ResearchPad - immunodeficiency-viruses 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[Adherence to antiretroviral therapy and associated factors among Human immunodeficiency virus positive patients accessing treatment at Nekemte referral hospital, west Ethiopia, 2019]]> https://www.researchpad.co/article/elastic_article_7637 Antiretroviral therapy has a remarkable clinical effect in reducing the progress of Acquired Immune Deficiency Syndrome. The clinical outcome of Anti-Retroviral therapy depends on strict adherence. Poor adherence reduces the effectiveness of antiretroviral therapy and increases viral replication. With changes in service delivery over time and differences in socio-demographic status from region to region, it is essential to measure adherence. Therefore, this study aimed to assess adherence to antiretroviral therapy and its associated factors among HIV/AIDS patients accessing treatment at Nekemte referral hospital, West Ethiopia.MethodsInstitutional based cross-sectional study was conducted on 311 HIV/AIDS patients from March 01 to March 30, 2019. The study participants were selected by a simple random sampling method and interviewed using structured questionnaires. Bivariable logistic regression was conducted to find an association between each independent variable and adherence to antiretroviral medication. Multivariable logistic regression was used to find the independent variables which best predict adherence. The statistical significance was measured using odds ratio at a 95% confidence interval with a p-value of less than 0.05.ResultsOut of a total of 311 patients sampled, 305 were participated in the study, making a response rate of 98.07%. From these 305 study participants,73.1% (95% CI = 68.2, 78.0) were adherent to their medication. Having knowledge about HIV and its treatment (AOR = 8.24, 95% CI: 3.10, 21.92), having strong family/social support (AOR = 6.21, 95% CI: 1.39, 27.62), absence of adverse drug reaction (AOR = 5.33, 95% CI: 1.95, 14.57), absence of comorbidity of other chronic diseases (AOR = 5.72, 95% CI: 1.91, 17.16) and disclosing HIV status to the family (AOR = 5.08, 95% CI: 2.09, 12.34) were significantly associated with an increased likelihood of adherence to antiretroviral medication.ConclusionThe level of adherence to antiretroviral therapy was found low compared to WHO recommendation. The clinician should emphasize reducing adverse drug reaction, detecting and treating co-morbidities early, improving knowledge through health education, and encouraging the patients to disclose their HIV status to their families. ]]> <![CDATA[Barriers to linking high-risk jail detainees to HIV pre-exposure prophylaxis]]> https://www.researchpad.co/article/N6cdd8894-eb56-44cf-b406-5a297c3ac14c

Individuals involved in the criminal justice (CJ) system continue to be at disproportionate risk for HIV infection, and often have a greater prevalence of substance use and sexual related risk behaviors relative to their non-CJ involved peers. Pre-exposure prophylaxis (PrEP), a once daily antiretroviral medicine, is an evidence-based approach for reducing the risk of contracting HIV but limited data exist regarding the use of PrEP among CJ populations, especially in the U.S. South. This study was conducted at the Pulaski County Regional Detention Facility (PCRDF) in Little Rock, Arkansas (AR), the largest county jail in the state. We explored knowledge about PrEP and HIV, perceptions about PrEP feasibility in both the jail and community settings and barriers to PrEP program implementation, through in-depth qualitative interviews with 21 jail detainees. We purposively sampled individuals based on specific self-reported risk behavior, including sexual risk (both heterosexual and same-sex) and drug related risk (e.g. IDU), among all eligible individuals. We identified five primary themes from the interviews: 1) accessing healthcare during community reentry was a low priority; 2) perception of risk and interaction with people with HIV was low; 3) there are many barriers to disclosing HIV risk behaviors in jail settings; 4) knowledge of PrEP is low but willingness to use is high; and 5) multiple barriers exist to PrEP uptake post-release. Our findings are contextually unique and therefore have important implications for future implementation of PrEP access either within jail settings or linkage to PrEP post release.

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<![CDATA[Feasibility of establishing an HIV vaccine preparedness cohort in a population of the Uganda Police Force: Lessons learnt from a prospective study]]> https://www.researchpad.co/article/Ne890bb8a-5661-4c39-82f7-6f40a2e69675

Background

Members of uniformed armed forces are considered to be at high risk for HIV infection and have been proposed as suitable candidates for participation in HIV intervention studies. We report on the feasibility of recruitment and follow up of individuals from the community of the Uganda Police Force (UPF) for an HIV vaccine preparedness study.

