Introduction Of Highly Active Antiretroviral Therapy Research Articles

Survival Among New Yorkers with HIV from 1981 to 2017: Inequities by Race/Ethnicity and Transmission Risk Persist into the Post-HAART Era.

Data on long-term survival among people with HIV (PWH) can inform the development of services for this population. An estimated 90,000 PWH live in New York City (NYC). Using HIV surveillance data, we conducted survival analysis of PWH diagnosed in NYC before and after introduction of highly active antiretroviral therapy (HAART) (pre-HAART cohort: 1981–1994; post-HAART cohort: 1995–2016). We created Kaplan–Meier curves by cohort and demographic factors, and Cox proportional hazards models to evaluate adjusted mortality risk by cohort. 205,584 adults and adolescents were diagnosed with HIV in NYC from 1981 to 2016, half each in the pre-HAART and post-HAART eras. The pre-HAART cohort had significantly poorer survival compared with the post-HAART cohort. Adjusted mortality risk in the pre-HAART cohort was almost threefold that in the post-HAART cohort (HR 2.84, 95% confidence interval [CI] 2.80–2.88). In sex- and risk-stratified models, men who have sex with men (MSM) had the largest difference in mortality risk pre-HAART versus post-HAART (HR 5.41, 95% CI 5.23–5.59). Race/ethnic disparities were pronounced among MSM, with Latino/Hispanic and White MSM having lower mortality than Black MSM. Females with heterosexual risk born outside the US had lower mortality than US-born women. The improvement in survival post-HAART was most pronounced for White people. Survival among persons diagnosed with HIV in NYC increased significantly since the introduction of HAART. However, among MSM and among PWH overall, improvements even post-HAART lagged for Black and Latino/Hispanic people, underscoring the need to address structural barriers, including racism, to achieve optimal health outcomes among people with HIV.

Assessing antiretroviral therapy success in HIV/AIDS morbidity and mortality trends in Brazil, 1990-2017: an interrupted time series study.

To describe the trends of HIV/AIDS metrics related to the burden of disease for Brazil between 1990 and 2017 we conducted a timeseries analysis for HIV/AIDS indicators by extracting data from the Global Burden of Disease study. We calculated traditional prevalence, incidence and mortality rates, the number of years lost by HIV-related deaths (YLL) and disability (YLD), and disability-adjusted life years (DALY). We estimated time series models and assessed the impact of highly active antiretroviral therapy (HAART) on the same indicators. In the set of disability-adjusted life years (DALY), the highest weight of its magnitude was due to YLL. There was a decline, especially after 1996, of DALY, mortality and YLL for HIV/AIDS. However, YLD, incidence, and prevalence increased over the same period. Also, the analysis of interrupted time series showed that the introduction of HAART into health policy had a significant impact on indicators, especially for DALY and YLL. We need to assess the quality of life of people living with HIV, especially among older adults. In addition, we need to focus on primary prevention, emphasizing methods to avoid infection and public policies should reflect this.

