Abbreviations: mL = microliter, 3TC = lamivudine, ANRS = National Agency for Research on AIDS and Viral Hepatitis, AOR =
adjusted odds ratio, ART = antiretroviraltreatment, ARV = antiretroviral, BMC = breast milk cell, CAV = cell-associated HIV, CD4 = cluster of differentiation 4, CFV = cell-free HIV, CI = conﬁdence interval, DNA = Deoxyribonucleic Acid, EBF = exclusive breastfeeding, g = gravitational force, HIV = human immunodeﬁciency virus, IBM = international business machine, INSERM = National institute for Health and Medical Research, IQR = inter quantile range, IRB = Institution Review Board, K + = Potassium, mL = milliliter, Na + = Sodium, o C = degrees Celsius, OR = odds ratio, PBS = phosphate buffered saline, PCR = polymerase chain reaction, PMTCT = prevention of mother to child transmission, PROMISE-PEP = promoting infant health and nutrition in Sub-Saharan Africa – Peri Exposure Prophylaxis, r = correlation coefﬁcient, RNA = Ribonucleic Acid, RT-PCR = Reverse Transcriptase - Polymerase Chain
Chronic immune activation and inflammation play a deleterious role during infection by the HIV type 1 (HIV-1) and persist despite fully suppressive antiretroviraltreatment (ART), increasing the risk of serious non- AIDS-related morbidity and mortality in treated patients . Although these alterations can be directly and indirectly enhanced by persistent production of type-I interferons (IFN) immune deregulation, loss of lymphoid tissue integrity and microbial translocation linked to HIV- 1 replication [2,3], virus coinfections might also play a key role. Indeed the cytomegalovirus (CMV) coinfection has been shown to increase the immune activation caused by HIV-1, whereas anti-CMV treatment can reduce such activation . Coinfection with hepatitis C virus (HCV) might play a similar role either directly or indirectly, by exposing to accelerated hepatic fibrosis progression, higher rates of liver failure and death , and has been associated with a 35% increased risk of overall mortality compared with HIV-1 monoinfection in the post-ART era . Whether such increased morbidity stems directly from HCV replication or results from collateral damages from long-standing inflammation induced by HCV coinfection remains unclear . In addition, a con- troversy persists as to whether the HCV coinfection increases immune activation linked to HIV-1 as compared with HIV-1 monoinfection [7–10].
HIV History Variables
The patients were either included at birth in The Agence Nationale de Recherche sur le SIDA et les Hépatites Virales (ANRS) EPF/ANRS CO10 national prospective multicenter cohort or were managed at the centers of the ANRS/CO10 cohort and diagnosed before the age of 13 years ( 1 ). Clinical and biological data were therefore collected for HIV-infected children via the completion of standardized questionnaires at six-month intervals, or were collected retrospectively after inclusion in the CLEAC study. All ART regimens initiated consisted of highly active antiretroviraltreatment (HAART; i.e., any combination of at least three different antiretroviral drugs or any combination including one protease inhibitor, or one non-nucleoside reverse transcriptase inhibitor or one integrase inhibitor). During the ﬁrst few weeks of life, 30 children received prophylactic ART consisting of zidovudine (n=21), zidovudine+lamivudine (n=5), zidovudine+lamivudine+ lopinavir (n=2) or zidovudine+lamivudine+nevirapine (n=2). For the last four of these children, the date of ﬁrst HAART (ART1) initiation was the date of prophylactic ART initiation, as treatment was continued without interruption after diagnosis. At the time of the study, all but one of the children were on HAART, the remaining child being on two nucleoside reverse transcriptase inhibitors and having an undetectable viral load.
Background: The long-term benefits of antiretroviraltreatment (ART) are associated with metabolic complications, especially lipodystrophy, which has been well described among HIV-infected adults and children on ART in developed settings. Specifically, stavudine, and to a lesser extent zidovudine and protease inhibitors (PI), have been consistently implicated in the development of lipodystrophy. In 2006, following advice from the WHO, Senegal began phasing out stavudine from first-line ART. The objectives of this cross-sectional analysis are to assess and identify risk factors affecting the prevalence of lipodystrophy in Senegalese children and adolescents on long-term ART participating in a cohort study. Methods: Lipodystrophy was clinically assessed in two- to 18-year-old children on ART for at least six months and with no concurrent severe acute malnutrition. Risk factors for lipodystrophy were identified using stepwise multivariable logistic regression. Explanatory variables included clinical and personal data, immunovirologic status, and therapeutic history.
