Peer Reviewed Publications « INFECTIOUS DISEASES INSTITUTE

Nakanjako D.1; Mayanja-Kizza, Ouma Wanyenze Mwesigire Namale Ssempiira Senkusu Colebunders Kamya H 1; J 2; R 2; D 2; A 1; J 2; J 2; R 3; M R 1

Tuberculosis and human immunodeficiency virus co-infections and their predictors at a hospital-based HIV/AIDS clinic in Uganda Journal Article

The International Journal of Tuberculosis and Lung Disease,, 14 (12), pp. 1621-1628, 0000.

Abstract | Links | BibTeX

@article{Nakanjako2010,
title = {Tuberculosis and human immunodeficiency virus co-infections and their predictors at a hospital-based HIV/AIDS clinic in Uganda},
author = {Nakanjako, D.1; Mayanja-Kizza, H.1; Ouma, J.2; Wanyenze, R.2; Mwesigire, D.2; Namale, A.1; Ssempiira, J.2; Senkusu, J.2; Colebunders, R.3; Kamya, M. R.1},
url = {https://www.idi-makerere.com/wp-content/uploads/2018/09/Tuberculosis-and-human-immunodeficiency-virus-co-infections-and-their-predictors-at-a-hospital-based-HIV-AIDS-clinic-in-Uganda.pdf},
journal = {The International Journal of Tuberculosis and Lung Disease,},
volume = {14},
number = {12},
pages = {1621-1628},
abstract = {SETTING: Mulago Hospital, Uganda.

OBJECTIVE: To evaluate the burden of TB-HIV (tuberculosis-human immunodeficiency virus) co-infections and their predictors in an urban hospital-based HIV programme.

DESIGN: Prospective observational study.

METHODS: Clinicians screened all patients with HIV/AIDS (acquired immune-deficiency syndrome) for previous and current TB treatment at enrolment and throughout follow-up.

RESULTS: Of 10 924 patients enrolled between August 2005 and February 2009, co-prevalent TB was 157/10 924 (1.4%), which included 88/157 (56%) with TB confirmed at enrolment and 65/157 (41%) with TB diagnoses established during follow-up in whom symptoms were present at enrolment. Male sex (adjusted odds ratio [aOR] 2.3, 95%CI 1.6–3.2) and body mass index (BMI) ≤20 kg/m2 (aOR 3.8, 95%CI 2.5–5.4) were associated with co-prevalent TB. Overall, 749/10 767 (7%) were diagnosed with incident TB at a higher rate among antiretroviral treatment (ART) patients (8/100 patient years of observation [PYO]) than non-ART patients (5/100 PYO, log rank P < 0.001). Female sex (adjusted hazard ratio [aHR] 1.4, 95%CI 1.2–1.7) and baseline BMI ≤ 20 (aHR 1.9, 95%CI 1.6–2.2) predicted incident TB.

CONCLUSION: Routine TB screening in the HIV/AIDS care programme identified a significant number of TB-HIV co-infections among patients with and without ART, and is therefore a potential strategy to improve HIV treatment outcomes in resource-limited settings. },
keywords = {},
pubstate = {published},
tppubtype = {article}
}

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Quinn, T C

The Academic Alliance for AIDS Care and Prevention in Africa Journal Article

The Hopkins HIV Report, 13 (6), pp. 1-4, 0000.

BibTeX

Kamya, Moses R; Semitala, Fred C; Quinn, Thomas C; Ronald, Allan; Njama-Meya, Denise; Mayanja-Kizza, Harriet; Katabira, Elly T; Spacek, Lisa A

Total lymphocyte count of 1200 is not a sensitive predictor of CD4 lymphocyte count among patients with HIV disease in Kampala, Uganda Journal Article

African Health Sciences, 4 (2), pp. 94-101, 0000.

Abstract | Links | BibTeX

@article{Kamya2004,
title = {Total lymphocyte count of 1200 is not a sensitive predictor of CD4 lymphocyte count among patients with HIV disease in Kampala, Uganda},
author = {Moses R Kamya and Fred C Semitala and Thomas C Quinn and Allan Ronald and Denise Njama-Meya and Harriet Mayanja-Kizza and Elly T Katabira and Lisa A Spacek},
url = {https://www.idi-makerere.com/wp-content/uploads/2018/09/Total-lymphocyte-count-of-1200-is-not-a-sensitive-predictor-of-CD4-lymphocyte-count-among-patients-with-HIV-disease-in-Kampala-Uganda.pdf},
journal = {African Health Sciences},
volume = {4},
number = {2},
pages = {94-101},
abstract = {INTRODUCTION:

Total Lymphocyte Count (TLC) has been found to be an inexpensive and useful marker for staging disease, predicting progression to AIDS and death and monitoring response to ART. However, the correlation between TLC and CD4 has not been consistent. Access to HAART is expanding in Kampala, Uganda, yet there are no published data evaluating the utility of TLC as inexpensive surrogate marker of CD4 cell count to help guide therapeutic decisions.
OBJECTIVE:

To evaluate clinical illnesses and total lymphocyte count (TLC) as surrogate markers of the CD4 cell count in HIV infected persons being considered for ART.
METHODS:

A total of 131 patients were enrolled and evaluated by clinical assessment, TLC and CD4 count. Clinical illnesses and TLC dichotomized at various cut-point values were used to determine the sensitivity, specificity, and positive and negative predictive values (PPV and NPV) for the diagnosis of CD4 count <200 cells/mm 3 among 100 participants fulfilling criteria for WHO clinical stage 2 and 3.
RESULTS:

A strong correlation was observed between TLC and CD4 (r = 0.73, p<0.0001). For all clinical syndromes, except pulmonary tuberculosis, the positive predictive values (PPV) for a CD4 count <200 cells/mm 3 were high (>80%) but the negative predictive values (NPV) were low. Using the WHO recommended TLC cut-off of 1200 cells/mm 3 to diagnose a CD4 less than 200 cells/mm 3 , the PPV was 100%, and the NPV was 32%.
CONCLUSION:

Our data showed a good correlation between TLC and CD4 cell count. However, the WHO recommended TLC cut-off of 1200 did not identify the majority of WHO stage 2 and 3 patients with CD4 counts less than 200 cells/mm 3 . A more rational use of TLC counts is to treat all patients with WHO stage 2 and 3 who have a TLC <1200 and to limit CD4 counts to patients who are symptomatic but have TLC of >1200.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}

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S, Prasad; E, Sopdie; D, Meya; A, Kalbarczyk; PJ., Garcia

Conceptual Framework of Mentoring in Low- and Middle-Income Countries to Advance Global Health Journal Article

The American Journal of Tropical Medicine and Hygiene , 100 (1_Suppl), pp. 9-14, 0000.

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E, Nakku-Joloba; EE, Pisarski; MA, Wyatt; TR, Muwonge; S, Asiimwe; CL, Celum; JM, Baeten; ET, Katabira; NC, Ware

Beyond HIV prevention: everyday life priorities and demand for PrEP among Ugandan HIV serodiscordant couples Journal Article

Journal of International AIDS society, 22 (1), 0000.

Abstract | Links | BibTeX

@article{E2019c,
title = {Beyond HIV prevention: everyday life priorities and demand for PrEP among Ugandan HIV serodiscordant couples},
author = {Nakku-Joloba E and Pisarski EE and Wyatt MA and Muwonge TR and Asiimwe S and Celum CL and Baeten JM and Katabira ET and Ware NC},
url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6338102/},
doi = {10.1002/jia2.25225},
journal = {Journal of International AIDS society},
volume = {22},
number = {1},
abstract = {INTRODUCTION:

Pre-exposure prophylaxis (PrEP) to prevent HIV infection is being rolled out in Africa. The uptake of PrEP to date has varied across populations and locations. We seek to understand the drivers of demand for PrEP through analysis of qualitative data collected in conjunction with a PrEP demonstration project involving East African HIV serodiscordant couples. Our goal was to inform demand creation by understanding what PrEP means - beyond HIV prevention - for the lives of users.
METHODS:

The Partners Demonstration Project evaluated an integrated strategy of PrEP and antiretroviral therapy (ART) delivery in which time-limited PrEP served as a "bridge" to long-term ART. Uninfected partners in HIV serodiscordant couples were offered PrEP at baseline and encouraged to discontinue once infected partners had taken ART for six months. We conducted 274 open-ended interviews with 93 couples at two Ugandan research sites. Interviews took place one month after enrolment and at later points in the follow-up period. Topics included are as follows: (1) discovery of serodiscordance; (2) decisions to accept/decline PrEP and/or ART; (3) PrEP and ART initiation; (4) experiences of using PrEP and ART; (5) PrEP discontinuation; (6) impact of PrEP and ART on the partnered relationship. Interviews were audio-recorded and transcribed. We used an inductive, content analytic approach to characterize meanings of PrEP stemming from its effectiveness for HIV prevention. Relevant content was represented as descriptive categories.
RESULTS:

