Prognosis of patients with HIV-1 infection starting antiretroviral therapy in sub-Saharan Africa: a collaborative analysis of scale-up programmes

Abstract Background. Many human immunodeficiency virus (HIV)-infected patients remain on nevirapine-based antiretroviral therapy (ART) despite safety and efficacy concerns. Switching to a rilpivirine-based regimen is an alternative, but there is little experience with rilpivirine in sub-Saharan Africa where induction of rilpivirine metabolism by nevirapine, HIV subtype, and dietary differences could potentially impact efficacy. Methods. We conducted an open-label noninferiority study of virologically suppressed (HIV-1 ribonucleic acid [RNA] < 50 copies/mL) HIV-1-infected Rwandan adults taking nevirapine plus 2 nucleos(t)ide reverse-transcriptase inhibitors. One hundred fifty participants were randomized 2:1 to switch to coformulated rilpivirine-emtricitabine-tenofovir disoproxil fumarate (referenced as the Switch Arm) or continue current therapy. The primary efficacy endpoint was HIV-1 RNA < 200 copies/mL at week 24 assessed by the US Food and Drug Administration Snapshot algorithm with a noninferiority margin of 12%. Results. Between April and September 2014, 184 patients were screened, and 150 patients were enrolled; 99 patients switched to rilpivirine-emtricitabine-tenofovir, and 51 patients continued their nevirapine-based ART. The mean age was 42 years and 43% of participants were women. At week 24, virologic suppression (HIV-1 RNA level <200 copies/mL) was maintained in 93% and 92% in the Switch Arm versus the continuation arm, respectively. The Switch Arm was noninferior to continued nevirapine-based ART (efficacy difference 0.8%; 95% confidence interval, −7.5% to +12.0%). Both regimens were generally safe and well tolerated, although 2 deaths, neither attributed to study medications, occurred in participants in the Switch Arm. Conclusions. A switch from nevirapine-based ART to rilpivirine-emtricitabine-tenofovir disoproxil fumarate had similar virologic efficacy to continued nevirapine-based ART after 24 weeks with few adverse events.

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Accessing antiretroviral therapy for children: Caregivers' voices

Health SA Gesondheid ◽

10.4102/hsag.v21i0.987 ◽

2016 ◽

Vol 21 ◽

pp. 331-338

Author(s):

Margaret Williams ◽

Dalena R.M. Van Rooyen ◽

Esmeralda J. Ricks

Keyword(s):

Antiretroviral Therapy ◽

Tertiary Care ◽

Scale Up ◽

Target Population ◽

Sub Saharan Africa ◽

Hiv Care ◽

Hiv Positive ◽

Eastern Cape ◽

Care Facilities ◽

Sub Saharan

Despite efforts to scale up access to antiretroviral therapy (ART), particularly at primary health care (PHC) facilities, antiretroviral therapy (ART) continues to be out of reach formany human immunodeficiency virus (HIV)-positive children in sub-Saharan Africa. In resource limited settings decentralisation of ART is required to scale up access to essential medication. Traditionally, paediatric HIV care has been provided in tertiary care facilities which have better human and material resources, but limited accessibility in terms of distance for caregivers of HIV-positive children. The focus of this article is on the experiences of caregivers whilst accessing ART for HIV-positive children at PHC (decentralised care) facilities in Nelson Mandela Bay (NMB) in the Eastern Cape, South Africa. A qualitative, explorative, descriptive and contextual research design was used. The target population comprised caregivers of HIV-positive children. Data were collected by means of indepth individual interviews, which were thematically analysed. Guba's model was usedto ensure trustworthiness. Barriers to accessing ART at PHC clinics for HIV-positive children included personal issues, negative experiences, lack of support and finance, stigma and discrimination. The researchers recommend standardised programmes be developed and implemented in PHC clinics to assist in providing treatment, care and support for HIV positive children.

