Background. Most human immunodeficiency virus (HIV) point-of-care tests detect antibodies (Ab) but not p²⁴ antigen (Ag) or RNA. In the absence of antibodies, p²⁴ antigen and RNA typically indicate ...acute HIV infection. We conducted a field evaluation of the Determine® HIV-1/2 Ag/Ab Combo rapid test (Combo RT). Methods. The antigen portion of the Combo RT (for acute HIV infection) was compared with a Roche Monitor HIV RNA polymerase chain reaction assay. The antibody portion of Combo RT (for established HIV infection) was compared with rapid test algorithms. Participants were enrolled at a sexually transmitted infection clinic and HIV testing and counseling center in Lilongwe, Malawi. Rapid testing was conducted with parallel testing in the clinic and serial testing in the center. The Combo RT was performed in clinic participants with negative or discordant antibody results and in all center participants. Results. Of the participants 838 were HIV negative, 163 had established HIV infection, and 8 had acute HIV infection. For detecting acute HIV infection, the antigen portion had a sensitivity of 0.000 and a specificity of 0.983. For detecting established HIV infection, the antibody portion had a sensitivity of 0.994 and a specificity of 0.992. Conclusions. Combo RT displayed excellent performance for detecting established HIV infection and poor performance for detecting acute HIV infection. In this setting, Combo RT is no more useful than current algorithms.
Background. Defining mucosal immune responses and inflammation to candidate human immunodeficiency virus type 1 (HIV-1) vaccines represents a current research priority for the HIV-1 vaccine field. In ...particular, it is unclear whether intramuscular immunization can elicit immune responses at mucosal surfaces in humans. Methods. In this double-blind, randomized, placebo-controlled clinical trial, we evaluated systemic and mucosal immune responses to a candidate adenovirus serotype 26 (Ad26) vectored HIV-1 envelop (Env) vaccine in baseline Ad26-seronegative and Ad26-seropositive healthy volunteers. Systematic mucosal sampling with rectal Weck-Cel sponges and rectal biopsies were performed. Results. Intramuscular immunization elicited both systemic and mucosal Env-specific humoral and cellular immune responses in the majority of subjects. Individuals with preexisting Ad26-specific neutralizing antibodies had vaccine-elicited immune responses comparable to those of subjects who were Ad26 seronegative. We also observed no increase in activated total or vector-specific mucosal CD4⁺ T lymphocytes following vaccination by either histopathology or flow cytometry. Conclusions. These data demonstrate that a single intramuscular administration of this Ad26-vectored HIV-1 Env vaccine elicited both systemic and mucosal immune responses in humans. Induction of antigen-specific humoral and cellular mucosal immunity was not accompanied by a detectable increase in mucosal inflammation.
Sepsis likely contributes to the high burden of infectious disease morbidity and mortality in low income countries. Data regarding sepsis management in sub-Saharan Africa are limited. We conducted a ...prospective observational study reporting the management and outcomes of severely septic patients in two Ugandan hospitals. We describe their epidemiology, management, and clinical correlates for mortality.
Three-hundred eighty-two patients fulfilled enrollment criteria for a severe sepsis syndrome. Vital signs, management and laboratory results were recorded. Outcomes measured included in-hospital and post-discharge mortality. Most patients were HIV-infected (320/377, 84.9%) with a median CD4+ T cell (CD4) count of 52 cells/mm(3) (IQR, 16-131 cells/mm(3)). Overall mortality was 43.0%, with 23.7% in-hospital mortality (90/380) and 22.3% post-discharge mortality (55/247). Significant predictors of in-hospital mortality included admission Glasgow Coma Scale and Karnofsky Performance Scale (KPS), tachypnea, leukocytosis and thrombocytopenia. Discharge KPS and early fluid resuscitation were significant predictors of post-discharge mortality. Among HIV-infected patients, CD4 count was a significant predictor of post-discharge mortality. Median volume of fluid resuscitation within the first 6 hours of presentation was 500 mLs (IQR 250-1000 mls). Fifty-two different empiric antibacterial regimens were used during the study. Bacteremic patients were more likely to die in hospital than non-bacteremic patients (OR 1.83, 95% CI = 1.01-3.33). Patients with Mycobacterium tuberculosis (MTB) bacteremia (25/249) had higher in-hospital mortality (OR 1.97, 95% CI = 1.19-327) and lower median CD4 counts (p = 0.001) than patients without MTB bacteremia.
