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Background: Early antiretroviral therapy (ART) during infancy reduces cognitive impairment due to HIV, but the extent of benefit is unclear.Setting: Children were recruited from hospital and health centers providing HIV care and treatment in Nairobi, Kenya.Methods: Cognitive, behavioral and motor outcomes were assessed in children with HIV (CWHIV) and early-ART (…

by The PLOS ONE Staff …

An error appeared in the 15 August 2022 issue of the journal (Person et al. “Principles for Ending Human Immunodeficiency Virus as an Epidemic in the United States: A Policy Paper of the Infectious Diseases Society of America and the HIV Medical Association.” Clin Infect Dis; 76(1): 1-9. https://doi.org/10.1093/cid/ciac626). In the title for this IDSA Feature, the “HIV Medical Association” should be replaced with the “HIV Medicine Association.”…

New England Journal of Medicine, Volume 388, Issue 4, Page 344-356, January 2023.

Abstract Background and aims Liver-associated complications still frequently lead to mortality in people with HIV (PWH), even though combined antiretroviral treatment (cART) has significantly improved overall survival. The quantification of circulating collagen fragments released during collagen formation and degradation correlate with the turnover of extracellular matrix (ECM) in liver disease. Here, we analysed the levels of ECM turnover markers PC3X, PRO-C5, and PRO-C6 in PWH and correlated these with hepatic fibrosis and steatosis. Methods This monocentre, retrospective study included 141 PWH. Liver stiffness and liver fat content were determined using transient elastography (Fibroscan) with integrated CAP function. Serum levels of formation of cross-linked type III collagen (PC3X), formation of type V collagen (PRO-C5) and formation type VI collagen (PRO-C6), also known as the hormone endotrophin, were measured with ELISA. Results Twenty-five (17.7%) of 141 PWH had clinical significant fibrosis with liver stiffness ≥ 7.1 kPa, and 62 PWH (44.0%) had steatosis with a CAP value > 238 dB/m. Study participants with fibrosis were older (p = 0.004) and had higher levels of AST (p = 0.037) and lower number of thrombocytes compared to individuals without fibrosis (p = 0.0001). PC3X and PRO-C6 were markedly elevated in PWH with fibrosis. Multivariable cox regression analysis confirmed PC3X as independently associated with hepatic fibrosis. PRO-C5 was significantly elevated in participants with presence of hepatic steatosis. Conclusion Serological levels of cross-linked type III collagen formation and endotrophin were significantly associated with liver fibrosis in PWH receiving cART and thus may be suitable as a non-invasive evaluation of liver fibrosis in HIV disease. …

This study aimed to investigate the factors associated with maintenance of viral suppression after antiretroviral therapy (ART) discontinuation.

AbstractBackgroundPeople with HIV (PWH) have increased cardiovascular risk. Higher leukocyte count has been associated with coronary artery disease (CAD) events in the general population. It is unknown whether the leukocyte-CAD association also applies to PWH.MethodsIn a case-control study nested within the Swiss HIV Cohort Study, we obtained uni- and multivariable odds ratios (OR) for CAD events, based on traditional and HIV-related CAD risk factors, leukocyte count, and confounders previously associated with leukocyte count.ResultsWe included 536 cases with a first CAD event (2000-2021; median age 56 years, 87% male, 84% with suppressed HIV-RNA) and 1464 event-free controls. Cases had higher latest leukocyte count prior to CAD event than controls (median [interquartile range], 6495 [5300-7995] vs. 5900 [4910-7200]; p < 0.01), but leukocytosis (>11000/uL) was uncommon (4.3% vs. 2.1%; p = 0.01). In the highest vs. lowest leukocyte quintile at latest time point prior to CAD event, participants had univariable CAD-OR = 2.27 (95% confidence interval, 1.63-3.15) and multivariable adjusted CAD-OR = 1.59 (1.09-2.30). For comparison, univariable CAD-OR for dyslipidemia, diabetes, and recent abacavir exposure were 1.58 (1.29-1.93), 2.19 (1.59-3.03), and 1.73 (1.37-2.17), respectively. Smoking and, to a lesser degree, alcohol and ethnicity attenuated the leukocyte-CAD association. Leukocytes measured up to 8 years pre-event were significantly associated with CAD events.ConclusionsPWH in Switzerland with higher leukocyte counts have an independently increased risk of CAD events, to a degree similar to traditional and HIV-related risk factors.

