Widespread Availability Of Antiretroviral Therapy Research Articles

Linkage Case Management and Posthospitalization Outcomes in People With HIV

Despite the widespread availability of antiretroviral therapy (ART), people with HIV still experience high mortality after hospital admission. To determine whether a linkage case management intervention (named "Daraja" ["bridge" in Kiswahili]) that was designed to address barriers to HIV care engagement could improve posthospital outcomes. Single-blind, individually randomized clinical trial to evaluate the effectiveness of the Daraja intervention. The study was conducted in 20 hospitals in Northwestern Tanzania. Five hundred people with HIV who were either not treated (ART-naive) or had discontinued ART and were hospitalized for any reason were enrolled between March 2019 and February 2022. Participants were randomly assigned 1:1 to receive either the Daraja intervention or enhanced standard care and were followed up for 12 months through March 2023. The Daraja intervention group (n = 250) received up to 5 sessions conducted by a social worker at the hospital, in the home, and in the HIV clinic over a 3-month period. The enhanced standard care group (n = 250) received predischarge HIV counseling and assistance in scheduling an HIV clinic appointment. The primary outcome was all-cause mortality at 12 months after enrollment. Secondary outcomes related to HIV clinic attendance, ART use, and viral load suppression were extracted from HIV medical records. Antiretroviral therapy adherence was self-reported and pharmacy records confirmed perfect adherence. The mean age was 37 (SD, 12) years, 76.8% were female, 35.0% had CD4 cell counts of less than 100/μL, and 80.4% were ART-naive. Intervention fidelity and uptake were high. A total of 85 participants (17.0%) died (43 in the intervention group; 42 in the enhanced standard care group); mortality did not differ by trial group (17.2% with intervention vs 16.8% with standard care; hazard ratio [HR], 1.01; 95% CI, 0.66-1.55; P = .96). The intervention, compared with enhanced standard care, reduced time to HIV clinic linkage (HR, 1.50; 95% CI, 1.24-1.82; P < .001) and ART initiation (HR, 1.56; 95% CI, 1.28-1.89; P < .001). Intervention participants also achieved higher rates of HIV clinic retention (87.4% vs 76.3%; P = .005), ART adherence (81.1% vs 67.6%; P = .002), and HIV viral load suppression (78.6% vs 67.1%; P = .01) at 12 months. The mean cost of the Daraja intervention was about US $22 per participant including startup costs. Among hospitalized people with HIV, a linkage case management intervention did not reduce 12-month mortality outcomes. These findings may help inform decisions about the potential role of linkage case management among hospitalized people with HIV. ClinicalTrials.gov Identifier: NCT03858998.

Enhancing quality of life and medication adherence for people living with HIV: the impact of an information system

BackgroundThe widespread availability of antiretroviral therapy has led to improvements in life expectancy and thus an increase in the number of people living with HIV/AIDS (PLWHA) worldwide. However, a similar increase in the number of newly-diagnosed patients in Cyprus suggests the need for solutions designed to improve monitoring, planning, and patient communication. In this study, we aimed to determine whether the use of an information system to manage PLWHA might contribute to improved quality of life and critical adherence to prescribed drug regimens and ongoing medical care.MethodsA randomized controlled trial study was conducted in Cyprus based on information that we collected using the highly valid and reliable Greek translation of the World Health Organization (WHO) Quality of Life (QOL) HIV-BREF questionnaire to assess sociodemographic variables and patient compliance. We distributed 200 questionnaires before implementing a Health Medical Care (HMC) information system at our clinic. Six months after implementing this system, 68 of the completed questionnaires were selected, including two groups of 34 participants who had been assigned at random to the intervention or the control group. Participants included PLWHA aged ≥ 18 years who had been receiving antiretroviral therapy for more than 12 months between July 15, 2020, and July 15, 2022.ResultsThe changes in baseline to six-month scores reported for the intervention group were significantly higher than in the control group in all six subscales assessed with the WHOQOL-HIV-BREF questionnaire, as well as in the assessment of compliance. Furthermore, compliance with treatment was associated with higher scores in the questionnaire subscales, including physical health, psychological health, degree of autonomy, social relationships, life circumstances, and spirituality/religious/personal beliefs. We also identified specific demographic factors and behaviors that were associated with better compliance with scheduled medical care and the prescribed drug regimen. Specifically, men exhibited better compliance than women and younger PLWHA exhibited better compliance than the elderly as did individuals who reported a higher level of educational attainment. Additionally, individuals who did not use addictive substances, consumed less alcohol, and were managed using the monitoring information system all exhibited better compliance compared to those in the control group.ConclusionThe results of this study suggest that management of PLWHA via the use of an information system can contribute to improved QOL and drug compliance.