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Risk scores for predicting early antiretroviral therapy mortality in sub-Saharan Africa to inform who needs intensification of care: a derivation and external validation cohort study

BMC Medicine ◽

10.1186/s12916-020-01775-8 ◽

2020 ◽

Vol 18 (1) ◽

Author(s):

Andrew F. Auld ◽

Katherine Fielding ◽

Tefera Agizew ◽

Alice Maida ◽

Anikie Mathoma ◽

...

Keyword(s):

Antiretroviral Therapy ◽

External Validation ◽

Scale Up ◽

Trial Data ◽

Sub Saharan Africa ◽

Stage Iii ◽

Prognostic Models ◽

Risk Scores ◽

People Living With Hiv ◽

Sub Saharan

Abstract Background Clinical scores to determine early (6-month) antiretroviral therapy (ART) mortality risk have not been developed for sub-Saharan Africa (SSA), home to 70% of people living with HIV. In the absence of validated scores, WHO eligibility criteria (EC) for ART care intensification are CD4 < 200/μL or WHO stage III/IV. Methods We used Botswana XPRES trial data for adult ART enrollees to develop CD4-independent and CD4-dependent multivariable prognostic models for 6-month mortality. Scores were derived by rescaling coefficients. Scores were developed using the first 50% of XPRES ART enrollees, and their accuracy validated internally and externally using South African TB Fast Track (TBFT) trial data. Predictive accuracy was compared between scores and WHO EC. Results Among 5553 XPRES enrollees, 2838 were included in the derivation dataset; 68% were female and 83 (3%) died by 6 months. Among 1077 TBFT ART enrollees, 55% were female and 6% died by 6 months. Factors predictive of 6-month mortality in the derivation dataset at p < 0.01 and selected for the CD4-independent score included male gender (2 points), ≥ 1 WHO tuberculosis symptom (2 points), WHO stage III/IV (2 points), severe anemia (hemoglobin < 8 g/dL) (3 points), and temperature > 37.5 °C (2 points). The same variables plus CD4 < 200/μL (1 point) were included in the CD4-dependent score. Among XPRES enrollees, a CD4-independent score of ≥ 4 would provide 86% sensitivity and 66% specificity, whereas WHO EC would provide 83% sensitivity and 58% specificity. If WHO stage alone was used, sensitivity was 48% and specificity 89%. Among TBFT enrollees, the CD4-independent score of ≥ 4 would provide 95% sensitivity and 27% specificity, whereas WHO EC would provide 100% sensitivity but 0% specificity. Accuracy was similar between CD4-independent and CD4-dependent scores. Categorizing CD4-independent scores into low (< 4), moderate (4–6), and high risk (≥ 7) gave 6-month mortality of 1%, 4%, and 17% for XPRES and 1%, 5%, and 30% for TBFT enrollees. Conclusions Sensitivity of the CD4-independent score was nearly twice that of WHO stage in predicting 6-month mortality and could be used in settings lacking CD4 testing to inform ART care intensification. The CD4-dependent score improved specificity versus WHO EC. Both scores should be considered for scale-up in SSA.

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Barriers to and enablers of uptake of and adherence to antiretroviral therapy in the context of integrated HIV and tuberculosis treatment among adults in sub-Saharan Africa: a protocol for a systematic literature review

BMJ Open ◽

10.1136/bmjopen-2019-031789 ◽

2019 ◽

Vol 9 (10) ◽

pp. e031789

Author(s):

Benjamin Momo Kadia ◽

Noah Fongwen Takah ◽

Christian Akem Dimala ◽

Adrian Smith

Keyword(s):