Methods

HIV-negative volunteers aged 18–49 years, were identified from UPF facilities situated in Kampala and Wakiso districts through community HIV counselling and testing. Potential volunteers were referred to the study clinic for screening, enrolment and quarterly visits for one year. HIV incidence, retention rates were estimated and expressed as cases per 100 person years of observation (PYO). Rate ratios were used to determine factors associated with retention using Poisson regression models.

Results

We screened 560 to enroll 500 volunteers between November 2015 and May 2016. One HIV seroconversion occurred among 431 PYO, for an incidence rate of 0.23/100 PYO (95% confidence interval [CI]: 0.03–1.64). Overall, retention rate was 87% at one year, and this was independently associated with residence duration (compared to <1 year, 1 to 5 years adjusted rate ratio (aRR) = 1.19, 95%CI: 1.00–1.44); and >5 years aRR = 1.34, 95%CI: 0.95–1.37); absence of genital discharge in the last 3 months (aRR = 1.97, 95% CI: 1.38–2.83, absence of genital ulcers (aRR = 1.90, 95%CI: 1.26–2.87, reporting of new sexual partner in the last month (aRR = 0.57, 95%CI: 0.45–0.71, being away from home for more than two nights (aRR = 1.27, 95%CI: 1.04–1.56, compared to those who had not travelled) and absence of knowledge on HIV prevention (aRR = 2.67, 95%CI: 1.62–4.39).

Conclusions

While our study demonstrates the feasibility of recruiting and retaining individuals from the UPF for HIV research, we did observe lower than anticipated HIV incidence, perhaps because individuals at lower risk of HIV infection may have been the first to come forward to participate or participants followed HIV risk reduction measures. Our findings suggest lessons for recruitment of populations at high risk of HIV infection.

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<![CDATA[“It is always better for a man to know his HIV status” – A qualitative study exploring the context, barriers and facilitators of HIV testing among men in Nairobi, Kenya]]> https://www.researchpad.co/article/N633bb09e-858a-4016-b37a-13e5d588b21f

HIV testing services are an important component of HIV program and provide an entry point for clinical care for persons newly diagnosed with HIV. Although uptake of HIV testing has increased in Kenya, men are still less likely than women to get tested and access services. There is, however, limited understanding of the context, barriers and facilitators of HIV testing among men in the country. Data are from in-depth interviews with 30 men living with HIV and 8 HIV testing counsellors that were conducted to gain insights on motivations and drivers for HIV testing among men in the city of Nairobi. Men were identified retroactively by examining clinical CD4 registers on early and late diagnosis (e.g. CD4 of ≥500 cells/mm, early diagnosis and <500 cells/mm, late diagnosis). Analysis involved identifying broad themes and generating descriptive codes and categories. Timing for early testing is linked with strong social support systems and agency to test, while cost of testing, choice of facility to test and weak social support systems (especially poor inter-partner relations) resulted in late testing. Minimal discussions occurred prior to testing and whenever there was dialogue it happened with partners or other close relatives. Interrelated barriers at individual, health-care system, and interpersonal levels hindered access to testing services. Specifically, barriers to testing included perceived providers attitudes, facility location and set up, wait time/inconvenient clinic times, low perception of risk, limited HIV knowled ge, stigma, discrimination and fear of having a test. High risk perception, severe illness, awareness of partner’s status, confidentiality, quality of services and supplies, flexible/extended opening hours, and pre–and post–test counselling were facilitators. Experiences between early and late testers overlapped though there were minor differences. In order to achieve the desired impact nationally and to attain the 90-90-90 targets, multiple interventions addressing both barriers and facilitators to testing are needed to increase uptake of testing and to link the positive to care.

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<![CDATA[Toward precision prescribing for methadone: Determinants of methadone deposition]]> https://www.researchpad.co/article/N51499fe4-a854-40f2-ac0e-5bd2b114360f

Background

Despite the World Health Organization listing methadone as an essential medication, effective dose selection is challenging, especially in racial and ethnic minority populations. Subtherapeutic doses can result in withdrawal symptoms while supratherapeutic doses can result in overdose and death. Although CYP3A4 was conventionally considered the principal methadone metabolizing enzyme, more recent data have identified CYP2B6 as the principal enzyme. CYP2B6 has ethnically-associated polymorphisms that affect the metabolic rate. Our objective was to investigate the effects of genetic and nongenetic factors on methadone metabolism.

Methods

We measured trough plasma methadone levels in 100 participants with opioid use disorder. We assessed methadone metabolism by calculating the metabolite ratio (major metabolite: 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine [EDDP] divided by methadone concentration). We assessed hepatic fibrosis and steatosis by transient elastography and CYP2B6 alleles, principally responsible for methadone metabolism. Mixed effects models modeled the data in 97 participants.

