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The end of HIV: Still a very long way to go, but progress continues
editorial
Publication date (Electronic):
30 November 2017
Journal:
PLoS Medicine
Publisher:
Public Library of Science
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Abstract
In an Editorial accompanying PLOS Medicine’s Special Issue on Advances in Prevention, Treatment and Cure of HIV/AIDS, Guest Editors Steven Deeks, Sharon Lewin, and Linda-Gail Bekker discuss priorities in the field and the content of the issue.
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Most cited references13
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HIV-1 persistence following extremely early initiation of antiretroviral therapy (ART) during acute HIV-1 infection: An observational study
Timothy J. Henrich, Hiroyu Hatano, Oliver Bacon … (2017)
Background It is unknown if extremely early initiation of antiretroviral therapy (ART) may lead to long-term ART-free HIV remission or cure. As a result, we studied 2 individuals recruited from a pre-exposure prophylaxis (PrEP) program who started prophylactic ART an estimated 10 days (Participant A; 54-year-old male) and 12 days (Participant B; 31-year-old male) after infection with peak plasma HIV RNA of 220 copies/mL and 3,343 copies/mL, respectively. Extensive testing of blood and tissue for HIV persistence was performed, and PrEP Participant A underwent analytical treatment interruption (ATI) following 32 weeks of continuous ART. Methods and findings Colorectal and lymph node tissues, bone marrow, cerebral spinal fluid (CSF), plasma, and very large numbers of peripheral blood mononuclear cells (PBMCs) were obtained longitudinally from both participants and were studied for HIV persistence in several laboratories using molecular and culture-based detection methods, including a murine viral outgrowth assay (mVOA). Both participants initiated PrEP with tenofovir/emtricitabine during very early Fiebig stage I (detectable plasma HIV-1 RNA, antibody negative) followed by 4-drug ART intensification. Following peak viral loads, both participants experienced full suppression of HIV-1 plasma viremia. Over the following 2 years, no further HIV could be detected in blood or tissue from PrEP Participant A despite extensive sampling from ileum, rectum, lymph nodes, bone marrow, CSF, circulating CD4+ T cell subsets, and plasma. No HIV was detected from tissues obtained from PrEP Participant B, but low-level HIV RNA or DNA was intermittently detected from various CD4+ T cell subsets. Over 500 million CD4+ T cells were assayed from both participants in a humanized mouse outgrowth assay. Three of 8 mice infused with CD4+ T cells from PrEP Participant B developed viremia (50 million input cells/surviving mouse), but only 1 of 10 mice infused with CD4+ T cells from PrEP Participant A (53 million input cells/mouse) experienced very low level viremia (201 copies/mL); sequence confirmation was unsuccessful. PrEP Participant A stopped ART and remained aviremic for 7.4 months, rebounding with HIV RNA of 36 copies/mL that rose to 59,805 copies/mL 6 days later. ART was restarted promptly. Rebound plasma HIV sequences were identical to those obtained during acute infection by single-genome sequencing. Mathematical modeling predicted that the latent reservoir size was approximately 200 cells prior to ATI and that only around 1% of individuals with a similar HIV burden may achieve lifelong ART-free remission. Furthermore, we observed that lymphocytes expressing the tumor marker CD30 increased in frequency weeks to months prior to detectable HIV-1 RNA in plasma. This study was limited by the small sample size, which was a result of the rarity of individuals presenting during hyperacute infection. Conclusions We report HIV relapse despite initiation of ART at one of the earliest stages of acute HIV infection possible. Near complete or complete loss of detectable HIV in blood and tissues did not lead to indefinite ART-free HIV remission. However, the small numbers of latently infected cells in individuals treated during hyperacute infection may be associated with prolonged ART-free remission.