Pneumocystis jirovecii pneumonia in people living with HIV: a review.

SUMMARYPneumocystis jirovecii is a ubiquitous opportunistic fungus that can cause life-threatening pneumonia. People with HIV (PWH) who have low CD4 counts are one of the populations at the greatest risk of Pneumocystis jirovecii pneumonia (PCP). While guidelines have approached the diagnosis, prophylaxis, and management of PCP, the numerous studies of PCP in PWH are dominated by the 1980s and 1990s. As such, most studies have included younger male populations, despite PCP affecting both sexes and a broad age range. Many studies have been small and observational in nature, with an overall lack of randomized controlled trials. In many jurisdictions, and especially in low- and middle-income countries, the diagnosis can be challenging due to lack of access to advanced and/or invasive diagnostics. Worldwide, most patients will be treated with 21 days of high-dose trimethoprim sulfamethoxazole, although both the dose and the duration are primarily based on historical practice. Whether treatment with a lower dose is as effective and less toxic is gaining interest based on observational studies. Similarly, a 21-day tapering regimen of prednisone is used for patients with more severe disease, yet other doses, other steroids, or shorter durations of treatment with corticosteroids have not been evaluated. Now with the widespread availability of antiretroviral therapy, improved and less invasive PCP diagnostic techniques, and interest in novel treatment strategies, this review consolidates the scientific body of literature on the diagnosis and management of PCP in PWH, as well as identifies areas in need of more study and thoughtfully designed clinical trials.

A community health worker and mobile health app intervention to improve adherence to HIV medication among persons with HIV: the CHAMPS study protocol

BackgroundPersons with HIV (PWH) can now achieve a near-normal life expectancy due to antiretroviral therapy (ART). Despite widespread availability of ART in the United States (US), many of the country’s approximate 1.1 million PWH are not achieving viral suppression due to poor ART adherence. Viral suppression rates are particularly low in Alabama (AL, 62%) and New York City (NYC, 67%). There is mixed evidence on the efficacy of community health workers (CHW) and mHealth interventions for improving ART adherence and viral suppression in PWH thus, we sought to combine these interventions and test the efficacy for improving health outcomes in PWH.MethodsThe CHAMPS study is a two-arm randomized controlled trial among 300 PWH with suboptimal primary care appointment adherence (n = 150 in AL and 150 in NYC) over the course of 12 months. Participants are randomly assigned to CHAMPS (intervention) or a standard-of-care (control) arm. Participants in the intervention arm are given a CleverCap pill bottle that syncs to the WiseApp to track medication adherence, reminds users to take their medication at a set time, and enables communication with CHW. All participants complete baseline, 6-month, and 12-month follow-up visits where surveys are administered and, CD4 and HIV-1 viral load are obtained through blood draw.DiscussionMaintaining ART adherence has significant implications in HIV management and transmission. mHealth technologies have been shown to optimize the provision of health services, produce positive changes in health behavior, and significantly improve health outcomes. CHW interventions also provide personal support to PWH. The combination of these strategies may provide the necessary intensity to increase ART adherence and clinic attendance among PWH at highest risk for low engagement. Delivering care remotely enables CHW to contact, assess, and support numerous participants throughout the day, reducing burden on CHW and potentially improving intervention durability for PWH. The adoption of the WiseApp coupled with community health worker sessions in the CHAMPS study has the potential to improve HIV health outcomes, and will add to the growing knowledge of mHealth and CHW efforts to improve PWH medication adherence and viral suppression.Trial registrationThis trial was registered with Clinicaltrials.gov (NCT04562649) on 9/24/20.