AN UNUSUAL CASE REPORT OF SARCOIDOSIS IN AN HIV PATIENT

SESSION TITLE: Fellows Diffuse Lung Disease Posters SESSION TYPE: Fellow Case Report Posters PRESENTED ON: October 18-21, 2020 INTRODUCTION: Coexistence of sarcoidosis in HIV patient is a rare phenomenon and has been attributed to the impairment of immune system that may interfere with granuloma formation.(1) We present an unusual case report of sarcoidosis in HIV patient. CASE PRESENTATION: 58-year-old female with history of HIV on highly active antiretroviral therapy (HAART) (CD4 count: 746 and viral load <20/ml) presented with incidental basilar pulmonary nodules during work up for abdominal pain. Subsequent CT chest showed multiple nodular densities in all lung fields with hilar and mediastinal lymphadenopathy. She is lifetime nonsmoker and had no respiratory symptoms. PET-CT showed avid mediastinal lymph nodes and bone lesions. Bronchoscopy with EBUS guided TBNA was inconclusive with negative fungal and mycobacterial cultures. Thereafter, IR guided bone biopsy was pursued which revealed non-caseating ” naked ” granulomas. Diagnosis of sarcoidosis was established after excluding other granulomatous inflammation, infection, and malignancy. No treatment was initiated as the patient was asymptomatic. DISCUSSION: The introduction of HAART has led to sustained increase in CD4+ T lymphocyte cells, consequently leading to the development of so called “immune restoration disease”. Sarcoidosis is an immune mediated systemic disease resulting from exaggerated cellular immune response to a variety of antigens or self-antigens, in which T lymphocyte triggering, proliferation, and activation is sustained by the CD4+ type 1 (TH1) lymphocytes. TH1 cells produce IFN-?, IL-2, and TNF leading to attraction and activation of mononuclear phagocytes that induce granuloma formation. These immunological features are not clearly exhibited in coexistent sarcoidosis/HIV infection. Before HAART therapy, reports indicated a prevalence of lymphocytic alveolitis due to an increase in CD8 cells, with a very low CD4/CD8 ratio. In a retrospective cohort study, it was concluded that the development of sarcoidosis appears to depend on preservation or restoration of peripheral CD4+ lymphocyte count exceeding 200 cells/µl compared to alternative specific etiologies of granulomatous inflammation.(2) It is worth noting that in all reported clinical cases, sarcoidosis developed several months after HAART therapy compared to acute onset of other typical immune reconstitution syndromes.(1) The need to initiate steroid therapy, as in other immune reconstitution granulomatous processes, remains controversial and is based on patient’s symptoms. CONCLUSIONS: Our case highlights the importance of considering “immune restoration disease” including sarcoidosis and other granulomatous inflammation/infection in HIV patient on HAART therapy with abnormal chest imaging in addition to slow growing lymphoproliferative disorder. Reference #1: Sarcoidosis and HIV infection: a case report and a review of the literature, Postgrad Med J. 2003;79:535–38 Reference #2: Sarcoidosis Following HIV Infection, Chest 2003 Sep; 124 (3), 929–935 DISCLOSURES: No relevant relationships by Moises Cossio, source=Web Response No relevant relationships by Domingo Franco-Palacios, source=Web Response No relevant relationships by Kushagra Gupta, source=Web Response No relevant relationships by Shahzad Hussain, source=Web Response No relevant relationships by Venkateswara Kollipara, source=Web Response No relevant relationships by Toribiong Uchel, source=Web Response

SUN-LB8 Cross Sex Hormone Therapy and Breast Cancer in Transgender Male to Female

Case Presentation: We are presenting a 53-year-old Male to Female transgender patient who has been receiving estradiol valerate injections every 14 days for 13 years and had no gender surgical reassignment procedures or breast implants. Her past medical history was significant for HIV on Highly Active Anti-retroviral therapy (HAART). No family history of breast cancer. She presented with severe bilateral left elbow, lower back and bilateral chest pain for 3 days. Chest CT done to exclude pulmonary embolism showed an incidental 4 cm right breast mass. Enlarged lymph nodes in the right axilla, scattered lytic lesions in the axial skeleton and the left humeral head were also noted. Breast exam was not performed until the significant findings were seen in CT chest and it showed a palpable hard-circumscribed subareolar right breast mass without skin changes. Ultrasound guided biopsy of the breast mass confirmed invasive ductal carcinoma of the breast. The patient had no previous mammogram testing. Oncology work-up was positive for estrogen and progesterone receptors but negative for human epidermal growth factor-2 receptor. The patient opted to return home in another state to seek treatment and further oncological workup but subsequently lost follow up. Discussion: Male to female breast cancer was first recognized in 1968. However, risk factors for this condition remain unclear. In our patient, long-term use of Cross-sex Hormone Therapy (CHT) represented a major risk factor for breast cancer. In a Dutch study, the risk of breast cancer increased during a relatively short duration of CHT and the cancer characteristics reassembled female pattern. As theoretically implicated, increased estrogen exposure in males may have a role in the proliferation of neoplastic breast epithelium. There are growing evidence to support increasing rates of breast cancer in HIV-positive population, making it a potential risk factor as well. Loss of CXCR-4 protective effect promoted by HIV virus may explain the increase in the breast cancer incidence after the introduction of HAART. In general, routine screening for breast cancer in MTF transgender population remains controversial. The Endocrine Society Clinical Practice guidelines suggest that MTF transsexual individuals who have no known increased risk of breast cancer should follow screening guidelines for biological women. While the Canadian Cancer Society recommends screening mammography every two years for MTF individuals taking CHT for more than 5 years and those between the ages of 50 and 69 years. Conclusion:Breast cancer in MTF transgender patients is associated with receiving CHT and represents diagnostic and treatment challenge. More research is need to comment on routine breast cancer screening in this population. However, physicians should remember performing a regular breast exam in MTF individuals looking for a possible mass.