Background: It has been reported that people living with HIV in West Africa exhibited the highest risks for chronic kidney disease (CKD) in the world. Here, we aimed at determining the CKD frequency and changes in kidney function during antiretroviraltreatment (ART) in a large cohort of HIV-patients followed in Burkina Faso. Methods: We included ART-naive adults who initiated ART at the Day Care Unit of the Souro Sanou University Hospital between 01/01/2007 and 12/31/2016. We assessed the estimated glomerular filtration rate (eGFR) by serum creatinine using the Modification of Diet in Renal Disease (MDRD) equation. Following the K/DOQI recommendations, CKD was defined as eGFR < 60 ml/min/1.73m 2 at two consecutive measurements at least 3 months apart. The factors associated with eGFR decline or CKD were identified by mixed linear regression and Cox regression, respectively. Results: Three thousand, one hundred and thirty-eight patients (72% women) were followed for a median (IQR) of 4.5(2.2 –6.9) years. At baseline, median eGFR (IQR) was 110.7(94.4–128.4) ml/min/1.73m 2 and 93 (3%) patients exhibited eGFR < 60 ml/min/1.73m 2 . The lowest-performing progressions of eGFR during the first year of ART were observed in patients with 40-49 yr. age range ( − 8.3[− 11.7;-5.0] ml/min/1.73m 2 , p < 0.001), age ≥ 50 yr. ( − 6.2[− 10.7;-1.8] ml/min/1.73m 2 , p = 0.006) and high blood pressure (HBP) (− 28.4[− 46.9;-9.9] ml/min/1.73m 2 , p = 0.003) at ART initiation. Regarding the ART exposure in patients with normal baseline eGFR, zidovudine (AZT) with protease inhibitor (PI) ( − 4.7[− 7.7;-1.6] ml/min/1.73m 2 , p = 0.002), tenofovir (TDF) + PI (− 13.1[− 17.4;-8.7] ml/min/1.73m 2 , p < 0.001), TDF without PI (− 3.2[− 5.0;-1.4] ml/min/1.73m 2 , p < 0.001), stavudine (d4T) + PI (− 8.5[− 14.6–2.4] ml/ min/1.73m 2 , p = 0.006) and d4T without PI (− 5.0[− 7.6–2.4] ml/min/1.73m 2 , p < 0.001) were associated with poorer eGFR progression. The prevalence of CKD was 0.5% and the incidence was 1.9 [1.3; 2.7] cases/1000 person-years. The risk of CKD was higher in patients with HBP (4.3[1.8;9.9], p = 0.001), 40-49 yr. patients (4.2[1.6;11.2], p = 0.004), ≥50 yr. patients (4.5[1.5;14.1], p = 0.009) and patients exposed to abacavir (ABC) or didanosine (ddI) based ART (13.1[4.0;42.9], p < 0.001).
15. Wandeler G, Keiser O, Pfeiffer K, Pestilli S, Fritz C, Labhardt ND, et al. Outcomes of antiretroviraltreatment programs in rural Southern Africa. J Acquir Immune Defic Syndr. 2012;59:9–16.
16. Fofana DB, Soulié C, Baldé A, Lambert‑Niclot S, Sylla M, Ait‑Arkoub Z, et al. High level of HIV‑1 resistance in patients failing long‑term first‑line antiretroviral therapy in Mali. J Antimicrob Chemother. 2014;69:2531–5. 17. Fall‑Malick FZ, Tchiakpe E, Ould Soufiane S, Diop‑Ndiaye H, Mouhamed‑ oune BA, Ould Horma BA, et al. Drug resistance mutations and genetic diversity in adults treated for HIV type 1 infection in Mauritania. J Med Virol. 2014;86:404–10.
2. Adam BD, Maticka-Tyndale E, Cohen JJ. Adherence practices among people living with HIV. AIDS care. 2003; 15(2):263–74. Epub 2003/07/15. https://doi.org/10.1080/0954012031000068407 PMID: 12856347 .
3. Brennan AT, Maskew M, Sanne I, Fox MP. The importance of clinic attendance in the first six months on antiretroviraltreatment: a retrospective analysis at a large public sector HIV clinic in South Africa. Journal of the International AIDS Society. 2010; 13:49. Epub 2010/12/08. https://doi.org/10.1186/1758- 2652-13-49 PMID: 21134297 ; PubMed Central PMCID: PMC3012655.