Children who are HIV-exposed and uninfected: evidence for action

Prior to widespread availability of antiretroviral therapy (ART) in sub-Saharan Africa, children who were HIV-exposed but uninfected (HEU) had increased mortality, morbidity and undernutrition compared with children who were HIV-unexposed. Scale-up of ART has led to impressive declines in vertical HIV transmission, but over 15 million children are now HEU, 90% of whom live in sub-Saharan Africa. There are ongoing health disparities among children who are HEU, with higher mortality, morbidity and stunting and modest impairments in early child development, which collectively hamper health and human capital in high prevalence countries. The underlying causes are multifactorial and include exposure to HIV, co-infections and a skewed antenatal inflammatory milieu, particularly if mothers start ART once they have advanced disease, as well as socioeconomic risk factors, which may cluster in HIV-affected households. Improving maternal health through early and sustained ART, ensuring optimal breastfeeding, and implementing evidence-based priority interventions for all children in areas of high HIV prevalence, will likely improve outcomes. A more comprehensive intervention package based on the Nurturing Care Framework may have particular benefits for children who are HEU, to close health gaps and ensure that the next generation of HIV-free children survive and thrive, and lead healthy and productive lives.

A type III effectiveness-implementation hybrid evaluation of a multicomponent patient navigation strategy for advanced-stage Kaposi’s sarcoma: protocol

BackgroundFor people with advanced-stage Kaposi’s sarcoma (KS), a common HIV-associated malignancy in sub-Saharan Africa, mortality is estimated to be 45% within 2 years after KS diagnosis, despite increasingly wide-spread availability of antiretroviral therapy and chemotherapy. For advanced-stage KS, chemotherapy in addition to antiretroviral therapy improves outcomes and saves lives, but currently, only ~50% of people with KS in western Kenya who have an indication for chemotherapy actually receive it. This protocol describes the evaluation of a multicomponent patient navigation strategy that addresses common barriers to service penetration of and fidelity to evidence-based chemotherapy among people with advanced-stage KS in Kenya.MethodsThis is a hybrid type III effectiveness-implementation study using a non-randomized, pre- post-design nested within a longitudinal cohort. We will compare the delivery of evidence-based chemotherapy for advanced-stage KS during the period before (2016–2020) to the period after (2021–2024), the rollout of a multicomponent patient navigation strategy. The multicomponent patient navigation strategy was developed in a systematic process to address key determinants of service penetration of and fidelity to chemotherapy in western Kenya and includes (1) physical navigation and care coordination, (2) video-based education, (3) travel stipend, (4) health insurance enrollment assistance, (5) health insurance stipend, and (6) peer mentorship. We will compare the pre-navigation period to the post-navigation period to assess the impact of this multicomponent patient navigation strategy on (1) implementation outcomes: service penetration (chemotherapy initiation) and fidelity (chemotherapy completion) and (2) service and client outcomes: timeliness of cancer care, mortality, quality of life, stigma, and social support. We will also describe the implementation process and the determinants of implementation success for the multicomponent patient navigation strategy.DiscussionThis study addresses an urgent need for effective implementation strategies to improve the initiation and completion of evidence-based chemotherapy in advanced-stage KS. By using a clearly specified, theory-based implementation strategy and validated frameworks, this study will contribute to a more comprehensive understanding of how to improve cancer treatment in advanced-stage KS.

Maternal Intervention to Prevent Mother-to-Child Transmission of HIV: Moving Beyond Antiretroviral Therapy.

Widespread availability of antiretroviral therapy among pregnant women living with HIV has greatly reduced the rate of mother-to-child transmission (MTCT) of HIV across the globe. However, while Joint United Nations Programme on HIV/AIDS has set targets to reduce the annual number of new pediatric HIV infections to fewer than 40,000 in 2018 and fewer than 20,000 in 2020, progress towards these targets has plateaued at an unacceptably high global estimate of greater than 160,000 children newly infected with HIV in 2018. Moreover, it has become clear that expansion of maternal antiretroviral therapy alone will not be sufficient to close the remaining gap and eliminate MTCT of HIV. Additional strategies such as maternal or infant passive and/or active immunization that synergize with maternal antiretroviral therapy will be required to end the pediatric HIV epidemic. In this review, we outline the landscape of existing maternal interventions and emerging maternal immune-based approaches to prevent MTCT of HIV.

