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Limbada M, Bwalya C, Macleod D, et al., 2021, A comparison of different community models of antiretroviral therapy delivery with the standard of care among stable HIV plus patients: rationale and design of a non-inferiority cluster randomized trial, nested in the HPTN 071 (PopART) study, Trials, Vol: 22, Pages: 1-12, ISSN: 1745-6215
BackgroundFollowing the World Health Organization’s (WHO) 2015 guidelines recommending initiation of antiretroviral therapy (ART) irrespective of CD4 count for all people living with HIV (PLHIV), many countries in sub-Saharan Africa have adopted this strategy to reach epidemic control. As the number of PLHIV on ART rises, maintenance of viral suppression on ART for over 90% of PLHIV remains a challenge to government health systems in resource-limited high HIV burden settings. Non facility-based antiretroviral therapy (ART) delivery for stable HIV+ patients may increase sustainable ART coverage in resource-limited settings. Within the HPTN 071 (PopART) trial, two models, home-based delivery (HBD) or adherence clubs (AC), were offered to assess whether they achieved similar viral load suppression (VLS) to standard of care (SoC). In this paper, we describe the trial design and discuss the methodological issues and challenges.MethodsA three-arm cluster randomized non-inferiority trial, nested in two urban HPTN 071 trial communities in Zambia, randomly allocated 104 zones to SoC (35), HBD (35), or AC (34). ART and adherence support were delivered 3-monthly at home (HBD), adherence clubs (AC), or clinic (SoC). Adult HIV+ patients defined as “stable” on ART were eligible for inclusion. The primary endpoint was the proportion of PLHIV with virological suppression (≤ 1000 copies HIV RNA/ml) at 12 months (± 3months) after study entry across all three arms. Viral load measurement was done at the routine government laboratories in accordance with national guidelines, annually. The study was powered to determine if either of the community-based interventions would yield a viral suppression rate drop compared to SoC of no more than 5% in its absolute value. Both community-based interventions were delivered by community HIV providers (CHiPs). An additional qualitative study using observations, interviews with PLHIV, and FGDs with co
Mubekapi-Musadaidzwa C, Wademan D, Peton N, et al., 2021, Motivating people living with HIV to initiate antiretroviral treatment outside national guidelines in three clinics in the HPTN 071 (PopART) trial, South Africa, AJAR-AFRICAN JOURNAL OF AIDS RESEARCH, Vol: 20, Pages: 32-41, ISSN: 1608-5906
Hargreaves JR, Pliakas T, Hoddinott G, et al., 2020, HIV stigma and viral suppression among people living with HIV in the context of universal test and treat: analysis of data from the HPTN 071 (PopART) trial in Zambia and South Africa, JAIDS: Journal of Acquired Immune Deficiency Syndromes, Vol: 85, Pages: 561-570, ISSN: 1525-4135
Background: The impact of HIV stigma on viral suppression among people living with HIV (PLHIV) is not well characterized.Setting: Twenty-one communities in Zambia and South Africa, nested within the HPTN 071 (PopART) trial.Methods: We analyzed data on viral suppression (<400 copies HIV RNA/mL) among 5662 laboratory-confirmed PLHIV aged 18–44 years who were randomly sampled within the PopART trial population cohort 24 months after enrolment (PC24). We collected data on experiences and internalization of stigma from those PLHIV who self-reported their HIV status (n = 3963/5662) and data on perceptions of stigma from a 20% random sample of all PLHIV (n = 1154/5662). We also measured stigma at the community-level among PLHIV, community members, and health workers. We analyzed the association between individual- and community-level measures of HIV stigma and viral suppression among PLHIV, adjusting for confounding.Results: Of all 5662 PLHIV, 69.1% were virally suppressed at PC24. Viral suppression was highest among those 3963 cohort participants who self-reported living with HIV and were on ART (88.3%), and lower among those not on treatment (37.5%). Self-identifying PLHIV who reported internalized stigma were less likely to be virally suppressed (75.0%) than those who did not (80.7%; adjusted risk ratio, 0.94 95% CI: 0.89 to 0.98). Experiences, perceptions, and community-level measures of stigma were not associated with viral suppression.Conclusion: Internalized stigma among PLHIV was associated with a lower level of viral suppression; other dimensions of stigma were not. Stigma reduction approaches that address internalized stigma should be an integral component of efforts to control the HIV epidemic.