Discovery of HIV serodiscordance resulted in fear of HIV transmission for couples, which led to loss of sexual intimacy in committed relationships, and to abandonment of plans for children. As a result, partners became alienated from each other. PrEP countered the threat to the relationship by reducing fear and reinstating hopes of having children together. Condom use worked against the re-establishment of intimacy and closeness. By increasing couples' sense of protection against HIV infection and raising the prospect of a return to "live sex" (sex without condoms), PrEP was perceived by couples as solving the problem of serodiscordance and preserving committed relationships.
CONCLUSIONS:

The most effective demand creation strategies for PrEP may be those that address the everyday life priorities of potential users in addition to HIV prevention.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}

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INTRODUCTION:

Pre-exposure prophylaxis (PrEP) to prevent HIV infection is being rolled out in Africa. The uptake of PrEP to date has varied across populations and locations. We seek to understand the drivers of demand for PrEP through analysis of qualitative data collected in conjunction with a PrEP demonstration project involving East African HIV serodiscordant couples. Our goal was to inform demand creation by understanding what PrEP means - beyond HIV prevention - for the lives of users.
METHODS:

The Partners Demonstration Project evaluated an integrated strategy of PrEP and antiretroviral therapy (ART) delivery in which time-limited PrEP served as a "bridge" to long-term ART. Uninfected partners in HIV serodiscordant couples were offered PrEP at baseline and encouraged to discontinue once infected partners had taken ART for six months. We conducted 274 open-ended interviews with 93 couples at two Ugandan research sites. Interviews took place one month after enrolment and at later points in the follow-up period. Topics included are as follows: (1) discovery of serodiscordance; (2) decisions to accept/decline PrEP and/or ART; (3) PrEP and ART initiation; (4) experiences of using PrEP and ART; (5) PrEP discontinuation; (6) impact of PrEP and ART on the partnered relationship. Interviews were audio-recorded and transcribed. We used an inductive, content analytic approach to characterize meanings of PrEP stemming from its effectiveness for HIV prevention. Relevant content was represented as descriptive categories.
RESULTS:

Discovery of HIV serodiscordance resulted in fear of HIV transmission for couples, which led to loss of sexual intimacy in committed relationships, and to abandonment of plans for children. As a result, partners became alienated from each other. PrEP countered the threat to the relationship by reducing fear and reinstating hopes of having children together. Condom use worked against the re-establishment of intimacy and closeness. By increasing couples' sense of protection against HIV infection and raising the prospect of a return to "live sex" (sex without condoms), PrEP was perceived by couples as solving the problem of serodiscordance and preserving committed relationships.
CONCLUSIONS:

The most effective demand creation strategies for PrEP may be those that address the everyday life priorities of potential users in addition to HIV prevention.

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J, Edwards; P, Arimi; F, Ssengooba; G, Mulholland; M, Markiewicz; EA, Bukusi; JT, Orikiiriza; A, Virkud; S, Weir

The HIV care continuum among resident and non-resident populations found in venues in East Africa cross-border areas Journal Article

BMC Infectious Diseases, 22 (1), 0000.

Abstract | Links | BibTeX

@article{J2019,
title = {The HIV care continuum among resident and non-resident populations found in venues in East Africa cross-border areas},
author = {Edwards J and Arimi P and Ssengooba F and Mulholland G and Markiewicz M and Bukusi EA and Orikiiriza JT and Virkud A and Weir S},
doi = {10.1002/jia2.25226.},
journal = {BMC Infectious Diseases},
volume = {22},
number = {1},
abstract = {INTRODUCTION:

HIV care and treatment in cross-border areas in East Africa face challenges perhaps not seen to the same extent in other geographic areas, particularly for mobile and migrant populations. Here, we estimate the proportion of people with HIV found in these cross-border areas in each stage of the HIV care and treatment cascade, including the proportion who knows their status, the proportion on treatment and the proportion virally suppressed.
METHODS:

Participants (n = 11,410) working or socializing in public places in selected East Africa cross border areas were recruited between June 2016 and February 2017 using the Priorities for Local AIDS Control Efforts method and administered a behavioural survey and rapid HIV test. This approach was designed to recruit a stratified random sample of people found in public spaces or venues in each cross border area. For participants testing positive for HIV, viral load was measured from dried blood spots. The proportion in each step of the cascade was estimated using inverse probability weights to account for the sampling design and informative HIV test refusals. Estimates are reported separately for residents of the cross border areas and non-residents found in those areas.
RESULTS:

Overall, 43% of participants with HIV found in cross-border areas knew their status, 87% of those participants were on antiretroviral therapy (ART), and 80% of participants on ART were virally suppressed. About 20% of people with HIV found in cross border areas were sampled outside their subdistrict or subcounty of residence. While both resident and non-resident individuals who knew their status were likely to be on ART (85% and 96% respectively), people on ART recruited outside their area of residence were less likely to be suppressed (64% suppressed; 95% CI: 43, 81) compared to residents (84% suppressed; 95% CI: 75, 93).
CONCLUSIONS:

People living in or travelling through cross-border areas may face barriers in learning their HIV status. Moreover, while non-residents were more likely to be on treatment than residents, they were less likely to be suppressed, suggesting gaps in continuity of care for people in East Africa travelling outside their area of residence despite timely initiation of treatment.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}

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INTRODUCTION:

HIV care and treatment in cross-border areas in East Africa face challenges perhaps not seen to the same extent in other geographic areas, particularly for mobile and migrant populations. Here, we estimate the proportion of people with HIV found in these cross-border areas in each stage of the HIV care and treatment cascade, including the proportion who knows their status, the proportion on treatment and the proportion virally suppressed.
METHODS:

Participants (n = 11,410) working or socializing in public places in selected East Africa cross border areas were recruited between June 2016 and February 2017 using the Priorities for Local AIDS Control Efforts method and administered a behavioural survey and rapid HIV test. This approach was designed to recruit a stratified random sample of people found in public spaces or venues in each cross border area. For participants testing positive for HIV, viral load was measured from dried blood spots. The proportion in each step of the cascade was estimated using inverse probability weights to account for the sampling design and informative HIV test refusals. Estimates are reported separately for residents of the cross border areas and non-residents found in those areas.
RESULTS:

Overall, 43% of participants with HIV found in cross-border areas knew their status, 87% of those participants were on antiretroviral therapy (ART), and 80% of participants on ART were virally suppressed. About 20% of people with HIV found in cross border areas were sampled outside their subdistrict or subcounty of residence. While both resident and non-resident individuals who knew their status were likely to be on ART (85% and 96% respectively), people on ART recruited outside their area of residence were less likely to be suppressed (64% suppressed; 95% CI: 43, 81) compared to residents (84% suppressed; 95% CI: 75, 93).
CONCLUSIONS:

People living in or travelling through cross-border areas may face barriers in learning their HIV status. Moreover, while non-residents were more likely to be on treatment than residents, they were less likely to be suppressed, suggesting gaps in continuity of care for people in East Africa travelling outside their area of residence despite timely initiation of treatment.

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S, Okoboi; A, Twimukye; O, Lazarus; B, Castelnuovo; Agaba C, Immaculate M; M, Nanfuka; A, Kambugu; R., King

Acceptability, perceived reliability and challenges associated with distributing HIV self-test kits to young MSM in Uganda: a qualitative study. Journal Article

Journal of International AIDS society, 22 (3), 0000.

Abstract | Links | BibTeX

@article{S2019c,
title = {Acceptability, perceived reliability and challenges associated with distributing HIV self-test kits to young MSM in Uganda: a qualitative study.},
author = {Okoboi S and Twimukye A and Lazarus O and Castelnuovo B and Agaba C, Immaculate M and Nanfuka M and Kambugu A and King R. },
url = {https://onlinelibrary.wiley.com/doi/full/10.1002/jia2.25269},
doi = {org/10.1002/jia2.25269},
journal = {Journal of International AIDS society},
volume = {22},
number = {3},
abstract = {
Introduction

HIV self‐testing is a flexible, accessible and acceptable emerging technology with a particular potential to identify people living with HIV who are reluctant to interact with conventional HIV testing approaches. We assessed the acceptability, perceived reliability and challenges associated with distributing HIV self‐test (HIVST) to young men who have sex with men (MSM) in Uganda.
Methods

Between February and May, 2018, we enrolled 74 MSM aged ≥18 years purposively sampled and verbally consented to participate in six focus group discussions (FGDs) in The AIDS Support Organization (TASO Masaka and Entebbe). We also conducted two FGDs of 18 health workers. MSM FGD groups included individuals who had; (1) tested greater than one year previously; (2) tested between six months and one year previously; (3) tested three to six months previously; (4) never tested. FGDs examined: (i) the acceptability of HIVST distribution; (iii) preferences for various HIVST distribution channels; (iv) perceptions about the accuracy of HIVST; (v) challenges associated with HIVST distribution. We identified major themes, developed and refined a codebook. We used Nvivo version 11 for data management.
Results

MSM participants age ranged between 19 and 30 years. Participants described HIVST as a mechanism that would facilitate HIV testing uptake in a rapid, efficient, confidential, non‐painful; and non‐stigmatizing manner. Overall, MSM preferred HIVST to the conventional HIV testing approaches. Health workers were in support of distributing HIVST kits through MSM peers. MSM participants were willing to distribute the kits and recommended HIVST to their peers and sexual partners. They suggested HIVST kit distribution model work similarly to the current condom and lubricant peer model being implemented by TASO. Preferred channels were peers, hot spots, drop‐in centres, private pharmacies and MSM friendly health facilities. Key concerns regarding use of HIVST were; unreliable HIVST results, social harm due to a positive result, need for a confirmatory test and linking both HIV positive and negative participants for additional HIV services.
Conclusions