by Benjamin H. Chi, Dorothy Sebikari, Sean S. Brummel, Patricia DeMarrais, Rachel Chamanga, Maxensia Owor, Sufia Dadabhai, Joan T. Price, Taha Taha, Jeffrey Stringer, Mary Glenn FowlerBackground Antiretroviral therapy (ART) is associated with high rates of adverse birth outcomes, including preterm birth and low birthweight. Studies suggest that progesterone and prolactin may play important intermediary roles. Methods We analyzed data from the Antenatal Component of the PROMISE trial, a multi-center study of pregnant women taking antiretroviral regimens (lopinavir/ritonavir-containing ART or zidovudine alone) to prevent mother-to-child HIV transmission. In a nested case-control study, we compared data from women who gave birth to preterm (…

Abstract Background Research on the immune response to inactivated COVID-19 vaccination among people living with HIV (PLWH) is limited, especially among those with low CD4+ T lymphocyte (CD4 cell) count. This prospective cohort study aimed to assess the humoral immune response to inactivated COVID-19 vaccination among PLWH compared to HIV negative controls (HNCs) and to determine the impact of CD4 cell count on vaccine response among PLWH. Methods The neutralizing antibodies (nAbs) and the specific IgM and IgG-binding antibody responses to the inactivated COVID-19 vaccine at the third month after the second dose of inactivated COVID-19 vaccination were measured among 138 PLWH and 35 HNCs. Multivariable logistic regression and multiple linear regression models were conducted to identify factors associated with the seroconversion rate of antibodies and the magnitude of anti-SARS-CoV-2 antibody titers, respectively. Results At the end of the third month after two doses of vaccination, the seroconversion rates of IgG were comparable between PLWH (44.9%; 95% CI 36.5–53.3%) and HNCs (60.0%; 95% CI 42.9–77.1%), respectively. The median titers and seroconversion rate of nAbs among PLWH were 0.57 (IQR: 0.30–1.11) log10 BAU/mL and 29.0% (95% CI 21.3–36.8%), respectively, both lower than those in HNCs (P < 0.05). After adjusting for age, sex, comorbidities, and CD4 cell count, the titers and seroconversion rate of nAbs were comparable between PLWH and HNCs (P > 0.05). Multivariable regression analyses showed that CD4 cell count < 200/μL was independently associated with lower titers and seroconversion rate of nAbs among PLWH (P < 0.05). A positive correlation was observed between the CD4 cell count and nAbs titers in PLWH (Spearman's ρ = 0.25, P = 0.0034). Conclusion Our study concluded that the immune response to inactivated COVID-19 vaccination among PLWH was independently associated with CD4 cell count, PLWH with lower CD4 cell count showed a weaker humoral immune response, especially those with CD4 cell count < 200/μL. This finding suggests that expanding COVID-19 vaccination coverage among PLWH is impendency. In addition, aggressive ART should be carried out for PLWH, especially for those with low CD4 cell count, to improve the immune response to vaccines. …

