World Health Organization Stage Research Articles

Symptom Burden in HIV-Infected Adults at Time of HIV Diagnosis in Rural Uganda

This study aimed to measure symptom burden prior to antitetroviral therapy (ART) initiation in a population of adults with low CD4 presenting for human immunodeficiency virus (HIV) care and treatment in Uganda, and to explore the relationship between World Health Organization (WHO) stage, CD4 count, and symptomatology. HIV-infected, ART-naïve adults with CD4 less than 200 cells per microliter referred from voluntary testing and counseling services in rural Uganda for potential enrollment into a large double-blinded placebo-controlled trial were invited to completed the Memorial Symptom Assessment Scale-Short Form (MSAS-SF). This is a validated symptom assessment tool that records the presence and severity of 37 physical and 4 psychological symptoms. Two hundred twelve subjects were enrolled. The mean total number of symptoms was 14.0 (standard deviation [SD] = 6). The 10 most common symptoms were pain (76%), weight loss (70%), itching (67%), feeling drowsy/tired (61%), and lack of energy (61%), numbness /tingling in hands or feet (57%), cough (53%) skin changes (52%), worry (51%), and lack of appetite (49%). The median number of symptoms was not associated with WHO stage CD4 count group. This study demonstrates that the burden of HIV-related symptoms in individuals presenting for care in Uganda is significant and debilitating.

Serum Uric Acid Levels and Renal Damage in Hyperuricemic Hypertensive Patients Treated With Renin-Angiotensin System Blockers

A correlation between hyperuricemia and renal target organ damage (TOD) was shown in hypertensive patients, locally mediated by the activation of renin-angiotensin system (RAS). We investigated whether high serum uric acid (UA) levels could negatively affect tubulointerstitial damage in hyperuricemic essential hypertensive patients with normal renal function, on treatment with RAS-blocking drugs. We studied 40 patients with World Health Organization stage I-II essential hypertension, 9 with high serum UA levels (hyperuricemic group) and 31 with normal serum UA levels (normouricemic group, either normouricemics, n = 15, or formerly hyperuricemics in chronic allopurinol treatment, n = 16). All patients were on RAS-blocking drugs (either angiotensin-converting enzyme inhibitors or angiotensin II receptors blockers). Evaluation of renal TOD included urinary albumin excretion (UAE), Doppler ultrasound renal resistive index (RRI) and renal volume-to-resistive index ratio (RV/RRI) measurements. Hyperuricemics had significantly higher RRI and lower RV/RRI values than normouricemics. Creatinine clearance and UAE were similar between groups. Linear regression analysis showed that RV/RRI values were inversely related to serum UA levels (r = -0.57, P < 0.01). The logistic regression analysis selected serum UA as an independent predictor of decreased RV/RRI (odds ratio 4.45, 95% CI 1.47-13.45, P = 0.01). In hyperuricemic hypertensives normal serum UA levels are associated with normal RV/RRI, integrated marker of tubulointerstitial damage and renal arteriolopathy, independently of RAS activation.

Bleomycin/interleukin-12 electrochemogene therapy for treating naturally occurring spontaneous neoplasms in dogs

On the basis of superior outcomes from electrochemogene therapy (ECGT) compared with electrochemotherapy in mice, we determined the efficacy of ECGT applied to spontaneous canine neoplasms. Intralesional bleomycin and feline interleukin-12 DNA (fIL-12 DNA) injection combined with translesional electroporation resulted in complete cure of two recurrent World Health Organization stage T(2b)N(0)M(0) oral squamous cell carcinomas (SCCs) and one T(2)N(0)M(0) acanthomatous ameloblastoma. Three remaining dogs, which had no other treatment options, had partial responses to ECGT; one had mandibular T(3b)N(2b)M(1) melanoma with pulmonary and lymph node metastases; one had cubital T(3)N(0)M(1) histiocytic sarcoma with spleen metastases; and one had soft palate T(3)N(0)M(0) fibrosarcoma. The melanoma dog had decrease in size of the primary tumor before recrudescence and euthanasia. The histiocytic sarcoma dog had resolution of the primary tumor, but was euthanized because of metastases 4 months after the only treatment. The dog with T(3)N(0)M(0) fibrosarcoma had tumor regression with recrudescence. Treatment was associated with minimal side effects and was easy to perform. It was associated with repair of bone lysis in cured dogs, it improved quality of life of dogs with partial responses and extended overall survival time. ECGT seems to be a safe and resulted in complete responses in SCC and acanthomatous ameloblastoma.