Novitsky V, Zahralban-Steele M, Moyo S, et al., 2020, Mapping of HIV-1C transmission networks reveals extensive spread of viral lineages across villages in Botswana treatment-as-prevention trial, Journal of Infectious Diseases, Vol: 222, Pages: 1670-1680, ISSN: 0022-1899
BackgroundPhylogenetic mapping of HIV-1 lineages circulating across defined geographical locations is promising for better understanding HIV transmission networks to design optimal prevention interventions.MethodsWe obtained near full-length HIV-1 genome sequences from people living with HIV (PLWH), including participants on antiretroviral treatment in the Botswana Combination Prevention Project, conducted in 30 Botswana communities in 2013–2018. Phylogenetic relationships among viral sequences were estimated by maximum likelihood.ResultsWe obtained 6078 near full-length HIV-1C genome sequences from 6075 PLWH. We identified 984 phylogenetically distinct HIV-1 lineages (molecular HIV clusters) circulating in Botswana by mid-2018, with 2–27 members per cluster. Of these, dyads accounted for 62%, approximately 32% (n = 316) were found in single communities, and 68% (n = 668) were spread across multiple communities. Men in clusters were approximately 3 years older than women (median age 42 years, vs 39 years; P < .0001). In 65% of clusters, men were older than women, while in 35% of clusters women were older than men. The majority of identified viral lineages were spread across multiple communities.ConclusionsA large number of circulating phylogenetically distinct HIV-1C lineages (molecular HIV clusters) suggests highly diversified HIV transmission networks across Botswana communities by 2018.
Stangl AL, Pliakas T, Mainga T, et al., 2020, The effect of universal testing and treatment on HIV stigma in 21 communities in Zambia and South Africa, AIDS, Vol: 34, Pages: 2125-2135, ISSN: 0269-9370
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Nkhoma K, Lwanga J, Ryan F, et al., 2020, Prospective interruption of therapy towards a cure for HIV (PITCH): experiences of patients on treatment interruption (TI), Annual Conference of the British HIV Association (BHIVA), Publisher: Wiley, Pages: 23-24, ISSN: 1464-2662
Background: Increasingly cure trials require a treatment interruption (TI) in order to evaluate whether an intervention has worked. In order to ensure that future TI trials are designed sensitively with participants at the heart of the process, we carried out qualitative interviews with individuals taking part in the PITCH TI study.Method: We recruited participants with primary HIV infection, who commenced ART within three months of diagnosis, have been on ART for at least two years with HIV‐1 DNA levels <3.25 log copies/million CD4 T cells, CD4 count >500 or CD4:8 ratio> 1, with suppressed plasma VL < 50 copies HIV RNA/ml.Upon ART cessation, for the first 12 weeks participants were required to undergo point‐ of‐care quantitative GeneXpert viral load testing on a twice per week basis, with additional visits if desired. In‐depth qualitative face‐to‐face interviews were conducted two weeks before, at least two weeks during and two weeks after TI. The interviews aimed to explore views and experiences about TI.Results: Five out of six participants participated: n=3 were interviewed before TI, n=5 were interviewed during TI and n=4 were interviewed after TI.Seven themes were identified: 1) Motivation to participate: all participants reported participation in TI was to help others in future. 2) Benefits of TI: Stopped experiencing ART side effects and being off treatment saved NHS money. 3) Challenges of TI: frequent appointments with NHS for blood test. 4) Risks associated with TI: passing on HIV if detectable. Participants used prevention tools (PrEP/condoms). 5) Vicious cycle of worry: anxious/worried their viral load was going up and that they might transmit HIV. 6) Being undetectable: participants knew that undetectable=untransmittable. 7) Treatment rotation: TI is not a cure butswapping treatment with the partner who has to take PrEP.Conclusion: Participants found that taking a TI as part of a cure trial to be a positive experience and valued the break f
Zacharopoulou P, Marchi E, Jones M, et al., 2020, Immune response regulation gene signatures predict time to viral rebound after antiretroviral treatment interruption in primary HIV infection, The 26th Annual Conference of the British HIV Association (BHIVA), Publisher: Wiley, Pages: 31-31, ISSN: 1464-2662
Background: Antiretroviral therapy (ART) can maintain undetectable plasma HIV viraemia, but on stopping therapy HIV can be detected in the blood (‘viral rebound’), generally within a few weeks. For some individuals, the time to rebound may be protracted – up to months or years – and in some ‘post‐treatment controllers’ no rebound is reported.Method: To explore the molecular differences between early and late rebounders, we present a longitudinal analysis of the host transcriptome that explores key genetic signatures associated with time to HIV rebound. We sequenced expressed host mRNA from South African women enrolled in the SPARTAC clinical trial, and who received treatment for up to 48 weeks, starting in primary infection. We studied CD4+ T‐cells sampled at ‘baseline’ before ART initiation and again at treatment interruption (wk 48). We used R and limma with voom to quantify and transform our data and Gene Set Enrichment Analysis software with the Reactome database to identify putative genetic signatures associated with clinical outcomesResults: We find statistically significant enrichment of over 20 gene sets when comparing different ‘time to rebound’ phenotypes. We show that gene sets involved in the regulation of the immune response, in particular the Interferon Type I and the Immunoregulatory interactions between lymphoid and non‐lymphoid cells sets are up‐regulated in late versus early rebounders as well as rebounders versuslikely elite controllers. Notably, pre‐ and post‐ART samples seem to share pathway enrichment in the aforementioned gene sets.Conclusion: These data suggest that specific components of the immune response may predict rapid rebound, post‐treatment control,and elite control and may help discovery of prognostic biomarkers for time to rebound and new interventions targeted at drug‐free HIV remission.