Patients presenting with sepsis syndromes to two Ugandan hospitals had late stage HIV infection and high mortality. Bacteremia, especially from MTB, was associated with increased in-hospital mortality. Most clinical predictors of in-hospital mortality were easily measurable and can be used for triaging patients in resource-constrained settings. Procurement of low cost and high impact treatments like intravenous fluids and empiric antibiotics may help decrease sepsis-associated mortality in resource-constrained settings.
Evidence suggests that person-centered care (PCC) has the potential to overcome inequities in access to HIV services, support quality care that is responsive to diverse needs while increasing ...efficiencies and resilience of the health system. Despite emerging evidence on the effectiveness of PCC, there is limited information available on how to assess it in diverse clinical settings. This work builds upon a systematic literature review published elsewhere by this study team to develop a PCC framework for HIV treatment service delivery. The PCC framework informed the development of the PCC assessment tool (PCC-AT) to assess the degree to which PCC activities are operationalized in diverse HIV treatment settings. The study objectives are to assess: (1) content validity of the PCC framework; (2) PCC-AT score consistency and reliability between health facility staff and clients; and (3) PCC-AT feasibility in HIV treatment settings. The study team will pilot the PCC-AT among staff in five health facilities and conduct subsequent focus group discussions (FGDs) to determine PCC-AT feasibility. Key informant interviews (KIIs) with clients will explore content validity among PLHIV relative to each subdomain of the PCC-AT and provide a basis to compare score concordance. Quantitative data among health facility staff will examine how many and which cadres participated in the PCC-AT pilot and FGD, years of experience, gender, and the time required to complete the PCC-AT. Information on clients will include total time accessing treatment at the study health facility, years since diagnosis, age and gender. Qualitative data analysis, using descriptive coding with NVivo or a similar software, will be drawn from transcripts from the PCC-AT pilots, FGDs and KIIs. PCC assessment is a novel approach that aims to help health facilities assess and strengthen their ability to deliver PCC services to improve client outcomes.
The Culture of AIDS in Africa presents 30 chapters offering a multifaceted, nuanced, and deeply affective portrait of the relationship between HIV/AIDS and the arts in Africa, including source ...material such as song lyrics and interviews.
We report persistent severe acute respiratory syndrome coronavirus 2 infection in a patient with HIV/AIDS; the virus developed spike N terminal domain and receptor binding domain neutralization ...resistance mutations. Our findings suggest that immunocompromised patients can harbor emerging variants of severe acute respiratory syndrome coronavirus 2.
Invasive fungal infections (IFIs) represent one of the main causes of morbimortality in immunocompromised patients. Pneumocystosis, cryptococcosis and histoplasmosis are the most frequently occurring ...IFIs in patients with acquired immunodeficiency syndrome (AIDS). Fungi, such as
Candida
spp. and
Aspergillus
spp., may cause severe diseases during the course of an HIV infection. Following the introduction of highly active anti-retroviral therapy, there has been a marked reduction of opportunistic fungal infections, which today is 20–25 % of the number of infections observed in the mid-1990s. This study is an observational and retrospective study aimed at the characterising IFI incidence and describing the epidemiology, clinical diagnostic and therapeutic features and denouement in HIV/AIDS patients. In HIV/AIDS patients, the IFI incidence is 54.3/1,000 hospitalisation/year, with a lethality of 37.7 %. Cryptococcosis represents the main opportunistic IFI in the population, followed by histoplasmosis. Nosocomial pathogenic yeast infections are caused principally by
Candida
spp., with a higher candidemia incidence at our institution compared to other Brazilian centres.