Distribution of HIVST kits by MSM peers is an acceptable strategy that can promote access to testing. HIVST was perceived by participants as beneficial because it would address many barriers that affect their acceptance of testing. However, a combined approach that includes follow‐up, linkage to HIV care and prevention services are needed for effective results.
},
keywords = {},
pubstate = {published},
tppubtype = {article}
}

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Introduction

HIV self‐testing is a flexible, accessible and acceptable emerging technology with a particular potential to identify people living with HIV who are reluctant to interact with conventional HIV testing approaches. We assessed the acceptability, perceived reliability and challenges associated with distributing HIV self‐test (HIVST) to young men who have sex with men (MSM) in Uganda.
Methods

Between February and May, 2018, we enrolled 74 MSM aged ≥18 years purposively sampled and verbally consented to participate in six focus group discussions (FGDs) in The AIDS Support Organization (TASO Masaka and Entebbe). We also conducted two FGDs of 18 health workers. MSM FGD groups included individuals who had; (1) tested greater than one year previously; (2) tested between six months and one year previously; (3) tested three to six months previously; (4) never tested. FGDs examined: (i) the acceptability of HIVST distribution; (iii) preferences for various HIVST distribution channels; (iv) perceptions about the accuracy of HIVST; (v) challenges associated with HIVST distribution. We identified major themes, developed and refined a codebook. We used Nvivo version 11 for data management.
Results

MSM participants age ranged between 19 and 30 years. Participants described HIVST as a mechanism that would facilitate HIV testing uptake in a rapid, efficient, confidential, non‐painful; and non‐stigmatizing manner. Overall, MSM preferred HIVST to the conventional HIV testing approaches. Health workers were in support of distributing HIVST kits through MSM peers. MSM participants were willing to distribute the kits and recommended HIVST to their peers and sexual partners. They suggested HIVST kit distribution model work similarly to the current condom and lubricant peer model being implemented by TASO. Preferred channels were peers, hot spots, drop‐in centres, private pharmacies and MSM friendly health facilities. Key concerns regarding use of HIVST were; unreliable HIVST results, social harm due to a positive result, need for a confirmatory test and linking both HIV positive and negative participants for additional HIV services.
Conclusions

Distribution of HIVST kits by MSM peers is an acceptable strategy that can promote access to testing. HIVST was perceived by participants as beneficial because it would address many barriers that affect their acceptance of testing. However, a combined approach that includes follow‐up, linkage to HIV care and prevention services are needed for effective results.

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Ross, Jonathan; Brazier, Ellen; Fatti, Geoffrey; Jaquet, Antoine; Tanon, Aristophane; Haas, Andreas D; Diero, Lameck; Castelnuovo, Barbara; Yiannoutsos, Constantin T; Nash, Denis; others,

Same-Day Antiretroviral Therapy (ART) Initiation as a Predictor of Loss to Follow-up and Viral Suppression Among People Living With Human Immunodeficiency Virus (HIV) in Sub-Saharan Africa Journal Article

Clinical Infectious Diseases, 0000.

BibTeX

Odongpiny ELA Cresswell F, Arinaitwe Nakate Kyenkya Lamorde Waitt Meya Kiragga A V J M C D A

High willingness to use injectable antiretroviral therapy among women who have been lost to follow-up from HIV programmes: A nested cross-sectional study. Journal Article

HIV Medicine, 23 ((4)), pp. PP. 319-323, 0000.

Abstract | Links | BibTeX

@article{ELA2022,
title = {High willingness to use injectable antiretroviral therapy among women who have been lost to follow-up from HIV programmes: A nested cross-sectional study.},
author = {Odongpiny ELA, Cresswell F, Arinaitwe A, Nakate V, Kyenkya J, Lamorde M, Waitt C, Meya D, Kiragga A. },
url = {https://pubmed.ncbi.nlm.nih.gov/35199432/},
doi = {10.1111/hiv.13260},
journal = {HIV Medicine},
volume = {23},
number = {(4)},
pages = {PP. 319-323},
abstract = {Abstract
Objectives: Efforts to achieve zero transmission of HIV to infants born to women living with HIV in sub-Saharan African are undermined by high rates of loss to follow-up in prevention of vertical transmission (PVT) programmes. The fear of HIV status disclosure through the discovery of pill bottles at home is a major contributor. Injectable antiretroviral therapy (ART) has proved to be efficacious in clinical trials and is discreet, offering a potential solution. We investigated the knowledge and willingness to use injectable ART among women who were lost to follow-up from the PVT programme in Uganda.

Methods: Women were traced by nurse counsellors and knowledge and opinions relating to injectable ART, including willingness to use it when it becomes available, were collected. Generalized linear models were used to determine predictors of willingness to use injectable ART.

Conclusions: Among 1023 women registered between 2017 and 2019 under the PVT programmes in Kampala and Wakiso districts, Uganda, 385 (38%) were lost to follow-up from care and 22% of these (83/385) were successfully traced and interviewed. Only 25% (21/83) had heard of injectable ART. Over half (55%, 46/83) were very willing to use injectable ART, 40% (33/83) were somewhat willing and four (5%) were not willing. Those who associated ART tablets with disclosure risk were more willing to consider injectable ART (adjusted odds ratio = 4.21; 95% confidence interval: 1.45-12.19; p = 0.008). We report high willingness to use injectable ART associated with fears that ART tablets were a potential source of HIV status disclosure. Injectable ART could be a solution for women who have challenges with disclosure.

Keywords: HIV/AIDS; PVT programme; injectable ART; loss to follow-up; nursing; pregnant.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}

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Cresswell, Fiona V; Lamorde, Mohammed

Implementation of long-acting antiretroviral therapy in low-income and middle-income countries. Journal Article

Current Opinion in HIV and AIDS, 17 ((3)), pp. PP. 127-134, 0000.

Abstract | Links | BibTeX

@article{Cresswell0000,
title = {Implementation of long-acting antiretroviral therapy in low-income and middle-income countries. },
author = {Cresswell, Fiona V and Lamorde, Mohammed},
url = {https://pubmed.ncbi.nlm.nih.gov/35439787/},
doi = {10.1097/COH.0000000000000732},
journal = {Current Opinion in HIV and AIDS},
volume = {17},
number = {(3)},
pages = {PP. 127-134},
abstract = {Purpose of review: With oral antiretroviral therapy, HIV has become a manageable chronic illness. However, UNAIDS targets for virologic suppression have not yet been attained in many low-income and middle-income countries (LMICs). Long-acting drug formulations hold promise to improve treatment outcomes. In this rapidly evolving area of research, we aim to review recent literature on the treatment of HIV with long-acting agents and identify implementation considerations for LMICs.

Recent findings: Randomized controlled trials have shown that monthly long-acting injectable cabotegravir (CAB) and rilpivirine (RPV) is noninferior to oral ART, and 2-monthly CAB/RPV is noninferior to monthly injections. However, few people from LMICs were included. A modelling study predicts that in sub-Saharan Africa, injectable CAB/RPV is best targeted to those with poor adherence (HIV viral load >1000 copies/ml) in whom cost-effectiveness is greatest and risk of contributing to further resistance is no greater than continuation of oral ART. Other promising agents, such as lenacapavir are under investigation and may prove particularly useful in heavily treatment-experienced adults.

Summary: Long-acting regimens are a promising advance in HIV treatment. By extending the dosing interval, increasing convenience and being discreet these regimens may reduce HIV treatment challenges. However, there are multiple implementation considerations in LMICs including the need for exclusion of hepatitis B, cold chain, oral bridging in case of missed dosing and switching during tuberculosis therapy. Efficacy and safety data are also awaited for settings without routine access to baseline resistance testing or regular viral load monitoring and for special populations, such as pregnancy, children and the elderly.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}

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policy review collaborators Lazarus JV Mark HE, Villota-Rivas Palayew Carrieri Colombo Ekstedt Esmat George Marchesini Novak Ocama Ratziu Razavi Romero-Gómez Silva Spearman CW Tacke Tsochatzis EA Yilmaz Younossi ZM Wong VW Zelber-Sagi Cortez-Pinto Anstee QM; NAFLD M A P M M G J G K P V H M M F Y S H

The global NAFLD policy review and preparedness index: Are countries ready to address this silent public health challenge? Journal Article

Journal of Hepatology, 76 (4), pp. pp. 771-780, 0000.

Abstract | Links | BibTeX

@article{JV2022,
title = {The global NAFLD policy review and preparedness index: Are countries ready to address this silent public health challenge?},
author = {Lazarus JV, Mark HE, Villota-Rivas M, Palayew A, Carrieri P, Colombo M, Ekstedt M, Esmat G, George J, Marchesini G, Novak K, Ocama P, Ratziu V, Razavi H, Romero-Gómez M, Silva M, Spearman CW, Tacke F, Tsochatzis EA, Yilmaz Y, Younossi ZM, Wong VW, Zelber-Sagi S, Cortez-Pinto H, Anstee QM; NAFLD policy review collaborators},
url = {https://www.journal-of-hepatology.eu/article/S0168-8278(21)02168-1/fulltext},
doi = {https://doi.org/10.1016/j.jhep.2021.10.025},
journal = {Journal of Hepatology},
volume = { 76},
number = {4},
pages = {pp. 771-780},
abstract = {Background & Aims
Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent, yet largely underappreciated liver condition which is closely associated with obesity and metabolic disease. Despite affecting an estimated 1 in 4 adults globally, NAFLD is largely absent on national and global health agendas.