Research Priorities to End the Adolescent HIV Epidemic in the United States: Viewpoint.

Youth represent 21% of new HIV diagnoses in the United States. Gay, bisexual, and transgender (GBT) youth, particularly those from communities of color, and youth who are homeless, incarcerated, in institutional settings, or engaging in transactional sex are most greatly impacted. Compared with adults, youth have lower levels of HIV serostatus awareness, uptake of antiretroviral therapy (ART), and adherence. Widespread availability of ART has revolutionized prevention and treatment for both youth at high risk for HIV acquisition and youth living with HIV, increasing the need to integrate behavioral interventions with biomedical strategies. The investigators of the Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN) completed a research prioritization process in 2019, focusing on research gaps to be addressed to effectively control HIV spread among American youth. The investigators prioritized research in the following areas: (1) innovative interventions for youth to increase screening, uptake, engagement, and retention in HIV prevention (eg, pre-exposure prophylaxis) and treatment services; (2) structural changes in health systems to facilitate routine delivery of HIV services; (3) biomedical strategies to increase ART impact, prevent HIV transmission, and cure HIV; (4) mobile technologies to reduce implementation costs and increase acceptability of HIV interventions; and (5) data-informed policies to reduce HIV-related disparities and increase support and services for GBT youth and youth living with HIV. ATN’s research priorities provide a roadmap for addressing the HIV epidemic among youth. To reach this goal, researchers, policy makers, and health care providers must work together to develop, test, and disseminate novel biobehavioral interventions for youth.

Effects of Urethritis on Human Immunodeficiency Virus (HIV) in Semen: Implications for HIV Prevention and Cure.

Prior to the widespread availability of antiretroviral therapy (ART), men living with human immunodeficiency virus (HIV) with urethritis had increased concentrations of HIV in semen. This study aims to better evaluate HIV shedding in men with urethritis receiving ART, and its implications for the cure of HIV. Men living with HIV with urethritis taking ART ≥12 weeks were enrolled at a sexually transmitted infections clinic in Lilongwe, Malawi. Study follow-up included visits at 1, 2, 4, 8, 12, 24, 36, and 48 weeks after urethritis diagnosis and treatment. Matched blood and semen samples were collected at all visits, and all additional episodes of urethritis were followed with extra visits 1, 2, and 4 weeks after treatment. There were 111 men enrolled in the study between January 2017-March 2019, and 77 (69%) were suppressed in the blood (<400 copies/mL). Among the 77 men, 87 episodes of urethritis were evaluated during follow-up. Of the 87 episodes, 15 episodes (17%) had instances of seminal viral shedding ≥400 copies/mL despite viral suppression in the blood. During nonurethritis follow-up, ≤6% of men at each visit had a viral load ≥400 copies/mL in the semen while maintaining viral suppression in the blood. An HIV cure requires the elimination of HIV from every body compartment, but available ART does not currently accomplish this. Our study highlights the male genital tract as a local source of HIV that can be reversibly activated. A better understanding of this phenomenon is important to advance the HIV cure field.

Plasmablastic lymphoma in Johannesburg, South Africa, in the era of widescale antiretroviral therapy use.

Plasmablastic lymphoma (PBL) is a clinically aggressive lymphoma which has a predilection for extranodal sites and is frequently HIV-associated. The incidence of non-Hodgkin lymphoma is thought to be reduced by widescale antiretroviral therapy (ART) coverage, but the literature is sparse as regards the impact of ART on the incidence of PBL and its outcomes in South Africa (SA). This study aimed to compare factors of interest in cases of PBL diagnosed before and after the widespread availability of ART in Johannesburg, SA. All cases of PBL diagnosed in the state sector hospitals of Johannesburg in 2007 and 2017 (before and after the widespread availability of ART, respectively) were extracted from the laboratory information system, and factors of interest compared. The majority (>95%) of cases of PBL were seen among people with HIV infection (PWH) at both time-points, and the proportion of patients on ART and with virological suppression (VS) increased significantly in 2017. However, the number of cases of PBL did not differ significantly between the twoyears assessed, comprising 46/397 (11.6%) and 53/582 (9.6%) of all lymphomas in 2007 and 2017, respectively (P=0.23). Ongoing risk for PBL among PWH with virological control and immunological recovery was evident in 2017, as 18.9% of the patients had both VS and CD4 counts >200 cells/μL at diagnosis. Inferior survival times were associated with elevated lactate dehydrogenase (LDH) levels and Epstein Barr virus (EBV) negativity, but were not influenced by the presence of AIDS, ART or VS. EBV negativity was significantly associated with VS, and appeared to flag a particularly aggressive form of the disease. Widescale ART coverage has not reduced the incidence of PBL in Johannesburg, and an ongoing risk for this disease among PWH with adequate virological control and immunological recovery persists.