Human immunodeficiency virus and intraocular inflammation in the era of highly active anti retroviral therapy - An update.

Intraocular inflammation in patients with human immunodeficiency virus (HIV) infection is commonly due to infectious uveitis. Ocular lesions due to opportunistic infections (OI) are the most common and have been described extensively in the pre highly active antiretroviral therapy (HAART) era. Many eye lesions were classified as acquired immunodeficiency syndrome (AIDS) defining illnesses. HAART-associated improvement in immunity of the individual has changed the pattern of incidence of these hitherto reported known lesions leading to a marked reduction in the occurrence of ocular OI. Newer ocular lesions and newer ocular manifestations of known agents have been noted. Immune recovery uveitis (IRU), the new menace, which occurs as part of immune recovery inflammatory syndrome (IRIS) in the eye, can present with significant ocular inflammation and can pose a diagnostic and therapeutic challenge. Balancing the treatment of inflammation with the risk of reactivation of OI is a task by itself. Ocular involvement in the HAART era can be due to the adverse effects of some systemic drugs used in the management of HIV/AIDS. Drug-associated retinal toxicity and other ocular side effects are being increasingly reported. In this review, we discuss the ocular manifestations in HIV patients and its varied presentations following the introduction of HAART, drug-associated lesions, and the current treatment guidelines.

A Review on Quinoline Derived Scaffolds as Anti-HIV Agents.

After restricting the proliferation of CD4+T cells, Human Immunodeficiency Virus (HIV), infection persists at a very fast rate causing Acquired Immunodeficiency Syndrome (AIDS). This demands the vigorous need of suitable anti-HIV agents, as existing medicines do not provide a complete cure and exhibit drawbacks like toxicities, drug resistance, side-effects, etc. Even the introduction of Highly Active Antiretroviral Therapy (HAART) failed to combat HIV/AIDS completely. The major breakthrough in anti-HIV discovery was marked with the discovery of raltegravir in 2007, the first integrase (IN) inhibitor. Thereafter, the discovery of elvitegravir, a quinolone derivative emerged as the potent HIV-IN inhibitor. Though many more classes of different drugs that act as anti-HIV have been identified, some of which are under clinical trials, but the recent serious focus is still laid on quinoline and its analogues. In this review, we have covered all the quinoline-based derivatives that inhibit various targets and are potential anti-HIV agents in various phases of the drug discovery.

Oral manifestations of human immunodeficiency virus/acquired immunodeficiency syndrome and their correlation with HAART and CD4+ T-cell count. A systematic review.

Event Abstract Back to Event Oral manifestations of human immunodeficiency virus/acquired immunodeficiency syndrome and their correlation with HAART and CD4+ T-cell count. A systematic review. Luca Oberti1*, Federica Gabrione1, Annalisa Palmieri2, Alberta Lucchese3, Francesco Carinci2 and Dorina Lauritano1 1 Università degli studi di Milano Bicocca, Department of Medicine and Surgery, Italy 2 University of Ferrara, Department of Morphology, Experimental Medicine and Surgery, Italy 3 Università degli Studi della Campania 'Luigi Vanvitelli' Naples, Multidisciplinary Department of Medical-Surgical and Dental Specialties, Italy Aim. This review aims to address oral manifestations of human immunodeficiency virus/acquired immunodeficiency syndrome and their correlation with Highly Active Antiretroviral Therapy (HAART) and CD4+ T-cell count. Materials and Methods. We reviewed 35 out of 179 articles on Medline sorted by the relevance option. The main purpose of this paper is to up-date of the main HIV-related oral manifestations and their correlation with HAART and CD4+ T-cell count. We considered 179 bibliographic references, from which we eliminated all case reports, all observational studies, and all the basic researches duplicating findings already published, with the aim of producing a review up-to-date as possible, and succinctly set out an overview of the rationale of HIV-related oral manifestations and their correlation with HAART and CD4+ T-cell count correlation between. We limited our review to 30 articles. Results. Oral candidiasis, oral hairy leukoplakia, Kaposi's sarcoma, and HSV infection are the lesions which have seen the major drop in their incidence after the HAART introduction. Furthermore, the increase in CD4+ T-cell count is not significantly correlated to the incidence decrease of every kind of oral lesions, but it is statistically significant only in relation to oral candidiasis (p-value < 0.001). Discussion. Oral lesions are important signs of immunodepression and with the introduction of HAART their incidence is strongly decreased, in particular in urban areas. Nevertheless, developing countries still have a high prevalence of these manifestations, because of the persistence of many risk factor, like the difficult in accessing to treatment, the poor oral hygiene, the low socioeconomic status and the late diagnosis. Especially in these areas of the world the simple evaluation of the oral lesions, of their condition and of their progression could represent a valid prognostic tool and could also allow to intercept patients still not diagnosed.

