A province-wide HIV initiative to accelerate initiation of treatment-as-prevention and virologic suppression in British Columbia, Canada: a population-based cohort study.

BACKGROUND: In 2010, HIV treatment as prevention (TasP), encompassing widespread HIV testing and immediate initiation of free antiretroviral treatment (ART), was piloted under the Seek and Treat for Optimal Prevention of HIV/AIDS initiative (STOP) in British Columbia, Canada. We compared the time from HIV diagnosis to treatment initiation, and from treatment initiation to first virologic suppression, before (2005-2009) and after (2010-2016) the implementation of STOP. METHODS: In this population-based cohort study, we used longitudinal data of all people living with an HIV diagnosis in BC from 1996 to 2017. We included those aged 18 years or older who had never received ART and had received an HIV diagnosis in the 2005-2016 period. We defined the virologic suppression date as the first date of at least 2 consecutive test results within 4 months with a viral load of less than 200 copies/mL. Negative binomial regression models assessed the effect of STOP on the time to ART initiation and suppression, adjusting for confounders. All p values were 2-sided, and we set the significance level at 0.05. RESULTS: Participants who received an HIV diagnosis before STOP (n = 1601) were statistically different from those with a diagnosis after STOP (n = 1700); 81% versus 84% were men (p = 0.0187), 30% versus 15% had ever injected drugs (p < 0.0001), and 27% versus 49% had 350 CD4 cells/µL or more at diagnosis (p < 0.0001). The STOP initiative was associated with a 64% shorter time from diagnosis to treatment (adjusted mean ratio 0.36, 95% confidence interval [CI] 0.34-0.39) and a 21% shorter time from treatment to suppression (adjusted mean ratio 0.79, 95% CI 0.73-0.85). INTERPRETATION: In a population with universal health coverage, a TasP intervention was associated with shorter times from HIV diagnosis to treatment initiation, and from treatment initiation to viral suppression. Our results show accelerating progress toward the United Nations' 90-90-90 target of people with HIV who have a diagnosis, those who are on antiretroviral therapy and those who are virologically suppressed, and support the global expansion of TasP to accelerate the control of HIV/AIDS.

Sarcoma de Kaposi anoperineal: uma rara apresentação / Perineal Kaposi's Sarcoma: a rare presentation

O sarcoma de Kaposi é uma neoplasia maligna associada à infecção pelo herpes vírus humano 8 em doentes imunossupressos. O sarcoma de Kaposi Epidêmico é o tipo epidemiológico mais frequente e afeta indivíduos VIH-positivos. A região anoperineal é raramente envolvida e as lesões suspeitas devem ser biopsiadas para confirmação histológica. A base do tratamento é a restauração imune do doente. Relatamos o caso de um jovem, com diagnóstico recente de infeção pelo VIH, sem tratamento, que foi admitido no serviço de infectologia apresentando sintomas constitucionais, adenomegalias inguinais e extensa lesão verrucosa e ulcerada na região anoperineal. As biópsias confirmaram o diagnóstico de sarcoma de Kaposi e o doente iniciou terapia antirretroviral e quimioterapia. Houve recuperação clínica, regressão das lesões e desaparecimento das adenomegalias. Este relato objetiva alertar as equipes médicas no sentido de se incluir o sarcoma de Kaposi no diagnóstico diferencial das lesões que afetam a região anoperineal.

Kaposi's sarcoma is a malignant neoplasm associated with human herpesvirus 8 infection in immunocompromised patients. Epidemic Kaposi's sarcoma is the most common epidemiological type and affects HIV-positive patients. Perineal involvement is rare, and suspicious lesions should be biopsied to confirm histological diagnosis. Treatment consists of restoring the patient's immune system. We report the case of a young patient recently diagnosed with HIV, without treatment, who was admitted to the Department of Infectious Diseases with nonspecific symptoms, inguinal lymphadenopathy, and an extensive verrucous ulcerated lesion in the perineal region. Biopsy confirmed the diagnosis of Kaposi's sarcoma, and the patient was started on antiretroviral therapy and chemotherapy. Clinical recovery was achieved, with lesion reduction and inguinal adenopathy resolution. This case report aims to encourage physicians to include Kaposi's sarcoma in the differential diagnosis of perineal lesions.

