Plasma sVCAM-1, antiretroviral therapy and mortality in HIV-1-infected West African adults.

OBJECTIVES: We report the association between pre-antiretroviral therapy (pre-ART) soluble vascular cell adhesion molecule-1 (sVCAM-1) levels and long-term mortality in HIV-infected West African adults participating in a trial of early ART in West Africa (Temprano ANRS 12136 trial). METHODS: The ART-naïve HIV-infected adults were randomly assigned to start ART immediately or defer ART until the WHO criteria were met. Participants who completed the trial follow-up were invited to participate in a post-trial phase (PTP). The PTP end-point was all-cause death. We used multivariable Cox proportional models to analyse the association between baseline sVCAM-1 and all-cause death, adjusting for ART strategy, sex, CD4 count, plasma HIV-1 RNA and peripheral blood mononuclear cell HIV-1 DNA levels. RESULTS: In all, 954 adults (77% women, median CD4 count of 387 cells/µL) were randomly assigned to start ART immediately (n = 477) or to defer initiation of ART (n = 477). They were followed for a median of 5.8 years [interquartile range (IQR): 5.2-6.3]. In multivariable analysis, the risk of death was significantly associated with baseline sVCAM-1 [≥1458 vs. < 1458 ng/mL; adjusted hazard ratio = 2.86, 95% confidence interval (CI): 1.60-5.11]. The 6-year probability of death rates were 14.4% (95%CI: 9.1-22.6) and 9.4% (5.4-16.1) in patients with baseline sVCAM-1 ≥ 1458 ng/mL randomized to deferred and immediate ART, respectively, and 3.8% (2.2-6.5) and 3.5% (1.9-6.3) in patients with baseline sVCAM-1 < 1458 ng/mL randomized to deferred and immediate ART. The median difference between pre-ART and 12-month sVCAM-1 levels in patients randomized to immediate ART was -252 (IQR: -587 to -61). CONCLUSIONS: Pre-ART sVCAM-1 levels were significantly associated with mortality, independently of whether ART was started immediately or deferred, but they significantly decreased after 12 months of ART.

Mortality in relation to hepatitis B virus (HBV) infection status among HIV-HBV co-infected patients in sub-Saharan Africa after immediate initiation of antiretroviral therapy.

It is unknown how past and active hepatitis B virus (HBV) infection affect immunorecovery and mortality in people with HIV who initiate tenofovir-based antiretroviral therapy (ART). Using data collected between 2008 and 2015, we studied people with HIV in sub-Saharan Africa initiating immediate ART in the Temprano randomized control trial. We classified participants into HBV groups at ART initiation: hepatitis B surface antigen (HBsAg)-positive with HBV DNA ≥ 2,000 IU/ml; HBsAg-positive with HBV DNA < 2,000 IU/ml; isolated HBcAb-positive; resolved infection (HBsAb-positive/HBcAb-positive); and HBV non-immune/vaccinated (HBcAb-negative). We compared square-root CD4-cell count increases using mixed-effect, non-linear regression adjusted for age, sex, baseline CD4 cell count, and HIV RNA. We compared all-cause mortality using Bayesian parametric survival regression. Among 879 participants, 24 (2.7%) had HBsAg with high HBV DNA, 76 (8.6%) HBsAg with low HBV DNA, 325 (37.0%) isolated anti-HBcAb, 226 (25.7%) resolved HBV infection and 228 (25.9%) HBV non-immune/vaccinated. We found no significant difference in CD4 cell increases between HBV-infection groups after adjustment (p = 0.16). Participants with HBsAg and high HBV DNA had the highest incidence of all-cause mortality (1.9/100 person-years, 95% Credibile Interval [CrI] = 1.0-3.4). By comparison, incidence rates of mortality were reduced by 57% (95%CrI = -79%, -13%), 60% (95%CrI = -82%, -12%) and 66% (95%CrI = -84%, -23%) in those who had isolated anti-HBcAb-positive, resolved HBV infection and HBV non-immune/vaccinated, respectively. In conclusion, individuals with HIV and past HBV infection or isolated anti-HBcAb-positive serology, much like HBV non-immune/vaccinated, experience lower mortality than those with HBsAg and high HBV DNA. Additional HBV-related management would not be necessary for these individuals.

Higher Mortality Despite Early Antiretroviral Therapy in Human Immunodeficiency Virus and Hepatitis B Virus (HBV)-Coinfected Patients With High HBV Replication.