Abstract Background Acute and early HIV (AEH) infection is characterized by a high viral load and infectivity. Approximately 50% of cases of HIV-1 transmission occur during AEH. Understanding sexual behaviour trajectories would be useful for predicting changes in the risk of HIV acquisition. However, few studies have investigated sexual behaviour trajectories and their association with AEH acquisition. This study identified behaviour trajectories among men who have sex with men (MSM), determined the risk of AEH infection, and compared risk factors between different behaviour trajectories. Methods The study was based on an ongoing prospective open cohort of voluntary HIV counselling and testing (VHCT) among MSM in Tianjin, China. From 2011 to 2019, 1974 MSM were recruited. Group-based trajectory modelling (GBTM) was used to identify behaviour trajectories by constructing a sexual risk behaviour score. Logistic regression and generalized estimating equation (GEE) were used to compare the risk of AEH infection and risk factors for different behaviour trajectories. All data analyses were performed using SAS 9.4. Results The incidence of AEH infection was 1.76/100 person-years, with 64 AEH infections documented in 3633 person-years of follow-up. Three sexual behaviour trajectories were identified: CL (consistently low risk, 35.46%), CH (consistently high risk, 42.71%) and HTL (high to low risk, 21.83%). MSM in the HTL and CH groups had higher AEH infection rates than MSM in the CL group (6.73%, 3.08% and 1.28%, respectively), with ORs of 5.54 (2.60, 11.82) and 2.44 (1.14, 5.25), respectively. MSM aged 30–50 years old and MSM who underwent HIV testing in the last year were more likely to be in the CH group and HTL group. In addition, the HTL group was characterized by a lower likelihood of local registration and a higher likelihood of working as a MSW. Conclusion MSM in the CH group and the HTL group had a higher risk of AEH infection. In the future, VHCT should be performed more often among younger MSM, and HIV counselling should be given the same priority as HIV testing. In addition, VHCT combined with PrEP may have a better preventive impact on MSM with a high risk of AEH infection. …

Objectives: HIV affects 36 million people globally with prevalence decreasing due to antiretroviral therapy (ART) and social awareness; transmission occurs during substance use. Cocaine usage independently affects brain activity and may result in reduced ART adherence. This study evaluates brain glucose metabolism measured by 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in cocaine users with HIV infection.Design: Sixty-three subjects were categorized into groups: 36 HIV infected (HIV+) and 27 non-HIV infected (HIV-) subjects. Each group was further split into cocaine users (CO+) and non-cocaine users (CO-). Of the HIV+, half were cocaine users and half were not. Of the HIV-, 14 were cocaine users and 13 were not. 18F-FDG-PET and low dose CT scans were performed on all subjects.Methods: Brain glucose metabolism was evaluated by 18F-FDG uptake in the whole brain, cortex, basal ganglia, and cerebellum 120 minutes after injection. ROVER software was used for image analysis and ROI masks were applied via an adaptive threshold system. ANOVA tests and t-tests were performed to assess the respective differences between the four groups.Results: Generally, the HIV+/CO+ group (group A) displayed the lowest levels of uptake whereas the HIV-/CO- group (group D) showed the highest; the HIV+/CO- and HIV-/CO+ groups (group B and C) showed intermediate levels of activity across the whole brain, cortex, basal ganglia, and cerebellum.Conclusion: HIV infection and cocaine usage were independently associated with a decrease in brain glucose uptake as measured by 18F-FDG PET/CT. When combined, positive HIV status and cocaine patients showed the most decreased 18F-FDG uptake.Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.