Causes and Outcomes of Admission and Investigation of Tuberculosis in Adults with Advanced HIV in South African Hospitals: Data from the TB Fast Track Trial.

Tuberculosis (TB) remains the leading cause of hospitalization and in-hospital mortality in HIV-positive adults. Using data from hospital and clinic files, research databases, and autopsy, we describe causes and outcomes of admissions, and assess investigations for TB among adults with advanced HIV who were hospitalized after enrollment into the TB Fast Track trial in South Africa (2013-2015). A total of 251 adults [median CD4 count, 37.5 cells/µL; interquartile range, 14-68 cells/µL; 152 (60.6%) on antiretroviral therapy] experienced 304 admissions. Ninety-five of 251 of the first admissions (37.8%) were TB related; the next most common causes were AIDS-related illnesses (41 of 251, 16.3%) and surgical causes (21 of 251, 8.4%). Of those admitted with previously undiagnosed TB, 60% had CD4 counts less than 50 cells/µL. Overall, 137 of 251 individuals died as inpatients or within 90 days of their first discharge. Case fatality rates were particularly high for those admitted with TB (66%) and bacterial infections (80%). In 144 admissions for whom anti-TB treatment had not been started before admission, a sputum-based TB investigation was recorded in only 12 of 57 admissions (21.1%) in whom one or more TB symptom was recorded (24 of 57 started on treatment), and 6 of 87 admissions (6.9%) in whom no TB symptoms were recorded (14 of 87 started on treatment). Hospitalized adults with advanced HIV are at high risk of death. TB was a common cause of hospitalization but was under-investigated, even in those with symptoms. In addition to early identification of TB and other AIDS-related illnesses during hospitalization of adults with advanced HIV, improved pre-hospital management strategies are needed to interrupt disease progression and reduce poor outcomes in this already vulnerable population.

Long term dual antiretroviral therapy: A real life retrospective countrywide Israeli study.

AIM: Combined antiretroviral treatment (cART) traditionally consists of three antiretroviral medications, while two-drug regimens (2DR), historically used infrequently, recently been suggested to be non-inferior to three-drug regimens, is emerging as a potential treatment option and is currently a recommended option for treatment initiation in many guidelines. PURPOSE: Characterize the indications and clinical efficacy of 2DR use at a real-life setting in a nation-wide survey. METHODS: A cross-sectional survey of Israeli patients treated by 2DR until July 2019, included demographic, immunologic, virologic, genotypic and biochemical/metabolic parameters at diagnosis, ART initiation, 2DR initiation and following 24, 48, 96 and 144 weeks of 2DR treatment. RESULTS: 176 patients were included in the study. In contrast to historical data implicating ART resistance and adverse effects as the major reasons leading to 2DR switching, treatment simplification was the main reason leading to 2DR treatment in 2019. 2DR that included INSTI and PI were more commonly used in cases of drug resistance, while a combination of INSTI and NNRTI was used in all other 2DR indications. A switch to 2DR induced a mean CD4 T cell increase from 599 cells/µl at treatment initiation to 680 cells/µl at 96 weeks of treatment p<0.001 and viral suppression improvement from 73.9% at initiation to 87.0% at 48 weeks of treatment (p = 0.004). PI and INSTI 2DR was inferior in suppressing viral levels compared to other 2DRs but used for subset of more complex patients. CONCLUSIONS: 2DR in a large-scale real-life nation-wide survey proved to be safe and effective. Most 2DRs, other than PI and INSTI, were similarly effective in suppressing HIV viremia and in elevating CD4 T cell counts.

Addressing an HIV cure in LMIC.

HIV-1 persists in infected individuals despite years of antiretroviral therapy (ART), due to the formation of a stable and long-lived latent viral reservoir. Early ART can reduce the latent reservoir and is associated with post-treatment control in people living with HIV (PLWH). However, even in post-treatment controllers, ART cessation after a period of time inevitably results in rebound of plasma viraemia, thus lifelong treatment for viral suppression is indicated. Due to the difficulties of sustained life-long treatment in the millions of PLWH worldwide, a cure is undeniably necessary. This requires an in-depth understanding of reservoir formation and dynamics. Differences exist in treatment guidelines and accessibility to treatment as well as social stigma between low- and-middle income countries (LMICs) and high-income countries. In addition, demographic differences exist in PLWH from different geographical regions such as infecting viral subtype and host genetics, which can contribute to differences in the viral reservoir between different populations. Here, we review topics relevant to HIV-1 cure research in LMICs, with a focus on sub-Saharan Africa, the region of the world bearing the greatest burden of HIV-1. We present a summary of ART in LMICs, highlighting challenges that may be experienced in implementing a HIV-1 cure therapeutic. Furthermore, we discuss current research on the HIV-1 latent reservoir in different populations, highlighting research in LMIC and gaps in the research that may facilitate a global cure. Finally, we discuss current experimental cure strategies in the context of their potential application in LMICs.