Racial disparities in incidence & survival of Kaposi's sarcoma in the United States.

Background & objectives:In the United States (US), Kaposi's sarcoma (KS) is usually seen in the patients affected by human immunodeficiency virus (HIV). The racial differences in the incidence rates and survival of patients with KS have been reported in the US. We undertook this study to analyse the disparities in the race-specific incidence rate and survival of KS patients of two different races in the US based on SEER (Surveillance, Epidemiology and End Results) database.Methods:Data on KS patients of African-American (AA) and non-Hispanic White (NHW) races who were diagnosed during 1973-2013 were extracted from SEER database to estimate the incidence rates and survival of KS patients.Results:A total of 18,388 NHWs and 3,455 AAs were diagnosed with KS. The age-adjusted incidence rate (AAIR) of KS in patients aged 20-44 yr was 3.8 times higher in AAs than in NHWs. The decline in AAIR of KS among NHWs started during 1989-1994 and preceded decline in the AAIR of AAs. After introduction of highly active antiretroviral therapy (HAART), the incidence continued to decline, but the decrease in the AAIR in AAs [annual percentage change (APC): −6.2; 95% confidence interval (CI): −8.8 to −3.5] was slower than that in NHWs (APC: −10.9; 95% CI: −12.6 to −9.1). The hazard ratio for all-cause mortality in KS patients of the AA race increased from 1.1 (95% CI: 1-1.2) in 1981-1995 to 1.55 (95% CI: 1.4-1.7) in 1996-2013 as compared to those of the NHW race.Interpretation & conclusions:Several significant racial disparities that emerged after HAART introduction in the incidence and survival of KS patients continued to persist, despite improvement in care of patients with HIV. Further studies need to be done to find out the underlying factors leading to these disparities.

Highly active antiretroviral therapy increases fibrinolytic and protein activity in pregnant women

BACKGROUNDVarious studies have examined optimal methods for Prevention of Mother to Child Transmission (PMTCT) of human immunodeficiency virus (HIV) and subsequent outcome of response to highly active antiretroviral therapy (HAART) as well as the impact of pregnancy on outcomes of HIV in the Pre-HAART era. Little is known of the impact of pregnancy in response to HAART in Africa. This study is aimed to evaluate euglobulin lysis time (ELT), protein C and protein S in HIV-positive pregnant women on HAART. METHODSThis was a cross-sectional study comprised of 150 participants attending Ante-Natal Clinic (ANC) in Central Hospital, Benin City. Pregnant women on HAART (Test subjects) (n=50, mean age 34 years), 50 pregnant newly diagnosed HIV-positive women that had not yet commenced HAART (n=50, mean age 31 years) and 50 pregnant HIV-negative women (n=50, mean age 30 years) which served as controls. The ELT was determined by methods described by Bain, protein C and protein S were determined using Enzyme Linked Immunosorbent Assay (ELISA). RESULTSThere was a significant increase in ELT in both pregnant women on HAART and not on HAART) when compared to HIV-negative pregnant women (p&lt;0.05). There was a significant decrease in protein C in test subjects when compared with controls (p&lt;0.05) and protein S increased significantly in HIV-positive pregnant women on HAART when compared to those not on HAART and HIV-negative pregnant women (p&lt;0.05). CONCLUSIONThere are changes in ELT, protein C and protein S parameters with the introduction of HAART in pregnancy.

The world-wide incidence of Kaposi's sarcoma in the HIV/AIDS era.