Objective: People living with HIV (PLWH) have a higher risk of type 2 diabetes (T2D) than HIV negative individuals. In the general population, diabetes risk scores are used to identify persons at risk of developing T2D, but little is known regarding their performance in PLWH.Design: Assessment of the capacity of five diabetes risk scores to predict T2D in PLWH.Methods: Prospective study including all Swiss HIV cohort study (SHCS) participants followed between 2009 and 2019. Five diabetes risk scores were assessed: FINDRISC versions 1 and 2, Balkau, Swiss Diabetes Association (SDA) and Kraege.Results: 3853 T2D-free PLWH (78.5% men, 39.9 ± 11.3 years) were included. After a median follow-up of 4.8 years (interquartile range 2.2–7.8), 62 participants (1,6%) developed T2D, corresponding to an incidence rate of 3.18 per 1,000 person-years (95% confidence interval: 2.47–4.08). Participants who developed T2D were older (48.7 ± 12.4 vs. 39.8 ± 11.2 years), more likely to be obese (22.6% vs. 7.4%), abdominally obese (9.7% vs. 1.5%), and to have a family history of diabetes (32.3% vs. 19.1%) than those without T2D. The AUC for incident T2D ranged between 0.72 (Kraege 16) and 0.81 (SDA, FINDRISC2 and Balkau). Sensitivity ranged between 3.2% (Balkau) and 67.7% (FINDRISC1) and specificity between 80.9% (FINDRISC1) and 98.3% (Balkau). Positive predictive values of all scores were below 20%, while negative predictive values were above 98%.Conclusion: In conclusion, our study shows that the performance of conventional diabetes risk scores in PLWH is promising, especially for Balkau and FINDRISC2 which showed good discriminatory power. These scores may help identify patients at low risk of T2D in whom careful assessment of modifiable T2D risk factors can be spared.Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.

Objective: To infer the timing of HIV acquisition in relation to self-reported events in the sexual life course of adolescent girls and young women (AGYW) who self-identify as female sex workers (FSW) in Mombasa, Kenya.Design: Next-generation viral sequencing of samples of AGYW living with HIV in the Transitions study, a cross-sectional bio-behavioural survey of AGYW aged 14–24 years in Mombasa, Kenya.Method: Dried blood spot (DBS) specimens were collected from study participants (n = 37, all FSW). A portion of the HIV pol gene was sequenced using an in-house next-generation sequencing assay for HIV drug resistance mutation genotyping. Estimated time since infection (ETI) was inferred using the HIV EVO web-based tool (https://hiv.biozentrum.unibas.ch/ETI/), and data on self-reported events were obtained from the survey.Results: The median ETI among FSW was 3.4 (IQR = 1.7, 6.3) years, with a median ETI of 1.5 years prior to entry into formal sex work. We estimated that 74.1% (95% CI 53.7–88.9%) of participants living with HIV and who self-identified as FSW likely acquired HIV prior to self-identification as a sex worker.Conclusion: Findings suggest a large fraction of prevalent HIV infection among AGYW engaged in sex work stems from acquisition prior to entry into formal sex work. Current HIV prevention programs tailored for sex workers may miss key opportunities for HIV prevention as they are designed to reach women after entry into formal sex work, signaling a need for tailored programs to reach high-risk AGYW earlier on in their sexual life course.Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.

Objectives: We sought to better understand factors associated with ovarian aging in women living with HIV (WLWH).Design: HIV has been associated with diminished fertility, younger age at menopause, and shorter leukocyte telomere length (LTL), a marker of cellular aging. We herein examine cross-sectional and longitudinal associations between LTL, Anti-Mullerian hormone (AMH), and HIV.Methods: We included WLWH and HIV-negative women 12–50 years of age in the CARMA cohort with ≥1 study visit(s). LTL and AMH were measured by qPCR and ELISA, respectively. Women were analysed in peak reproductive (…

Objective: This study describes adverse events following immunization (AEFIs) and the development of SARS-COV-2 antibodies after Sputnik V, AstraZeneca, and Sinopharm COVID-19 vaccination in PWH.Methods: N = 595 adult PWH at an HIV center in Argentina from March-December 2021 were enrolled. Analysis included participants who received COVID-19 vaccination with Sputnik V, AstraZeneca, and Sinopharm, and did not receive mRNA COVID-19 vaccines. Clinical data, and local or systemic AEFI variables were collected using an online questionnaire after the first dose. Detection of S1-RBD IgG antibodies was performed between days 28–60 after the second dose in a subsample (SARS-CoV-2 IgG chemiluminescent immunoassay, Siemens). A multivariable logistic regression and spearman test were used for analyses.Results: Mean age was 46.1 years (SD = 11.8); 70.4% were male; and median CD4+ T cells count was 659 (500–852) cells/mL. AEFIs were reported in 214 (36.0%) participants. More participants reported AEFIs after Sputnik V (29.4%) and AstraZeneca (47.5%) than Sinopharm (13.9%) (χ2 = 35.85, p …