Results

Participants were largely male (58%), minority (61% African American) and non-Hispanic (68%). Forty percent were HCV mono-infected, 40% were uninfected, and 20% were HCV/HIV co-infected. Female sex had significant effects on (R)- and (S)-methadone metabolism (p = 0.016 and p = 0.044, respectively). CYP2B6 loss of function (LOF) alleles significantly affected (S)-methadone metabolism (p = 0.012). Body mass index (BMI) significantly affected (R)-methadone metabolism (p = 0.034). Methadone metabolism appeared to be lower in males, in individuals with LOF alleles, and elevated BMI.

Conclusions

Genetic analysis, especially in minority populations, is essential to delivering individualized treatments. Although the principal methadone metabolizing enzyme remains controversial, our results suggest that sex, CYP2B6 genotype, and BMI should be incorporated into multivariate models to create methadone dosing algorithms. Methadone dosing algorithms should facilitate medication delivery, improve patient satisfaction, and diminish overdose potential.

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<![CDATA[The inhibitor of apoptosis proteins antagonist Debio 1143 promotes the PD-1 blockade-mediated HIV load reduction in blood and tissues of humanized mice]]> https://www.researchpad.co/article/N65563527-6ce7-4ff1-862d-df2c817374ce

The immune checkpoint programmed cell death protein 1 (PD-1) plays a major role in T cell exhaustion in cancer and chronic HIV infection. The inhibitor of apoptosis protein antagonist Debio 1143 (D1143) enhances tumor cell death and synergizes with anti-PD-1 agents to promote tumor immunity and displayed HIV latency reversal activity in vitro. We asked in this study whether D1143 would stimulate the potency of an anti-human PD-1 monoclonal antibody (mAb) to reduce HIV loads in humanized mice. Anti-PD-1 mAb treatment decreased PD-1+ CD8+ cell population by 32.3% after interruption of four weeks treatment, and D1143 co-treatment further reduced it from 32.3 to 73%. Anti-PD-1 mAb administration reduced HIV load in blood by 94%, and addition of D1143 further enhanced this reduction from 94 to 97%. D1143 also more profoundly promoted with the anti-PD-1-mediated reduction of HIV loads in all tissues analyzed including spleen (71 to 96.4%), lymph nodes (64.3 to 80%), liver (64.2 to 94.4), lung (64.3 to 80.1%) and thymic organoid (78.2 to 98.2%), achieving a >5 log reduction of HIV loads in CD4+ cells isolated from tissues 2 weeks after drug treatment interruption. Ex vivo anti-CD3/CD28 stimulation increased the ability to activate exhausted CD8+ T cells in infected mice having received in vivo anti-PD-1 treatment by 7.9-fold (5 to 39.6%), and an additional increase by 1.7-fold upon D1143 co-treatment (39.6 to 67.3%). These findings demonstrate for the first time that an inhibitor of apoptosis protein antagonist enhances in a statistically manner the effects of an immune check point inhibitor on antiviral immunity and on HIV load reduction in tissues of humanized mice, suggesting that the combination of two distinct classes of immunomodulatory agents constitutes a promising anti-HIV immunotherapeutic approach.

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<![CDATA[Long term outcomes and prognostics of visceral leishmaniasis in HIV infected patients with use of pentamidine as secondary prophylaxis based on CD4 level: a prospective cohort study in Ethiopia]]> https://www.researchpad.co/article/5c784fedd5eed0c48400792b

Background

The long-term treatment outcome of visceral leishmaniasis (VL) patients with HIV co-infection is complicated by a high rate of relapse, especially when the CD4 count is low. Although use of secondary prophylaxis is recommended, it is not routinely practiced and data on its effectiveness and safety are limited.

Methods

A prospective cohort study was conducted in Northwest Ethiopia from August 2014 to August 2017 (NCT02011958). HIV-VL patients were followed for up to 12 months. Patients with CD4 cell counts below 200/μL at the end of VL treatment received pentamidine prophylaxis starting one month after parasitological cure, while those with CD4 count ≥200 cells/μL were followed without secondary prophylaxis. Compliance, safety and relapse-free survival, using Kaplan-Meier analysis methods to account for variable time at risk, were summarised. Risk factors for relapse or death were analysed.