Sustainability of First-Line Antiretroviral Regimens: Findings From a Large HIV Treatment Program in Western Kenya

To describe first change or discontinuation in combination antiretroviral treatment (cART) among previously treatment naive, HIV-infected adults in a resource-constrained setting. The United States Agency for International Development-Academic Model Providing Access to Healthcare Partnership has enrolled >90,000 HIV-infected patients at 18 clinics throughout western Kenya. Patients in this analysis were aged > or =18 years, previously antiretroviral treatment naive, and initiated to cART between January 2006 and November 2007, with at least 1 follow-up visit. A treatment change or discontinuation was defined as change of regimen including single drug substitutions or a complete halting of cART. There were 14,162 patients eligible for analysis and 10,313 person-years of follow-up, of whom 1376 changed or stopped their cART. Among these, 859 (62%) changed their regimen (including 514 patients who had a single drug substitution) and 517 (38%) completely discontinued cART. The overall incidence rate (IR) of cART changes or stops per 100 person-years was 13.3 [95% confidence interval (CI): 12.7-14.1]. The incidence was much higher in the first year of post-cART initiation (IR: 25.0, 95% CI: 23.6-26.3) compared with the second year (IR: 2.4, 95% CI: 2.0-2.8). The most commonly cited reason was toxicity (46%). In multivariate regression, individuals were more likely to discontinue cART if they were World Health Organization stage III/IV [adjusted hazard ratio (AHR): 1.37, 95% CI: 1.11-1.69] or were receiving a zidovudine-containing regimen (AHR: 4.44, 95% CI: 3.35-5.88). Individuals were more likely to change their regimen if they were aged > or =38 years (AHR: 1.44, 95% CI: 1.23-1.69), had to travel more than 1 hour to clinic (AHR: 1.34, 95% CI: 1.15-1.57), had a CD4 at cART initiation < or =111 cells/mm3 (AHR: 1.51, 95% CI: 1.29-1.77), or had been receiving a zidovudine-containing regimen (AHR: 3.73, 95% CI: 2.81-4.95). Those attending urban clinics and those receiving stavudine-containing regimens were less likely to experience either a discontinuation or a change of their cART. These data suggest a moderate incidence of cART changes and discontinuations among this large population of adults in western Kenya. Mostly occurring within 12 months of cART initiation, and primarily due to toxicity, older individuals, those with more advanced disease, and those using zidovudine are at higher risk of experiencing a change or a discontinuation in their cART.

Thirty-Five–Year Follow-Up Analysis of Clinical and Pathologic Outcomes of Thymoma Surgery

The impact of myasthenia gravis on patients with thymoma is still controversial when perioperative and long-term outcomes are analyzed. With the unique opportunity of a 35-year follow-up in a single institution, thymomatous myasthenia gravis cohort, we investigated the influence of early and long-term clinical predictors. We reviewed a surgical series of 317 (1972 to 2007) patients with thymoma: clinical and pathologic features were analyzed as prognostic factors matched against the short- and long-term survival and recurrence rates. Male to female ratio was 153:164; median age, 49 years. Myasthenia gravis coexisted in 276 patients (87.1%). Thymomas were classified according to the Masaoka (42.0% stage I, 32.2% stage II, 21.5% stage III, and 4.4% stage IV) and the World Health Organization (3.5% type A, 9.5% type AB, 19.2% type B1, 57.7% type B2, 8.2% type B3, and 1.9% thymic carcinoma) staging systems. The resection was complete in 295 patients (93.1%). Operative mortality and morbidity were respectively 1.6% and 7.6%. No differences were recorded in postoperative outcome stratifying for myasthenia gravis or comorbidities. Mean follow-up was 144.7 +/- 104.4 months. The overall 5-, 10-, 20-, and 30-year survival rates were 89.9%, 84.1%, 73%, and 58.6%, respectively. The completeness of resection (p < 0.001), the Masaoka staging (p = 0.010), and the World Health Organization classification (p < 0.001) all significantly influenced the long-term survival (univariate analysis). Only completeness of resection was significantly correlated with a better prognosis (p < 0.001) in multivariate analysis. Masaoka staging (p < 0.001) and World Health Organization classification (p < 0.001) significantly correlated with the disease-free survival in the univariate and multivariate analyses as significant prognostic factors (Masaoka, p < 0.001; World Health Organization, p = 0.011). Myasthenia gravis patients showed a better prognosis in terms of long-term survival (p = 0.046) and disease-free survival (p = 0.012) in the univariate analysis. We confirm the evidence that the clinical staging and the histologic classification influence long-term survival. The presence of myasthenia gravis was not significantly related to operative outcome, but prolongs both long-term survival and disease-free survival.