Abrupt and altered cell-type specific DNA methylation profiles in blood during acute HIV infection persists despite prompt initiation of ART.

HIV-1 disrupts the host epigenetic landscape with consequences for disease pathogenesis, viral persistence, and HIV-associated comorbidities. Here, we examined how soon after infection HIV-associated epigenetic changes may occur in blood and whether early initiation of antiretroviral therapy (ART) impacts epigenetic modifications. We profiled longitudinal genome-wide DNA methylation in monocytes and CD4+ T lymphocytes from 22 participants in the RV254/SEARCH010 acute HIV infection (AHI) cohort that diagnoses infection within weeks after estimated exposure and immediately initiates ART. We identified monocytes harbored 22,697 differentially methylated CpGs associated with AHI compared to 294 in CD4+ T lymphocytes. ART minimally restored less than 1% of these changes in monocytes and had no effect upon T cells. Monocyte DNA methylation patterns associated with viral load, CD4 count, CD4/CD8 ratio, and longitudinal clinical phenotypes. Our findings suggest HIV-1 rapidly embeds an epigenetic memory not mitigated by ART and support determining epigenetic signatures in precision HIV medicine. Trial Registration: NCT00782808 and NCT00796146.

Short-term mortality from HIV-infected persons diagnosed from 2012 to 2016: Impact of late diagnosis of HIV infection.

ABSTRACT: We investigated the temporal trends of short-term mortality (death within 1 year of diagnosis) and cause-specific deaths in human immunodeficiency virus (HIV)-infected persons by stage of HIV infection at diagnosis. We also assessed the impact of late diagnosis (LD) on short-term mortality.Epidemiological records of HIV-infected Singapore residents from the National HIV Registry were linked to death records from the Registry of Births and Deaths for observational analyses. Newly-diagnosed HIV cases with available cluster of differentiation 4 count at time of diagnosis in a 5-year period from 2012 to 2016 were included in the study. Hazard ratios (HRs) and 95% confidence interval (CI) of LD for all deaths excluding suicides and self-inflicted or accidental injuries, and HIV/ acquired immunodeficiency syndrome (AIDS)-related deaths occurring within 1 year post-diagnosis were calculated using Cox proportional hazards regression models with adjustment for age at HIV/AIDS diagnosis. Population attributable risk proportions (PARPs) were then calculated using the adjusted HRs.Of the 1990 newly-diagnosed HIV cases included in the study, 7.2% had died by end of 2017, giving an overall mortality rate of 2.16 per 100 person-years (PY) (95% CI 1.82-2.54). The mortality rate was 3.81 per 100 PY (95% CI 3.15-4.56) in HIV cases with LD, compared with 0.71 (95% CI 0.46-1.05) in non-LD (nLD) cases. Short-term mortality was significantly higher in LD (9.1%) than nLD cases (1.1%). Of the 143 deaths reported between 2012 and 2017, 58.0% were HIV/AIDS-related (nLD 28.0% vs LD 64.4%). HIV/AIDS-related causes represented 70.4% of all deaths which occurred during the first year of diagnosis (nLD 36.4% vs LD 74.7%). The PARP of short-term mortality due to LD was 77.8% for all deaths by natural causes, and 87.8% for HIV/AIDS-related deaths.The mortality rate of HIV-infected persons with LD was higher than nLD, especially within 1 year of diagnosis, and HIV/AIDS-related causes constituted majority of these deaths. To reduce short-term mortality, persons at high risk of late-stage HIV infection should be targeted in outreach efforts to promote health screening and remove barriers to HIV testing and treatment.

The Architecture of Circulating Immune Cells Is Dysregulated in People Living With HIV on Long Term Antiretroviral Treatment and Relates With Markers of the HIV-1 Reservoir, Cytomegalovirus, and Microbial Translocation.

