Leprosy and HIV coinfection: a critical approach

An increase in leprosy among HIV patients, similar to that observed in patients with TB, was expected approximately 20 years ago. Studies conducted in the 1990s together with those reported recently seemed to indicate that a coinfection with HIV did not alter the incidence and the clinical spectrum of leprosy and that each disease progressed as a single infection. By contrast, in countries with a high seroprevalence of HIV, TB was noted to increase. Explanations may be provided by the differences in the incubation time, the biology and toxicity of Mycobacterium leprae and Mycobacterium tuberculosis. After the introduction of HAART the leprosy-HIV coinfection manifested itself as an immune reconstitution inflammatory syndrome (IRIS), typically as paucibacillary leprosy with type 1 leprosy reaction. The incidence of leprosy in HIV-infected patients has never been properly investigated. IRIS-leprosy is probably underestimated and recent data showed that the incidence of leprosy in HIV patients under HAART was higher than previously thought.     

Immune reconstitution inflammatory syndrome in a large multicenter cohort study: case definition and comparability

Evaluation of: Novak RM, Richardson JT, Buchacz K et al.; HIV Outpatient Study (HOPS) Investigators. Immune reconstitution inflammatory syndrome: incidence and implications for mortality. AIDS 26(6), 721–730 (2012).

This study was nested within the HIV Outpatient Study cohort and investigated the incidence and risk factors for immune reconstitution inflammatory syndrome (IRIS) and the impact of IRIS on mortality. IRIS was defined as a new type B or C AIDS-defining condition or one of a range of mucocutaneous or autoimmune conditions diagnosed within 180 days of starting a new combination antiretroviral therapy regimen, provided there was a documented HIV viral load or CD4 response. IRIS occurred in 10.6% of the 2610 patients. Risk factors independently associated with IRIS included high HIV viral load and low CD4 count. IRIS related to type B or C AIDS-defining conditions was associated with subsequent mortality. Deaths among IRIS cases occurred over 3 years (median) after the IRIS event, making it unlikely that these deaths were directly attributable to IRIS. The IRIS case definition used has important differences when compared with previously published IRIS case definitions thereby affecting comparability of these findings, but this was a pragmatic definition for a large multicenter cohort study utilizing a central database.     

HIV and TB coinfection: using adjusted doses of lopinavir/ritonavir with rifampin

Evaluation of: Decloedt E, McIlleron H, Smith P, Merry C, Orrell C, Maartens G. Pharmacokinetics of lopinavir in HIV-infected adults receiving rifampin with adjusted doses of lopinavir–ritonavir tablets. Antimicrob. Agents Chemother. 55(7), 3195–3200 (2011).

HIV and TB coinfection is a widespread problem, especially in resource-limited settings. Interactions between drugs metabolized through cytochrome P450 enzymes and p-glycoprotein efflux pump, such as rifampin and HIV protease inhibitors, complicate the management of both pathologies when they coexist. The article by Decloedt et al. elegantly assesses the pharmacokinetics of three twice-daily escalating doses of lopinavir/ritonavir (400/100 mg, 600/150 mg and 800/200 mg), together with 600 mg daily of rifampin in 21 black African HIV-infected patients without TB. The article also reports safety, tolerability and virological outcomes after 3 weeks. Doubling lopinavir/ritonavir dose overcomes rifampin induction effect with good tolerability. However, concerns arise regarding the real interactions, tolerability and virological efficacy in HIV-TB-coinfected patients, which may differ from healthy volunteers or HIV-infected patients without TB.     

Coccidioidomycosis of cervical lymph nodes in an HIV-infected patient with immunologic reconstitution on potent HAART: a rare observation in a nonendemic area

Coccidioidomycosis is caused by the dimorphic fungus Coccidioides immitis, which is endemic in southwestern United States. We report a case of coccidioidomycosis of cervical lymph nodes that occurred early after the introduction of highly active antiretroviral therapy during the phase of immune system recovery, demonstrating a rare disease in a nonendemic area.     

Evidence base for using corticosteroids to treat HIV-associated immune reconstitution syndrome

Most of the evidence supporting the use of corticosteroids (steroids) for immune reconstitution syndrome (IRS) comes from case reports or retrospective series and is of low quality. However, when steroids are used, they have usually been associated with clinical improvement or resolution of IRS. Except in the case of hepatitis B- or C-associated IRS, there have been no reports of worsening of the IRS or adverse outcome due to steroid use. After ruling out other conditions which can mimic IRS, clinicians should strongly consider steroids when managing IRS associated with mycobacterial or fungal pathogens when there is severe disease, or when other measures have failed.     