Immune reconstitution inflammatory syndrome involving the skin

Immune reconstitution inflammatory syndrome (IRIS) occurs in 10-25% of unselected patients starting highly active antiretroviral therapy (HAART). About 52-78% of these cases involve cutaneous features. To describe the prevalence and incidence of new dermatological conditions within 6 months of patients starting HAART, and to specify the clinical and immunological features and time of onset in patients responding to HAART. A retrospective cohort analysis was performed of 59 treatment-naive patients started on HAART and followed up for 6 months by a clinician trained in dermatology. Medical records were reviewed for new dermatological conditions diagnosed clinically. In all, 30 patients (50.8%) developed 45 new skin conditions at a median of 8 weeks (range 3-24 weeks) after starting HAART. The incidence rate was 104.5 cases per 100 patient-years. Diagnoses included seborrhoeic dermatitis (nine patients), anogenital herpes (seven patients), acne, tinea and folliculitis (six patients each), Kaposi's sarcoma, herpes zoster, genital warts and eczema (two patients each), and molluscum contagiosum, planar warts and pityriasis versicolor (one patient each). Significantly more women (23/38; 60.5%) than men (7/21; 33.3%) (P < 0.05) developed new skin lesions after starting HAART. Baseline median CD4 counts in those with and without IRIS were 60/microL and 62/microL, respectively, and in both groups, the counts increased to > 90/microL by week 12. Baseline median viral load was > 100,000 copies/mL and was < or = 32 copies/mL by week 12. In both groups, the majority of patients were in World Health Organization stages 3 and 4. New skin lesions were very common in this cohort, with the majority being women and patients with very low baseline CD4 counts.

Estimation of adult antiretroviral treatment coverage in South Africa.

To estimate the annual numbers of individuals receiving antiretroviral treatment in South Africa up to mid-2008, and the coverage of antiretroviral treatment in adults according to various definitions of need. Antiretroviral coverage is defined as the number of patients receiving antiretroviral treatment at a point in time, divided by the number needing treatment. Numbers of patients receiving antiretroviral treatment are estimated from public sector data, and data provided by disease management programmes and NGO programmes. The unmet need for treatment in adults is estimated using a Markov model of HIV progression in adults, combined with estimates of annual new HIV infections from a national AIDS and demographic model. By the middle of 2008, 568 000 adults and children were receiving antiretroviral treatment in South Africa, with the public health sector accounting for 79% of this total. Using the current Department of Health criteria for defining antiretroviral eligibility (CD4+ count <200/microl or World Health Organization (WHO) stage 4), antiretroviral coverage in adults was 40.2% in 2008--up from 4.9% in 2004. Coverage increases to 54.2% if eligibility is based on WHO stage 4 only, but falls to 22.2% if the Southern African HIV Clinicians Society guidelines are used to define eligibility. Coverage in 2008 varied between provinces, from 25.8% in the Free State to 71.7% in the Western Cape. Significant progress has been made in expanding access to antiretroviral treatment in South Africa since 2004, but a substantial unmet need for treatment in adults remains.