Long-term changes in the immune system of successfully treated people living with HIV (PLHIV) remain incompletely understood. In this study, we assessed 108 white blood cell (WBC) populations in a cohort of 211 PLHIV on stable antiretroviral therapy and in 56 HIV-uninfected controls using flow cytometry. We show that marked differences exist in T cell maturation and differentiation between PLHIV and HIV-uninfected controls: PLHIV had reduced percentages of CD4+ T cells and naïve T cells and increased percentages of CD8+ T cells, effector T cells, and T helper 17 (Th17) cells, together with increased Th17/regulatory T cell (Treg) ratios. PLHIV also exhibited altered B cell maturation with reduced percentages of memory B cells and increased numbers of plasmablasts. Determinants of the T and B cell composition in PLHIV included host factors (age, sex, and smoking), markers of the HIV reservoir, and CMV serostatus. Moreover, higher circulating Th17 percentages were associated with higher plasma concentrations of interleukin (IL) 6, soluble CD14, the gut homing chemokine CCL20, and intestinal fatty acid binding protein (IFABP). The changes in circulating lymphocytes translated into functional changes with reduced interferon (IFN)- γ responses of peripheral blood mononuclear cells to stimulation with Candida albicans and Mycobacterium tuberculosis. In conclusion, this comprehensive analysis confirms the importance of persistent abnormalities in the number and function of circulating immune cells in PLHIV on stable treatment.

Impact of HBeAg status on immune recovery in HIV/HBV co-infected patients after highly active antiretroviral therapy.

A retrospective analysis was conducted on HIV-infected patients whose continuously HAART strategy was lamivudine +tenofovir+ efavirenz. Propensity matching for 35 HBeAg-positive/HIV co-infected patients, 35 HBeAg-negative/HIV co-infected patients, and 70 HIV mono-infected patients. Immune recovery (including CD4 cells count, CD4/CD8 ratio, CD4 count multiples and CD4/CD8 multiples) of HBeAg-negative/HIV co-infected group are continuously lower than HBeAg-positive/HIV co-infected group and HIV mono-infected group. The result indicated that the mechanisms associated with HBeAg-negative may be involved in the regulation of immune recovery after HAART.

Impact of hematocrit on point-of-care C-reactive protein-based tuberculosis screening among people living with HIV initiating antiretroviral therapy in Uganda.

Point-of-care C-reactive protein (POC CRP) testing is a potential tuberculosis (TB) screening tool for people living with HIV (PLHIV). Unlike lab-based assays, POC assays do not routinely adjust CRP levels for hematocrit, potentially resulting in TB screening status misclassification. We compared the diagnostic accuracy of unadjusted and hematocrit-adjusted POC CRP for culture-confirmed TB among PLHIV with CD4 cell-count ≤350 cells/uL initiating antiretroviral therapy (ART) in Uganda. We prospectively enrolled consecutive adults, measured POC CRP (Boditech; normal <8 mg/L), collected two spot sputum specimens for comprehensive TB testing, and extracted pre-ART hematocrit from clinic records. Of the 605 PLHIV included, hematocrit-adjusted POC CRP had similar sensitivity (80% vs 81%, difference +1% [95% CI -3 to +5], P= 0.56) and specificity (71% vs 71%, difference 0% [95% CI -1 to +1], P= 0.56) for culture-confirmed TB, relative to unadjusted POC CRP. When used for TB screening, POC CRP may not require adjustment for hematocrit. However, larger studies may be required if differences close to the clinically meaningful threshold are to be detected.

The scale-up of antiretroviral therapy coverage was strongly associated with the declining tuberculosis morbidity in Africa during 2000-2018.

OBJECTIVES: Antiretroviral therapy (ART) reduces the risk of tuberculosis (TB). We aimed to examine the association between ART coverage scale-up on the changes in TB incidence in Africa from 2000 to 2018. STUDY DESIGN: The design of the study is a retrospective ecological study. METHODS: Data for 54 countries were obtained from several institutional-based sources, including the World Health Organization, the Joint United Nations Programme on HIV/AIDS, and the World Bank. A fixed-effects regression method of longitudinal data analysis was used to estimate the association between ART coverage and changes in TB incidence rate during 2000-2018. Statistical analyses were conducted using STATA 15.0/IC. RESULTS: The TB incidence declined significantly, by an average of 2.3% per year during 2000-2018. The highest significant declines occurred in eastern and southern Africa. In adjusted analysis, each 1% increase in ART coverage was associated with a 3.97 per 100,000 decline of TB incidence. However, the marginal effects of ART on overall population TB incidence was dependent on the prevalence of human immunodeficiency virus infection. CONCLUSIONS: Investment in the widespread scale-up of ART may contribute to the control of the TB epidemic in Africa. However, interventions are also needed to augment the effect of ART on population TB incidence.

