scholarly journals A Multi-Disciplinary Care Model for People with Drug-Resistant HIV: The AMPATH HIV Drug Resistance Clinic in Kenya

2019 ◽  
Vol 2 (1) ◽  
Author(s):  
Bilal Jawed ◽  
John Humphery ◽  
Adrian Gardner

Background: HIV mortality has decreased with the availability of ART (antiretroviral therapy) in resource-limited settings, resulting in an increase in the number of people living with HIV (PLHIV) globally. This increase in PLHIV has shifted the HIV-care model from an acute to a chronic approach requiring more effort to combat barriers to viral suppression such as long-term adherence to ART, stigma, and drug resistance. An increasing number of PLHIV are failing “2nd line” protease-inhibitor based ART as a result of these barriers, leaving these patients with limited options for treatment. To address this issue, the Academic Model Providing Access to Healthcare (AMPATH) created a multidisciplinary HIV-drug resistance clinic focusing on supporting patients failing second-line ART in 2015. The objective of this study is to describe the implementation of the AMPATH DRC in western Kenya. Methods: The HIV Drug Resistance Clinic (DRC) accepts patients from over 20 surrounding HIV clinics in a setting with over 100,000 PLHIV. The DRC identifies and enrolls patients failing second-line ART defined as ≥ 2 viral loads ≥ 1,000 copies/mL despite adherence interventions. The multidisciplinary team consists of HIV-specialist physicians, trained HIV-peer counselors, clinical pharmacists, and social workers who collaborate with patients in clinic to identify barriers to adherence and implement patient-centered interventions to mitigate barriers to adherence, treat drug resistance, and maximize the efficacy of ART. The DRC staff has expertise in ART regimen selection for patients with advance HIV drug resistance through analysis of drug resistant test results (i.e. HIV genotype). Over 600 patients have received care at the DRC since 2015. Personal role: Identifying barriers and facilitators to implementation of DRCs in regional AMPATH sites, data abstraction to determine DRC clinical outcomes, and introduction of DRT results in the AMPATH MRS. Moving Forward: By building the capacity of clinical leaders in decentralized regional AMPATH sites, we hope to expand the DRC care model within the AMPATH network. 

2013 ◽  
Vol 207 (suppl_2) ◽  
pp. S49-S56 ◽  
Author(s):  
Mina C. Hosseinipour ◽  
Ravindra K Gupta ◽  
Gert Van Zyl ◽  
Joseph J. Eron ◽  
Jean B. Nachega

Viruses ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 877 ◽  
Author(s):  
Birkneh Tilahun Tadesse ◽  
Olivia Tsai ◽  
Adugna Chala ◽  
Tolossa Eticha Chaka ◽  
Temesgen Eromo ◽  
...  

Pediatric human immunodeficiency virus (HIV) care in resource-limited settings remains a major challenge to achieving global HIV treatment and virologic suppression targets, in part because the administration of combination antiretroviral therapies (cART) is inherently complex in this population and because viral load and drug resistance genotyping are not routinely available in these settings. Children may also be at elevated risk of transmission of drug-resistant HIV as a result of suboptimal antiretroviral administration for prevention of mother-to-child transmission. We investigated the prevalence and the correlates of pretreatment HIV drug resistance (PDR) among HIV-infected, cART-naive children in Ethiopia. We observed an overall PDR rate of 14%, where all cases featured resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs): ~9% of participants harbored resistance solely to NNRTIs while ~5% harbored resistance to both NNRTIs and nucleoside reverse transcriptase inhibitors (NRTIs). No resistance to protease inhibitors was observed. No sociodemographic or clinical parameters were significantly associated with PDR, though limited statistical power is noted. The relatively high (14%) rate of NNRTI resistance in cART-naive children supports the use of non-NNRTI-based regimens in first-line pediatric treatment in Ethiopia and underscores the urgent need for access to additional antiretroviral classes in resource-limited settings.


2017 ◽  
Vol 15 (4) ◽  
Author(s):  
Elodie Teclaire Ngo-Malabo ◽  
Paul Alain Ngoupo ◽  
Serge Alain Sadeuh-Mba ◽  
Emmanuel Akongnwi ◽  
Robert Banaï ◽  
...  

Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1125
Author(s):  
Sontaga Manyana ◽  
Lilishia Gounder ◽  
Melendhran Pillay ◽  
Justen Manasa ◽  
Kogieleum Naidoo ◽  
...  

Affordable, sensitive, and scalable technologies are needed for monitoring antiretroviral treatment (ART) success with the goal of eradicating HIV-1 infection. This review discusses use of Sanger sequencing and next generation sequencing (NGS) methods for HIV-1 drug resistance (HIVDR) genotyping, focusing on their use in resource limited settings (RLS). Sanger sequencing remains the gold-standard method for detecting HIVDR mutations of clinical relevance but is mainly limited by high sequencing costs and low-throughput. NGS is becoming a more common sequencing method, with the ability to detect low-abundance drug-resistant variants and reduce per sample costs through sample pooling and massive parallel sequencing. However, use of NGS in RLS is mainly limited by infrastructure costs. Given these shortcomings, our review discusses sequencing technologies for HIVDR genotyping, focusing on common in-house and commercial assays, challenges with Sanger sequencing in keeping up with changes in HIV-1 treatment programs, as well as challenges with NGS that limit its implementation in RLS and in clinical diagnostics. We further discuss knowledge gaps and offer recommendations on how to overcome existing barriers for implementing HIVDR genotyping in RLS, to make informed clinical decisions that improve quality of life for people living with HIV.