Mortality and Virologic Outcomes After Access to Antiretroviral Therapy Among a Cohort of HIV-Infected Women Who Received Single-Dose Nevirapine in Lusaka, Zambia

Single-dose nevirapine (SDNVP) for prevention of mother-to-child HIV transmission selects mutations conferring resistance to nonnucleoside reverse transcriptase inhibitor (NNRTI)-based therapy. We investigated mortality and virologic and clinical outcomes after introduction of antiretroviral treatment (ART) among a cohort of women given SDNVP. When ART programs were introduced in 2004 in Lusaka, Zambia, we were completing a trial of infant feeding, which involved following HIV-infected women who received SDNVP between 2001 and 2005. Women still in follow-up or who could be contacted were evaluated for eligibility for ART (CD4 count <200 or <350 and World Health Organization stage >or=3) and started on NNRTI-based therapy if eligible. We compared mortality in the cohort of women before and after ART access, and examined, among women initiating ART, whether virologic response was better allowing a longer time to elapse between SDNVP and treatment initiation. In the cohort of 872 women, mortality more than halved after ART became available (relative hazard = 0.46, 95% confidence interval: 0.23 to 0.91, P = 0.03). Of 161 SDNVP-exposed women followed on NNRTI-based ART, 70.8% suppressed (viral load <400 copies/mL). Only 3 of 8 SDNVP-exposed women (37.5%) <6 months of starting therapy suppressed compared with 13 of 22 (59.1%) who started 6-12 months, 44 of 61 (72.1%) 12-24 months, and 54 of 70 (77.1%) >24 months after exposure (chi2 trend P = 0.01). Most SDNVP-exposed women respond well to NNRTI-based therapy, but there was an attenuation of therapy efficacy that persisted to 12 months after exposure. Women should be screened for ART eligibility during pregnancy and started on effective regimens before delivery.

HIV Testing Rates and Outcomes in a South African Community, 2001-2006: Implications for Expanded Screening Policies

Revised World Health Organization recommendations seek to increase HIV testing. We assessed the need for expanded testing in South Africa by examining current testing and treatment trends among a high prevalence population. We determined the numbers of adults receiving HIV testing and antiretroviral treatment (ART) during 2001-2006 using testing registers linked to patient records from 2 health care facilities believed responsible for virtually all HIV services available to the population. We evaluated annual population testing rates using census population counts; proportions of clients testing seropositive (yield); CD4 counts and World Health Organization stage at diagnosis; and ART initiation rates. HIV testing rates rose from 4% in 2001 to 20% in 2006 (P < 0.001) and were highest among pregnant females receiving provider-initiated testing. Yield for first-time testers decreased from 47% in 2001 to 28% in 2006; annual incidence of seroconversion among initially HIV-negative retesters was 1.9%. Median CD4 counts and World Health Organization stage distributions for newly diagnosed clients remained stable. HIV-infected clients receiving ART within 6 months of eligibility increased from 0% in 2001 to 68% in 2006 (P < 0.001). Population testing and ART initiation rates rose dramatically during 2001-2006. Yet, yield remained high, and HIV-infected persons continued to receive late diagnoses. These findings highlight the continuing need for expanded testing and linkage to care.

Total Lymphocyte Count and World Health Organization Pediatric Clinical Stage as Markers to Assess Need to Initiate Antiretroviral Therapy Among Human Immunodeficiency Virus-Infected Children in Moshi, Northern Tanzania

The World Health Organization (WHO) has recommended the use of clinical staging alone and with total lymphocyte count to identify HIV infected children in need of antiretroviral therapy (ART) in resource-limited settings, when CD4 cell count is not available. We prospectively enrolled children obtaining care for HIV infection at the Kilimanjaro Christian Medical Centre Pediatric Infectious Diseases Clinic in Moshi, Tanzania between March 2004 and May 2006 for this cohort study. One hundred ninety two (89.7%) of 214 children met WHO ART initiation criteria based on clinical staging or CD4 cell count. Several low-cost measures identified individuals who met WHO ART initiation criteria to the following degree: WHO stages 3 or 4 had 87.5% (95% CI, 82.8-92.1) sensitivity and, by definition, 100% (CI, 100-100) specificity; WHO recommended advance disease TLC cutoffs: sensitivity = 23.9% (95% CI, 17.3-30.5) specificity = 78.2% (95% CI, 67.3-89.1). Low TLC was a common finding, (50 of 214; 23%); however, it did not improve the sensitivity or specificity of clinical staging in identifying the severely immunosuppressed stage 2 children. Growth failure or use of total lymphocyte counts in isolation were not reliable indicators of severe immunosuppression or need to initiate ART. The use of total lymphocyte count does not improve the ability to identify children in need of ART compared with clinical staging alone. Low absolute lymphocyte count did not correlate with severe immunosuppression based on CD4 cell count in this cohort.