Physician and patient prediction of adherence to antiretroviral therapy in HIV positive people in Saint-Petersburg, Russia.

Adherence to antiretroviral therapy (ART) results in HIV viral suppression, which is one of the main 90-90-90 targets. Little is known about the accuracy of provider and patient predictions of retention in care and adherence to ART. To address this gap, we conducted a longitudinal analysis of 100 HIV positive people newly eligible for ART initiation (based on the Russian guidelines of ART prescription) in St. Petersburg, Russia. We assessed the association between predictions prior to ART initiation by each patient or their primary HIV physician and treatment outcomes of ART retention and adherence assessed by review of pharmacy and laboratory data. We observed that physicians' prediction was less accurate than ART outcomes compared to that of their patients. Providers should not rely on anticipated adherence and discuss openly the concerns about adherence with patients to identify those who need intervention to improve adherence.

HIV/SARS-CoV-2 coinfection: A global perspective.

Since its first appearance in Wuhan, China, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread throughout the world and has become a global pandemic. Several medical comorbidities have been identified as risk factors for coronavirus disease 2019 (COVID-19). However, it remains unclear whether people living with human immunodefeciency virus (PLWH) are at an increased risk of COVID-19 and severe disease manifestation, with controversial suggestion that HIV-infected individuals could be protected from severe COVID-19 by means of antiretroviral therapy or HIV-related immunosuppression. Several cases of coinfection with HIV and SARS-CoV-2 have been reported from different parts of the globe. This review seeks to provide a holistic overview of SARS-CoV-2 infection in PLWH.

AIDS incidence and survival in a hospital-based cohort of HIV-positive patients from São Paulo, Brazil: The role of IFN-λ4 polymorphisms.

Few studies have reported the prognosis of human immunodeficiency virus (HIV)-positive patients followed for a long time in Brazil, particularly those including pre and post-HAART eras. The polymorphisms of interferon (IFN)-λ4 have been postulated as possibly associated with the pathogenesis of HIV infection. The aim of this study was to describe the incidence and mortality from a cohort of HIV-positive patients as well as whether IFN-λ4 gene polymorphisms (SNP rs8099917 and SNP rs12979860) were associated with HIV/acquired immune deficiency syndrome (AIDS) progression. We followed 402 patients for up to 30 years; 347 of them began follow-up asymptomatic, without any AIDS-defining opportunistic disease and/or a lymphocytes T CD4+ count of 350 cells/mm3 or lower. We determined the probability of the asymptomatic subjects to remain AIDS-free, and the risk of death for those entering the study already with an AIDS diagnosis, as well as for subjects developing AIDS during follow-up. We compared the prognosis of patients with two different polymorphisms for the genes encoding for IFN-λ4, variants rs8099917 and rs12979860. The follow-up time of the 347 asymptomatic-at-entry subjects was 3687 person-years. IFN-λ4 rs8099917 polymorphisms were not associated with AIDS progression, but IFN-λ4 rs12979860 wild type genotype (CC) was associated with higher mortality compared to CT and TT, with an increased probability of death from AIDS (P = .01). In conclusion, genetic variations in IFN-λ4 on rs12979860 polymorphisms in HIV-infected patients may drive mortality risk.

Mother-child separation among women living with HIV and their children in the first four years postpartum in South Africa.