Kaposi's sarcoma (KS) is a multicentric angioproliferative cancer of endothelial origin typically occurring in the context of immunosuppression or immunodeficiency. Consequently, KS is one of the most common cancers in HIV-infected individuals and frequently occurs among transplant recipients. Nevertheless, its incidence in different populations is not well understood. We searched online databases for publications on KS incidence. A random-effect meta-analysis was performed to combine the KS incidences and incidence rate ratios (IRRs) for associated risk factors. Seventy-six eligible studies representing 71 time periods were included. For HIV-infected people, the overall KS incidence was 481.54 per 100000 person-years with a 95% confidential interval (CI) of 342.36-677.32 per 100000 person-years. HIV-infected men who have sex with men (MSM) had the highest incidence of KS (1397.11 per 100000 person-years; 95% CI 870.55-2242.18 per 100000 person-years). The incidence of KS was significantly lower in female than in male individuals (IRR 3.09; 95% CI 1.70-5.62). People receiving highly active antiretroviral therapy (HAART) had a lower incidence compared with people who had never received HAART (IRR 6.57; 95% CI 1.91-24.69). The incidence of KS was 68.59 (95% CI 31.39-149.86) per 100000 person-years in transplant recipients, 52.94 (95% CI 39.90-70.20) per 100000 person-years in children with HIV infection, and 1.53 (95% CI 0.33-7.08) per 100000 person-years in the general population. Globally, a relatively high incidence of KS was found among HIV-seropositive people and, in particular, in HIV-infected MSM. The introduction of HAART has largely prevented the development of KS, but it has not entirely removed the challenge of KS. In Africa, in particular, KS imposes a very heavy disease burden, which can mainly be attributed to the high prevalence of KS-associated herpesvirus and poor access to HAART.

Plasma L-Carnitine and L-Lysine Concentrations in HIV-Infected Patients.

Background:Virus infections are associated with significant alterations in host cells amino acids profiles that support biosynthetic demands necessary for production of viral progeny. Amino acids play an important role in the pathogenesis of all virus-related infections both as basic substrates for protein synthesis and as regulators in many metabolic pathways.Objective:Our aim was to determine the changes in plasma L-carnitine levels and its amino acid precursor (L-lysine) in HIV-infected patients.Methods:We performed a case-control study of 430 HIV-1 infected males (non-vegetarians) without any restriction in the nourishment, before highly active antiretroviral therapy (HAART) and 125 HIV-1 subjects after the introduction of HAART who were periodically monitored in the Municipal Center of HIV/AIDS prophylaxis, Surgut, Russian FederationResults:The plasma total (TC) and free (FC) L-carnitine concentrations markedly decreased with the clinical stages of HIV infection. The mean plasma TC, FC and L-lysine levels were significantly lower in asymptomatic stage (A) and advanced CDC stages (B, C) HIV-infected patients compared with our reference values. The total and free L-carnitine and its amino acid precursor concentrations mild increased in HIV-infected subjects after the introduction of HAART.Our data revealed that L-lysine amino acid and its derivative (TC) levels were negatively correlated with viral load and inversely with CD4 count lymphocytes in the total cohort.Conclusion:The study results show that there was evidence for an association between plasma L-carnitine, L-lysine and HIV-1 RNA levels, immunological markers and clinical stages of HIV infection. The obtained data indicate that level changes of these host essential nutritional elements can play an important role in the HIV life cycle. These findings are important for understanding the pathophysiology of HIV infection and must be considered in further research for the development of new approaches in the treatment of the disease.

Incidence, clinical presentation, and outcome of HIV-1-associated cryptococcal meningitis during the highly active antiretroviral therapy era: a nationwide cohort study.