Ring K, Freeman C, Weston R, et al., 2020, Is treatment emergent weight gain on dolutegravir-based antiretroviral therapy reversible following discontinuation? A retrospective cohort study, The 26th Annual Conference of the British HIV Association (BHIVA), Publisher: Wiley, Pages: 24-24, ISSN: 1464-2662
Background: Weight gain following initiation of antiretroviral therapy (ART) is well described, particularly as part of “return‐to‐health”, however specific associations between weight gain and dolutegravir (DTG) have been reported.We evaluated weight changes following DTG therapy discontinuation amongst a cohort of adults living with HIV at one London centre.Method: Study design is a retrospective cohort study undertaken between November 2015 and December 2019. Eligible participants were on DTG ≥4 months and switched to a non‐DTG regimen with 6‐month minimum follow‐up post‐switch. We collected data on age, ethnicity, gender, CD4 count at time of DTG start, reason for discontinuation, NRTI backbone, weight/BMI prior to DTG start, at time of switch, and at 6 months post‐switch. Statistical analysis was descriptive, a comparison was made between those who gained significant weight and those who didn't using Fisher's exact test.Results: A total of 65 patients met our inclusion criteria, mean age was 45, mean CD4 count was 608 and mean time on DTG was 506 days. Data is available on weight for 46/65; of these 78% (36/46) gained weight during therapy. The average weight change on DTG was +2.54kg. Mean BMI increased from 25.70kg/m2 to 27.92kg/m2. 54% (25/46) gained significant weight (>2 kg). Of this group, 60% (15/25) were on ABC/3TC, 36% (9/25) were on TDF and 4% (1/25) were on F/TAF (Table P23.1).
Elliott T, Kim S, Beddows S, et al., 2020, Detection of HPV vaccine-specific antibodies in young women with perinatally acquired HIV: an observational cross-sectional cohort study, Publisher: WILEY, Pages: 55-55, ISSN: 1464-2662
Khan M, Tosswill J, Haddow J, et al., 2020, Virological and immunological evaluation of individuals with spontaneous persistent viral control without ART, Publisher: WILEY, Pages: 12-12, ISSN: 1464-2662
Pasvol T, Teh J, Balfoussia D, et al., 2020, Fertility evaluation in adults with perinatally acquired HIV-1 infection: a cross-sectional observational study, Publisher: WILEY, Pages: 38-38, ISSN: 1464-2662
Ryan F, Uzu H, Lwanga J, et al., 2020, Clinical experiences of carrying out antiretroviral treatment interruption within HIV cure trials, Publisher: WILEY, Pages: 66-66, ISSN: 1464-2662
Johnson SM, Teh J, Pasvol T, et al., 2020, Hospitalisation across the ages: transitioning young people with perinatally acquired HIV (PaHIV), Publisher: WILEY, Pages: 54-55, ISSN: 1464-2662
Foster C, Smith C, Walley A, et al., 2020, Bone health in perinatal HIV: the BONDY study, Publisher: WILEY, Pages: 41-42, ISSN: 1464-2662
Khara S, Kim S, Fidler S, et al., 2020, Dolutegravir use in a cohort of treatment-experienced young adults with perinatally acquired HIV, Publisher: WILEY, Pages: 28-28, ISSN: 1464-2662
Kim S, Khara S, Foster C, et al., 2020, Tolerability of dolutegravir-containing ART regimens in a cohort of youth living with perinatallyacquired HIV, Publisher: WILEY, Pages: 28-28, ISSN: 1464-2662
Viljoen L, Bond VA, Reynolds LJ, et al., 2020, Universal HIV testing and treatment and HIV stigma reduction: a comparative thematic analysis of qualitative data from the HPTN 071 (PopART) trial in South Africa and Zambia, Sociology of Health and Illness: a journal of medical sociology, Vol: 43, Pages: 167-185, ISSN: 0141-9889
Despite continued development of effective HIV treatment, expanded access to care and advances in prevention modalities, HIV‐related stigma persists. We examine how, in the context of a universal HIV‐testing and treatment trial in South Africa and Zambia, increased availability of HIV services influenced conceptualisations of HIV. Using qualitative data, we explore people’s stigma‐related experiences of living in ‘intervention’ and ‘control’ study communities. We conducted exploratory data analysis from a qualitative cohort of 150 households in 13 study communities, collected between 2016 and 2018. We found that increased availability of HIV‐testing services influenced conceptualisations of HIV as normative (non‐exceptional) and the visibility of people living with HIV (PLHIV) in household and community spaces impacted opportunities for stigma. There was a shift in community narratives towards individual responsibility to take up (assumingly) widely available service – for PLHIV to take care of their own health and to prevent onward transmission. Based on empirical data, we show that, despite a growing acceptance of HIV‐related testing services, anticipated stigma persists through the mechanism of shifting responsibilisation. To mitigate the responsibilisation of PLHIV, heath implementers need to adapt anti‐stigma messaging and especially focus on anticipated stigma.