OBJECTIVES: Mother-child pairs may separate during early life, yet the health impacts thereof are unclear. We explored the patterns and impact of separation among women living with HIV (WLHIV) and their children in South Africa. METHODS: WLHIV who had initiated antiretroviral therapy (ART) during pregnancy received HIV viral load (VL) testing and completed a timeline questionnaire of mother-child separation since delivery at 3-5 years post-partum. Health care usage was abstracted from routine medical records. We examined associations between separation and (a) maternal health outcomes (engagement in HIV care and HIV viral suppression, [VS]) and (b) child health outcomes (post-breastfeeding HIV testing and immunisation completion), using logistic regression. RESULTS: Of 346 mother-child pairs (median maternal age at antenatal ART initiation, 28 years), 24% were ever separated (median time to first separation 20 months, interquartile range [IQR] 9, 31). Most separated children were living with their grandmothers (65/83, 78%). Mothers who ever separated were younger, and more likely to be employed, and to reside in informal housing than those who never separated. Any separation reduced the odds of VS ≤ 50 copies/mL at four years post-partum (odds ratio 0.57; 95% CI 0.34-0.93); associations were similar for VL ≤ 1000 copies/mL and maternal engagement in care. No association was found between separation and child confirmatory HIV testing or immunisation completion. CONCLUSIONS: In this setting, mother-child separation is common in the first four years of life and appears associated with suboptimal maternal outcomes. Further research is required to understand the drivers and implications of mother-child separation.

OBJECTIFS: Les couples mère-enfant peuvent être séparés au début de la vie, mais les effets sur la santé ne sont pas clairs. Nous avons exploré les modèles et l'impact de la séparation chez les femmes vivant avec le VIH (PVVIH) et leurs enfants en Afrique du Sud. MÉTHODES: Les PVVIH qui avaient initié un traitement antirétroviral (ART) pendant la grossesse ont subi un test de charge virale du VIH (CV) et ont rempli un questionnaire chronologique sur la séparation mère-enfant depuis l'accouchement à 3-5 ans post-partum. L'utilisation des soins de santé a été extraite des dossiers médicaux de routine. Nous avons examiné les associations entre la séparation et (a) les résultats pour la santé maternelle (engagement dans les soins du VIH et la suppression virale du VIH [SV]) et (b) les résultats pour la santé de l'enfant (dépistage du VIH après l'allaitement et achèvement de la vaccination), en utilisant la régression logistique. RÉSULTATS: Sur 346 couples mère-enfant (âge maternel médian au début de l'ART prénatal, 28 ans), 24% ont été séparés (délai médian jusqu'à la première séparation 20 mois, intervalle interquartile [IQR] 9 à 31). La plupart des enfants séparés vivaient avec leurs grands-mères (65/83, 78%). Les mères qui ont vécu une telle séparation étaient plus jeunes et plus susceptibles d'avoir un emploi et de vivre dans un logement informel que celles qui ne l'ont jamais vécue. Toute séparation réduisait les chances de SV ≤50 copies/mL à quatre ans après l'accouchement (odds ratio 0,57; IC95%: 0,34-0,93); les associations étaient similaires pour la CV ≤1000 copies/mL et l'engagement de la mère dans les soins. Aucune association n'a été trouvée entre la séparation et le test de confirmation du VIH chez l'enfant ou l'achèvement de la vaccination. CONCLUSIONS: Dans ce contexte, la séparation mère-enfant est courante au cours des quatre premières années de la vie et semble associée à des résultats maternels sous-optimaux. Des recherches supplémentaires sont nécessaires pour comprendre les facteurs et les implications de la séparation mère-enfant.

Implementation and operational feasibility of SAMBA I HIV-1 semi-quantitative viral load testing at the point-of-care in rural settings in Malawi and Uganda.

OBJECTIVE: We monitored a large-scale implementation of the Simple Amplification-Based Assay semi-quantitative viral load test for HIV-1 version I (SAMBA I Viral Load = SAMBA I VL) within Médecins Sans Frontières' HIV programmes in Malawi and Uganda, to assess its performance and operational feasibility. METHODS: Descriptive analysis of routine programme data between August 2013 and December 2016. The dataset included samples collected for VL monitoring and tested using SAMBA I VL in five HIV clinics in Malawi (four peripheral health centres and one district hospital), and one HIV clinic in a regional referral hospital in Uganda. SAMBA I VL was used for VL testing in patients who had been receiving ART for between 6 months and ten years, to determine whether plasma VL was above or below 1000 copies/mL of HIV-1, reflecting ART failure or efficacy. Randomly selected samples were quantified with commercial VL assays. SAMBA I instruments and test performance, site throughput, and delays in communicating results to clinicians and patients were monitored. RESULTS: Between August 2013 and December 2016 a total of 60 889 patient samples were analysed with SAMBA I VL. Overall, 0.23% of initial SAMBA I VL results were invalid; this was reduced to 0.04% after repeating the test once. Global test failure, including instrument failure, was 1.34%. Concordance with reference quantitative testing of VL was 2620/2727, 96.0% (1338/1382, 96.8% in Malawi; 1282/1345, 95.3% in Uganda). For Chiradzulu peripheral health centres and Arua Hospital HIV clinic, where testing was performed on-site, same-day results were communicated to clinicians for between 91% and 97% of samples. Same-day clinical review was obtained for 84.7% across the whole set of samples tested. CONCLUSIONS: SAMBA I VL testing is feasible for monitoring cohorts of 1000 to 5000 ART-experienced patients. Same-day results can be used to inform rapid clinical decision-making at rural and remote health facilities, potentially reducing time available for development of resistance and conceivably helping to reduce morbidity and mortality.