Results

Fifty-four HIV patients were followed. The probability of relapse-free survival at one year was 50% (95% confidence interval [CI]: 35–63%): 53% (30–71%) in 22 patients with CD4 ≥200 cells/μL without pentamidine prophylaxis and 46% (26–63%) in 29 with CD4 <200 cells/μL who started pentamidine. Three patients with CD4 <200 cells/μL did not start pentamidine. Amongst those with CD4 ≥200 cells/μL, VL relapse was an independent risk factor for subsequent relapse or death (adjusted rate ratio: 5.42, 95% CI: 1.1–25.8). Except for one case of renal failure which was considered possibly related to pentamidine, there were no drug-related safety concerns.

Conclusion

The relapse-free survival rate for VL patients with HIV was low. Relapse-free survival of patients with CD4 count <200cells/μL given pentamidine secondary prophylaxis appeared to be comparable to patients with a CD4 count ≥200 cells/μL not given prophylaxis. Patients with relapsed VL are at higher risk for subsequent relapse and should be considered a priority for secondary prophylaxis, irrespective of their CD4 count.

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<![CDATA[Dynamics of leukocyte telomere length in pregnant women living with HIV, and HIV-negative pregnant women: A longitudinal observational study]]> https://www.researchpad.co/article/5c897779d5eed0c4847d2db4

Background

HIV-mediated inflammation and immune activation can accelerate telomere attrition. In addition, antiretrovirals can inhibit telomerase, possibly shortening telomeres. We examined the longitudinal dynamics of leukocyte telomere length (LTL) during pregnancy in a unique cohort of women living with HIV (WLWH) treated with combination antiretroviral therapy (cART), and HIV-negative control women.

Methods

Blood was collected at three visits during pregnancy, at 13–23, >23–30, and >30–40 weeks of gestation, and for WLWH only, at 6 weeks post-partum. LTL was measured by qPCR and both cross-sectional and longitudinal (MANOVA) models were used to examine possible predictors of LTL among participants who attended all three visits during pregnancy.

Results

Among WLWH (n = 64) and HIV-negative women (n = 41), within participant LTL were correlated throughout pregnancy (p<0.001). LTL was shorter among WLWH at first visit, but this difference waned by the second visit. WLWH who discontinued cART post-partum experienced a decrease in LTL. Longitudinally, LTL was similar in both groups and increased as gestation progressed, a change that was more pronounced among women under 35 years. Among WLWH, both smoking throughout pregnancy (p = 0.04) and receiving a ritonavir-boosted protease inhibitor-based regimen (p = 0.03) were independently associated with shorter LTL.

Conclusions

LTL increases as pregnancy progresses; the reasons for this are unknown but may relate to changes in blood volume, hormones, and/or cell subset distribution. While our observations need confirmation in an independent cohort, our data suggest that although some cART regimens may influence LTL, being on cART appears overall protective and that stopping cART post-partum may negatively impact LTL. The effect of smoking on LTL is clearly negative, stressing the importance of smoking cessation.

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<![CDATA[PhyloPi: An affordable, purpose built phylogenetic pipeline for the HIV drug resistance testing facility]]> https://www.researchpad.co/article/5c8823b3d5eed0c484638e7d

Introduction

Phylogenetic analysis plays a crucial role in quality control in the HIV drug resistance testing laboratory. If previous patient sequence data is available sample swaps can be detected and investigated. As Antiretroviral treatment coverage is increasing in many developing countries, so is the need for HIV drug resistance testing. In countries with multiple languages, transcription errors are easily made with patient identifiers. Here a self-contained blastn integrated phylogenetic pipeline can be especially useful. Even though our pipeline can run on any unix based system, a Raspberry Pi 3 is used here as a very affordable and integrated solution.

Performance benchmarks

The computational capability of this single board computer is demonstrated as well as the utility thereof in the HIV drug resistance laboratory. Benchmarking analysis against a large public database shows excellent time performance with minimal user intervention. This pipeline also contains utilities to find previous sequences as well as phylogenetic analysis and a graphical sequence mapping utility against the pol area of the HIV HXB2 reference genome. Sequence data from the Los Alamos HIV database was analyzed for inter- and intra-patient diversity and logistic regression was conducted on the calculated genetic distances. These findings show that allowable clustering and genetic distance between viral sequences from different patients is very dependent on subtype as well as the area of the viral genome being analyzed.

Availability

The Raspberry Pi image for PhyloPi, source code of the pipeline, sequence data, bash-, python- and R-scripts for the logistic regression, benchmarking as well as helper scripts are available at http://scholar.ufs.ac.za:8080/xmlui/handle/11660/7638 and https://github.com/ArmandBester/phylopi. The PhyloPi image and the source code are published under the GPLv3 license. A demo version of the PhyloPi pipeline is available at http://phylopi.hpc.ufs.ac.za/.