BackgroundHuman immunodeficiency virus (HIV) infection with advanced immunosuppression predisposes to cryptococcal meningitis (CM). We describe the incidence, clinical presentation, and outcome of CM in HIV-infected individuals during the highly active antiretroviral therapy (HAART) era.MethodsA nationwide, population-based cohort of HIV-infected individuals was used to estimate incidence and mortality of CM including risk factors. A description of neurological symptoms of CM at presentation and follow-up in the study period 1995–2014 was included in this study.ResultsAmong 6,351 HIV-infected individuals, 40 were diagnosed with CM. The incidence rates were 3.7, 1.8, and 0.3 per 1000 person-years at risk in 1995–1996, 1997–1999, and 2000–2014, respectively. Initiation of HAART was associated with decreased risk of acquiring CM [incidence rate ratio (IRR), 0.1 (95% CI, 0.05–0.22)]. African origin was associated with increased risk of CM [IRR, 2.05 (95% CI, 1.00–4.20)]. The main signs and symptoms at presentation were headache, cognitive deficits, fever, neck stiffness, nausea, and vomiting. All individuals diagnosed with CM had a CD4+ cell count <200 cells/µl [median 26; interquartile range (IQR), 10–50)]. Overall, mortality following CM was high and mortality in the first 4 months has not changed substantially over time. However, individuals who survived generally had a favorable prognosis, with 86% (18/21) returning to the pre-CM level of activity.ConclusionThe incidence of HIV-associated CM has decreased substantially after the introduction of HAART. To further decrease CM incidence and associated mortality, early HIV diagnosis and HAART initiation seems crucial.

Mother-to-child HIV transmissions in Israel, 1985-2011.

Mother-to-child transmission (MTCT) is the leading cause of paediatric HIV-infection in Israel. This study aimed to assess MTCT rates and analyse temporal changes in relation to highly active antiretroviral therapy (HAART) introduction in 1996. This historical prospective study included all HIV-infected women who delivered in Israel between 1988 and 2011. Demographic, clinical, laboratory and therapy characteristics were compared between HIV-infected newborns with all others, and between infants born before and after 1996. Of all 796 infants born in Israel to HIV-infected women, 25 (3·1%) were infected. MTCT rates decreased significantly after HAART introduction compared with infants who were born before 1996 (16·3% vs. 1·7%). Mothers who infected vertically were more likely to be younger, Ethiopian-born, delivered trans-vaginally, not treated with HAART during pregnancy/labour and delivered before 1996 compared with mothers who did not transmit the HIV to their neonates. Newborns who did not receive antiretroviral therapy postpartum were more commonly HIV-infected and their mortality rate was higher. In conclusion, HAART during pregnancy/labour decreased MTCT significantly. Most MTCT in Israel was recorded among Ethiopian migrants, yet, in decreasing rates. Continuous efforts should be employed to encourage early HIV testing and allow effective HAART to pregnant women who belong to a key risk-group.

Trends in the incidence of AIDS-defining and non-AIDS-defining cancers in people living with AIDS: a population-based study from São Paulo, Brazil.

People living with AIDS are at increased risk of developing certain cancers. Since the introduction of the highly active antiretroviral therapy (HAART), the incidence of AIDS-defining cancers (ADCs) has decreased in high-income countries. The objective of this study was to analyse trends in ADCs and non-AIDS-defining cancers (NADCs) in HIV-positive people with a diagnosis of AIDS, in comparison to the general population, in São Paulo, Brazil. A probabilistic record linkage between the 'Population-based Cancer Registry of São Paulo' and the AIDS notification database (SINAN) was conducted. Cancer trends were assessed by annual per cent change (APC). In people with AIDS, 2074 cancers were diagnosed. Among men with AIDS, the most frequent cancer was Kaposi's sarcoma (469; 31.1%), followed by non-Hodgkin lymphoma (NHL; 304; 20.1%). A decline was seen for ADCs (APC = -14.1%). All NADCs have increased (APC = 7.4%/year) significantly since the mid-2000s driven by the significant upward trends of anal (APC = 24.6%/year) and lung cancers (APC = 15.9%/year). In contrast, in men from the general population, decreasing trends were observed for these cancers. For women with AIDS, the most frequent cancer was cervical (114; 20.2%), followed by NHL (96; 17.0%). Significant declining trends were seen for both ADCs (APC = -15.6%/year) and all NADCs (APC = -15.8%/year), a comparable pattern to that found for the general female population. Trends in cancers among people with AIDS in São Paulo showed similar patterns to those found in developed countries. Although ADCs have significantly decreased, probably due to the introduction of HAART, NADCs in men have shown an opposite upward trend.

PREVALENCE OF ADVERSE DRUG REACTIONS AMONG HIV/AIDS PATIENTS ON HAART IN UNIVERSITY OF MAIDUGURI TEACHING HOSPITAL (UMTH), NIGERIA: A FOUR-YEAR RETROSPECTIVE STUDY

BackgroundCurrent evidence on highly active antiretroviral therapy (HAART) indicates that each person will have to take the drugs for life [1]. Since 2000, the prevalence of HIV in Nigeria has...