Brief Report: HIV-Associated Hodgkin Lymphoma Involving the Bone Marrow Identifies a Very High-Risk Subpopulation in the Era of Widescale Antiretroviral Therapy Use in Johannesburg, South Africa

Background: The incidence of HIV-associated Hodgkin lymphoma (HIV-HL) has not dropped in the era of widespread antiretroviral therapy (ART), and there have reportedly been shifts in the most prevalent variants encountered. In this study, factors of interest in cases of HIV-HL diagnosed before and after the widespread availability of ART in Johannesburg, South Africa, were compared. Methods: All cases of HIV-HL diagnosed in 2007 and 2017 were extracted from the laboratory information system, and pertinent factors compared. Results: The number of cases of HL increased significantly over the period assessed, but without a clear increase in the incidence of HIV-HL. As has been reported previously, the proportion of HIV-HL subclassified as the Nodular Sclerosis and Mixed Cellularity subtypes increased and decreased respectively over the period. The number of unclassifiable cases also increased significantly largely because of more frequent diagnosis in bone marrow (BM). BM involvement was highly prevalent at both timepoints (51.7% in 2007 vs 66.2% in 2017; P = 0.18), but was more frequently associated with multiple cytopenias in 2017. Despite significant ART upscaling, the median CD4 count was significantly lower in 2017 (242.5 cells/μL in 2007 vs 85.5 in 2017; P = 0.002). This particularly affected patients with BM involvement, and the median survival time was significantly shorter among BM+ patients diagnosed in 2017 as compared to those diagnosed in 2007. Notably, 40.8% of the patients with BM involvement diagnosed in 2017 died before the diagnosis was established. Conclusion: HIV-HL with BM involvement identifies a very high-risk subpopulation in the post-ART era.

The Changing Epidemiology of HIV-Associated Adult Meningitis, Uganda 2015-2017.

BackgroundCentral nervous system (CNS) infections remain a major public health problem in Sub-Saharan Africa, causing 15%–25% of AIDS-related deaths. With widespread availability of antiretroviral therapy (ART) and the introduction of improved diagnostics, the epidemiology of infectious meningitis is evolving.MethodsWe prospectively enrolled adults presenting with HIV-associated meningitis in Kampala and Mbarara, Uganda, from March 2015 to September 2017. Participants had a structured, stepwise diagnostic algorithm performed of blood cryptococcal antigen (CrAg), CSF CrAg, Xpert MTB/RIF for tuberculous (TB) meningitis (TBM), Biofire multiplex polymerase chain reaction, and traditional microscopy and cultures.ResultsWe screened 842 consecutive adults with HIV presenting with suspected meningitis: 57% men, median age 35 years, median CD4 26 cells/mcL, and 55% presented on ART. Overall, 60.5% (509/842) were diagnosed with first-episode cryptococcal meningitis and 7.4% (62/842) with second episode. Definite/probable TB meningitis was the primary diagnosis in 6.9% (58/842); 5.3% (n = 45) had microbiologically confirmed (definite) TB meningitis. An additional 7.8% (66/842) did not meet the diagnostic threshold for definite/probable TBM but received empiric TBM therapy. Bacterial and viral meningitis were diagnosed in 1.3% (11/842) and 0.7% (6/842), respectively. The adoption of a cost-effective stepwise diagnostic algorithm allowed 79% (661/842) to have a confirmed microbiological diagnosis at an average cost of $44 per person.ConclusionsDespite widespread ART availability, Cryptococcus remains the leading cause of HIV-associated meningitis. The second most common etiology was TB meningitis, treated in 14.7% overall. The increased proportion of microbiologically confirmed TBM cases reflects the impact of new improved molecular diagnostics.