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<![CDATA[Voluntary medical male circumcision (VMMC) for prevention of heterosexual transmission of HIV and risk compensation in adult males in Soweto: Findings from a programmatic setting]]> https://www.researchpad.co/article/5c8acc83d5eed0c48498f8f2

Background

Clinical trials have clearly shown a reduction in HIV acquisition through voluntary medical male circumcision (VMMC). However, data assessing risk compensation under programmatic conditions is limited.

Methods

This was a prospective cohort of HIV seronegative males aged 18–40 years receiving VMMC between November 2012 and July 2014. HIV serostatus was determined pre and post VMMC. Risk compensation was defined as a decrease in condom use at last sex act and/or an increase in concurrent sexual relationships, both measured twelve months post-circumcision.

Results

A total of 233 males were enrolled and underwent voluntary medical male circumcision (VMMC) for prevention against HIV. There was no evidence of risk compensation post-circumcision as defined in this study. Significant increases in proportion of participants in the 18–24 years age group who knew the HIV status of their sexual partner (39% to 56%, p = 0.0019), self-reported condom use at last sex act (21% to 34%, p = 0.0106) and those reporting vaginal sexual intercourse in the past 12 months (67% to 79%, p-value = <0.0001) were found. In both 18–24 and 25–40 years age groups, there was a significant increase in perception of being at risk of contracting HIV (70% to 84%, p-value = <0.0001).

Conclusion

No significant risk compensation was observed in this study on comparing pre-and post-circumcision behaviour. An increase in proportion of participants in the 18–24 years age group who had vaginal intercourse in the first 12 months post-circumcision as a possibility of risk compensation was minimal and negated by an increase in proportion of those reporting using a condom at the last sex act, increase in knowledge of partner’s HIV status and lack of increase in alcohol post-circumcision.

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<![CDATA[Food insecurity and violence in a prospective cohort of women at risk for or living with HIV in the U.S.]]> https://www.researchpad.co/article/5c89779fd5eed0c4847d31be

Background

Food insecurity and violence are two major public health issues facing U.S. women. The link between food insecurity and violence has received little attention, particularly regarding the temporal ordering of events. The present study used data from the Women’s Interagency Human Immunodeficiency Virus Study to investigate the longitudinal association of food insecurity and violence in a cohort of women at risk for or living with HIV.

Methods

Study participants completed six assessments from 2013–16 on food insecurity (operationalized as marginal, low, and very low food security) and violence (sexual or physical, and psychological). We used multi-level logistic regression, controlling for visits (level 1) nested within individuals (level 2), to estimate the association of experiencing violence.

Results

Among 2,343 women (8,528 visits), we found that victims of sexual or physical violence (odds ratio = 3.10; 95% confidence interval: 1.88, 5.19) and psychological violence (odds ratio = 3.00; 95% confidence interval: 1.67, 5.50) were more likely to report very low food security. The odds of experiencing violence were higher for women with very low food security at both the current and previous visit as compared to only the current visit. HIV status did not modify these associations.

Conclusions

Food insecurity was strongly associated with violence, and women exposed to persistent food insecurity were even more likely to experience violence. Food programs and policy must consider persistent exposure to food insecurity, and interpersonal harms faced by food insecure women, such as violence.

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<![CDATA[Empowering HIV-infected women in low-resource settings: A pilot study evaluating a patient-centered HIV prevention strategy for reproduction in Kisumu, Kenya]]> https://www.researchpad.co/article/5c897736d5eed0c4847d26fe

Background

Female positive/male negative HIV-serodiscordant couples express a desire for children and may engage in condomless sex to become pregnant. Current guidelines recommend antiretroviral treatment in HIV-serodiscordant couples, yet HIV RNA viral suppression may not be routinely assessed or guaranteed and pre-exposure prophylaxis may not be readily available. Therefore, options for becoming pregnant while limiting HIV transmission should be offered and accessible to HIV-affected couples desiring children.

Methods

A prospective pilot study of female positive/male negative HIV-serodiscordant couples desiring children was conducted to evaluate the acceptability, feasibility, and effectiveness of timed vaginal insemination. Eligible women were 18–34 years with regular menses. Prior to timed vaginal insemination, couples were observed for two months, and tested and treated for sexually transmitted infections. Timed vaginal insemination was performed for up to six menstrual cycles. A fertility evaluation and HIV RNA viral load assessment was offered to couples who did not become pregnant.

