV+ host to form innate and adaptive responses to HIV and other pathogens.

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