Methods
We collected data from 102 countries, accounting for 86% of the world population, on NAFLD policies, guidelines, civil society engagement, clinical management, and epidemiologic data. A preparedness index was developed by coding questions into 6 domains (policies, guidelines, civil awareness, epidemiology and data, NAFLD detection, and NAFLD care management) and categorising the responses as high, medium, and low; a multiple correspondence analysis was then applied.

Results
The highest scoring countries were India (42.7) and the United Kingdom (40.0), with 32 countries (31%) scoring zero out of 100. For 5 of the domains a minority of countries were categorised as high-level while the majority were categorised as low-level. No country had a national or sub-national strategy for NAFLD and <2% of the different strategies for related conditions included any mention of NAFLD. National NAFLD clinical guidelines were present in only 32 countries.

Conclusions
Although NAFLD is a pressing public health problem, no country was found to be well prepared to address it. There is a pressing need for strategies to address NAFLD at national and global levels.

Lay summary
Around a third of the countries scored a zero on the NAFLD policy preparedness index, with no country scoring over 50/100. Although NAFLD is a pressing public health problem, a comprehensive public health response is lacking in all 102 countries. Policies and strategies to address NAFLD at the national and global levels are urgently needed.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}

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Paton NI Musaazi J, Kityo Walimbwa Hoppe Balyegisawa Asienzo Kaimal Mirembe Lugemwa Ategeka Borok Mugerwa Siika Odongpiny ELA Castelnuovo Kiragga Kambugu NADIA Trial Team. C S A A J A G A G M H A B A A;

Efficacy and safety of dolutegravir or darunavir in combination with lamivudine plus either zidovudine or tenofovir for second-line treatment of HIV infection (NADIA): week 96 results from a prospective, multicentre, open-label, factorial, randomised, non-inferiority trial Journal Article

The Lancet HIV, 9 (6), pp. E381-E391, 0000.

Abstract | Links | BibTeX

@article{NI2022,
title = {Efficacy and safety of dolutegravir or darunavir in combination with lamivudine plus either zidovudine or tenofovir for second-line treatment of HIV infection (NADIA): week 96 results from a prospective, multicentre, open-label, factorial, randomised, non-inferiority trial},
author = {Paton NI, Musaazi J, Kityo C, Walimbwa S, Hoppe A, Balyegisawa A, Asienzo J, Kaimal A, Mirembe G, Lugemwa A, Ategeka G, Borok M, Mugerwa H, Siika A, Odongpiny ELA, Castelnuovo B, Kiragga A, Kambugu A; NADIA Trial Team. },
doi = {https://doi.org/10.1016/S2352-3018(22)00092-3},
journal = {The Lancet HIV},
volume = {9},
number = {6},
pages = {E381-E391},
abstract = {Background
WHO guidelines recommend dolutegravir plus two nucleoside reverse transcriptase inhibitors (NRTIs) for second-line HIV therapy, with NRTI switching from first-line tenofovir to zidovudine. We aimed to examine whether dolutegravir is non-inferior to darunavir, the best-in-class protease inhibitor drug, and whether maintaining tenofovir in second-line therapy is non-inferior to switching to zidovudine.
Methods
In this prospective, multicentre, open-label, factorial, randomised, non-inferiority trial (NADIA), participants with confirmed HIV first-line treatment failure (HIV-1 RNA ≥1000 copies per mL) were recruited at seven clinical sites in Kenya, Uganda, and Zimbabwe. Following a 2 × 2 factorial design and stratified by site and screening HIV-1 RNA concentration, participants were randomly assigned (1:1:1:1) to receive a 96-week regimen containing either dolutegravir (50 mg once daily) or ritonavir-boosted darunavir (800 mg of darunavir plus 100 mg of ritonavir once daily) in combination with either tenofovir (300 mg once daily) plus lamivudine (300 mg once daily) or zidovudine (300 mg twice daily) plus lamivudine (150 mg twice daily). The NRTI drugs allocated by randomisation were administered orally in fixed-dose combination pills; other drugs were administered orally as separate pills. The previously reported primary outcome was the proportion of participants with a plasma HIV-1 RNA concentration of less than 400 copies per mL at 48 weeks. Here, we report the main secondary outcome: the proportion of participants with a plasma HIV-1 RNA concentration of less than 400 copies per mL at 96 weeks (non-inferiority margin 12%). We analysed this outcome and safety outcomes in the intention-to-treat population, which excluded only those who were randomly assigned in error and withdrawn before receiving trial drugs. This study was registered at ClinicalTrials.gov, NCT03988452, and is complete.
Findings
Between July 30 and Dec 18, 2019, we screened 783 patients and enrolled 465. One participant was randomly assigned in error and immediately withdrawn. The remaining 464 participants were randomly assigned to receive either dolutegravir (n=235) or ritonavir-boosted darunavir (n=229) and to receive lamivudine plus either tenofovir (n=233) or zidovudine (n=231). At week 96, 211 (90%) of 235 participants in the dolutegravir group and 199 (87%) of 229 participants in the darunavir group had HIV-1 RNA less than 400 copies per mL (percentage point difference 2·9, 95% CI −3·0 to 8·7), indicating non-inferiority. Nine (4%) participants (all in the dolutegravir group) developed dolutegravir resistance; no participants developed darunavir resistance (p=0·0023). In the other randomised comparison, 214 (92%) of 233 patients in the tenofovir group and 196 (85%) of 231 patients in the zidovudine group had HIV-1 RNA less than 400 copies per mL (percentage point difference 7·0, 95% CI 1·2 to 12·8), showing non-inferiority and indicating the superiority of tenofovir (p=0·019). The proportions of participants with any grade 3–4 adverse event were similar between the dolutegravir (26 [11%]) and darunavir (28 [12%]) groups and between the tenofovir (22 [9%]) and zidovudine (32 [14%]) groups. There were no deaths related to study medication.
Interpretation
Dolutegravir-based and darunavir-based regimens maintain good viral suppression during 96 weeks; dolutegravir is non-inferior to darunavir but is at greater risk of resistance in second-line therapy. Tenofovir should be continued in second-line therapy, rather than being switched to zidovudine.
Funding
Janssen.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}

Close

Background
WHO guidelines recommend dolutegravir plus two nucleoside reverse transcriptase inhibitors (NRTIs) for second-line HIV therapy, with NRTI switching from first-line tenofovir to zidovudine. We aimed to examine whether dolutegravir is non-inferior to darunavir, the best-in-class protease inhibitor drug, and whether maintaining tenofovir in second-line therapy is non-inferior to switching to zidovudine.
Methods
In this prospective, multicentre, open-label, factorial, randomised, non-inferiority trial (NADIA), participants with confirmed HIV first-line treatment failure (HIV-1 RNA ≥1000 copies per mL) were recruited at seven clinical sites in Kenya, Uganda, and Zimbabwe. Following a 2 × 2 factorial design and stratified by site and screening HIV-1 RNA concentration, participants were randomly assigned (1:1:1:1) to receive a 96-week regimen containing either dolutegravir (50 mg once daily) or ritonavir-boosted darunavir (800 mg of darunavir plus 100 mg of ritonavir once daily) in combination with either tenofovir (300 mg once daily) plus lamivudine (300 mg once daily) or zidovudine (300 mg twice daily) plus lamivudine (150 mg twice daily). The NRTI drugs allocated by randomisation were administered orally in fixed-dose combination pills; other drugs were administered orally as separate pills. The previously reported primary outcome was the proportion of participants with a plasma HIV-1 RNA concentration of less than 400 copies per mL at 48 weeks. Here, we report the main secondary outcome: the proportion of participants with a plasma HIV-1 RNA concentration of less than 400 copies per mL at 96 weeks (non-inferiority margin 12%). We analysed this outcome and safety outcomes in the intention-to-treat population, which excluded only those who were randomly assigned in error and withdrawn before receiving trial drugs. This study was registered at ClinicalTrials.gov, NCT03988452, and is complete.
Findings
Between July 30 and Dec 18, 2019, we screened 783 patients and enrolled 465. One participant was randomly assigned in error and immediately withdrawn. The remaining 464 participants were randomly assigned to receive either dolutegravir (n=235) or ritonavir-boosted darunavir (n=229) and to receive lamivudine plus either tenofovir (n=233) or zidovudine (n=231). At week 96, 211 (90%) of 235 participants in the dolutegravir group and 199 (87%) of 229 participants in the darunavir group had HIV-1 RNA less than 400 copies per mL (percentage point difference 2·9, 95% CI −3·0 to 8·7), indicating non-inferiority. Nine (4%) participants (all in the dolutegravir group) developed dolutegravir resistance; no participants developed darunavir resistance (p=0·0023). In the other randomised comparison, 214 (92%) of 233 patients in the tenofovir group and 196 (85%) of 231 patients in the zidovudine group had HIV-1 RNA less than 400 copies per mL (percentage point difference 7·0, 95% CI 1·2 to 12·8), showing non-inferiority and indicating the superiority of tenofovir (p=0·019). The proportions of participants with any grade 3–4 adverse event were similar between the dolutegravir (26 [11%]) and darunavir (28 [12%]) groups and between the tenofovir (22 [9%]) and zidovudine (32 [14%]) groups. There were no deaths related to study medication.
Interpretation
Dolutegravir-based and darunavir-based regimens maintain good viral suppression during 96 weeks; dolutegravir is non-inferior to darunavir but is at greater risk of resistance in second-line therapy. Tenofovir should be continued in second-line therapy, rather than being switched to zidovudine.
Funding
Janssen.