Antiretroviral Therapy ◽

Meta Analysis ◽

Scale Up ◽

Integrated Treatment ◽

Sub Saharan Africa ◽

Treatment Programs ◽

Quantitative Studies ◽

Final Study ◽

Registration Number ◽

Sub Saharan

IntroductionThe scale-up of integrated Human Immunodeficiency Virus (HIV) and tuberculosis (TB) treatment has been an important intervention to curb the burden of HIV and TB co-infection worldwide. Uptake of and adherence to antiretroviral therapy (ART) are key determinants of the quality and therapeutic endpoints of this intervention. This study aims to conduct an up-to-date collection and synthesis of evidence on barriers to and facilitators of uptake of and adherence to ART in HIV/TB integrated treatment programs in sub-Saharan Africa (SSA).MethodA systematic review of peer-reviewed literature on the uptake of and adherence to ART in the context of integrated therapy for HIV and TB in SSA will be performed. We will review qualitative and quantitative studies reporting on the uptake of and adherence to ART during integrated treatment for TB and HIV among adults. These will include studies that involve HIV-infected TB patients initiating ART and studies involving PLWHA already on ART who are newly diagnosed with TB. Qualitative studies, quantitative studies, randomised trials and observational studies will be included. Six databases including Medline and Embase will be searched for relevant studies published from March 2004 to July 2019. Two authors will independently screen the search output and retrieve full texts of eligible studies. Disagreements between the two authors will be resolved by arbitration by a third author. Data will be abstracted from the eligible studies and synthesis will be done through descriptive synthesis for qualitative data and meta-analysis for quantitative data.Ethics and disseminationThis study will be a review of the literature and will not involve primary collection of individuals’ data. Amendments to the protocol will be documented in the final review. The final study will be published in a peer-reviewed journal and presented at conferences. The review is expected to contribute to improving strategies to enhance uptake of and adherence to ART in integrated care.PROSPERO registration numberCRD42019131933.

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HIV Cerebrospinal Fluid Escape and Neurocognitive Pathology in the Era of Combined Antiretroviral Therapy: What Lies Beneath the Tip of the Iceberg in Sub-Saharan Africa?

Brain Sciences ◽

10.3390/brainsci8100190 ◽

2018 ◽

Vol 8 (10) ◽

pp. 190 ◽

Cited By ~ 7

Author(s):

Dami Collier ◽

Lewis Haddow ◽

Jay Brijkumar ◽

Mahomed-Yunus Moosa ◽

Laura Benjamin ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Antiretroviral Therapy ◽

Scale Up ◽

Severe Form ◽

Hiv Treatment ◽

Sub Saharan Africa ◽

The Central Nervous System ◽

Independent Replication ◽

Sub Saharan ◽

Csf Escape

Neurocognitive impairment remains an important HIV-associated comorbidity despite combination antiretroviral therapy (ART). Since the advent of ART, the spectrum of HIV-associated neurocognitive disorder (HAND) has shifted from the most severe form to milder forms. Independent replication of HIV in the central nervous system despite ART, so-called cerebrospinal fluid (CSF) escape is now recognised in the context of individuals with a reconstituted immune system. This review describes the global prevalence and clinical spectrum of CSF escape, it role in the pathogenesis of HAND and current advances in the diagnosis and management. It highlights gaps in knowledge in sub-Saharan Africa where the HIV burden is greatest and discusses the implications for this region in the context of the global HIV treatment scale up.

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Monitoring and switching of first-line antiretroviral therapy in adult treatment cohorts in sub-Saharan Africa: collaborative analysis

The Lancet HIV ◽

10.1016/s2352-3018(15)00087-9 ◽

2015 ◽

Vol 2 (7) ◽

pp. e271-e278 ◽

Cited By ~ 66

Author(s):

Andreas D Haas ◽

Olivia Keiser ◽

Eric Balestre ◽

Steve Brown ◽

Emmanuel Bissagnene ◽

...