High ongoing burden of cryptococcal disease in Africa despite antiretroviral roll out

Cryptococcosis is now the commonest cause of adult meningitis in much of Southern and East Africa [1]. Despite currently available antifungal therapies, acute mortality ranges from 30 to over 50% in published series [2, 3]. The result is that cryptococcal infection accounts for 10-20 % of mortality in HIV-infected cohorts from Sub Saharan Africa [1], and recently published estimates by Park et al (AIDS 20th February 2009, issue 23, 525-30) place the overall toll at an estimated 504,000 deaths in sub-saharan Africa annually [4]. As part of an ongoing programme of work aimed at improving management of cryptococcal meningitis, we have prospectively monitored the number of new India Ink positive cases of cryptococcal meningitis diagnosed at GF Jooste Hospital, Cape Town, South Africa, for the last 6 years (2003-8). This is a public sector adult hospital serving a population of 1.3 million (including a large part of Khayelitsha township, population 500,000, with HIV antenatal seroprevalence of 32.7% in 2006 [5]). During this period, the area served by the hospital, and referral patterns for patients, have not changed. Antiretroviral therapy (ART) access has been substantially increased in the public sector clinics in the hospital's referral area from 660 adult patients on ART at the end of 2003 to 13,985 by the end of 2008, based on figures from the provincial reporting system described elsewhere [6]. It is estimated that 60% of adults with new World Health Organization (WHO) stage IV HIV disease in this setting are now accessing ART [6]. But despite this increase in the proportion of eligible patients receiving ART, the absolute number of patients with advanced disease not accessing treatment has remained constant or increased in recent years, due to the evolution of the epidemic [6]. This is in keeping with our finding that there has been no reduction in the number of new India Ink positive cases of cryptococcal meningitis presenting to our hospital over this period (Figure 1). Figure 1 Number of adult patients on anti-retroviral therapy (ART) in the hospital referral area, and the number of patients with India Ink positive cryptococcal meningitis presenting to the hospital by year, 2003-2008. There has been a major effort to expand access to ART throughout sub-Saharan Africa over recent years. However despite implementation of successful treatment programmes, in many settings the numbers of people progressing to advanced immunosuppression exceeds the capacity of ART programmes, and large numbers patients presenting to health services with advanced HIV and opportunistic infections die without accessing ART. The result is that the “treatment gap” is not narrowed, and AIDS-related illness such as cryptococcal meningitis and the associated mortality are not reduced. This is illustrated by the fact that, in the Western Cape Province, where GF Jooste hospital is located, the proportion of adult patients starting ART with CD4 counts below 50 cells/μl has fallen from 51.3% in 2001 to 21.5% in 2005 in line with increased access to care [6], while the absolute numbers of patients in this category has increased. Furthermore, unpublished aggregate data from the laboratory information system in the Province, further demonstrates that, irrespective of ART, the absolute numbers of all adult patients known to the health care system with CD4 counts below 100 cells/μl is increasing year-on-year (personal communication, Meg Osler, Provincial Government of Western Cape). As these large numbers of patients with low CD4 counts not yet accessing ART remain at high risk of opportunistic infection, the burden of cryptococcal meningitis is likely to continue undiminished in many areas, despite increasing access to ART. These data reinforce the urgent need to improve the acute management of cryptococcal meningitis, and to facilitate earlier diagnosis and treatment, especially now that access to ART offers the possibility of a good long term prognosis, provided patients survive the acute cryptococcal infection [7]. This needs to be specifically addressed as an integral part of the response to the HIV epidemic in Africa, along with earlier HIV diagnosis and access to ART.