Findings

Forty female positive/male negative HIV-serodiscordant couples were enrolled; 17 (42.5%) exited prior to timed vaginal insemination. Twenty-three couples (57.5%) were introduced to timed vaginal insemination; eight (34.8%) achieved pregnancy, and six live births resulted without a case of HIV transmission. Seven couples completed a fertility evaluation. Four women had no demonstrable tubal patency bilaterally; one male partner had decreased sperm motility. Five women had unilateral/bilateral tubal patency; and seven women had an HIV RNA viral load (≥ 400 copies/mL).

Conclusion

Timed vaginal insemination is an acceptable, feasible, and effective method for attempting pregnancy. Given the desire for children and inadequate viral suppression, interventions to support safely becoming pregnant should be integrated into HIV prevention programs.

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<![CDATA[Assessing the role of transmission chains in the spread of HIV-1 among men who have sex with men in Quebec, Canada]]> https://www.researchpad.co/article/5c89773dd5eed0c4847d27bf

Background

Phylogenetics has been used to investigate HIV transmission among men who have sex with men. This study compares several methodologies to elucidate the role of transmission chains in the dynamics of HIV spread in Quebec, Canada.

Methods

The Quebec Human Immunodeficiency Virus (HIV) genotyping program database now includes viral sequences from close to 4,000 HIV-positive individuals classified as Men who have Sex with Men (MSMs), collected between 1996 and early 2016. Assessment of chain expansion may depend on the partitioning scheme used, and so, we produce estimates from several methods: the conventional Bayesian and maximum likelihood-bootstrap methods, in combination with a variety of schemes for applying a maximum distance criterion, and two other algorithms, DM-PhyClus, a Bayesian algorithm that produces a measure of uncertainty for proposed partitions, and the Gap Procedure, a fast non-phylogenetic approach. Sequences obtained from individuals in the Primary HIV Infection (PHI) stage serve to identify incident cases. We focus on the period ranging from January 1st 2012 to February 1st 2016.

Results and conclusion

The analyses reveal considerable overlap between chain estimates obtained from conventional methods, thus leading to similar estimates of recent temporal expansion. The Gap Procedure and DM-PhyClus suggest however moderately different chains. Nevertheless, all estimates stress that longer older chains are responsible for a sizeable proportion of the sampled incident cases among MSMs. Curbing the HIV epidemic will require strategies aimed specifically at preventing such growth.

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<![CDATA[Effects of highly active antiretroviral therapy on semen parameters of a cohort of 770 HIV-1 infected men]]> https://www.researchpad.co/article/5c78500cd5eed0c484007bb8

Background

HIV-1 infected patients show impaired semen parameters. Currently, it is not clear whether HIV-1 infection itself or antiretroviral therapy have an effect on semen parameters. We aim evaluate semen quality in a large cohort of fertile HIV-1 infected men under stable highly active antiretroviral therapy (HAART) and to assess the effect of HAART type and duration on semen parameters.

Materials and methods

Between January 2010 and June 2014, we enrolled in a retrospective case-control study 770 HIV-1 patients under stable HAART asking a reproductive counselling with their HIV negative partner. Co-infections with HBV or HCV, genital tract infections and known causes of infertility represented exclusion criteria. Semen samples were analysed and compared with the WHO reference values. A multivariate analysis including HAART type and duration, age, viral load and CD4 count, was performed on 600 patients out of 770.

Results

The median values of all semen parameters were significantly lower among HIV-1 infected patients compared to the WHO reference group, with a significant proportion of patients having values below the 5th percentile of the WHO reference value. In a multivariate analysis, only age and viral load negatively impacted progressive motility (β -0.3 (95% CI: -0.5; -0.0) %, p<0.05) and semen morphology (β -0.00 (95% CI: -0.00; -0.00) %, p≤0.01), while no associations were detected as regards HAART type and duration.

Conclusions

HIV-1 infected patients showed a significant impairment of semen parameters compared to the reference values. HAART type and duration showed no associations with semen quality. Further research is needed to investigate implications for clinical care of HIV infected men desiring a child.

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<![CDATA[Antiretroviral adherence and virologic suppression in partnered and unpartnered HIV-positive individuals in southern Brazil]]> https://www.researchpad.co/article/5c803c70d5eed0c484ad896d

Background

An undetectable serum HIV-1 load is key to effectiveness of antiretroviral (ARV) therapy, which depends on adherence to treatment. We evaluated factors possibly associated with ARV adherence and virologic response in HIV-infected heterosexual individuals.

Methods

A cross-sectional study was conducted in 200 HIV-1 serodiscordant couples and 100 unpartnered individuals receiving ARV treatment at a tertiary hospital in southern Brazil. All subjects provided written informed consent, answered demographic/behavioral questionnaires through audio computer-assisted self-interviews (ACASI), and collected blood and vaginal samples for biological markers and assessment of sexually transmitted infections (STIs). HIV-negative partners were counseled and tested for HIV-1.