Edited by: Joris Hemelaar, University of Oxford, United Kingdom Reviewed by: Fernando Gonzalez-Candelas, University of Valencia, Spain Dimitrios Paraskevis, National and Kapodistrian University of Athens, Greece *Correspondence: Kristel Van Laethem email@example.com Specialty section: This article was submitted to Virology, a section of the journal Frontiers in Microbiology Received: 13 October 2018 Accepted: 11 March 2019 Published: 26 March 2019 Citation: Vinken L, Fransen K, Cuypers L, Alexiev I, Balotta C, Debaisieux L, Seguin-Devaux C, García Ribas S, Gomes P, Incardona F, Kaiser R, Ruelle J, Sayan M, Paraschiv S, Paredes R, Peeters M, Sönnerborg A, Vancutsem E, Vandamme A-M, Van den Wijngaert S, Van Ranst M, Verhofstede C, Stadler T, Lemey P and Van Laethem K (2019) Earlier Initiation of AntiretroviralTreatment Coincides With an Initial Control of the HIV-1 Sub-Subtype F1 Outbreak Among Men-Having-Sex-With-Men in Flanders, Belgium. Front. Microbiol. 10:613. doi: 10.3389/fmicb.2019.00613
Cardiovascular diseases and lung cancer are becoming competing causes of death in people living with HIV and AIDS on antiretroviraltreatment [1, 2]. Recent evidence suggests that the prevalence of cigarette smoking among HIV-infected patients is elevated compared to the general population, smoking being a well-established risk factor for several diseases including pulmonary infectious diseases, lung cancer and cardiovascular diseases [2-7]. Prognosis of lung cancer is dramatically worse in the HIV-infected population as compared to the non-infected population [8, 9]. In the case of cardiovascular diseases, smoking’s negative effects add to the risks already posed by increased lipid level, increased insulin resistance and diabetes which are frequent in patients receiving antiretroviral treatments . Given the association between smoking and adverse health outcomes, smoking cessation programs are clearly needed in HIV-infected patients .
Abstract The aim of this study was to investigate factors associated with better health-related quality of life (HRQL) during the first three years after starting PI-containing antiretroviraltreatment. Clinical, social and behavioural data from the APROCO cohort enabled us to analyze simultaneously the association between HRQL and patients’ relationships with their health care providers. A self-administered questionnaire collected information about HRQL (MOS-SF36) and relationships with medical staff (trust and satisfaction with information). Two aggregate scores, the physical (PCS) and mental (MCS) component summaries (adjusted for baseline HRQL), were used as dependent variables in the linear regressions to identify factors associated with HRQL. We had complete longitudinal data for 360 of the 611 patients followed through M36. Factors independently associated with a high MCS were (male) gender, no more than one change in treatment, (few) self- reported symptoms and trust in the physician. Factors independently associated with high PCS levels were employment, no children, (few) self-reported symptoms and satisfaction with the information and explanations provided by the medical staff. These results underline the need to improve patient /
infected. 1 To prevent HIV transmission and help those who live with HIV to have access to care and treatment in due time, the con- sensus today is that individuals should be diagnosed as early as possible in the course of HIV infection, that is to say, before eligibil- ity criteria for antiretroviral therapy (ART) initiation are met. Once an individual is diag- nosed HIV positive, there are several steps up to ART initiation, known as the HIV cascade: 2–4 (1) from HIV diagnosis to linkage to HIV care, (2) from linkage to HIV care to ART eligibility, (3) from ART eligibil- ity to ART initiation. Continuum in HIV care through these different steps is critical for individuals to receive adequate clinical and biological monitoring, and to initiate ART immediately on becoming eligible in order to minimise early morbidity and mortality. It has indeed been shown that people who engaged in HIV care prior to eligibility were more likely to initiate and remain on ART than those entering in care when already
The main limitation of our study is the cohort sample size, with relatively small numbers per treatment group, thus affecting the precision of some MTCT rates and the power to fully perform statistical comparisons between groups. How- ever, we were able to document that the upper conﬁdence limit of the cumulative MTCT rate at 12 mo was less than 7% in the HAART-treated population where breast-feeding was commonly practiced for 5 mo, whereas natural risk may have exceeded 30% [10,11]. Also this study is not a comparative study, but a description of two tiers with one group receiving HAART and another group a short-course of ARVs for PMTCT based on HIV disease staging. Thus, comparisons between the two tiers should be interpreted with caution. A more convincing group for the comparison would be a group of HIV-infected pregnant women eligible for ART who did not receive it. However, it would be unethical to perform such a study in a setting where HAART is available for women who meet eligibility criteria.