Objective: People living with HIV (PLWHIV) are increasingly experiencing non-communicable complications, including renal impairment, which are associated with worse clinical outcomes. Limited information exists surrounding renal impairment in paediatric PLWHIV, of which the majority live in sub-Saharan Africa, and further information is required to guide clinical practice. This study describes the prevalence of new or worsening renal impairment in adolescents commencing antiretroviral therapy (ART) in Zimbabwe and associated risk factors.Design: Retrospective cohort study.Methods: Data were collected between January 2010 to January 2019 from the medical records of adolescents aged 12–17 years initiating ART at an outpatient HIV clinic in Zimbabwe. Renal function (eGFR) was calculated using the Full Age Spectrum formula. Proteinuria was defined as a single urine dipstick score of ≥1+. Potential predictors of renal impairment at follow-up were assessed by logistical regression.Results: 266 adolescents were included in analysis. Baseline renal impairment (eGFR…

Tropical Medicine &International Health, Accepted Article.

AbstractBackgroundCabotegravir (CAB) + rilpivirine (RPV) dosed intramuscularly monthly or every 2 months is a complete long-acting (LA) regimen for the maintenance of HIV-1 virologic suppression. Here, we report the ATLAS-2M study Week 152 results.MethodsATLAS-2M is a Phase 3b, randomized, multicenter study assessing the efficacy and safety of CAB+RPV LA every 8 weeks (Q8W) vs. every 4 weeks (Q4W). Virologically suppressed (HIV-1 RNA <50 copies/mL) individuals were randomized to receive CAB+RPV LA Q8W or Q4W. Endpoints included the proportion of participants with plasma HIV-1 RNA ≥50 copies/mL and <50 copies/mL, incidence of confirmed virologic failure (CVF; two consecutive measurements of ≥200 copies/mL), safety, and tolerability.Results1045 participants received CAB+RPV LA (Q8W, n=522; Q4W, n=523). CAB+RPV LA Q8W demonstrated noninferior efficacy vs. Q4W dosing, with 2.7% (n=14) and 1.0% (n=5) of participants having HIV-1 RNA ≥50 copies/mL, respectively. The adjusted treatment difference in proportions was 1.7% (95% CI 0.1 to 3.3), meeting the pre-specified noninferiority threshold of 4%. At Week 152, 87% of participants maintained HIV-1 RNA <50 copies/mL (Q8W, 87% [n=456]; Q4W, 86% [n=449]). Overall, 12 (2.3%) participants in the Q8W arm and two (0.4%) participants in the Q4W arm had CVF. Eight and 10 participants with CVF had treatment-emergent resistance-associated mutations to RPV and integrase inhibitors, respectively. Safety profiles were comparable, with no new safety signals observed since Week 48.ConclusionsThese data demonstrate the durability of virologic suppression with CAB+RPV LA Q8W or Q4W for ∼3 years, and confirm the long-term efficacy, safety, and tolerability of CAB+RPV LA as a complete regimen for the maintenance of HIV-1 virologic suppression.

Abstract: Background: Research trial participation may influence health outcomes regardless of the intervention assigned but is often not assessed.Setting: We investigated how participation in an HIV prevention trial (the HIV Prevention Trials Network (HPTN) 068 study) affected health outcomes four years after the study in adolescent girls and young women (AGYW) in South Africa beyond effects of the tested intervention.Methods: We developed an analytical cohort that included the HPTN 068 trial participants from the Agincourt Health and Demographic Surveillance System (AHDSS) and resembled HPTN 068 trial enrollees (aged 13 to 20 years and in grades 8-11 in 2011) using inverse probability of treatment weights. We estimated risk differences (RD) for the association between trial participation and education and early parity (age…