Results

The study population mean age was 39.9 years, 53.6% were female, 62.5% were Caucasian, 52.6% had incomplete or complete elementary education, 63.1% resided in Porto Alegre. Demographic, behavioral and biological marker characteristics were similar between couples and single individuals. There was an association between adherence reported on ACASI and an undetectable serum viral load (P<0.0001). Logistic regression analysis demonstrated that single-tablet ARV-regimens were independently associated with adherence (OR = 2.3; 95CI%: 1.2–4.4; P = 0.011) after controlling for age, gender, education, marital status, personal income, ARV regimen, and median time of ARV use. A positive correlation between genital secretion PCR results and serum viral load was significant in the presence of STIs (r = 0.359; P = 0.017). Although HIV PCR detection in vaginal secretions was more frequent in women with detectable viremia (9/51, 17.6%), it was also present in 7 of 157 women with undetectable serum viral loads (4.5%), p = 0.005.

Conclusions

ARV single tablet regimens are associated with adherence. Detectable HIV-1 may be present in the genital secretions of women with undetectable viremia which means there is potential for HIV transmission in adherent individuals with serologic suppression.

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<![CDATA[Economic and public health impact of decentralized HIV viral load testing: A modelling study in Kenya]]> https://www.researchpad.co/article/5c803c61d5eed0c484ad883e

Kenya has the world’s 4th largest HIV burden. Various strategies to control the epidemic have been implemented, including the implementation of viral load (VL) testing to monitor HIV patients on ARVs. Like many resource limited settings, Kenya’s healthcare system faces serious challenges in effectively providing quality health services to its population. Increased investments to strengthen the country’s capacity to diagnose, monitor and treat diseases, particularly HIV and TB, continue to be made but are still inadequate in the face of global health goals like the UNAIDS 90:90:90 which require scaling up of VL tests amid existing constraints. In Kenya, there is an increase in the demand for VL tests amidst these existing constraints. The GeneXpert system is a diagnostic point-of-care technology that can quantify, amongst others, HIV VL. Currently, GeneXpert technology is widely distributed in Kenya for testing of tuberculosis. This study aimed to determine the economic and public health impact of incorporating VL test modules on the existing GeneXpert infrastructure. Markov models were constructed for different populations (non-pregnant adults, pregnant women and children). The scenarios analysed were 100% centralized VL testing compared to 50% GeneXpert plus 50% centralized VL testing, with time horizons of 5 years for the adult and child populations, and 31 months for the pregnant population. Incremental effectiveness was measured in terms of the number of HIV transmissions or opportunistic infections avoided when implementing the GeneXpert scenario compared to a 100% centralized scenario. The model indicated that, for all three populations combined, the GeneXpert scenario resulted in 117 less HIV transmissions and 393 less opportunistic infections. The cost decreased by $21,978,755 for the non-pregnant and pregnant adults and $22,808,533 for non-pregnant adults, pregnant adults and children. The model showed that GeneXpert would cost less and be more effective in terms of total cost per HIV transmission avoided and the total cost per opportunistic infection avoided, except for the pregnant population, when considered separately.

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<![CDATA[HIV self-testing in Spain: A valuable testing option for men-who-have-sex-with-men who have never tested for HIV]]> https://www.researchpad.co/article/5c6dc9f4d5eed0c48452a5cf

Background

We assessed the capacity of HIV self-testing to promote testing among untested men who have sex with men (MSM) and determined the most benefited subpopulations.

Methods

An online questionnaire was disseminated on several gay websites in Spain from September 2012 to April 2013. We used Poisson regression to estimate factors associated with the intention to use self-testing if already available. Among those who reported intention of use, we assessed several aspects related to the testing and linkage to care process by type of barrier reported: low perceived risk (LR), structural barriers (SB) and fear of testing positive (FTP).

Results

Of 2589 never-tested MSM, 83% would have used self-testing if already available. Intention of use was associated with age ≥30 (adj.PR, 95%CI: 1.05, 1.01–1.10), having had protected (adj.PR, 95%CI: 1.15, 1.02–1.30) or unprotected (adj.PR, 95%CI: 1.21, 1.07–1.37) anal intercourse and reporting FTP (adj.PR, 95%CI: 1.12, 1.05–1.20) or SB to access HIV testing (adj.PR, 95%CI: 1.23, 1.19–1.28). Among those who reported intention of using a self-testi, 78.3% declared it their preferred option (83.8% in the SB group; p<0.001), and 56.8% would always use this testing option (60.9% among the SB group; p = 0.001). In the case of obtaining a positive self-test, 69.3% would seek confirmatory testing, 15.3% would self-test again before taking any decision and 13.0% reported not being sure of what they would do.