Mortality of HIV-Infected Patients Starting Antiretroviral Therapy in Sub-Saharan Africa: Comparison with HIV-Unrelated Mortality

Mortality in HIV-infected patients who have access to highly active antiretroviral therapy (ART) has declined in sub-Saharan Africa, but it is unclear how mortality compares to the non-HIV-infected population. We compared mortality rates observed in HIV-1-infected patients starting ART with non-HIV-related background mortality in four countries in sub-Saharan Africa. Patients enrolled in antiretroviral treatment programmes in Côte d'Ivoire, Malawi, South Africa, and Zimbabwe were included. We calculated excess mortality rates and standardised mortality ratios (SMRs) with 95% confidence intervals (CIs). Expected numbers of deaths were obtained using estimates of age-, sex-, and country-specific, HIV-unrelated, mortality rates from the Global Burden of Disease project. Among 13,249 eligible patients 1,177 deaths were recorded during 14,695 person-years of follow-up. The median age was 34 y, 8,831 (67%) patients were female, and 10,811 of 12,720 patients (85%) with information on clinical stage had advanced disease when starting ART. The excess mortality rate was 17.5 (95% CI 14.5-21.1) per 100 person-years SMR in patients who started ART with a CD4 cell count of less than 25 cells/microl and World Health Organization (WHO) stage III/IV, compared to 1.00 (0.55-1.81) per 100 person-years in patients who started with 200 cells/microl or above with WHO stage I/II. The corresponding SMRs were 47.1 (39.1-56.6) and 3.44 (1.91-6.17). Among patients who started ART with 200 cells/microl or above in WHO stage I/II and survived the first year of ART, the excess mortality rate was 0.27 (0.08-0.94) per 100 person-years and the SMR was 1.14 (0.47-2.77). Mortality of HIV-infected patients treated with combination ART in sub-Saharan Africa continues to be higher than in the general population, but for some patients excess mortality is moderate and reaches that of the general population in the second year of ART. Much of the excess mortality might be prevented by timely initiation of ART.

Validation of 2006 WHO Prediction Scores for True HIV Infection in Children Less than 18 Months with a Positive Serological HIV Test

IntroductionAll infants born to HIV-positive mothers have maternal HIV antibodies, sometimes persistent for 18 months. When Polymerase Chain Reaction (PCR) is not available, August 2006 World Health Organization (WHO) recommendations suggest that clinical criteria may be used for starting antiretroviral treatment (ART) in HIV seropositive children <18 months. Predictors are at least two out of sepsis, severe pneumonia and thrush, or any stage 4 defining clinical finding according to the WHO staging system.Methods and ResultsFrom January 2005 to October 2006, we conducted a prospective study on 236 hospitalized children <18 months old with a positive HIV serological test at the national reference hospital in Kigali. The following data were collected: PCR, clinical signs and CD4 cell count.Current proposed clinical criteria were present in 148 of 236 children (62.7%) and in 95 of 124 infected children, resulting in 76.6% sensitivity and 52.7% specificity. For 87 children (59.0%), clinical diagnosis was made based on severe unexplained malnutrition (stage 4 clinical WHO classification), of whom only 44 (50.5%) were PCR positive. Low CD4 count had a sensitivity of 55.6% and a specificity of 78.5%.ConclusionAs PCR is not yet widely available, clinical diagnosis is often necessary, but these criteria have poor specificity and therefore have limited use for HIV diagnosis. Unexplained malnutrition is not clearly enough defined in WHO recommendations. Extra pulmonary tuberculosis (TB), almost impossible to prove in young children, may often be the cause of malnutrition, especially in HIV-affected families more often exposed to TB. Food supplementation and TB treatment should be initiated before starting ART in children who are staged based only on severe malnutrition.