Close

Odongpiny ELA Cresswell F, Arinaitwe Nakate Kyenkya Lamorde Waitt Meya Kiragga A V J M C D A

High willingness to use injectable antiretroviral therapy among women who have been lost to follow-up from HIV programmes: A nested cross-sectional study Journal Article

HIV Medicine, 23 (4), pp. 319-323, 0000.

Abstract | Links | BibTeX

@article{ELA2022b,
title = {High willingness to use injectable antiretroviral therapy among women who have been lost to follow-up from HIV programmes: A nested cross-sectional study},
author = {Odongpiny ELA, Cresswell F, Arinaitwe A, Nakate V, Kyenkya J, Lamorde M, Waitt C, Meya D, Kiragga A. },
url = { https://doi.org/10.1111/hiv.13260},
journal = {HIV Medicine},
volume = {23},
number = {4},
pages = {319-323},
abstract = {Objectives
Efforts to achieve zero transmission of HIV to infants born to women living with HIV in sub-Saharan African are undermined by high rates of loss to follow-up in prevention of vertical transmission (PVT) programmes. The fear of HIV status disclosure through the discovery of pill bottles at home is a major contributor. Injectable antiretroviral therapy (ART) has proved to be efficacious in clinical trials and is discreet, offering a potential solution. We investigated the knowledge and willingness to use injectable ART among women who were lost to follow-up from the PVT programme in Uganda.

Methods
Women were traced by nurse counsellors and knowledge and opinions relating to injectable ART, including willingness to use it when it becomes available, were collected. Generalized linear models were used to determine predictors of willingness to use injectable ART.

Conclusions
Among 1023 women registered between 2017 and 2019 under the PVT programmes in Kampala and Wakiso districts, Uganda, 385 (38%) were lost to follow-up from care and 22% of these (83/385) were successfully traced and interviewed. Only 25% (21/83) had heard of injectable ART. Over half (55%, 46/83) were very willing to use injectable ART, 40% (33/83) were somewhat willing and four (5%) were not willing. Those who associated ART tablets with disclosure risk were more willing to consider injectable ART (adjusted odds ratio = 4.21; 95% confidence interval: 1.45–12.19; p = 0.008).

We report high willingness to use injectable ART associated with fears that ART tablets were a potential source of HIV status disclosure. Injectable ART could be a solution for women who have challenges with disclosure.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}

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Cresswell FV, Lamorde M

Implementation of long-acting antiretroviral therapy in low-income and middle-income countries Journal Article

Current Opinion in HIV and AIDS, 17 (3), pp. 127-134, 0000.

Abstract | Links | BibTeX

@article{FV2022,
title = {Implementation of long-acting antiretroviral therapy in low-income and middle-income countries},
author = {Cresswell FV, Lamorde M. },
url = {https://www.ingentaconnect.com/content/wk/coh/2022/00000017/00000003/art00004},
journal = {Current Opinion in HIV and AIDS},
volume = {17},
number = {3},
pages = {127-134},
abstract = {Purpose of review

With oral antiretroviral therapy, HIV has become a manageable chronic illness. However, UNAIDS targets for virologic suppression have not yet been attained in many low-income and middle-income countries (LMICs). Long-acting drug formulations hold promise to improve treatment outcomes. In this rapidly evolving area of research, we aim to review recent literature on the treatment of HIV with long-acting agents and identify implementation considerations for LMICs.

Recent findings

Randomized controlled trials have shown that monthly long-acting injectable cabotegravir (CAB) and rilpivirine (RPV) is noninferior to oral ART, and 2-monthly CAB/RPV is noninferior to monthly injections. However, few people from LMICs were included. A modelling study predicts that in sub-Saharan Africa, injectable CAB/RPV is best targeted to those with poor adherence (HIV viral load >1000 copies/ml) in whom cost-effectiveness is greatest and risk of contributing to further resistance is no greater than continuation of oral ART. Other promising agents, such as lenacapavir are under investigation and may prove particularly useful in heavily treatment-experienced adults.Summary

Long-acting regimens are a promising advance in HIV treatment. By extending the dosing interval, increasing convenience and being discreet these regimens may reduce HIV treatment challenges. However, there are multiple implementation considerations in LMICs including the need for exclusion of hepatitis B, cold chain, oral bridging in case of missed dosing and switching during tuberculosis therapy. Efficacy and safety data are also awaited for settings without routine access to baseline resistance testing or regular viral load monitoring and for special populations, such as pregnancy, children and the elderly.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}

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policy review collaborators. Lazarus JV Mark HE, Villota-Rivas Palayew Carrieri Colombo Ekstedt Esmat George Marchesini Novak Ocama Ratziu Razavi Romero-Gómez Silva Spearman CW Tacke Tsochatzis EA Yilmaz Younossi ZM Wong VW Zelber-Sagi Cortez-Pinto Anstee QM; NAFLD M A P M M G J G K P V H M M F Y S H

The global NAFLD policy review and preparedness index: Are countries ready to address this silent public health challenge? Journal Article

Journal of Hepatology, 76 (4), pp. 771-780, 0000.

Abstract | Links | BibTeX

@article{JV2022b,
title = {The global NAFLD policy review and preparedness index: Are countries ready to address this silent public health challenge?},
author = {Lazarus JV, Mark HE, Villota-Rivas M, Palayew A, Carrieri P, Colombo M, Ekstedt M, Esmat G, George J, Marchesini G, Novak K, Ocama P, Ratziu V, Razavi H, Romero-Gómez M, Silva M, Spearman CW, Tacke F, Tsochatzis EA, Yilmaz Y, Younossi ZM, Wong VW, Zelber-Sagi S, Cortez-Pinto H, Anstee QM; NAFLD policy review collaborators.},
url = {https://www.sciencedirect.com/science/article/pii/S0168827821021681},
journal = {Journal of Hepatology},
volume = {76},
number = {4},
pages = { 771-780},
abstract = {Background & Aims
Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent, yet largely underappreciated liver condition which is closely associated with obesity and metabolic disease. Despite affecting an estimated 1 in 4 adults globally, NAFLD is largely absent on national and global health agendas.

Methods
We collected data from 102 countries, accounting for 86% of the world population, on NAFLD policies, guidelines, civil society engagement, clinical management, and epidemiologic data. A preparedness index was developed by coding questions into 6 domains (policies, guidelines, civil awareness, epidemiology and data, NAFLD detection, and NAFLD care management) and categorising the responses as high, medium, and low; a multiple correspondence analysis was then applied.

Results
The highest scoring countries were India (42.7) and the United Kingdom (40.0), with 32 countries (31%) scoring zero out of 100. For 5 of the domains a minority of countries were categorised as high-level while the majority were categorised as low-level. No country had a national or sub-national strategy for NAFLD and <2% of the different strategies for related conditions included any mention of NAFLD. National NAFLD clinical guidelines were present in only 32 countries.

Conclusions
Although NAFLD is a pressing public health problem, no country was found to be well prepared to address it. There is a pressing need for strategies to address NAFLD at national and global levels.

Lay summary
Around a third of the countries scored a zero on the NAFLD policy preparedness index, with no country scoring over 50/100. Although NAFLD is a pressing public health problem, a comprehensive public health response is lacking in all 102 countries. Policies and strategies to address NAFLD at the national and global levels are urgently needed.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}

Close

R, Nabatanzi; L, Bayigga; S, Cose; S, Rowland-Jones; G, Canderan; M, Joloba; D, Nakanjako

Aberrant natural killer (NK) cell activation and dysfunction among ART-treated HIV-infected adults in an African cohort Journal Article

Clinical Immunology (0lando, Fla), pp. 55-60, 0000.

Abstract | Links | BibTeX

Paton NI Musaazi J, Kityo Walimbwa Hoppe Balyegisawa Asienzo Kaimal Mirembe Lugemwa Ategeka Borok Mugerwa Siika Odongpiny ELA Castelnuovo Kiragga Kambugu NADIA Trial Team. C S A A J A G A G M H A B A A;

Efficacy and safety of dolutegravir or darunavir in combination with lamivudine plus either zidovudine or tenofovir for second-line treatment of HIV infection (NADIA): week 96 results from a prospective, multicentre, open-label, factorial, randomised, non-inferiority trial Journal Article

The Lancet HIV, 9 (6), pp. 381-393, 0000.