Baseline CD4 and mortality trends in the South African human immunodeficiency virus programme: Analysis of routine data.

BackgroundDespite widespread availability of antiretroviral therapy (ART) in South Africa, there remains a considerable burden of human immunodeficiency virus (HIV)-related morbidity and mortality.ObjectivesTo describe ART initiation and outcome trends over time, with a focus on clients presenting with advanced HIV-infection, so as to identify interventions to reduce morbidity and mortality.MethodsRoutine TIER.Net data from HIV-infected adults who had a documented baseline CD4 count and were newly initiating ART in Johannesburg or Mopani districts from 2004 to 2017 were analysed. Trends in baseline CD4 count and 5-year mortality were investigated and the population initiating ART with CD4 < 200 cells/mm3 was described.ResultsThe Johannesburg and Mopani data sets comprised 203 131 and 101 814 records, respectively. Although median CD4 count increased over time, the proportion of initiations at CD4 < 200 cells/mm3 in 2017 remained high (Johannesburg 39%, Mopani 35%). Mortality was significantly increased among clients with CD4 < 200 compared to those with higher baseline counts (p < 0.001). Even though mortality among clients with low CD4 declined over time, likely because of improved drug regimens, in 2016–2017 mortality was still significantly increased among these clients (p < 0.001). Delivery of cotrimoxazole prophylaxis to clients with low CD4 declined over time to < 30% in 2017 and was associated with clinical stage. Presentation with CD4 < 200 cells/mm3 was associated with older age, male gender and hospitalisation.ConclusionA concerningly large proportion of South Africans still initiate ART at low CD4 counts. This is associated with increased mortality and requires targeted interventions to improve delivery of prophylactic regimens and early engagement in care.

The impact of the availability of antiretroviral therapy on personal and community fear of HIV/AIDS, and HIV prevention practices in Rwimi, Uganda: A mixed-method study

The impact of the widespread availability of antiretroviral therapy (ART) on the human immunodeficiency virus and acquired immune deficiency syndrome (HIV/AIDS) related attitudes, behaviours and practices of the general population in Sub-Saharan Africa is understudied. We assessed the impact of ART availability on the fear of HIV/ AIDS (measured at both community and personal levels) and HIV prevention practices in Rwimi, Uganda using a cross-sectional survey. The fear of HIV/AIDS was described as a perceived threat to either self and/or community regarding the risk of contracting the disease, whereby the higher the perception of the threat, the greater the fear. We assessed associations between the outcomes of the dependent variables on both the community and personal fear of HIV/AIDS, and the independent variables of HIV/AIDS-related knowledge and demographics. Qualitative data was also generated from focus group discussions (FGD) on the context of the fear of HIV/AIDS and HIV pre- vention practices. The majority of participants (89.4%; males - 86.8%; females - 90.8%) felt that ART availability has reduced the fear of HIV/AIDS in the community. In contrast, fewer participants (22.4%; males - 24.4%; females – 21.2%) mentioned that their personal fear of HIV/AIDS has been reduced with the availability of ART. From the qualitative study, factors identified as influencing the fear of HIV/AIDS included stigma, fear of infection, and the inconvenience of being on ART. Although fear of HIV/AIDS persists, the fear is reduced because of the availability of life-prolonging ART. HIV prevention practices are influenced by socio-cultural norms (gender roles, relationship dynamics, power and trust), which, we argue, should be considered when de-signing sustainable HIV/AIDS prevention programs.

Cytomegalovirus Infection of the Gastrointestinal Tract in Soweto, South Africa: A Look Back at the Clinical and Histological Features over 8 Years

Despite the widespread availability of antiretroviral therapy, Cytomegalovirus (CMV) infection remains an important cause of morbidity and mortality in sub-Saharan Africa. CMV gastrointestinal tract infection is poorly described. This retrospective study was undertaken to describe the clinical and histological features of biopsy confirmed CMV infection of the gastrointestinal tract in a large teaching hospital with a high prevalence of Human Immunodeficiency Virus (HIV) infection.