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HIV pre-exposure prophylaxis and early antiretroviral treatment among female sex workers in South Africa: Results from a prospective observational demonstration project
Robyn Eakle, Gabriela B Gomez, Niven Naicker … (2017)
Background Operational research is required to design delivery of pre-exposure prophylaxis (PrEP) and early antiretroviral treatment (ART). This paper presents the primary analysis of programmatic data, as well as demographic, behavioural, and clinical data, from the TAPS Demonstration Project, which offered both interventions to female sex workers (FSWs) at 2 urban clinic sites in South Africa. Methods and findings The TAPS study was conducted between 30 March 2015 and 30 June 2017, with the enrolment period ending on 31 July 2016. TAPS was a prospective observational cohort study with 2 groups receiving interventions delivered in existing service settings: (1) PrEP as part of combination prevention for HIV-negative FSWs and (2) early ART for HIV-positive FSWs. The main outcome was programme retention at 12 months of follow-up. Of the 947 FSWs initially seen in clinic, 692 were HIV tested. HIV prevalence was 49%. Among those returning to clinic after HIV testing and clinical screening, 93% of the women who were HIV-negative were confirmed as clinically eligible for PrEP (n = 224/241), and 41% (n = 110/270) of the women who were HIV-positive had CD4 counts within National Department of Health ART initiation guidelines at assessment. Of the remaining women who were HIV-positive, 93% were eligible for early ART (n = 148/160). From those eligible, 98% (n = 219/224) and 94% (n = 139/148) took up PrEP and early ART, respectively. At baseline, a substantial fraction of women had a steady partner, worked in brothels, and were born in Zimbabwe. Of those enrolled, 22% on PrEP (n = 49/219) and 60% on early ART (n = 83/139) were seen at 12 months; we observed high rates of loss to follow-up: 71% (n = 156/219) and 30% (n = 42/139) in the PrEP and early ART groups, respectively. Little change over time was reported in consistent condom use or the number of sexual partners in the last 7 days, with high levels of consistent condom use with clients and low use with steady partners in both study groups. There were no seroconversions on PrEP and 7 virological failures on early ART among women remaining in the study. Reported adherence to PrEP varied over time between 70% and 85%, whereas over 90% of participants reported taking pills daily while on early ART. Data on provider-side costs were also collected and analysed. The total cost of service delivery was approximately US$126 for PrEP and US$406 for early ART per person-year. The main limitations of this study include the lack of a control group, which was not included due to ethical considerations; clinical study requirements imposed when PrEP was not approved through the regulatory system, which could have affected uptake; and the timing of the implementation of a national sex worker HIV programme, which could have also affected uptake and retention. Conclusions PrEP and early ART services can be implemented within FSW routine services in high prevalence, urban settings. We observed good uptake for both PrEP and early ART; however, retention rates for PrEP were low. Retention rates for early ART were similar to retention rates for the current standard of care. While the cost of the interventions was higher than previously published, there is potential for cost reduction at scale. The TAPS Demonstration Project results provided the basis for the first government PrEP and early ART guidelines and the rollout of the national sex worker HIV programme in South Africa.
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HIV prevalence and behavioral and psychosocial factors among transgender women and cisgender men who have sex with men in 8 African countries: A cross-sectional analysis.
Tonia Poteat, Benjamin Ackerman, Daouda Diouf … (2017)
Sub-Saharan Africa bears more than two-thirds of the worldwide burden of HIV; however, data among transgender women from the region are sparse. Transgender women across the world face significant vulnerability to HIV. This analysis aimed to assess HIV prevalence as well as psychosocial and behavioral drivers of HIV infection among transgender women compared with cisgender (non-transgender) men who have sex with men (cis-MSM) in 8 sub-Saharan African countries.
Author and article information
Journal
Journal ID (nlm-ta): PLoS Med
Journal ID (iso-abbrev): PLoS Med
Journal ID (publisher-id): plos
Journal ID (pmc): plosmed
Title:
PLoS Medicine
Publisher:
Public Library of Science
(San Francisco, CA USA
)
ISSN
(Print):
1549-1277
ISSN
(Electronic):
1549-1676
Publication date
(Electronic):
30
November
2017
Publication date Collection:
November
2017
Volume: 14
Issue: 11
Electronic Location Identifier: e1002466
Affiliations
[1
]
Department of Medicine, University of California, San Francisco, San Francisco, California,
United States of America
Author notes
I have read the journal’s policy and the authors of this manuscript have the following competing interests: SD is an advisor to InnaVirVax, Bionor Pharma and Bryologix and receives grant support from Gilead, Merck and ViiV. SL’s institution has received funding for investigator-initiated industry-sponsored studies from Merck, Gilead, Viiv Healthcare and Tetralogic and has also acted on the advisory board for and as consultancy to Callimune, Tetralogic, and InnaVirVax. LGB is employed by the Desmond Tutu HIV Centre, UCT and the Desmond Tutu HIV Foundation. She has received honoraria for technical inputs from Jansen and Merck in the last 5 years and her organisation has benefited from grants from Gilead, Merck and ViiV. SD, SL, and LGB served as guest editors on PLOS Medicine’s Special Issue on Advances in HIV Prevention, Treatment and Cure.
* E-mail:
Steven.Deeks@
123456ucsf.edu
Author information
Steven G. Deeks
http://orcid.org/0000-0001-6371-747X
Article
Publisher ID: PMEDICINE-D-17-03872DOI: 10.1371/journal.pmed.1002466
PMC ID: 5708775
PubMed ID: 29190733
SO-VID: 01c5222d-4bae-495c-b771-22fc88f4d97d
Copyright © © 2017 Deeks et al
License:
This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
History
Page count
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Tables: 0,
Pages: 4
Funding
The authors received no specific funding for this work.
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