Toxoplasmic encephalitis relapse rates with pyrimethamine-based therapy: systematic review and meta-analysis

Toxoplasmic encephalitis (TE) is caused by Toxoplasma gondii infection and can be a life-threatening disease in immunocompromised patients. This study evaluated the rate of relapse associated with pyrimethamine-based maintenance therapy (i.e. secondary prophylaxis) in patients with human immunodeficiency virus (HIV) or AIDs treated prior to and after the common use (i.e. 1996) of highly active antiretroviral therapy (HAART) (pre-HAART and post-HAART, respectively). PubMed, Google Scholar, and Cochrane databases were searched to 6 June 2016 using search terms: pyrimethamine, Daraprim, Fansidar, Metakelfin, Fansimef, 5-(4-chlorophenyl)-6-ethyl-2,4-pyrimidinediamine, encephalitis, cerebral, toxoplasmosis, toxoplasmic, and gondii. Single-arm cohort, retrospective, and randomized studies were included. Twenty-six studies with 1,596 patients were included in the analysis; twenty pre-HAART (n = 1,228) studies and six post-HAART (n = 368) were performed. Pooled proportions test for pyrimethamine-based therapy from pre-HAART studies indicated a relapse rate of 19.2% and 18.9% from the fixed-effects and random-effects models, respectively. The relapse rate in the post-HAART studies was 11.1% (fixed and random effects). Continuous therapy was suggestive of lower incidence of relapse compared with intermittent therapy in the pre-HAART era (range, 18.7 to 17.3% vs. 20.9 to 25.6%, respectively). These findings indicate that the likelihood of relapse associated with pyrimethamine-based therepy in patients with HIV and TE decreased after the introduction of HAART to approximately 11%. The findings have important implications as relapse may affect a patient’s disease severity and prognosis, increase utilization of health care resources, and result in additional health care expenditure.

A historical review of HIV prevention and care initiatives in British Columbia, Canada: 1996-2015.

Introduction: British Columbia has made significant progress in the treatment and prevention of HIV since 1996, when Highly Active Antiretroviral Therapy (HAART) became available. However, we currently lack a historical summary of HIV prevention and care interventions implemented in the province since the introduction of HAART and how they have shaped the HIV epidemic. Guided by a socio-ecological framework, we present a historical review of biomedical and health services, community and structural interventions implemented in British Columbia from 1996–2015 to prevent HIV transmission or otherwise enhance the cascade of HIV care. Methods: We constructed a historical timeline of HIV interventions implemented in BC between 1996 and 2015 by reviewing publicly available reports, guidelines and other documents from provincial health agencies, community organizations and AIDS service organizations, and by conducting searches of peer-reviewed literature through PubMed and Ovid MEDLINE. We collected further programmatic information by administering a data collection form to representatives from BC’s regional health authorities and an umbrella agency representing 45 AIDS Service organizations. Using linked population-level health administrative data, we identified key phases of the HIV epidemic in British Columbia, as characterized by distinct changes in HIV incidence, HAART uptake and the provincial HIV response. Results and Discussion: In total, we identified 175 HIV prevention and care interventions implemented in BC from 1996 to 2015. We identify and describe four phases in BC’s response to HIV/AIDS: the early HAART phase (1996–1999); the harm reduction and health service scale-up phase (2000–2005); the early Treatment as Prevention phase (2006–2009); and the STOP HIV/AIDS phase (2010-present). In doing so, we provide an overview of British Columbia’s universal and centralized HIV treatment system and detail the role of community-based and provincial stakeholders in advancing innovative prevention and harm reduction approaches, as well as “seek, test, treat and retain” strategies. Conclusions: The review provides valuable insight into British Columbia’s HIV response, highlights emerging priorities, and may inform future efforts to evaluate the causal impact of interventions.

Cancer incidence and all-cause mortality in HIV-positive patients in Northeastern Algeria before and during the era of highly active antiretroviral therapy.