Outcomes of human immunodeficiency virus–infected and –exposed children undergoing surgery—a prospective study

Aim Human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) is a worldwide pandemic. Mother-to-child transmission programs should theoretically minimize vertical transfer of the virus, but with variable effectiveness of implementation a significant number of children become infected and may present for emergency, diagnostic, and elective surgery. The aim of this study was to prospectively document the clinical presentation, the spectrum of pathology, and surgical outcomes of patients presenting to our hospital. This formed part of a pilot study of a collaborative international working group studying HIV infection in children, which included the Buzzi Children's Hospital Milan, Italy; the University of San Diego, California, USA; and the Red Cross War Memorial Children's Hospital and University of Cape Town, School of Adolescent and Child Health, Cape Town, South Africa. Method Clinical data from all children admitted to the surgical service of the Red Cross War Memorial Children's Hospital between July 2004 and December 2006 with either a history of HIV exposure (born to an HIV-infected mother) or confirmation of HIV infection by ELISA or polymerase chain reaction was collected. The clinical course was documented prospectively for the duration of admission and subsequent follow-up as recorded in case records review. The spectrum of pathology, surgical intervention, outcome, complications, World Health Organization stage of AIDS, and type of antiretroviral therapy were all noted. Comparative outcomes and subgroup analysis were not done in this part of the study. Results One hundred and thirteen patients were included in the study over the 30-month period. The average age was 24 months (1 day to 11 years). Seventy-nine (70%) of the 113 patients were infected and 34 (30%) were exposed, 9 of whom subsequently tested negative. Of the infected group, 53 (67%) patients were on antiretroviral therapy. The extent of disease in the infected group of patients according to the 2006 World Health Organization criteria was as follows: stage 1, 4 (5%); stage 2, 12 (15%); stage 3, 51 (65%); and stage 4, 12 (15%). All patients had nutritional assessments and were plotted on growth curves. Sixty-two (54%) were found to be malnourished and 41 (36%) of the children were found to have comorbid disease processes. Eighteen patients (16%) were treated with antibiotics or conservative therapy alone. The remaining 95 patients (84%) underwent an average of 1.6 procedures (range, 1-35), 59 (52%) in an elective manner and 36 (31%) as an emergency. When assessing the relationship of HIV to the presenting disease state, 58 (73.4%) had HIV-related diseases and 52 (46%) presented with sepsis. A total of 29 (25%) patients had surgical complications of which 6 (20%) were not considered to be HIV related. Nine (31%) had, in retrospect, incorrect management of the presenting disease, leaving 14 (48%) who potentially had HIV-related complications of poor wound healing and sepsis. A total of 100 (88%) were discharged alive, 6 (5.3%) died, and 7 (6 %) were lost to follow-up. Long-term follow-up of 50 patients for an average of 8 months revealed one further mortality. Conclusion Human immunodeficiency virus–positive and –exposed patients present a unique challenge in management which is complicated by concomitant disease and poor nutrition. These patients require an expanded differential diagnosis. We believe that, although on the surface there may be a higher complication rate, this needs to be confirmed in an expanded comparative cohort study, which is underway and that patients should still receive the benefit of full surgical intervention.

Sustained Immunological Responses to Highly Active Antiretroviral Therapy at 36 Months in a Ghanaian HIV Cohort

Two hundred thirty-seven Ghanaian human immunodeficiency virus-infected patients who were starting antiretroviral therapy underwent clinical and immunological monitoring for 3 years. Seventy-eight percent of patients had disease classified as World Health Organization stage III or IV. The mean increase in the CD4 cell count was 395 cells/mm(3), 13% of patients experienced immunological failure, and 8% of patients switched treatment to a second-line regimen. However, two-thirds of patients who experienced immunological failure did not switch treatment, and 31% of all patients were lost to follow-up.

Two-year virologic outcomes of an alternative AIDS care model: evaluation of a peer health worker and nurse-staffed community-based program in Uganda.

There is growing concern about the human resources needed to care for increasing numbers of patients receiving antiretroviral therapy in resource-limited settings. We evaluated an alternative model, community-based, comprehensive antiretroviral program staffed primarily by peer health workers and nurses. We conducted a retrospective cohort study of patients receiving antiretroviral therapy during the first 10 months of program enrollment beginning in late 2003. Virologic, immunologic, clinical, and adherence data were collected. Of 360 patients started on treatment, 258 (72%) were active and on therapy approximately 2 years later. Viral load testing demonstrated that 86% of active patients (211/246 tested) had a viral load <400 copies per milliliter. The median CD4 increase for active patients was 197 cells per cubic millimeter (interquartile range, 108-346). Patients with either a history of antiretroviral use or lack of CD4 response were more likely to experience virologic failure. Survival was 84% at 1 year and 82% at 2 years. World Health Organization stage 4 was predictive of both not sustaining therapy and increased mortality. A community-based antiretroviral treatment program in a resource-limited setting can provide excellent AIDS care over at least a 2-year period. A comprehensive program based upon peer health workers and nurses provides an effective alternative model for AIDS care.