Background: In human immunodeficiency virus (HIV)-infected patients, hepatitis B virus (HBV) coinfection increases the risk of disease progression. Tenofovir plus emtricitabine/lamivudine (TDF/XTC)-based antiretroviral therapy (ART), which suppresses HIV and HBV replication, has the potential for decreasing this risk. Here, we analyze the association between HBV replication, early ART, and mortality in West African adults. Methods: The Temprano randomized controlled trial assessed the benefits of immediately initiating vs deferring ART in HIV-infected adults with high CD4 counts. After trial completion, participants continued follow-up in a posttrial phase. We analyzed the association between HBV status, immediate ART, and mortality over the entire trial and posttrial follow-up using multivariable Cox proportional hazards regression. Results: A total of 2052 HIV-infected adults (median baseline CD4 count, 464 cells/µL) were followed for 9394 person-years. At baseline, 1862 (91%) were HIV monoinfected and 190 (9%) HIV/HBV coinfected. Of the latter, 135 (71%) had plasma HBV DNA <2000 IU/mL and 55 (29%) HBV DNA ≥2000 IU/mL. The 60-month probability of death was 11.8% (95% confidence interval [CI], 5.4%-24.5%) in coinfected patients with HBV DNA ≥2000 IU/mL; 4.4% (95% CI, 1.9%-10.4%) in coinfected patients with HBV DNA <2000 IU/mL; and 4.2% (95% CI, 3.3%-5.4%) in HIV-monoinfected patients. Adjusting for ART strategy (immediate vs deferred), the hazard ratio of death was 2.74 (95% CI, 1.26-5.97) in coinfected patients with HBV DNA ≥2000 IU/mL and 0.90 (95% CI, .36-2.24) in coinfected patients with HBV DNA <2000 IU/mL compared to HIV-monoinfected patients. There was no interaction between ART strategy and HBV status for mortality. Conclusions: African HIV/HBV-coinfected adults with high HBV replication remain at heightened risk of mortality in the early ART era. Further studies are needed to assess interventions combined with early ART to decrease mortality in this population. Clinical Trials Registration: NCT00495651.

Trends in HIV testing, the treatment cascade, and HIV incidence among men who have sex with men in Africa: a systematic review and meta-analysis.

BACKGROUND: Gay, bisexual, and other men who have sex with men (MSM) are disproportionately affected by HIV. In Africa, MSM face structural barriers to HIV prevention and treatment that increase their vulnerability to HIV acquisition and transmission, and undermine the HIV response. In this systematic review, we aimed to explore progress towards increases in HIV testing, improving engagement in the HIV treatment cascade, and HIV incidence reductions among MSM in Africa. METHODS: We searched Embase, MEDLINE, Global Health, Scopus, and Web of Science for cross-sectional and longitudinal studies reporting HIV testing, knowledge of status, care, antiretroviral therapy (ART) use, viral suppression, and HIV incidence among MSM in Africa published between Jan 1, 1980, and March 3, 2023. We pooled surveys using Bayesian generalised linear mixed-effects models, used meta-regression to assess time trends, and compared HIV incidence estimates among MSM with those of all men. FINDINGS: Of 9278 articles identified, we included 152 unique studies published in 2005-23. In 2020, we estimate that 73% (95% credible interval [CrI] 62-87) of MSM had ever tested for HIV. HIV testing in the past 12 months increased over time in central, western, eastern, and southern Africa (odds ratio per year [ORyear] 1·23, 95% CrI 1·01-1·51, n=46) and in 2020 an estimated 82% (70-91) had tested in the past 12 months, but only 51% (30-72) of MSM living with HIV knew their HIV status. Current ART use increased over time in central and western (ORyear 1·41, 1·08-1·93, n=9) and eastern and southern Africa (ORyear 1·37, 1·04-1·84, n=17). We estimated that, in 2020, 73% (47-88) of all MSM living with HIV in Africa were currently on ART. Nevertheless, we did not find strong evidence to suggest that viral suppression increased, with only 69% (38-89) of MSM living with HIV estimated to be virally suppressed in 2020. We found insufficient evidence of a decrease in HIV incidence over time (incidence ratio per year 0·96, 95% CrI 0·63-1·50, n=39), and HIV incidence remained high in 2020 (6·9 per 100 person-years, 95% CrI 3·1-27·6) and substantially higher (27-199 times higher) than among all men. INTERPRETATION: HIV incidence remains high, and might not be decreasing among MSM in Africa over time, despite some increases in HIV testing and ART use. Achieving the UNAIDS 95-95-95 targets for diagnosis, treatment, and viral suppression equitably for all requires renewed focus on this key population. Combination interventions for MSM are urgently required to reduce disparities in HIV incidence and tackle the social, structural, and behavioural factors that make MSM vulnerable to HIV acquisition. FUNDING: US National Institutes of Health, UK Medical Research Council, Canadian Institutes of Health Research, and Fonds de Recherche du Québec-Santé. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