Evangeli M, Foster C, Musiime V, et al., 2020, A randomised feasibility trial of an intervention to support sharing of HIV status for 18-25-year olds living with perinatally acquired HIV compared with standard care: HIV Empowering Adults' Decisions to Share-UK/Uganda Project (HEADS-UP), Pilot and Feasibility Studies, Vol: 6, Pages: 141-141, ISSN: 2055-5784
Abstract: Background: Young adults with perinatally acquired HIV (PAH) face several challenges, including adhering to antiretroviral therapy (ART), managing the risk of onward HIV transmission and maintaining positive well-being. Sharing one's HIV status with others (onward HIV disclosure) may assist with these challenges by facilitating emotional and practical support. Rates of HIV status sharing are, however, low in this population. There are no existing interventions focused on sharing one's HIV status for young adults living with PAH. The HEADS-UP study is designed to develop and test the feasibility of an intervention to help the sharing of HIV status for young adults with PAH. Methods: The study is a 30-month multi-site randomised feasibility study across both a high-income/low-HIV prevalence country (UK) and a low-income/high-HIV prevalence country (Uganda). Phase 1 (12 months) will involve developing the intervention using qualitative interviews with 20 young people living with PAH (ten in the UK-18 to 29 years; ten in Uganda-18 to 25 years), 20 of their social network (friends, family, sexual partners as defined by the young person; ten in the UK, ten in Uganda) and ten professionals with experience working with young adults with PAH (five in the UK, five in Uganda). Phase 2 (18 months) involves conducting a randomised feasibility parallel group trial of the intervention alongside current standard of care condition in each country (main study) with 18- to 25-year olds with PAH. A sample size of 94 participants per condition (intervention or standard of care; 188 participants in total: 47 in each condition in each country) with data at both the baseline and 6-month follow-up time points, across UK and Ugandan sites will be recruited. Participants in the intervention condition will also complete measures immediately post-intervention. Face-to-face interviews will be conducted with ten participants in both countries immediately pos
Bonsall D, Golubchik T, de Cesare M, et al., 2020, A comprehensive genomics solution for HIV surveillance and clinical monitoring in low-income settings, Journal of Clinical Microbiology, Vol: 58, Pages: 1-13, ISSN: 0095-1137
Viral genetic sequencing can be used to monitor the spread of HIV drug resistance, identify appropriate antiretroviral regimes, and characterize transmission dynamics. Despite decreasing costs, next-generation sequencing (NGS) is still prohibitively costly for routine use in generalized HIV epidemics in low- and middle-income countries. Here, we present veSEQ-HIV, a high-throughput, cost-effective NGS sequencing method and computational pipeline tailored specifically to HIV, which can be performed using leftover blood drawn for routine CD4 cell count testing. This method overcomes several major technical challenges that have prevented HIV sequencing from being used routinely in public health efforts; it is fast, robust, and cost-efficient, and generates full genomic sequences of diverse strains of HIV without bias. The complete veSEQ-HIV pipeline provides viral load estimates and quantitative summaries of drug resistance mutations; it also exploits information on within-host viral diversity to construct directed transmission networks. We evaluated the method’s performance using 1,620 plasma samples collected from individuals attending 10 large urban clinics in Zambia as part of the HPTN 071-2 study (PopART Phylogenetics). Whole HIV genomes were recovered from 91% of samples with a viral load of >1,000 copies/ml. The cost of the assay (30 GBP per sample) compares favorably with existing VL and HIV genotyping tests, proving an affordable option for combining HIV clinical monitoring with molecular epidemiology and drug resistance surveillance in low-income settings.