People living with HIV (PLHIV) constitute an espe- cially vulnerable population as they bear particularly large disease-related health expenses which may severely affect their household welfare [ 2 ]. Catastrophic health expenditure (CHE) - which assess the financial hardship caused by out-of-pocket payments for health on house- hold welfare - is very high in this population, although some studies suggest that access to antiretroviral treat- ment (ART) and longer time on ART may decrease its risk [ 3 , 4 ]. To foster access to care and reduce the bur- den of health expenditures on PLHIV, several sub- Saharan African countries, including Cameroon, have adopted a policy of removing ART-related fees. How- ever, evidence for this policy’s success is limited. In par- ticular, little is known about the effects of free ART on CHE according to PLHIV socioeconomic status, and es- pecially on the financial risks faced by the poorest groups in this vulnerable population. This information is crucial for decision makers, to identify the strengths and weaknesses of current policy and tailor future policy accordingly.
réservoir viral et en protégeant le système immunitaire des nourrissons des dommages viro- induits.
HIV-1 infection has several distinctive features in children compared to adults, especially (i) the occurrence of the primary infection during a period of high vulnerability because of the immaturity of the immune system, which partly explains that around 15% of children experience a rapidly unfavourable clinical course with death before 3-4 years-of-age (in the absence of antiretroviral therapy (ART)), and (ii) the capacity of immune restoration under ART is higher in children than in adults, which is probably partly explained by an improved thymic activity. Thus, it has recently been suggested that early ART initiation in HIV-1- infected children could protect the immune system from HIV-induced damages during the critical period of immunological immaturity. This “protective” effect could have a long-term impact, partly because specific immune responses against HIV could be developed more efficiently in case of later re-exposure to HIV viremia. Finally, early ART initiation could also have virological benefits, because of the drastic reduction of the size of the viral reservoir.
The aim of this review is to propose a narrative overview of the role of antiretroviral therapies (ART) in the onset of metabolic alterations and modified adiposity observed in persons living with HIV (PLWH). Due to the replacement of initial ART by newer molecules, ART effect on metabolic parameters and adiposity has markedly evolved. We present here rapidly some historical data, important since these first-generation drugs were still used recently in some countries and since they could present long-lasting effects. We also present effects related to contemporary ART, since, unexpectedly, some of them affect adiposity. These alterations have been only recently recognized and are not reviewed in the previous general reviews on the subject.
Despite our restrictions regarding the time interval between the last negative and first-positive HIV test dates, a substantial proportion of individuals (mainly among those who initiated cART during chronic infection) had an HIV test window between 30 days and 1 year, allowing for some uncertainty regarding the exact time of seroconversion. It is noteworthy though that, for almost two-thirds of the pretreated individuals, the accuracy in the estimation of the seroconversion date was excellent and most of them initiated their transient treatment very soon after their seroconversion, having viral loads which were much higher compared to typical set-point levels. Thus, although we did not specifically aim to study individuals treated during acute infection, a substantial proportion of the pretreated individuals started cART very close to the time of seroconversion and this allowed us to investigate whether the gap between seroconversion and ART initiation modified our findings.
The Antiretroviral Therapy Cohort Collaboration (ART-CC) is a collaboration of 15 HIV cohort studies from Canada, Europe and the United States that was established in 2001. The collaboration has been described in detail elsewhere [ 23 – 26 ] . Briefly, prospective cohort studies were eligible for participation if they had enrolled at least 100 HIV-1 infected patients aged 16 years who had: (1) not previously – ≥
received antiretroviraltreatment, (2) started ART with a combination of at least three antiretroviral drugs after 1996, and (3) been followed for a median duration of at least one year after ART initiation. The database was updated in 2007 to additionally include patients who had started ART up until 31 December 2005 with follow up until 1 July 2006. All cohorts have been approved by their local ethics committees or institutional review boards, use standardised methods of data collection, and schedule follow-up visits at least once every six months.
We thank the Agence nationale de recherche sur le sida et les hépatites virales (ANRS) 1220 Primo-CI Group, the trained interviewers and supervi- sors and the medical staff from the following HIV treatment facilities: Medical Unit (MU) Baptist Nkwen, MU Cameroon Baptist Church Mboppi Douala, MU St Luc Mbalmayo, MU Police Yaoundé, MU District Hospital Mbengwi, MU St Vincent Dschang, MU Baptist Muntengene, District Hospital (DH) Ambam, Accredited Treatment Centre (ATC) Bertoua, MU DH Poli, MU DH Ayos, MU DH Ny- lon, ATC General Hospital Yaoundé, MU Presbyterian Church Sakbayeme, MU DH Messamena, MU DH Ba- touri, ATC Gynaecology-Obstetrics- Pediatrics Hospital Yaoundé, MU St