Tissue and molecular features of aging in HIV infection

The widespread availability of antiretroviral therapy for all patients living with HIV (PLHIV) has radically transformed their health span and increased their life expectancy these last years. However, despite these optimistic data, some concerns about the impossible complete eradication of latent forms of the virus integrated into the host genome remain. Indeed, no treatment can cure HIV infection exists, and although immune system state is improving under treatment, it is never completely restored. While neither the effects related to the persistence of the virus or the side effects of treatments on long-term effect on the body is discussed, functional changes associated with premature aging are increasingly observed and described in HIVIP recent years. Thus, cardiovascular dysfunction, brain damage, immune hyperactivity or cancer considered as normal events in an elderly man it is also described in HIVIP. So this review is a detailed update on the condition of HIV infection accelerated aging.

Funding and Innovation in Diseases of Neglected Populations: The Paradox of Cryptococcal Meningitis.

It is estimated that fungal infections cause 1 million deaths annually, accounting for 50% of all AIDS-related deaths [1]. In this specific patient group, data from 2009 revealed that fungal meningitis is responsible for approximately 500,000 deaths each year [2]. The most common fungal pathogen infecting the brain is Cryptococcus neoformans, a yeast-like pathogen that is highly efficient in causing damage to immunosuppressed human hosts [3]. The fungus, which is widespread in the environment, primarily reaches the lung after inhalation of environmental cells and disseminates to the brain in the immunosuppressed host. Clinical studies in humans in combination with animal models of neurological cryptococcosis enabled the classification of the disease into different syndromes, including meningitis, encephalitis, meningoencephalitis, ventriculitis, increased intracranial pressure, and space-occupying lesions [3]. According to the Centers for Disease Control and Prevention (CDC) of the United States, cryptococcal meningitis is a global problem. Estimates by Park and colleagues indicated that approximately 957,900 cases (range, 371,700–1,544,000) of cryptococcal meningitis occur each year, resulting in 624,700 deaths (range, 125,000–1,124,900) by three months after infection [2]. Currently, estimates of global disease burden, including disability-adjusted life year (DALY), are not available, since cryptococcosis is not separately reported. Most cases are opportunistic infections that occur among people with HIV/AIDS. Although the widespread availability of antiretroviral therapy (ART) in developed countries has helped reduce cryptococcal infections in these areas, it is still a major problem in developing countries where access to healthcare is limited. Throughout much of sub-Saharan Africa, for example, Cryptococcus is now the most common cause of adult meningitis, which may kill as many people each year as tuberculosis [2]. The high fatality rate, especially in developing countries, stems from late diagnosis, access only to the least effective treatments, and from drug resistance when treated.

Anemia, Blood Transfusion Requirements and Mortality Risk in Human Immunodeficiency Virus-Infected Adults Requiring Acute Medical Admission to Hospital in South Africa.

Background. Morbidity and mortality remain high among hospitalized patients infected with human immunodeficiency virus (HIV) in sub-Saharan Africa despite widespread availability of antiretroviral therapy. Severe anemia is likely one important driver, and some evidence suggests that blood transfusions may accelerate HIV progression and paradoxically increase short-term mortality. We investigated the relationship between anemia, blood transfusions, and mortality in a South African district hospital.Methods. Unselected consecutive HIV-infected adults requiring acute medical admission to a Cape Town township district hospital were recruited. Admission hemoglobin concentrations were used to classify anemia severity according to World Health Organization/AIDS Clinical Trials Group criteria. Vital status was determined at 90 days, and Cox regression analyses were used to determine independent predictors of mortality.Results. Of 585 HIV-infected patients enrolled, 578 (98.8%) were included in the analysis. Anemia was detected in 84.8% of patients and was severe (hemoglobin, 6.5–7.9 g/dL) or life-threatening (hemoglobin, <6.5 g/dL) in 17.3% and 13.3%, respectively. Within 90 days of the date of admission, 13.5% (n = 78) patients received at least 1 blood transfusion with red cell concentrate and 77 (13.3%) patients died. In univariable analysis, baseline hemoglobin and receipt of blood transfusion were associated with increased mortality risk. However, in multivariable analysis, neither hemoglobin nor receipt of a blood transfusion were independently associated with greater mortality risk. Acquired immune deficiency syndrome-defining illnesses other than tuberculosis and impaired renal function independently predicted mortality.Conclusions. Newly admitted HIV-infected adults had a high prevalence of severe or life-threatening anemia and blood transfusions were frequently required. However, after adjustment for confounders, blood transfusions did not confer an increased mortality risk.