Pickles M, Cori A, Probert W, et al., 2020, PopART-IBM, a highly efficient stochastic individual-based simulation model of generalised HIV epidemics developed in the context of the HPTN 071 (PopART) trial
<jats:title>Abstract</jats:title><jats:p>Mathematical models are powerful tools in HIV epidemiology, producing quantitative projections of key indicators such as HIV incidence and prevalence. In order to improve the accuracy of predictions, such models need to incorporate a number of behavioural and biological heterogeneities, especially those related to the sexual network within which HIV transmission occurs. An individual-based model, which explicitly models sexual partnerships, is thus often the most natural type of model to choose. In this paper we present PopART-IBM, a computationally efficient individual-based model capable of simulating 50 years of an HIV epidemic in a large, high-prevalence community in under a minute. We show how the model calibrates within a Bayesian inference framework to detailed age- and sex-stratified data from multiple sources on HIV prevalence, awareness of HIV status, ART status, and viral suppression for an HPTN 071 (PopART) study community in Zambia, and present future projections of HIV prevalence and incidence for this community in the absence of trial intervention.</jats:p>
Jones HS, Floyd S, Stangl A, et al., 2020, Association between HIV stigma and antiretroviral therapy adherence among adults living with HIV: baseline findings from the HPTN 071 (PopART) trial in Zambia and South Africa, Tropical Medicine and International Health, Vol: 25, Pages: 1246-1260, ISSN: 1360-2276
ObjectivesAdherence to antiretroviral therapy (ART) leads to viral suppression for people living with HIV (PLHIV) and is critical for both individual health and reducing onward HIV transmission. HIV stigma is a risk factor that can undermine adherence. We explored the association between HIV stigma and self‐reported ART adherence among PLHIV in 21 communities in the HPTN 071 (PopART) trial in Zambia and the Western Cape of South Africa.MethodsWe conducted a cross‐sectional analysis of baseline data collected between 2013 and 2015, before the roll‐out of trial interventions. Questionnaires were conducted, and consenting participants provided a blood sample for HIV testing. Poor adherence was defined as self‐report of not currently taking ART, missing pills over the previous 7 days or stopping treatment in the previous 12 months. Stigma was categorised into three domains: community, health setting and internalised stigma. Multivariable logistic regression was used for analysis.ResultsAmong 2020 PLHIV self‐reporting ever taking ART, 1888 (93%) were included in multivariable analysis. Poor ART adherence was reported by 15.8% (n = 320) of participants, and 25.7% (n = 519) reported experiencing community stigma, 21.5% (n = 434) internalised stigma, and 5.7% (n = 152) health setting stigma. PLHIV who self‐reported previous experiences of community and internalised stigma more commonly reported poor ART adherence than those who did not (aOR 1.63, 95% CI 1.21 −2.19, P = 0.001 and aOR 1.31, 95% CI 0.96–1.79, P = 0.09).ConclusionsHIV stigma was associated with poor ART adherence. Roll‐out of universal treatment will see an increasingly high proportion of PLHIV initiated on ART. Addressing HIV stigma could make an important contribution to supporting lifelong ART adherence.
Hensen B, Schaap AJ, Mulubwa C, et al., 2020, Who accepts and who uses community-based secondary distribution HIV self-testing (HIVST) kits? findings from the intervention arm of a cluster-randomized trial of HIVST distribution nested in four HPTN 071 (PopART) communities in Zambia, JAIDS: Journal of Acquired Immune Deficiency Syndromes, Vol: 84, Pages: 355-364, ISSN: 1525-4135
Background: HPTN 071 (PopART) was a community-randomized trial of a universal testing-and-treatment intervention on HIV incidence at population level in Zambia and South Africa. In Zambia, a trial of community-based distribution of HIV self-testing (HIVST) kits, including secondary distribution, as an option for HIV-testing was nested within 4 PopART intervention communities. We used data from the intervention arm of the nested trial to measure levels of and factors associated with acceptance and use of secondary distribution HIVST kits.Methods: Community HIV care providers offered the PopART combination HIV-prevention intervention door-to-door, systematically visiting all households and enumerating all household members. From 1 February to 30 April 2017, individuals aged 16 years and older consenting to PopART were offered the option to HIV self-test, if eligible for HIV-testing services. Individuals aged 18 years and older who reported a partner absent during household visits were offered an HIVST kit for secondary distribution to this partner. We used two data sources to measure acceptance and use of secondary distribution HIVST kits.Results: Among 9105 individuals aged 18 years and older consenting to PopART, 9.1% (n = 825) accepted an HIVST kit for secondary distribution. Approximately 55.8% reported that the kit had been used. Women were more likely to accept, and men more likely to use, secondary distribution HIVST kits. Kits were more likely to be used by individuals aged 30+ and who had not participated in a previous round of PopART. Approximately 6.8% had a reactive result.Conclusions: Community-based secondary distribution of HIVST kits reached men absent during community HIV care provider household visits and is a complement to facility- and community-based HIV-testing services, which often miss men.