Conclusion

HIV self-testing in Spain has the potential of becoming a highly used testing methodology for untested MSM and could represent the gateway to testing especially among older, at risk MSM who report SB or FTP as main barriers to testing.

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<![CDATA[“Even if she’s really sick at home, she will pretend that everything is fine.”: Delays in seeking care and treatment for advanced HIV disease in Kinshasa, Democratic Republic of Congo]]> https://www.researchpad.co/article/5c6dc9efd5eed0c48452a55d

Introduction

HIV prevalence in the Democratic Republic of Congo (DRC) is estimated to be 1.2%, and access to HIV testing and treatment remains low across the country. Despite advances in treatment, HIV continues to be one of the main reasons for hospitalisation and death in low- and middle-income countries, including DRC, but the reasons why people delay seeking health-care when they are extremely sick remain little understood. People in Kinshasa, DRC, continue to present to health-care facilities in an advanced stage of HIV when they are close to death and needing intensive treatment.

Methods

This qualitative study was conducted in one health-care facility in Kinshasa. A total of 24 in-depth interviews with purposively selected health-care workers, patients and care-givers were conducted. Patients were currently or previously hospitalised with advanced HIV, defined as CD4 count <200 cells/μl. Patients included those who had previously started antiretroviral treatment (ART), and those who had not. Participant observation was also carried out. Interviews were audio-recorded, translated from French and Lingala into English, transcribed, coded and thematically analysed using NVivo.

Results

The main reasons for delaying access to health-care were stigmatisation, religious beliefs and limited economic resources. Stigmatisation meant that people feared disclosing their HIV status and thus did not receive support from their families. Religious leaders were reported to have encouraged people not to take ART. Patients delayed seeking treatment as they could not afford it, and health-care workers believed that staff at other facilities in Kinshasa were delaying HIV diagnoses for economic benefit.

Conclusions

Delays in accessing care and treatment linked to stigma, religious beliefs and economic factors contribute to explaining the persistence of advanced HIV within this context. Access to free HIV-testing, ART and treatment of opportunistic infections; counselling; training of health-care workers; support for care-givers and stigma reduction strategies are urgently needed to prevent unnecessary deaths.

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<![CDATA[Health system barriers to implementation of TB preventive strategies in South African primary care facilities]]> https://www.researchpad.co/article/5c6f14b4d5eed0c48467a684

Background

Isoniazid preventive therapy (IPT) is a key component of TB/HIV control, but few countries achieve high IPT coverage.

Methods

Using a behavioural COM-B design approach, the intervention consisted of a training on IPT guidelines and tuberculin skin testing (TST), identification of the optimal IPT implementation strategy by the health care workers (HCWs) of 3 primary care clinics, and a 2-month mentoring period. Using routine register data, TST and IPT uptake was determined 3 months before and 5 months after the intervention. Records were reviewed to identify factors associated with IPT initiation and HCW fidelity to the guidelines. A survey among HCWs was conducted to determine barriers to IPT.

Results

Two clinics implemented TST-guided IPT for all clients receiving HIV care, one clinic decided against use of TST. According to routine register data, the proportion of clients initiating IPT increased substantially at the clinic not opting for TST (6% vs 36%), but minimally (34% vs 37% and 0.7% vs 3%) in the two other clinics. TST uptake did not increase (0 vs 0% and 0.5%). In addition to poor IPT uptake, HCW fidelity to investigation for TB and timing of IPT initiation was poor, with only 68% of symptomatic patients investigated and IPT initiation delayed to a median of 374 days post-ART initiation. In multivariate analysis, pregnancy (aOR 18.62, 95% CI 6.99–53.46), recent HIV diagnosis (aOR 3.65, 95% CI 1.73–7.41), being on ART (aOR 9.44, 95% CI 3.05–36.17), and CD4 <500 cells/mm3 (aOR 2.19, 95% CI 1.22–4.18) were associated with IPT initiation. Time needed to perform a TST, motivating patients to return for TST reading, and low IPT patient awareness were the main barriers to IPT implementation.

Conclusion

Despite using a behavioural intervention framework including training and participatory development of the clinic IPT strategy, HCW fidelity to the guidelines was poor, resulting in low TST coverage and low IPT uptake under primary care conditions. To achieve the benefits of IPT, health system level approaches including TST-free guidelines and sensitization are needed.

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