Abstract | Links | BibTeX

@article{NI2022b,
title = {Efficacy and safety of dolutegravir or darunavir in combination with lamivudine plus either zidovudine or tenofovir for second-line treatment of HIV infection (NADIA): week 96 results from a prospective, multicentre, open-label, factorial, randomised, non-inferiority trial},
author = {Paton NI, Musaazi J, Kityo C, Walimbwa S, Hoppe A, Balyegisawa A, Asienzo J, Kaimal A, Mirembe G, Lugemwa A, Ategeka G, Borok M, Mugerwa H, Siika A, Odongpiny ELA, Castelnuovo B, Kiragga A, Kambugu A; NADIA Trial Team.},
url = {https://www.thelancet.com/journals/lanhiv/article/PIIS2352-3018(22)00092-3/fulltext},
journal = {The Lancet HIV},
volume = {9},
number = {6},
pages = {381-393},
abstract = {Background
WHO guidelines recommend dolutegravir plus two nucleoside reverse transcriptase inhibitors (NRTIs) for second-line HIV therapy, with NRTI switching from first-line tenofovir to zidovudine. We aimed to examine whether dolutegravir is non-inferior to darunavir, the best-in-class protease inhibitor drug, and whether maintaining tenofovir in second-line therapy is non-inferior to switching to zidovudine.
Methods
In this prospective, multicentre, open-label, factorial, randomised, non-inferiority trial (NADIA), participants with confirmed HIV first-line treatment failure (HIV-1 RNA ≥1000 copies per mL) were recruited at seven clinical sites in Kenya, Uganda, and Zimbabwe. Following a 2 × 2 factorial design and stratified by site and screening HIV-1 RNA concentration, participants were randomly assigned (1:1:1:1) to receive a 96-week regimen containing either dolutegravir (50 mg once daily) or ritonavir-boosted darunavir (800 mg of darunavir plus 100 mg of ritonavir once daily) in combination with either tenofovir (300 mg once daily) plus lamivudine (300 mg once daily) or zidovudine (300 mg twice daily) plus lamivudine (150 mg twice daily). The NRTI drugs allocated by randomisation were administered orally in fixed-dose combination pills; other drugs were administered orally as separate pills. The previously reported primary outcome was the proportion of participants with a plasma HIV-1 RNA concentration of less than 400 copies per mL at 48 weeks. Here, we report the main secondary outcome: the proportion of participants with a plasma HIV-1 RNA concentration of less than 400 copies per mL at 96 weeks (non-inferiority margin 12%). We analysed this outcome and safety outcomes in the intention-to-treat population, which excluded only those who were randomly assigned in error and withdrawn before receiving trial drugs. This study was registered at ClinicalTrials.gov, NCT03988452, and is complete.
Findings
Between July 30 and Dec 18, 2019, we screened 783 patients and enrolled 465. One participant was randomly assigned in error and immediately withdrawn. The remaining 464 participants were randomly assigned to receive either dolutegravir (n=235) or ritonavir-boosted darunavir (n=229) and to receive lamivudine plus either tenofovir (n=233) or zidovudine (n=231). At week 96, 211 (90%) of 235 participants in the dolutegravir group and 199 (87%) of 229 participants in the darunavir group had HIV-1 RNA less than 400 copies per mL (percentage point difference 2·9, 95% CI −3·0 to 8·7), indicating non-inferiority. Nine (4%) participants (all in the dolutegravir group) developed dolutegravir resistance; no participants developed darunavir resistance (p=0·0023). In the other randomised comparison, 214 (92%) of 233 patients in the tenofovir group and 196 (85%) of 231 patients in the zidovudine group had HIV-1 RNA less than 400 copies per mL (percentage point difference 7·0, 95% CI 1·2 to 12·8), showing non-inferiority and indicating the superiority of tenofovir (p=0·019). The proportions of participants with any grade 3–4 adverse event were similar between the dolutegravir (26 [11%]) and darunavir (28 [12%]) groups and between the tenofovir (22 [9%]) and zidovudine (32 [14%]) groups. There were no deaths related to study medication.
Interpretation
Dolutegravir-based and darunavir-based regimens maintain good viral suppression during 96 weeks; dolutegravir is non-inferior to darunavir but is at greater risk of resistance in second-line therapy. Tenofovir should be continued in second-line therapy, rather than being switched to zidovudine.
Funding
Janssen.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}

Close

Background
WHO guidelines recommend dolutegravir plus two nucleoside reverse transcriptase inhibitors (NRTIs) for second-line HIV therapy, with NRTI switching from first-line tenofovir to zidovudine. We aimed to examine whether dolutegravir is non-inferior to darunavir, the best-in-class protease inhibitor drug, and whether maintaining tenofovir in second-line therapy is non-inferior to switching to zidovudine.
Methods
In this prospective, multicentre, open-label, factorial, randomised, non-inferiority trial (NADIA), participants with confirmed HIV first-line treatment failure (HIV-1 RNA ≥1000 copies per mL) were recruited at seven clinical sites in Kenya, Uganda, and Zimbabwe. Following a 2 × 2 factorial design and stratified by site and screening HIV-1 RNA concentration, participants were randomly assigned (1:1:1:1) to receive a 96-week regimen containing either dolutegravir (50 mg once daily) or ritonavir-boosted darunavir (800 mg of darunavir plus 100 mg of ritonavir once daily) in combination with either tenofovir (300 mg once daily) plus lamivudine (300 mg once daily) or zidovudine (300 mg twice daily) plus lamivudine (150 mg twice daily). The NRTI drugs allocated by randomisation were administered orally in fixed-dose combination pills; other drugs were administered orally as separate pills. The previously reported primary outcome was the proportion of participants with a plasma HIV-1 RNA concentration of less than 400 copies per mL at 48 weeks. Here, we report the main secondary outcome: the proportion of participants with a plasma HIV-1 RNA concentration of less than 400 copies per mL at 96 weeks (non-inferiority margin 12%). We analysed this outcome and safety outcomes in the intention-to-treat population, which excluded only those who were randomly assigned in error and withdrawn before receiving trial drugs. This study was registered at ClinicalTrials.gov, NCT03988452, and is complete.
Findings
Between July 30 and Dec 18, 2019, we screened 783 patients and enrolled 465. One participant was randomly assigned in error and immediately withdrawn. The remaining 464 participants were randomly assigned to receive either dolutegravir (n=235) or ritonavir-boosted darunavir (n=229) and to receive lamivudine plus either tenofovir (n=233) or zidovudine (n=231). At week 96, 211 (90%) of 235 participants in the dolutegravir group and 199 (87%) of 229 participants in the darunavir group had HIV-1 RNA less than 400 copies per mL (percentage point difference 2·9, 95% CI −3·0 to 8·7), indicating non-inferiority. Nine (4%) participants (all in the dolutegravir group) developed dolutegravir resistance; no participants developed darunavir resistance (p=0·0023). In the other randomised comparison, 214 (92%) of 233 patients in the tenofovir group and 196 (85%) of 231 patients in the zidovudine group had HIV-1 RNA less than 400 copies per mL (percentage point difference 7·0, 95% CI 1·2 to 12·8), showing non-inferiority and indicating the superiority of tenofovir (p=0·019). The proportions of participants with any grade 3–4 adverse event were similar between the dolutegravir (26 [11%]) and darunavir (28 [12%]) groups and between the tenofovir (22 [9%]) and zidovudine (32 [14%]) groups. There were no deaths related to study medication.
Interpretation
Dolutegravir-based and darunavir-based regimens maintain good viral suppression during 96 weeks; dolutegravir is non-inferior to darunavir but is at greater risk of resistance in second-line therapy. Tenofovir should be continued in second-line therapy, rather than being switched to zidovudine.
Funding
Janssen.

Close

Ashiru-Oredope D Garraghan F, Olaoye Krockow EM Matuluko Nambatya Babigumira PA Tuck Amofah Ankrah Barrett Benedict Boaitey KP Buabeng KO Cavanagh Charani Chikatula Ghebrehewet Islam Jani YH Johnston Lamorde Malinga Mirfenderesky Rutter Sneddon Skone-James O A W C G D S P S E E S J E M A M V J R

Development and Implementation of an Antimicrobial Stewardship Checklist in Sub-Saharan Africa: A Co-Creation Consensus Approach. Healthcare (Basel). Journal Article

Healthcare (Basel). , 10 (9), pp. 1-14, 0000.