Mann JFS, Pankrac J, Klein K, et al., 2020, A targeted reactivation of latent HIV-1 using an activator vector in patient samples from acute infection., EBioMedicine, Vol: 59, Pages: 1-15, ISSN: 2352-3964
BACKGROUND: During combined anti-retroviral treatment, a latent HIV reservoir persists within resting memory CD4 T cells that initiates viral recrudescence upon treatment interruption. Strategies for HIV-1 cure have largely focused on latency reversing agents (LRAs) capable of reactivating and eliminating this viral reservoir. Previously investigated LRAs have largely failed to achieve a robust latency reversal sufficient for reduction of latent HIV pool or the potential of virus-free remission in the absence of treatment. METHODS: We utilize a polyvalent virus-like particle (VLP) formulation called Activator Vector (ACT-VEC) to 'shock' provirus into transcriptional activity. Ex vivo co-culture experiments were used to evaluate the efficacy of ACT-VEC in relation to other LRAs in individuals diagnosed and treated during the acute stage of infection. IFN-γ ELISpot, qRT-PCR and Illumina MiSeq were used to evaluate antigenicity, latency reversal, and diversity of induced virus respectively. FINDINGS: Using samples from HIV+ patients diagnosed and treated at acute/early infection, we demonstrate that ACT-VEC can reverse latency in HIV infected CD4 T cells to a greater extent than other major recall antigens as stimuli or even mitogens such as PMA/Iono. Furthermore, ACT-VEC activates more latent HIV-1 than clinically tested HDAC inhibitors or protein kinase C agonists. INTERPRETATION: Taken together, these results show that ACT-VEC can induce HIV reactivation from latently infected CD4 T cells collected from participants on first line combined antiretroviral therapy for at least two years after being diagnosed and treated at acute/early stage of infection. These findings could provide guidance to possible targeted cure strategies and treatments. FUNDING: NIH and CIHR.
Phiri MM, Kumar R, Gachie T, et al., 2020, Factors encouraging men to test for HIV for the first time in HPTN 071 (PopART) communities in Zambia, Publisher: JOHN WILEY & SONS LTD, Pages: 87-88
Bwalya C, Simwinga M, Hensen B, et al., 2020, Social response to the delivery of HIV self-testing in households: experiences from four Zambian HPTN 071 (PopART) urban communities, AIDS Research and Therapy, Vol: 17, Pages: 1-12, ISSN: 1742-6405
BackgroundDoor-to-door distribution of HIV self-testing kits (HIVST) has the potential to increase uptake of HIV testing services (HTS). However, very few studies have explored the social response to and implications of door-to-door including secondary distribution of HIVST on household relations and the ability of individuals to self-test with or without supervision within households.MethodsA CRT of HIVST distribution was nested within the HPTN 071 (PopART) trial, in four Zambian communities randomised to receive the PopART intervention. The nested HIVST trial aimed to increase knowledge of HIV status at population level. Between February 1 and April 30, 2017, 66 zones (clusters) within these four communities were randomly allocated to either the PopART standard of care door-to-door HTS (33 clusters) or PopART standard of care door-to-door HTS plus oral HIVST (33 clusters). In clusters randomised to HIVST, trained Community HIV care provider (CHiPs) visited households and offered individuals aged ≥ 16 and eligible for an offer of HTS the choice of HIV testing using HIVST or routine door-to-door HTS (finger-prick RDT). To document participants’ experiences with HIVST, Interviews (n = 40), observations (n = 22) and group discussions (n = 91) with household members and CHiPs were conducted. Data were coded using Atlas.ti 7 and analysed thematically.ResultsThe usage and storage of HIVST kits was facilitated by familiarity with and trust in CHiPs, the novelty of HIVST, and demonstrations and supervision provided by CHiPs. Door-to-door distribution of HIVST kits was appreciated for being novel, convenient, private, empowering, autonomous and easy-to-use. Literacy and age influenced accurate usage of HIVST kits. The novelty of using oral fluids to test for HIV raised questions, some anxiety and doubts about the accuracy of HIVST. Although HIVST protected participants from experiencing clinic-based stigma, it