People living with HIV (PLHIV) are more likely than the general population to develop AIDS‐defining malignancies (ADMs) and several non‐ADMs (NADMs). Information is lacking on survival outcomes and ...cause‐specific mortality after cancer diagnosis among PLHIV. We investigated causes of death within 5 years of cancer diagnosis in PLHIV enrolled in European and North American HIV cohorts starting antiretroviral therapy (ART) 1996–2015, aged ≥16 years, and subsequently diagnosed with cancer. Cancers were grouped: ADMs, viral NADMs and nonviral NADMs. We calculated cause‐specific mortality rates (MR) after diagnosis of specific cancers and compared 5‐year survival with the UK and France general populations. Among 83,856 PLHIV there were 4,436 cancer diagnoses. Of 603 deaths after ADM diagnosis, 292 (48%) were due to an ADM. There were 467/847 (55%) and 74/189 (39%) deaths that were due to an NADM after nonviral and viral NADM diagnoses, respectively. MR were higher for diagnoses between 1996 and 2005 versus 2006–2015: ADMs 102 (95% CI 92–113) per 1,000 years versus 88 (78–100), viral NADMs 134 (106–169) versus 111 (93–133) and nonviral NADMs 264 (232–300) versus 226 (206–248). Estimated 5‐year survival for PLHIV diagnosed with liver (29% 19–39%), lung (18% 13–23%) and cervical (75% 63–84%) cancer was similar to general populations. Survival after Hodgkin's lymphoma diagnosis was lower in PLHIV (75% 67–81%). Among ART‐treated PLHIV diagnosed with cancer, MR and causes of death varied by cancer type, with mortality highest for liver and lung cancers. Deaths within 5 years of NADM diagnoses were more likely to be from cancer than AIDS.
What's new?
People with HIV live longer than they used to, thanks to advances in antiretroviral therapy. These improvements reduced the incidence of AIDS‐defining malignancies, such as Kaposi's sarcoma, but the increased life expectancy has led to more diagnoses of cancers not traditionally associated with HIV. Here, the authors studied cause‐specific mortality among people with HIV diagnosed with cancer. For those people, within 5 years after a cancer diagnosis, cause of death was more likely to be cancer than AIDS. Survival rates after diagnosis varied by cancer type, but were similar to rates among the general population.
Self-amplifying messenger RNA (mRNA) of positive-strand RNA viruses are effective vectors for in situ expression of vaccine antigens and have potential as a new vaccine technology platform well ...suited for global health applications. The SAM vaccine platform is based on a synthetic, self-amplifying mRNA delivered by a nonviral delivery system. The safety and immunogenicity of an HIV SAM vaccine encoding a clade C envelope glycoprotein formulated with a cationic nanoemulsion (CNE) delivery system was evaluated in rhesus macaques. The HIV SAM vaccine induced potent cellular immune responses that were greater in magnitude than those induced by selfamplifying mRNA packaged in a viral replicon particle (VRP) or by a recombinant HIV envelope protein formulated with MF59 adjuvant, anti-envelope binding (including anti-V1V2), and neutralizing antibody responses that exceeded those induced by the VRP vaccine. These studies provide the first evidence in nonhuman primates that HIV vaccination with a relatively low dose (50µg) of formulated self-amplifying mRNA is safe and immunogenic.
To determine the effect of introduction of highly active antiretroviral therapy (HAART) on survival following AIDS dementia complex (ADC).
Australian AIDS notification data in the period 1993-2000 ...were examined. In order to examine the impact of HAART, two periods of AIDS diagnoses were chosen: pre-HAART (1993-1995) and HAART (1996-2000). Median survival was based on Kaplan-Meier estimates, with examination of factors influencing survival in a Cox proportional hazards model.
In the period 1993-2000 in Australia, 5017 initial AIDS illnesses were diagnosed among 4351 AIDS patients. The proportion of AIDS cases with ADC increased from 5.2% in 1993-1995 to 6.8% in 1996-2000 (P = 0.029). Median survival following AIDS increased from 19.6 months for those diagnosed with AIDS in 1993-1995 to 39.6 months for those diagnosed in 1996-2000 (P < 0.0005). Median survival following ADC increased to a greater extent than that for all other AIDS illnesses, from 11.9 months in 1993-1995 to 48.2 in 1996-2000 (P < 0.0005). Most striking was the increase in survival among those with ADC and a CD4 cell count < 100 x 10(6) cells/l at diagnosis; 5.1 months in 1993-1995 to 38.5 months in 1996-2000 (P < 0.0005).
Although there has been a proportional increase in ADC at AIDS diagnosis, survival following ADC has improved markedly in the era of HAART.
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