OBJECTIF: Nous avons suivi une mise en œuvre à grande échelle du test de la charge virale semi-quantitative du VIH -1 basé sur de Test de Simple Amplification version I (SAMBA I Viral Load = SAMBA I VL) au sein des programmes VIH de Médecins Sans Frontières au Malawi et en Ouganda, afin d'évaluer sa performance et sa faisabilité opérationnelle. MÉTHODES: Analyse descriptive des données du programme de routine entre août 2013 et décembre 2016. L'ensemble des données comprenait des échantillons collectés pour le suivi de la CV et testés à l'aide de SAMBA I VL dans cinq cliniques VIH au Malawi (quatre centres de santé périphériques et un hôpital de district), et une clinique VIH dans un hôpital régional de référence en Ouganda. SAMBA I VL a été utilisé pour le test de la CV chez les patients qui recevaient l'ART depuis 6 mois à dix ans, afin de déterminer si la CV plasmatique était supérieure ou inférieure à 1000 copies/ml de VIH-1, reflétant l'échec ou l'efficacité de l'ART. Des échantillons sélectionnés aléatoirement ont été quantifiés avec des tests de CV commerciaux. Les instruments de SAMBA I et les performances des tests, le débit du site et les délais dans la communication des résultats aux cliniciens et aux patients ont été suivis. RÉSULTATS: Entre août 2013 et décembre 2016, un total de 60.889 échantillons de patients ont été analysés avec SAMBA I VL. Dans l'ensemble, 0,23% des résultats initiaux de SAMBA I VL étaient invalides; ceux-ci ont été été réduits à 0,04% après avoir répété le test une fois. L'échec global du test, y compris l'échec de l'instrument, était de 1,34%. La concordance avec les tests quantitatifs de référence de la CV était de 2620/2727; 96,0% (1338/1382; 96,8% au Malawi; 1282/1345; 95,3% en Ouganda). Pour les centres de santé périphériques de Chiradzulu et la clinique VIH de l'hôpital d'Arua, où les tests ont été effectués sur place, les résultats ont été communiqués le jour même aux cliniciens pour entre 91% et 97% des échantillons. Un examen clinique le jour même a été obtenu pour 84,7% de l'ensemble des échantillons testés. CONCLUSIONS: Le test SAMBA I VL est réalisable pour le suivi de cohortes de 1.000 à 5.000 patients déjà sous ART. Les résultats le jour même peuvent être utilisés pour éclairer la prise de décision clinique rapide dans les établissements de santé ruraux et éloignés, réduisant potentiellement le temps disponible pour le développement de la résistance et contribuant éventuellement à réduire la morbidité et la mortalité.

Serum levels of vasoactive factors in HIV-infected pre-eclamptic women on HAART.