Clusters of cases of pneumocystis pneumonia and Kaposi’s sarcoma in New York and California in men who had sex with men were early harbingers of the acquired immunodeficiency syndrome (AIDS) epidemic. The syndrome was also soon noted to be associated with a high incidence of aggressive B-cell lymphomas. As the AIDS definition crystallized, Kaposi’s sarcoma, aggressive B-cell lymphomas, and invasive cervical cancer were considered to be AIDS-defining cancers when they developed in patients with human immunodeficiency virus (HIV) infection. Additional cancers are now known to be associated with HIV (Table 1). The term HIV-associated cancer is used here to describe this larger group of cancers (both AIDS-defining and non–AIDS-defining cancers) that have an increased incidence among patients with HIV infection. In addition, incidental cancers also may develop in patients with HIV infection.

Randomized-trial data on the risks and benefits of antiretroviral therapy (ART) as compared with zidovudine and single-dose nevirapine to prevent transmission of the human immunodeficiency virus (HIV) in HIV-infected pregnant women with high CD4 counts are lacking.

Data from randomized trials are lacking on the benefits and risks of initiating antiretroviral therapy in patients with asymptomatic human immunodeficiency virus (HIV) infection who have a CD4+ count of more than 350 cells per cubic millimeter.

Progressive immune dysfunction and the acquired immunodeficiency syndrome (AIDS) develop in most persons with untreated infection with human immunodeficiency virus type 1 (HIV-1) but in only approximately 20 to 30% of persons infected with HIV type 2 (HIV-2); among persons infected with both types, the natural history of disease progression is poorly understood.

Antiretroviral preexposure prophylaxis is a promising approach for preventing human immunodeficiency virus type 1 (HIV-1) infection in heterosexual populations.

The optimal time for the initiation of antiretroviral therapy for asymptomatic patients with human immunodeficiency virus (HIV) infection is uncertain.

There is considerable genetic diversity among viruses of different subtypes (designated A to J) in the major group of human immunodeficiency virus type 1 (HIV-1), the form of HIV that is dominant in the global epidemic. If available, HIV-1 sequences pre-dating the recognition of AIDS could be crucial in defining the time of origin and the subsequent evolution of these viruses in humans. The oldest known case of HIV-1 infection was reported to be that of a sailor from Manchester who died of an AIDS-like illness in 1959; however, the authenticity of this case has not been confirmed. Genetic analysis of sequences from clinical materials obtained from 1971 to 1976 from members of a Norwegian family infected earlier than 1971 showed that they carried viruses of the HIV-1 outlier group, a variant form that is mainly restricted to West Africa. Here we report the amplification and characterization of viral sequences from a 1959 African plasma sample that was previously found to be HIV-1 seropositive. Multiple phylogenetic analyses not only authenticate this case as the oldest known HIV-1 infection, but also place its viral sequence near the ancestral node of subtypes B and D in the major group, indicating that these HIV-1 subtypes, and perhaps all major-group viruses, may have evolved from a single introduction into the African population not long before 1959.

A retrovirus belonging to the family of recently discovered human T-cell leukemia viruses (HTLV), but clearly distinct from each previous isolate, has been isolated from a Caucasian patient with signs and symptoms that often precede the acquired immune deficiency syndrome (AIDS). This virus is a typical type-C RNA tumor virus, buds from the cell membrane, prefers magnesium for reverse transcriptase activity, and has an internal antigen (p25) similar to HTLV p24. Antibodies from serum of this patient react with proteins from viruses of the HTLV-I subgroup, but type-specific antisera to HTLV-I do not precipitate proteins of the new isolate. The virus from this patient has been transmitted into cord blood lymphocytes, and the virus produced by these cells is similar to the original isolate. From these studies it is concluded that this virus as well as the previous HTLV isolates belong to a general family of T-lymphotropic retroviruses that are horizontally transmitted in humans and may be involved in several pathological syndromes, including AIDS.