Cryptococcal meningitis with atypical paradoxical inflammatory reactions after antifungal treatment in acquired immune deficiency syndrome: A case report

Cryptococcal meningitis (CM) is a life-threatening disease that primarily affects patients with human immunodeficiency virus (HIV). Antifungal therapy with antiretroviral treatment (ART) usually leads to the clinical remission of CM; however, in some cases, these treatments exacerbate intracranial inflammation because of paradoxical inflammatory reaction or immune reconstitution inflammatory syndrome (IRIS). Here we report two CM cases that presented atypical clinical courses attributed to paradoxical inflammatory reactions.The first case was a 43-year-old man with headache and vertigo diagnosed with CM and HIV. The patient's CM not only was refractory to the antifungal combination therapy of liposomal amphotericin B (L-AMB) and fluconazole (FLCZ) but suddenly worsened because of a paradoxical inflammatory reaction after 18 days of treatment. He passed away from brain herniation on day 23. The second case was a 43-year-old man diagnosed with CM and HIV. After receiving antifungal therapy and ART, the patient's status was stable for more than 3 years with undetectable HIV-RNA. He suddenly presented with brain inflammation and was diagnosed with IRIS due to CM (CM-IRIS). His brain lesions were migratory and refractory to various antifungal therapies such as L-AMB, FLCZ, flucytosine, and intrathecal amphotericin B. Although the cryptococcal antigen in the patient's cerebrospinal fluid gradually diminished after continuous antifungal therapies, his cognitive function declined, and right hemiparesis persisted.These two cases of CM presented atypical clinical courses, presumably because of paradoxical inflammatory reactions. It should be noted that the onset of CM-IRIS may not necessarily depend on the timing of ART initiation.     

Recent advances in AIDS-related cryptococcal meningitis treatment with an emphasis on resource limited settings

Introduction: Recent advances in the treatment and prevention of cryptococcal meningitis have the potential to decrease AIDS-related deaths.

Areas covered: Targeted screening for asymptomatic cryptococcal antigenemia in persons with AIDS is a cost effective method for reducing early mortality in patients on antiretroviral therapy. For persons with symptomatic cryptococcal meningitis, optimal initial management with amphotericin and flucytosine improves survival compared to alternative therapies; however, amphotsericin is difficult to administer and flucytosine has not been available in middle or low income countries, where cryptococcal meningitis is most prevalent.

Expert commentary: Improved care for cryptococcal meningitis patients in resource-limited settings is possible, and new treatment possibilities are emerging.     

Rehabilitation outcome of progressive multifocal leukoencephalopathy in HIV-positive patients: a report of two cases

Purpose: To describe the rehabilitation treatment and outcome of progressive multifocal leukoencephalopathy (PML) in the context of Human Immunodeficiency Virus (HIV).

Method: The medical history of two HIV-positive patients with PML was reviewed; information on their neurological impairments, rehabilitation treatment and outcome was gathered.

Results: The patients, a 47-year-old married man and a 34-year-old single man, both suffered from dense right hemiplegia and motor aphasia. Their rehabilitation course was delayed and prolonged: they were suitable for intensive multidisciplinary rehabilitation only 8 months or more after the initial presentation. Their treatment in outpatient rehabilitation daycare three times a week, that lasted 7 months on average, resulted in slow and steady functional improvement. At the end of the rehabilitation treatment, both patients were living at home, able to express themselves, and able to walk independently with an assistive device. They remained with moderate disability (modified Rankin scale of 3).

Conclusion: PML patients require prolonged multidisciplinary rehabilitation treatment; however, considerable progress can be achieved.

• Implications for Rehabilitation

• Progressive multifocal leukoencephalopathy (PML) is a disabling disease occurring in particular in the context of Human Immunodeficiency Virus (HIV).

• Presently a growing number of HIV-positive PML patients eventually survive the disease and remain with severe neurological impairments.

• PML patients require prolonged multidisciplinary rehabilitation treatment, and considerable progress can be achieved.

     

人免疫缺陷病毒感染的实验室检测及进展

实验室检测是诊断人免疫缺陷病毒感染的主要手段,可以从基因水平、蛋白水平和细胞水平进行检测.本文对HIV感染诊断的各种方法及进展作一概述.     

Moral distress among Ugandan nurses providing HIV care: A critical ethnography

Background

The phenomenon of moral distress among nurses has been described in a variety of high-income countries and practice settings. Defined as the biopsychosocial, cognitive, and behavioural effects experienced by clinicians when their values are compromised by internal or external constraints, it results from the inability to provide the desired care to patients. No research has been reported that addresses moral distress in severely resource-challenged regions such as sub-Saharan Africa.