To assess cancer incidence and all-cause mortality trends in HIV-positive patients in Algeria before and during the highly active antiretroviral therapy (HAART) era. Cross-sectional study. We used hospital-based data of patients with HIV/AIDS between January 1988 and December 2010. Cancer incidence, standardized mortality ratios (SMRs), risk of death, and proportion of HIV-positive patients treated before and during the HAART era were calculated. The joinpoint model was used to assess the magnitude of changes in SMRs. In 1988-2010, 156 patients were diagnosed as HIV-positive. During pre-HAART era, Kaposi sarcoma (KS) incidence was 5%. After the introduction of HAART, KS incidence decreased to 2%. No other AIDS-related cancer was diagnosed during the study. One-third died (52/156), of which 83.6% died in the same year as or in the year after HIV diagnosis; median age at death (interquartile range) was 34.5 (11.8) years. Yearly risk of death declined from 100% in 1998 to 8% in 2010; percentage of patients treated with HAART increased from 13% in 1998 to >80% after 2002. Overall SMR decreased from 200.2 (95% confidence interval [95% CI], 123.2-325.2) before the HAART era to 91.4 (95% CI, 66.0-126.6) thereafter. From 2003, yearly SMRs decreased significantly by 66.1% (P < 0.05) until 2006 but not thereafter. Since 1998, the proportion of HIV-positive patients treated with HAART increased, reaching 84% in 2010, all-cause mortality decreased, and cancer remained rare. However, almost all patients who died during the study seemed to be diagnosed at a late stage of the disease, emphasizing the need for earlier diagnosis of HIV in Algeria.

AIDS-Related Kaposi’s sarcoma and Associated Immune Reconstitution Inflammatory Syndrome

Kaposi's sarcoma (KS) associated with AIDS (AIDS-KS) is the most prevalent neoplasia among patients with AIDS. Its incidence has decreased dramatically in recent years due to the widespread use of highly active antiretroviral therapy (HAART). Paradoxically, in relation to the introduction of HAART it may occur a worsening or development of AIDS-KS despite the improvement of the immune function. This unusual process is called immune reconstitution syndrome in Kaposi's sarcoma (IRIS-KS) and should not be confused with a failure of HAART. Early identification of AIDS-KS and previous or combined use of chemotherapy with HAART appears to be the most effective treatment to prevent the consequences of IRIS-SK.

Risk of Severe Non AIDS Events Is Increased among Patients Unable to Increase their CD4+ T-Cell Counts >200+/μl Despite Effective HAART.

BackgroundImmunological non-response (INR) despite virological suppression is associated with AIDS-defining events/death (ADE). Little is known about its association with serious non-AIDS-defining events (nADE).MethodsPatients highly-active antiretroviral therapy (HAART) with <200 CD4+/μl and achieving HIV-RNA <50 copies/ml within 12 (±3) months were categorized as INR if CD4+ T-cell count at year 1 was <200/μl. Predictors of nADE (malignancies, severe infections, renal failure—ie, estimated glomerular filtration rate <30 ml/min, cardiovascular events and liver decompensation) were assessed using multivariable Cox models. Follow-up was right-censored in case of HAART discontinuation or confirmed HIV-RNA>50.Results1221 patients were observed for a median of 3 (IQR: 1.3-6.1) years. Pre-HAART CD4+ were 77/μl (IQR: 28-142) and 56% of patients had experienced an ADE. After 1 year, CD4+ increased to 286 (IQR: 197-387), but 26.1% of patients were INR. Thereafter, 86 nADE (30.2% malignancies, 27.9% infectious, 17.4% renal, 17.4% cardiovascular, 7% hepatic) were observed, accounting for an incidence of 1.83 events (95%CI: 1.73-2.61) per 100 PYFU. After adjusting for measurable confounders, INR had a significantly greater risk of nADE (HR 1.65; 95%CI: 1.06-2.56). Older age (per year, HR 1.03; 95%CI: 1.01-1.05), hepatitis C co-infection (HR 2.09; 95%CI: 1.19-3.7), a history of previous nADE (HR 2.16; 95%CI: 1.06-4.4) and the occurrence of ADE during the follow-up (HR 2.2; 95%CI: 1.15-4.21) were other independent predictors of newly diagnosed nADE.ConclusionsPatients failing to restore CD4+ to >200 cells/μl run a greater risk of serious nADE, which is intertwined or predicted by AIDS progression. Improved management of this fragile population and innovative therapy able to induce immune-reconstitution are urgently needed. Also, our results strengthen the importance of earlier diagnosis and HAART introduction.