Abstract | Links | BibTeX

@article{D2022b,
title = {Development and Implementation of an Antimicrobial Stewardship Checklist in Sub-Saharan Africa: A Co-Creation Consensus Approach. Healthcare (Basel). },
author = {Ashiru-Oredope D, Garraghan F, Olaoye O, Krockow EM, Matuluko A, Nambatya W, Babigumira PA, Tuck C, Amofah G, Ankrah D, Barrett S, Benedict P, Boaitey KP, Buabeng KO, Cavanagh S, Charani E, Chikatula E, Ghebrehewet S, Islam J, Jani YH, Johnston E, Lamorde M, Malinga A, Mirfenderesky M, Rutter V, Sneddon J, Skone-James R. },
url = {https://www.mdpi.com/2227-9032/10/9/1706},
journal = {Healthcare (Basel). },
volume = {10},
number = {9},
pages = {1-14},
abstract = {Abstract: Antimicrobial stewardship (AMS) initiatives promote the responsible use of antimicrobials
in healthcare settings as a key measure to curb the global threat of antimicrobial resistance (AMR).
Defining the core elements of AMS is essential for developing and evaluating comprehensive AMS
programmes. This project used co-creation and Delphi consensus procedures to adapt and extend the
existing published international AMS checklist. The overall objective was to arrive at a contextualised
checklist of core AMS elements and key behaviours for use within healthcare settings in Sub-Saharan
Africa, as well as to implement the checklist in health institutions in four African countries. The AMS
checklist tool was developed using a modified Delphi approach to achieve local expert consensus
on the items to be included on the checklist. Fourteen healthcare/public health professionals from
Tanzania, Zambia, Uganda, Ghana and the UK were invited to review, score and comment on
items from a published global AMS checklist. Following their feedback, 8 items were rephrased,
and 25 new items were added to the checklist. The final AMS checklist tool was deployed across
19 healthcare sites and used to assess AMS programmes before and after an AMS intervention in 14 of the 19 sites. The final tool comprised 54 items. Across the 14 sites, the completed checklists
consistently showed improvements for all the AMS components following the intervention. The
greatest improvements observed were the presence of formal multidisciplinary AMS structures (79%)
and the execution of a point-prevalence survey (72%). The elements with the least improvement
were access to laboratory/imaging services (7%) and the presence of adequate financial support
for AMS (14%). In addition to capturing the quantitative and qualitative changes associated with
the AMS intervention, project evaluation suggested that administering the AMS checklist made
unique contributions to ongoing AMS activities. Furthermore, 29 additional AMS activities were
reported as a direct result of the prompting checklist questions. Contextualised, co-created AMS
tools are necessary for managing antimicrobial use across healthcare settings and increasing local
AMS ownership and commitment. This study led to the development of a new AMS checklist, which
proved successful in capturing AMS improvements in Tanzania, Zambia, Uganda, and Ghana. The
tool also made unique contributions to furthering local AMS efforts. This study extends the existing
AMS materials for low- and middle-income countries and provides empirical evidence for successful
use in practice.
Keywords: AMS checklist; antimicrobial prescribing; CwPAMS; Global-PPS; antimicrobial stewardship},
keywords = {},
pubstate = {published},
tppubtype = {article}
}

Close

Abstract: Antimicrobial stewardship (AMS) initiatives promote the responsible use of antimicrobials
in healthcare settings as a key measure to curb the global threat of antimicrobial resistance (AMR).
Defining the core elements of AMS is essential for developing and evaluating comprehensive AMS
programmes. This project used co-creation and Delphi consensus procedures to adapt and extend the
existing published international AMS checklist. The overall objective was to arrive at a contextualised
checklist of core AMS elements and key behaviours for use within healthcare settings in Sub-Saharan
Africa, as well as to implement the checklist in health institutions in four African countries. The AMS
checklist tool was developed using a modified Delphi approach to achieve local expert consensus
on the items to be included on the checklist. Fourteen healthcare/public health professionals from
Tanzania, Zambia, Uganda, Ghana and the UK were invited to review, score and comment on
items from a published global AMS checklist. Following their feedback, 8 items were rephrased,
and 25 new items were added to the checklist. The final AMS checklist tool was deployed across
19 healthcare sites and used to assess AMS programmes before and after an AMS intervention in 14 of the 19 sites. The final tool comprised 54 items. Across the 14 sites, the completed checklists
consistently showed improvements for all the AMS components following the intervention. The
greatest improvements observed were the presence of formal multidisciplinary AMS structures (79%)
and the execution of a point-prevalence survey (72%). The elements with the least improvement
were access to laboratory/imaging services (7%) and the presence of adequate financial support
for AMS (14%). In addition to capturing the quantitative and qualitative changes associated with
the AMS intervention, project evaluation suggested that administering the AMS checklist made
unique contributions to ongoing AMS activities. Furthermore, 29 additional AMS activities were
reported as a direct result of the prompting checklist questions. Contextualised, co-created AMS
tools are necessary for managing antimicrobial use across healthcare settings and increasing local
AMS ownership and commitment. This study led to the development of a new AMS checklist, which
proved successful in capturing AMS improvements in Tanzania, Zambia, Uganda, and Ghana. The
tool also made unique contributions to furthering local AMS efforts. This study extends the existing
AMS materials for low- and middle-income countries and provides empirical evidence for successful
use in practice.
Keywords: AMS checklist; antimicrobial prescribing; CwPAMS; Global-PPS; antimicrobial stewardship

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Paton, NI

Efficacy and safety of dolutegravir or darunavir in combination with lamivudine plus either zidovudine or tenofovir for second-line treatment of HIV infection (NADIA): week 96 results from a prospective, multicentre, open-label, factorial, randomised, non-inferiority trial. Journal Article

Lancet HIV., 9 (6), pp. e381-e393, 0000.

Abstract | Links | BibTeX

@article{NI2022c,
title = {Efficacy and safety of dolutegravir or darunavir in combination with lamivudine plus either zidovudine or tenofovir for second-line treatment of HIV infection (NADIA): week 96 results from a prospective, multicentre, open-label, factorial, randomised, non-inferiority trial.},
author = {Paton, NI},
url = {https://pubmed.ncbi.nlm.nih.gov/35460601/},
doi = {10.1016/S2352-3018(22)00092-3},
journal = {Lancet HIV.},
volume = {9},
number = {6},
pages = {e381-e393},
abstract = {Background: WHO guidelines recommend dolutegravir plus two nucleoside reverse transcriptase inhibitors (NRTIs) for second-line HIV therapy, with NRTI switching from first-line tenofovir to zidovudine. We aimed to examine whether dolutegravir is non-inferior to darunavir, the best-in-class protease inhibitor drug, and whether maintaining tenofovir in second-line therapy is non-inferior to switching to zidovudine.

Methods: In this prospective, multicentre, open-label, factorial, randomised, non-inferiority trial (NADIA), participants with confirmed HIV first-line treatment failure (HIV-1 RNA ≥1000 copies per mL) were recruited at seven clinical sites in Kenya, Uganda, and Zimbabwe. Following a 2 × 2 factorial design and stratified by site and screening HIV-1 RNA concentration, participants were randomly assigned (1:1:1:1) to receive a 96-week regimen containing either dolutegravir (50 mg once daily) or ritonavir-boosted darunavir (800 mg of darunavir plus 100 mg of ritonavir once daily) in combination with either tenofovir (300 mg once daily) plus lamivudine (300 mg once daily) or zidovudine (300 mg twice daily) plus lamivudine (150 mg twice daily). The NRTI drugs allocated by randomisation were administered orally in fixed-dose combination pills; other drugs were administered orally as separate pills. The previously reported primary outcome was the proportion of participants with a plasma HIV-1 RNA concentration of less than 400 copies per mL at 48 weeks. Here, we report the main secondary outcome: the proportion of participants with a plasma HIV-1 RNA concentration of less than 400 copies per mL at 96 weeks (non-inferiority margin 12%). We analysed this outcome and safety outcomes in the intention-to-treat population, which excluded only those who were randomly assigned in error and withdrawn before receiving trial drugs. This study was registered at ClinicalTrials.gov, NCT03988452, and is complete.

Findings: Between July 30 and Dec 18, 2019, we screened 783 patients and enrolled 465. One participant was randomly assigned in error and immediately withdrawn. The remaining 464 participants were randomly assigned to receive either dolutegravir (n=235) or ritonavir-boosted darunavir (n=229) and to receive lamivudine plus either tenofovir (n=233) or zidovudine (n=231). At week 96, 211 (90%) of 235 participants in the dolutegravir group and 199 (87%) of 229 participants in the darunavir group had HIV-1 RNA less than 400 copies per mL (percentage point difference 2·9, 95% CI -3·0 to 8·7), indicating non-inferiority. Nine (4%) participants (all in the dolutegravir group) developed dolutegravir resistance; no participants developed darunavir resistance (p=0·0023). In the other randomised comparison, 214 (92%) of 233 patients in the tenofovir group and 196 (85%) of 231 patients in the zidovudine group had HIV-1 RNA less than 400 copies per mL (percentage point difference 7·0, 95% CI 1·2 to 12·8), showing non-inferiority and indicating the superiority of tenofovir (p=0·019). The proportions of participants with any grade 3-4 adverse event were similar between the dolutegravir (26 [11%]) and darunavir (28 [12%]) groups and between the tenofovir (22 [9%]) and zidovudine (32 [14%]) groups. There were no deaths related to study medication.

Interpretation: Dolutegravir-based and darunavir-based regimens maintain good viral suppression during 96 weeks; dolutegravir is non-inferior to darunavir but is at greater risk of resistance in second-line therapy. Tenofovir should be continued in second-line therapy, rather than being switched to zidovudine.
},
keywords = {},
pubstate = {published},
tppubtype = {article}
}

Close

Background: WHO guidelines recommend dolutegravir plus two nucleoside reverse transcriptase inhibitors (NRTIs) for second-line HIV therapy, with NRTI switching from first-line tenofovir to zidovudine. We aimed to examine whether dolutegravir is non-inferior to darunavir, the best-in-class protease inhibitor drug, and whether maintaining tenofovir in second-line therapy is non-inferior to switching to zidovudine.