Aim

To describe the manifestation and impact of moral distress as it was experienced by Ugandan nurses who provided care to HIV-infected or -affected people.

Method

A critical ethnography was conducted with 24 acute care and public health nurses at a large referral centre in Uganda. Data were collected through interviews, observation, and focus group discussions.

Results

Participants described their passion for nursing and commitment to patients. They experienced moral distress when a lack of resources put patients’ wellbeing at risk. The trauma imposed by systemic challenges on the nursing profession was acknowledged, as was the perception that the public blamed nurses for poor patient outcomes. However, participants were determined to serve to the best of their abilities and to take satisfaction from any contributions they were able to make. They cited the importance of education in the development of their capacity to provide care with a positive attitude, and demonstrated a collective resilience as they discussed strategies for addressing issues that affected them and their colleagues.

Conclusions

The experience of moral distress among nurses in Uganda differed somewhat from the experience of nurses in high-income countries. Constraints imposed by the inability to implement skills and knowledge to their fullest extent, as well as a lack of resources and infrastructure may result in the omission of care for patients. Moral distress appears to manifest within a relational and contextual environment and participants focussed on the impact for patients, communities, and the nursing profession as a whole, rather than on their own personal suffering. The opportunity for continuing education led to strategies to transform personal attitudes and practice as well as to enhance the presentation of the profession to the public.     

Correlates of fatigue in HIV infection prior to AIDS: a pilot study

Fatigue is widely recognized as a significant source of morbidity in persons with human immunodeficiency virus (HIV) infection, yet there are few data examining fatigue in this population. We present pilot data assessing the relationship between fatigue and various physical and psychosocial measures in 20 men with HIV infection prior to the clinical development of acquired immunodeficiency syndrome (AIDS). Fatigue was measured by a visual analogue scale (VAS) and the Fatigue Assessment Inventory (FAI). No statistically significant associations were found between fatigue measures and physical parameters including haemoglobin, haematocrit, albumin, total protein, and physical dimension score of the Sickness Impact Profile (SIP). The FAI correlated well with Beck's Depression Inventory and SIP — Psychosocial Dimension (r = 0·72 and 0·81, respectively; p < 0·001.) Both the FAI and VAS held moderate associations with the total SIP score. The SIP profile was similar to that observed in a sample of persons with chronic fatigue but without HIV infection, reported previously. Although the sample size is small, our data suggest a stronger association with psychosocial, rather than physical, parameters among persons with HIV infection and fatigue. The implications for clinical management and further research are discussed.     

Redesigned HIV antibodies exhibit enhanced neutralizing potency and breadth

Several HIV envelope-targeting (Env-targeting) antibodies with broad and potent neutralizing activity have been identified and shown to have unusual features. Of these, the PG9 antibody has a long heavy chain complementarity determining region 3 (HCDR3) and possesses unique structural elements that interact with protein and glycan features of the HIV Env glycoprotein. Here, we used the Rosetta software suite to design variants of the PG9 antibody HCDR3 loop with the goal of identifying variants with increased potency and breadth of neutralization for diverse HIV strains. One variant, designated PG9_N100_FY, possessed increased potency and was able to neutralize a diverse set of PG9-resistant HIV strains, including those lacking the Env N160 glycan, which is critical for PG9 binding. An atomic resolution structure of the PG9_N100_FY fragment antigen binding (Fab) confirmed that the mutated residue retains the paratope surface when compared with WT PG9. Differential scanning calorimetry experiments revealed that the mutation caused a modest increase in thermodynamic stability of the Fab, a feature predicted by the computational model. Our findings suggest that thermodynamic stabilization of the long HCDR3 in its active conformation is responsible for the increased potency of PG9_N100_FY, and strategies aimed at stabilizing this region in other HIV antibodies could become an important approach to in silico optimization of antibodies.     

Opportunistic infections and immune reconstitution inflammatory syndrome in HIV-1-infected adults in the combined antiretroviral therapy era: a comprehensive review

Despite the availability of effective combined antiretroviral treatment, many patients still present with advanced HIV infection, often accompanied by an AIDS-defining disease. A subgroup of patients starting antiretroviral treatment under these clinical conditions may experience paradoxical worsening of their disease as a result of an exaggerated immune response towards an active (but also subclinical) infectious agent, despite an appropriate virological and immunological response to the treatment. This clinical condition, known as immune reconstitution inflammatory syndrome, may cause significant morbidity and even mortality if it is not promptly recognized and treated. This review updates current knowledge about the incidence, diagnostic criteria, risk factors, clinical manifestations, and management of opportunistic infections and immune reconstitution inflammatory syndrome in the combined antiretroviral treatment era.