Keyword(s):

Antiretroviral Therapy ◽

Sub Saharan Africa ◽

Adult Treatment ◽

First Line ◽

Collaborative Analysis ◽

Sub Saharan

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Formative Evaluation of Antiretroviral Therapy Scale-Up Efficiency in Sub-Saharan Africa

AIDS Patient Care and STDs ◽

10.1089/apc.2007.0008 ◽

2007 ◽

Vol 21 (11) ◽

pp. 871-888 ◽

Cited By ~ 21

Author(s):

Glenn Wagner ◽

Gery Ryan ◽

Stephanie Taylor

Keyword(s):

Antiretroviral Therapy ◽

Formative Evaluation ◽

Scale Up ◽

Sub Saharan Africa ◽

Sub Saharan

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Scale-up of antiretroviral treatment in sub-Saharan Africa is accompanied by increasing HIV-1 drug resistance mutations in drug-naive patients

AIDS ◽

10.1097/qad.0b013e32834bbbe9 ◽

2011 ◽

Vol 25 (17) ◽

pp. 2183-2188 ◽

Cited By ~ 50

Author(s):

Avelin F. Aghokeng ◽

Charles Kouanfack ◽

Christian Laurent ◽

Eugenie Ebong ◽

Arrah Atem-Tambe ◽

...

Keyword(s):

Drug Resistance ◽

Antiretroviral Treatment ◽

Scale Up ◽

Sub Saharan Africa ◽

Resistance Mutations ◽

Drug Resistance Mutations ◽

Drug Naïve ◽

Sub Saharan ◽

Hiv 1

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Adult Antiretroviral Therapy and Child Health: Evidence from Scale-up in Zambia

The American Economic Review ◽

10.1257/aer.103.3.456 ◽

2013 ◽

Vol 103 (3) ◽

pp. 456-461 ◽

Cited By ~ 13

Author(s):

Adrienne M Lucas ◽

Nicholas L Wilson

Keyword(s):

Antiretroviral Therapy ◽

Economic Benefit ◽

Scale Up ◽

Sub Saharan Africa ◽

Infected Adult ◽

Triple Difference ◽

Sub Saharan ◽

Multigenerational Effects ◽

And Child Health ◽

Weight For Age

One in five Zambian children lives with an HIV/AIDS-infected adult. We estimate the effect that the availability of adult antiretroviral therapy (ART) has on the health of such children. Using a triple difference specification, we find that adult access to ART resulted in increased weight-for-age and decreased incidence of stunting among children younger than 60 months who resided with an infected father or other infected adult in an intact household. Because the increased availability of adult ART in sub-Saharan Africa has multigenerational effects, cost-effectiveness estimates restricted to direct recipients understate the economic benefit of the treatment.

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The Lazarus Effect and the Labour Market: Evidence from At-Scale Antiretroviral Therapy in Zambia

Journal of African Economies ◽

10.1093/jae/ejaa001 ◽

2020 ◽

Vol 29 (4) ◽

pp. 397-411

Author(s):

Nicholas Wilson

Keyword(s):

Antiretroviral Therapy ◽

Causal Effect ◽

Supply And Demand ◽

Scale Up ◽

Employment Outcomes ◽

Sub Saharan Africa ◽

Sample Mean ◽

Triple Difference ◽

Quasi Experimental ◽

Sub Saharan

Abstract Between 2000 and 2015, access to life-saving antiretroviral therapy (ART) in sub-Saharan Africa increased from virtually 0% to approximately 40% coverage. Despite the promise of ART to improve health, a variety of supply- and demand-side factors suggest at-scale ART may not improve employment outcomes. To measure the causal effect of ART on employment outcomes, I use triple-difference regression analysis, exploiting spatial, temporal and demographic variation in intensity of ART exposure during scale-up in Zambia. My results suggest that local ART introduction increased employment of likely HIV+ adults by eight percentage points, or approximately 15% relative to the sample mean. Cash employment and employment for no pay—the first and second largest employment categories in Zambia, respectively—each comprised roughly one-half of the employment gains. Temporal and spatial heterogeneity analyses support a causal interpretation of the results. These findings appear to be the first at-scale quasi-experimental evidence suggesting that ART, the single largest item in many countries’ foreign health aid budgets, can improve employment outcomes among the targeted.

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