2021 ◽  
Vol 6 (1) ◽  
pp. 29
Author(s):  
Cruz S. Sebastião ◽  
Joana Morais ◽  
Miguel Brito

The increase in HIV infection and drug-resistant strains is an important public health concern, especially in resource-limited settings. However, the identification of factors related to the propagation of infectious diseases represents a crucial target offering an opportunity to reduce health care costs as well as deepening the focus on preventing infection in high-risk groups. In this study, we investigate the factors related to drug resistance among HIV-infected pregnant women in Luanda, the capital city of Angola. This was a part of a cross-sectional study conducted with 42 HIV-positive pregnant women. A blood sample was collected, and HIV-1 genotyping was carried out using an in-house method. Multivariate analyses were performed to determine the interaction between sociodemographic characteristics and drug resistance. HIV drug resistance was detected in 44.1% of the studied population. High probabilities of drug resistance were observed for HIV-infected pregnant women living in rural areas (AOR: 2.73; 95% CI: 0.50–14.9) with high educational level (AOR: 6.27; 95% CI: 0.77–51.2) and comorbidities (AOR: 5.47; 95% CI: 0.28–106) and infected with a HIV-1 non-B subtype other than subtype C (AOR: 1.60; 95% CI: 0.25–10.3). The present study reports high HIV drug resistance. Furthermore, older-age, rural areas, high educational levels, unemployed status, having comorbidities, and HIV-1 subtypes were factors related to drug resistance. These factors impact on drug susceptibility and need to be urgently addressed in order to promote health education campaigns able to prevent the spread of drug-resistant HIV strains in Angola.


2021 ◽  
Vol 22 (10) ◽  
pp. 5304
Author(s):  
Ana Santos-Pereira ◽  
Vera Triunfante ◽  
Pedro M. M. Araújo ◽  
Joana Martins ◽  
Helena Soares ◽  
...  

The success of antiretroviral treatment (ART) is threatened by the emergence of drug resistance mutations (DRM). Since Brazil presents the largest number of people living with HIV (PLWH) in South America we aimed at understanding the dynamics of DRM in this country. We analyzed a total of 20,226 HIV-1 sequences collected from PLWH undergoing ART between 2008–2017. Results show a mild decline of DRM over the years but an increase of the K65R reverse transcriptase mutation from 2.23% to 12.11%. This increase gradually occurred following alterations in the ART regimens replacing zidovudine (AZT) with tenofovir (TDF). PLWH harboring the K65R had significantly higher viral loads than those without this mutation (p < 0.001). Among the two most prevalent HIV-1 subtypes (B and C) there was a significant (p < 0.001) association of K65R with subtype C (11.26%) when compared with subtype B (9.27%). Nonetheless, evidence for K65R transmission in Brazil was found both for C and B subtypes. Additionally, artificial neural network-based immunoinformatic predictions suggest that K65R could enhance viral recognition by HLA-B27 that has relatively low prevalence in the Brazilian population. Overall, the results suggest that tenofovir-based regimens need to be carefully monitored particularly in settings with subtype C and specific HLA profiles.


Author(s):  
Hanh T Pham ◽  
Brunna M Alves ◽  
Sunbin Yoo ◽  
Meng A Xiao ◽  
Jing Leng ◽  
...  

Abstract Objectives The development of HIV drug resistance against the integrase strand transfer inhibitor dolutegravir is rare. We report here the transient detection, by near full-genome ultradeep sequencing, of minority HIV-1 subtype B variants bearing the S153F and R263K integrase substitutions in the proviral DNA from blood cells of one patient who successfully initiated dolutegravir-based ART, over 24 weeks. Our objective was to study the effects of these substitutions. Methods Strand transfer and DNA-binding activities of recombinant integrase proteins were measured in cell-free assays. Cell-based resistance, infectivity and replicative capacities were measured using molecular clones. Structural modelling was performed to understand experimental results. Results R263K emerged first, followed by the addition of S153F at Week 12. By Week 24, both mutations remained present, but at lower prevalence. We confirmed the coexistence of S153F and R263K on single viral genomes. Combining S153F or S153Y with R263K decreased integration and viral replicative capacity and conferred high levels of drug resistance against all integrase inhibitors. Alone, S153Y and S153F did little to infectivity or dolutegravir resistance. We identified altered DNA binding as a mechanism of resistance. The patient remained with undetectable viral loads at all timepoints. Conclusions Drug-resistant minority variants have often been reported under suppressive ART. Our study adds to these observations by unravelling a progression towards higher levels of resistance through a novel pathway despite continuous undetectable viral loads. Poorly replicative HIV drug-resistant minority proviral variants did not compromise viral suppression in one individual treated with dolutegravir.


Author(s):  
Sharon Connor ◽  
Hanna K. Welch

As HIV treatments become more effective and accessible, people living with HIV (PLWH) are achieving longer lifespans; however, this aging population also faces a greater risk of age-related co-morbidities. Many chronic diseases affect people living with HIV disproportionately, including diabetes, ischemic heart disease, and congestive heart failure. Patient-centered healthcare should aim to optimize quality and length of life while also considering the person’s value system. Motivational interviewing (MI) has been effective in helping PLWH to better manage chronic diseases requiring behavioral modification in both high- and low-resource settings. MI is a useful approach in the complex care of PLWH and medical co-morbidities. MI can promote self-management integrating HIV care as well as other co-morbidities in the context of social and cultural factors. This chapter discusses the application of MI to achieve better control of co-morbid medical conditions in PLWH.


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