Foster C, Ayers S, Fidler S, 2020, Antiretroviral adherence for adolescents growing up with HIV: understanding real life, drug delivery and forgiveness, Therapeutic Advances in Infectious Disease, Vol: 7, Pages: 1-12, ISSN: 2049-9361
Poorer adherence to medication is normal in adolescence and is one of a range of risk-taking behaviours common during a developmental stage that encompasses enormous cognitive, physical, sexual, social and emotional change. For adolescents living with human immunodeficiency virus (HIV) infection, poor adherence to antiretroviral therapy (ART) confers two significant challenges: poor health, but also the specific additional burden of onward transmission to partners. Late adolescence (15–19 years) is the only age group where HIV-associated mortality is rising, driven by poor adherence to ART and lack of access to second-line therapy, particularly amongst surviving perinatally infected young people. A previous lack of well-powered randomised multimodal behavioural ART adherence interventions specifically targeting adolescents is now being addressed and ongoing studies registered to ClinicalTrials.gov are described in the context of previous data. Accepting that despite enhanced support, some adolescents will continue to struggle with adherence, we must address how best to use existing ART agents to reduce mortality and allow adolescents the time to mature into adult life. Single-tablet regimens with a high genetic barrier to resistance based on integrase inhibitors and boosted protease inhibitors exist, but global access, in resource limited settings of young people living with HIV reside, is limited. Pragmatically, such regimens tolerate the intermittent adherence so characteristic of adolescence, preserving immune function, without the rapid evolution of resistance. The potential role of long-acting injectable ART, specifically cabotegravir and rilpivirine, is discussed and future strategies including ultra-long-acting drug-delivery systems and broadly neutralising monoclonal antibodies explored.
Martin GE, Pace M, Shearer FM, et al., 2020, Levels of human immunodeficiency virus DNA are determined before ART initiation and linked to CD8 T-Cell activation and memory expansion, Journal of Infectious Diseases, Vol: 221, Pages: 1135-1145, ISSN: 0022-1899
Initiation of antiretroviral therapy (ART) in early compared with chronic human immunodeficiency virus (HIV) infection is associated with a smaller HIV reservoir. This longitudinal analysis of 60 individuals who began ART during primary HIV infection (PHI) investigates which pre- and posttherapy factors best predict HIV DNA levels (a correlate of reservoir size) after treatment initiation during PHI. The best predictor of HIV DNA at 1 year was pre-ART HIV DNA, which was in turn significantly associated with CD8 memory T-cell differentiation (effector memory, naive, and T-bet−Eomes− subsets), CD8 T-cell activation (CD38 expression) and T-cell immunoglobulin and mucin-domain containing-3 (Tim-3) expression on memory T cells. No associations were found for any immunological variables after 1 year of ART. Levels of HIV DNA are determined around the time of ART initiation in individuals treated during PHI. CD8 T-cell activation and memory expansion are linked to HIV DNA levels, suggesting the importance of the initial host-viral interplay in eventual reservoir size.