In South Africa, pre-eclampsia (PE) and human immunodeficiency virus (HIV) infection are major causes of pregnancy-related deaths. This study aimed to measure serum levels of endothelin-1 (ET-1), endothelial nitric oxide synthase (eNOS), soluble fms-like tyrosine kinase 1 (sFlt-1), soluble endoglin (sEng) and placental growth factor (PlGF) in HIV-infected highly active antiretroviral therapy (HAART)-treated and HIV-uninfected PE and normotensive women to ascertain if HIV/HAART alters their concentrations. Mean sFlt-1 levels were significantly up-regulated in the PE (HIV-uninfected 4.39 ± 1.29; HIV-infected 5.10 ± 1.10 ng/ml) compared to normotensive women (HIV-uninfected 2.59 ± 0.83; HIV-infected 2.20 ± 0.85 ng/ml). Mean PlGF levels were significantly lower in HIV-uninfected PE vs. HIV-infected normotensive women (29.69 ± 4.47 pg/ml vs. 32.86 ± 6.46 pg/ml; p = .002). In conclusion, PE women with HIV exhibited significantly low serum PlGF, ET-1 and eNOS levels. Infection with HIV may have further increased the sFlt-1 levels.IMPACT STATEMENTWhat is already known on this subject? In PE, the numerous identified local and circulating bioactive factors differed in concentrations when compared to normal pregnancy.What do the results of this study add? PE women with HIV exhibited significantly low serum PlGF, ET-1 and eNOS levels as well as increased levels of sFlt-1.What are the implications of these findings for clinical practice and/or further research? Understanding the link between PE, HIV and HAART during pregnancy will improve prognosis, management and treatment strategies for women clinically.

Antiretroviral therapy among patients with HIV in Almaty, Kazakhstan: the implication for HIV-associated tuberculosis control.

INTRODUCTION: Antiretroviral therapy (ART) is an effective preventive strategy against tuberculosis (TB) in people living with HIV (PLWH). In Kazakhstan, according to the revised HIV treatment guideline (2017), ART should be initiated immediately after HIV diagnosis established, regardless of CD4+ count. AIM: To evaluate the impact of early initiation of ART on TB infection in PLWH registered in the Center of Prevention and Control of AIDS, Almaty, Kazakhstan, between 2008 and 2018. METHODOLOGY: A retrospective cohort study was conducted using the data of 4,053 patients from electronic HIV case management system (2008-2018) (EHCMS). RESULTS: The study revealed low rates (12.6%) of rapid ART (≤ 1 month after HIV diagnosis). Patients in the rapid ART initiation group were less likely to develop TB compared with those who started treatment >1 month after the HIV detection (odds ratio 1.6; 95% confidence interval [1.1, 2.2]; p = 0.00799). Interestingly, the risk for developing TB among patients receiving ART ≥ 1 month after HIV diagnosis was significantly higher compared with those not taking any treatment. The latter was explained by several confounding not addressed during the analysis, since ART was prescribed to patients with primarily deeper immunodeficiency, while the patients not receiving ART were less immunocompromised. CONCLUSION: Despite the recently changed HIV treatment guideline in Kazakhstan, ART is still initiated based on the disease severity. In 2018, the initiation of ART during the first month after HIV diagnosis increased by 50%. However, it is necessary to reduce the time to initiation of ART for all patients.

Characteristics of HIV-positive pregnant women and HIV- and antiretroviral therapy-exposed fetuses: A case-control study.

INTRODUCTION: This study determined risk factors, obstetric comorbidities, and fetal conditions among HIV-positive mothers to improve their maternal care. METHODOLOGY: This retrospective case-control study included HIV-positive pregnant women 18 years of age or older and age-, parity-, and delivery method-matched HIV-negative controls between 2011 and 2018. Those who had stillbirth were excluded. Baseline demographics, labor process, CD4 count, plasma HIV viral load, and antiretroviral therapy (ART) regimen were recorded. Fetal conditions were recorded as well. RESULTS: Forty HIV-positive women (45 parities; 22 via NSD, 23 via C/S) were included, with 45 HIV-negative parities as controls. Twenty-nine (72.5%) HIV-positive women had illicit drug use. In the HIV-positive group, 17% received ART prior to first perinatal visit, and 75.6% reached viral suppression pre-delivery. Zidovudine and ritonavir-boosted lopinavir were the majorly prescribed ART. Mild perineal lacerations via NSD were observed in HIV-positive women. Fetal body weight was lower in HIV- and ART-exposed fetuses (2665 vs 3010 g, p < 0.001). Preterm delivery PTB (28.9% vs 8.9%, p= 0.015) and small-for gestational age SGA (28.9% vs 8.8%, p = 0.003) rates were higher in the HIV-positive group. There was no vertical transmission of HIV. CONCLUSIONS: HIV-positive women tend to deliver fetuses with low body weight and have higher SGA and PTB rates. Given that most women received zidovudine and protease inhibitors, benefits of newer agents for HIV-positive pregnancies should be studied.