[Aortic aneurism dissection in an adult patient with tuberculosis infected with HIV-1 during immune reconstitution inflammatory syndrome]. / Dissection aortique anévrismale chez un adulte infecté par le VIH-1 dans le cadre d'un syndrome de reconstitution immune avec tuberculose.

We here report the case of a 35-year old man with HIV-1 but with no previous medical-surgical history hospitalized in Abidjan, Côte d'Ivoire, due to fever, cough, dyspnea, chest pain and unfolding of the aortic arch observed on chest x-ray a week after having started antiretroviral therapy (ART). CT angiography of the thoracic aorta showed overall, extended aortic ectasia with mural thrombus. Transesophageal echocardiography objectified type A ascending aortic dissection (Stanford classification). The diagnosis of tuberculosis was confirmed based on Mycobacterium tuberculosis culture isolation. Eight years after, the patient was still alive without surgical treatment and complained of intermittent chest pain. Blood pressure was stable with moderate renal failure. We here report a rare case of aortic aneurism dissection in an adult patient with tuberculosis infected with HIV-1 during immune reconstitution inflammatory syndrome.

High correlation between Framingham equations with BMI and with lipids to estimate cardiovascular risks score at baseline in HIV-infected adults in the Temprano trial, ANRS 12136 in Côte d'Ivoire.

CONTEXT: Data on cardiovascular risk (CVR) score among HIV-infected patients in sub-Saharan Africa are scarce. Our first objective was to compare the CVR score of Framingham utilizing BMI and lipids at baseline, and secondary to assess evolution of CVR score over time at Month 30 in the Temprano trial. METHODS: HIV-infected adults with CD4 <800/mm3 without criteria for initiating ART were included and followed for 30 months in the Temprano trial, which assessed the benefits and risks of early antiretroviral treatment (ART) vs deferred ART. CVR score was estimated at baseline and Month-30 using Framingham equations with either BMI or lipids and classified as high (>20%), moderate (10-20%), and low risk (<10%). At baseline, we compare these two estimations utilizing the Pearson correlation test and analyze the increasing CV risk score over time by Proportional odds cumulative logit models for people attending the Month-30 (M30) visit. RESULTS: Among the 2056 patients, 78% were women, median age was 35 years, and median CD4 count was 464/mm3, 6.8% were obese, 6.3% had hypertension, 7.8% were smokers (1.8% women, 26.8% men), 19% had Total Cholesterol (TC) >5mmol/L, and 1% diabetes at baseline. At baseline the concordance between the two Framingham equations was excellent (r = 0.95; p<0.0001). Among the 1700 patients who attended M30 visit and with available data, 1.3% had a high CV risk score at baseline and 3.1% at M30 visit using Framingham equation with BMI. Adjusted odds ratio (aOR) of being at a higher CV risk score at M30 visit compared to a higher CV risk score at M0 visit was 1.35 (CI 95% 1.17-1.57). Stratified by sex, the increasing CV risk score was OR 1.73 (CI 95%: 1.30-2.29) for women and OR 1.24 (CI 95%: 1.02-1.50) for men. Early ART was not associated with an increasing CV risk score (p = 0.88). Results for the 1422 patients with Framingham equation using lipids were similar. CONCLUSION: In a large trial evaluating early ART for HIV infection in Côte d'Ivoire, Framingham equation with BMI and lipids were highly correlated and CV risk score increases over time. Early ART was not significantly associated with this increasing CV risk score.

Early antiretroviral therapy initiation in west Africa has no adverse social consequences: a 24-month prospective study.

Based on social indicators collected within the TEMPRANO-ANRS12136 trial, we assessed the social consequences of early antiretroviral therapy (ART) initiation in west Africa. We did not observe any significant differences in the levels or the time trends of various social indicators, including union status, HIV disclosure and HIV-related discrimination, between early and deferred ART initiation. Early ART does not carry detectable adverse social consequences that could impair its clinical and preventive benefits.