Floyd S, Shanaube K, Yang B, et al., 2020, HIV testing and treatment coverage achieved after 4 years across 14 urban and peri-urban communities in Zambia and South Africa: An analysis of findings from the HPTN 071 (PopART) trial, PLoS Medicine, Vol: 17, Pages: 1-30, ISSN: 1549-1277
BackgroundIn 2014, the Joint United Nations Programme on HIV/AIDS (UNAIDS) set the 90-90-90 targets: that 90% of people living with HIV know their HIV status, that 90% of those who know their HIV-positive status are on antiretroviral therapy (ART), and that 90% of those on treatment are virally suppressed. The aim was to reach these targets by 2020. We assessed the feasibility of achieving the first two targets, and the corresponding 81% ART coverage target, as part of the HIV Prevention Trials Network (HPTN) 071 Population Effects of Antiretroviral Therapy to Reduce HIV Transmission (PopART) community-randomized trial.Methods and findingsThe study population was individuals aged ≥15 years living in 14 urban and peri-urban “PopART intervention” communities in Zambia and South Africa (SA), with a total population of approximately 600,000 and approximately 15% adult HIV prevalence. Community HIV care providers (CHiPs) delivered the PopART intervention during 2014–2017. This was a combination HIV prevention package including universal home-based HIV testing, referral of HIV-positive individuals to government HIV clinic services that offered universal ART (Arm A) or ART according to national guidelines (Arm B), and revisits to HIV-positive individuals to support linkage to HIV care and retention on ART. The intervention was delivered in 3 “rounds,” each about 15 months long, during which CHiPs visited all households and aimed to contact all individuals aged ≥15 years at least once.In Arm A in Round 3 (R3), 67% (41,332/61,402) of men and 86% (56,345/65,896) of women in Zambia and 56% (17,813/32,095) of men and 71% (24,461/34,514) of women in SA participated in the intervention, among 193,907 residents aged ≥15 years. Following participation, HIV status was known by 90% of men and women in Zambia and by 78% of men and 85% of women in SA. The median time from CHiP referral of HIV-positive individuals to ART initiation was approximatel
Fidler S, Stӧhr W, Pace M, et al., 2020, A randomized comparison of antiretroviral therapy alone versus antiretroviral therapy with a 'kick-and-kill' approach, on measures of the HIV reservoir amongst participants with recent HIV infection: the RIVER trial, The Lancet, Vol: 395, Pages: 888-898, ISSN: 0140-6736
Background: Antiretroviral therapy (ART) cannot cure HIV infection because of a persistent reservoir of latently infected cells. Approaches that force HIV transcription from these cells, making them susceptible to killing - termed ‘kick and kill’ - have been explored as a strategy towards an HIV cure. RIVER is the first randomized trial to determine the impact of ART alone versus ART plus ‘kick-and-kill’ on markers of the HIV reservoir.Methods: RIVER (Trial registration: NCT02336074) was an open-label, multicenter, 1:1 randomized controlled trial of ART-only (control) versus ART plus the histone deacetylase inhibitor vorinostat (the ‘kick’) and replication-deficient viral vector vaccines encoding conserved HIV sequences ChAdV63.HIVconsv-prime, MVA.HIVconsv-boost T-cell vaccination (the ‘kill’) (ART+V+V; intervention) in HIV-positive adults treated in recent HIV-infection. The primary endpoint was total HIV DNA in peripheral blood CD4+ T-cells at weeks 16 and 18 post-randomization. Secondary endpoints included safety, alternative measures of the HIV reservoir including quantitative viral outgrowth, HIV-specific T-cell frequencies, and CD8+ T-cell mediated viral inhibition.Findings: Between December 2015 and November 2017, 60 HIV-positive male participants were randomized (computer-based and stratified by time since diagnosis; 30 participants in each trial arm) and completed the study interventions, with no loss-to-follow-up. There were no intervention-related serious adverse events. Mean total HIV DNA at weeks 16 and 18 was 3.02 log10 copies HIV DNA/106 CD4+ T-cells in the control and 3.06 log10 copies HIV DNA/106 CD4+ T-cells in the intervention arm, with no statistically significant difference (mean difference of 0.04 (95%CI -0.03, 0.11) log10 total HIV DNA copies/106 CD4+ T-cells (p=0.26)). Interpretation: This ‘kick-and-kill’ approach conferred no significant benefit compared to ART alone on measures of
Capoferri AA, Lamers SL, Grabowski MK, et al., 2020, Recombination analysis of near full-length HIV-1 sequences and the identification of a potential new circulating recombinant form from Rakai, Uganda., AIDS Research and Human Retroviruses, ISSN: 0889-2229
The Phylogenetics And Networks for Generalized HIV Epidemics in Africa (PANGEA-HIV) consortium has been vital in the generation and examination of near full-length HIV-1 sequences generated from Sub-Saharan Africa. In this study, we examined a subset (n = 275) of sequences from Rakai, Uganda, collected between August 2011 and January 2015. Sequences were initially screened with COMET for subtyping and then evaluated using bootscanning and phylogenetic inference. Among 275 sequences, 38.6% were subtype D, 19.3% were subtype A, 2.9% were subtype C, and 39.3% were recombinant. The recombinants were structurally diverse in the number of breakpoints observed, the location of recombinant segments, and represented subtypes, with AD recombinants accounting for the majority of all recombinants (29.8%). Within the AD subpopulation, we identified a potential new circulating recombinant form in five individuals where the polymerase gene was subtype D and most of env was subtype A (D-A junctures at HXB2 6760 and 8709). While the breakpoints were identical for the viruses from these individuals, the viral fragments did not cluster together. These results suggest selection for a viral strain where properties of the subtype A and subtype D portions of the virus confer a survival advantage. The continued study of recombinants will increase our breadth of knowledge for the genetic diversity and evolution of HIV-1, which can further contribute to our understanding toward a universal HIV-1 vaccine.
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