Maternal HIV status associated with under-five mortality in rural Northern Malawi: a prospective cohort study.

Under-five mortality is decreasing but with little change in neonatal mortality rates. We examined the effect of maternal HIV status on under-five mortality and cause of death since widespread availability of antiretroviral therapy in rural Malawi. Children born in 2006-2011 in the Karonga demographic surveillance area were included. Maternal HIV status was available from HIV serosurveys. Age-specific mortality rate ratios for children born to HIV-positive and HIV-negative mothers were obtained by fitting a Poisson model accounting for child clustering by mother and adjusting for potential confounders. Cause of death was ascertained by verbal autopsy. There were 352 deaths among 6913 under-five singleton children followed for 20,754 person-years (py), giving a mortality rate of 17.0/1000 py overall, 218/1000 py (16.5/1000 live births) in neonates, 20/1000 py (17.4/1000 live births) in postneonatal infants, and 8/1000 py in 1-4 years old. Comparing those born to HIV-positive and HIV-negative mothers, the rate ratio adjusted for child age, sex, maternal age, parity, and drinking water source was 1.5 (95% confidence interval [CI]: 0.6 to 3.7) in neonates, 11.5 (95% CI: 7.2 to 18.5) in postneonatal infants, and 4.6 (95% CI: 2.7 to 7.9) in 1-4 years old. Birth injury/asphyxia, neonatal sepsis, and prematurity contributed >70% of neonatal deaths, whereas acute infections, malaria, diarrhea, and pneumonia accounted for most deaths in older children. Maternal HIV status had little effect on neonatal mortality but was associated with much higher mortality in the postneonatal period and among older children. Greater attention to HIV care in pregnant women and mothers should help improve child survival, but broader interventions are needed to reduce neonatal mortality.

Coming home to die? The association between migration and mortality in rural Tanzania before and after ART scale-up

Background Prior to the scale-up of antiretroviral therapy (ART), demographic surveillance cohort studies showed higher mortality among migrants than residents in many rural areas. Objectives This study quantifies the overall and AIDS-specific mortality between migrants and residents prior to ART, during ART scale-up, and after widespread availability of ART in Rufiji district in Tanzania. Design In Health and Demographic Surveillance System (HDSS), the follow-up of individuals aged 15–59 years was categorized into three periods: before ART (1998–2003), during ART scale-up (2004–2007), and after widespread availability of ART (2008–2011). Residents were those who never migrated within and beyond HDSS, internal migrants were those who moved within the HDSS, and external migrants were those who moved into the HDSS from outside. Mortality rates were estimated from deaths and person-years of observations calculated in each time period. Hazard ratios were estimated to compare mortality between migrants and residents. AIDS deaths were identified from verbal autopsy, and the odds ratio of dying from AIDS between migrants and residents was estimated using the multivariate logistic regression model. Results Internal and external migrants experienced higher overall mortality than residents before the introduction of ART. After widespread availability of ART overall mortality were similar for internal and external migrants. These overall mortality experiences observed were similar for males and females. In the multivariate logistic regression model, adjusting for age, sex, education, and social economic status, internal migrants had similar likelihood of dying from AIDS as residents (adjusted odds ratio [AOR]=1.14, 95% confidence interval [CI]: 0.70–1.87) while external migrants were 70% more likely to die from AIDS compared to residents prior to the introduction of ART (AOR=1.70, 95% CI: 1.06–2.73). After widespread availability of ART with the same adjustment factors, the odds of dying from AIDS were similar for internal migrants and residents (AOR=1.56, 95% CI: 0.80–3.04) and external migrants and residents (AOR=1.42, 95% CI: 0.76–2.66). Conclusions Availability of ART has reduced the number of HIV-infected migrants who would otherwise return home to die. This has reduced the burden on rural communities who had cared for the return external migrants.