Methods: In this prospective, multicentre, open-label, factorial, randomised, non-inferiority trial (NADIA), participants with confirmed HIV first-line treatment failure (HIV-1 RNA ≥1000 copies per mL) were recruited at seven clinical sites in Kenya, Uganda, and Zimbabwe. Following a 2 × 2 factorial design and stratified by site and screening HIV-1 RNA concentration, participants were randomly assigned (1:1:1:1) to receive a 96-week regimen containing either dolutegravir (50 mg once daily) or ritonavir-boosted darunavir (800 mg of darunavir plus 100 mg of ritonavir once daily) in combination with either tenofovir (300 mg once daily) plus lamivudine (300 mg once daily) or zidovudine (300 mg twice daily) plus lamivudine (150 mg twice daily). The NRTI drugs allocated by randomisation were administered orally in fixed-dose combination pills; other drugs were administered orally as separate pills. The previously reported primary outcome was the proportion of participants with a plasma HIV-1 RNA concentration of less than 400 copies per mL at 48 weeks. Here, we report the main secondary outcome: the proportion of participants with a plasma HIV-1 RNA concentration of less than 400 copies per mL at 96 weeks (non-inferiority margin 12%). We analysed this outcome and safety outcomes in the intention-to-treat population, which excluded only those who were randomly assigned in error and withdrawn before receiving trial drugs. This study was registered at ClinicalTrials.gov, NCT03988452, and is complete.

Findings: Between July 30 and Dec 18, 2019, we screened 783 patients and enrolled 465. One participant was randomly assigned in error and immediately withdrawn. The remaining 464 participants were randomly assigned to receive either dolutegravir (n=235) or ritonavir-boosted darunavir (n=229) and to receive lamivudine plus either tenofovir (n=233) or zidovudine (n=231). At week 96, 211 (90%) of 235 participants in the dolutegravir group and 199 (87%) of 229 participants in the darunavir group had HIV-1 RNA less than 400 copies per mL (percentage point difference 2·9, 95% CI -3·0 to 8·7), indicating non-inferiority. Nine (4%) participants (all in the dolutegravir group) developed dolutegravir resistance; no participants developed darunavir resistance (p=0·0023). In the other randomised comparison, 214 (92%) of 233 patients in the tenofovir group and 196 (85%) of 231 patients in the zidovudine group had HIV-1 RNA less than 400 copies per mL (percentage point difference 7·0, 95% CI 1·2 to 12·8), showing non-inferiority and indicating the superiority of tenofovir (p=0·019). The proportions of participants with any grade 3-4 adverse event were similar between the dolutegravir (26 [11%]) and darunavir (28 [12%]) groups and between the tenofovir (22 [9%]) and zidovudine (32 [14%]) groups. There were no deaths related to study medication.

Interpretation: Dolutegravir-based and darunavir-based regimens maintain good viral suppression during 96 weeks; dolutegravir is non-inferior to darunavir but is at greater risk of resistance in second-line therapy. Tenofovir should be continued in second-line therapy, rather than being switched to zidovudine.

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Ross, Jonathan; Brazier, Ellen; Fatti, Geoffrey; Jaquet, Antoine; Tanon, Aristophane; Haas, Andreas D; Diero, Lameck; Castelnuovo, Barbara; Yiannoutsos, Constantin T; Nash, Denis; others,

Same-Day Antiretroviral Therapy (ART) Initiation as a Predictor of Loss to Follow-up and Viral Suppression Among People Living With Human Immunodeficiency Virus (HIV) in Sub-Saharan Africa Journal Article

Clinical Infectious Diseases, 0000.

BibTeX

Damalie Nakanjako Diane Kendall, Nelson Sewankambo Myat Htoo Razak Bonface Oduor Theresa Odero Patricia Garcia K; Farquhar, Carey

Building and Sustaining Effective Partnerships for Training the Next Generation of Global Health Leaders Journal Article

Annals of Global Health, 87 (1), pp. 66, 0000.

Abstract | Links | BibTeX

@article{Nakanjako2021,
title = {Building and Sustaining Effective Partnerships for Training the Next Generation of Global Health Leaders},
author = {Damalie Nakanjako, Diane Kendall, Nelson K. Sewankambo, Myat Htoo Razak, Bonface Oduor, Theresa Odero, Patricia Garcia and Carey Farquhar},
doi = {DOI: 10.5334/aogh.3214},
journal = {Annals of Global Health},
volume = {87},
number = {1},
pages = {66},
abstract = {Introduction:

Partnerships are essential to creating effective global health leadership training programs. Global pandemics, including the HIV/AIDS pandemic, and more recently the COVID-19 pandemic, have tested the impact and stability of healthcare systems. Partnerships must be fostered to prepare the next generation of leaders to collaborate effectively and improve health globally.

Objectives:

We provide key matrices that predict success of partnerships in building global health leadership capacity. We highlight opportunities and challenges to building effective partnerships and provide recommendations to promote development of equitable and mutually beneficial partnerships.

Findings:

Critical elements for effective partnership when building global health leadership capacity include shared strategic vision, transparency and excellent communication, as well as intentional monitoring and evaluation of the partnership, not just the project or program. There must be recognition that partnerships can be unpredictable and unequal, especially if the end is not defined early on. Threats to equitable and effective partnerships include funding and co-funding disparities between partners from high-income and low-income countries, inequalities, unshared vision and priorities, skewed decision-making levels, and limited flexibility to minimize inequalities and make changes. Further, imbalances in power, privilege, position, income levels, and institutional resources create opportunities for exploitation of partners, particularly those in low-income countries, which widens the disparities and limits success and sustainability of partnerships. These challenges to effective partnering create the need for objective documentation of disparities at all stages, with key milestones to assess success and the environment to sustain the partnerships and their respective goals.

Conclusions:

Developing effective and sustainable partnerships requires a commitment to equality from the start by all partners and an understanding that there will be challenges that could derail otherwise well-intended partnerships. Guidelines and training on evaluation of partnerships exist and should be used, including generic indicators of equity, mutual benefit, and the added value of partnering.

Key Takeaways

Effective partnerships in building global health leadership capacity require shared strategic vision and intentional monitoring and evaluation of goals

Inequalities in partnerships may arise from disparities in infrastructure, managerial expertise, administrative and leadership capacity, as well as limited mutual benefit and mutual respect

To promote equitable and effective partnerships, it is critical to highlight and monitor key measures for success of partnerships at the beginning of each partnership and regularly through the lifetime of the partnership.

We recommend that partnerships should have legal and financial laws through executed memoranda of understanding, to promote accountability and facilitate objective monitoring and evaluation of the partnership itself.

More research is needed to understand better the contextual predictors of the broader influence and sustainability of partnership networks in global health leadership training.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}

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Introduction:

Partnerships are essential to creating effective global health leadership training programs. Global pandemics, including the HIV/AIDS pandemic, and more recently the COVID-19 pandemic, have tested the impact and stability of healthcare systems. Partnerships must be fostered to prepare the next generation of leaders to collaborate effectively and improve health globally.

Objectives:

We provide key matrices that predict success of partnerships in building global health leadership capacity. We highlight opportunities and challenges to building effective partnerships and provide recommendations to promote development of equitable and mutually beneficial partnerships.

Findings:

Critical elements for effective partnership when building global health leadership capacity include shared strategic vision, transparency and excellent communication, as well as intentional monitoring and evaluation of the partnership, not just the project or program. There must be recognition that partnerships can be unpredictable and unequal, especially if the end is not defined early on. Threats to equitable and effective partnerships include funding and co-funding disparities between partners from high-income and low-income countries, inequalities, unshared vision and priorities, skewed decision-making levels, and limited flexibility to minimize inequalities and make changes. Further, imbalances in power, privilege, position, income levels, and institutional resources create opportunities for exploitation of partners, particularly those in low-income countries, which widens the disparities and limits success and sustainability of partnerships. These challenges to effective partnering create the need for objective documentation of disparities at all stages, with key milestones to assess success and the environment to sustain the partnerships and their respective goals.

Conclusions:

Developing effective and sustainable partnerships requires a commitment to equality from the start by all partners and an understanding that there will be challenges that could derail otherwise well-intended partnerships. Guidelines and training on evaluation of partnerships exist and should be used, including generic indicators of equity, mutual benefit, and the added value of partnering.

Key Takeaways

Effective partnerships in building global health leadership capacity require shared strategic vision and intentional monitoring and evaluation of goals

Inequalities in partnerships may arise from disparities in infrastructure, managerial expertise, administrative and leadership capacity, as well as limited mutual benefit and mutual respect

To promote equitable and effective partnerships, it is critical to highlight and monitor key measures for success of partnerships at the beginning of each partnership and regularly through the lifetime of the partnership.

We recommend that partnerships should have legal and financial laws through executed memoranda of understanding, to promote accountability and facilitate objective monitoring and evaluation of the partnership itself.

More research is needed to understand better the contextual predictors of the broader influence and sustainability of partnership networks in global health leadership training.

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