The impact of the President's Emergency Plan for AIDS Relief on expansion of HIV care services for adult patients in western Kenya

The President's Emergency Plan for AIDS Relief committed $15 billion to addressing HIV in resource-poor settings. To assess the impact of The President's Emergency Plan for AIDS Relief on the treatment services of an HIV care program. Cohort study utilizing computerized medical records of nonpregnant adults enrolled into the Academic Model for the Prevention and Treatment of HIV/AIDS system, in western Kenya between 27 November 2001 and 24 July 2006. Number of clinics and patients enrolled in Academic Model for the Prevention and Treatment of HIV/AIDS, as well as patient demographics, immunologic, and clinical characteristics during three periods defined by the availability of combination antiretroviral therapy (cART). Enrollment as of May 2006 was 23,539. Mean monthly enrollment increased from 64 to 815 between periods 1 and 3. The median CD4 cell count at enrollment during period 3 (172 cells/microl) was significantly higher than for period 2 (119 cells/microl; P < 0.001). World Health Organization stage at enrollment differed significantly between periods with 6.7% having stage 4 disease in period 3 compared with 13.8% during period 1 (P < 0.001). Significantly more patients had complete documentation of cART eligibility, during period 3 as compared with the previous periods. Time from enrollment to cART initiation decreased from a median of 64 weeks in period 1 to 12 weeks during period 3 (P < 0.001). The President's Emergency Plan for AIDS Relief funding has allowed Academic Model for the Prevention and Treatment of HIV/AIDS to significantly increase the number of individuals receiving HIV care and provided the ability to expand services allowing for identification of patients earlier in their disease process.

Combination antiretroviral therapy in population affected by conflict: outcomes from large cohort in northern Uganda

Objective To measure the clinical and immunological outcomes of HIV positive adult patients receiving combination antiretroviral therapy in conflict affected northern Uganda.Design Prospective cohort study.Setting Gulu District, northern Uganda.Participants 1625...

Spontaneous regression of symptomatic thymoma caused by infarction

We herein report a 38-year-old man who had spontaneous regression of a thymoma with repeating episodes of chest pain that initially occurred 2 years earlier when the tumor was 35 mm in the long axis. Left video-assisted thoracoscopic thymothymectomy was performed. Pathology examination showed a thymoma 15 mm in the long axis, classified B2 in the World Health Organization classification and stage II by Masaoka staging. The feeding arteriole of the tumor, occluded by organized thrombi, was suggested to be the cause of coagulation necrosis. The patient recovered well from surgery without complication and with no episodes of chest pain at the 9-month outpatient follow-up.

Second-line antiretroviral therapy in resource-limited settings: the experience of Médecins Sans Frontières

To describe the use of second-line protease-inhibitor regimens in Médecins Sans Frontières HIV programmes, and determine switch rates, clinical outcomes, and factors associated with survival. We used patient data from 62 Médecins Sans Frontières programmes and included all antiretroviral therapy-naive adults (> 15 years) at the start of antiretroviral therapy and switched to a protease inhibitor-containing regimen with at least one nucleoside reverse transcriptase inhibitor change after more than 6 months of nonnucleoside reverse transcriptase inhibitor first-line use. Cumulative switch rates and survival curves were estimated using Kaplan-Meier methods, and mortality predictors were investigated using Poisson regression. Of 48,338 adults followed on antiretroviral therapy, 370 switched to a second-line regimen after a median of 20 months (switch rate 4.8/1000 person-years). Median CD4 cell count at switch was 99 cells/microl (interquartile ratio 39-200; n = 244). A lopinavir/ritonavir-based regimen was given to 51% of patients and nelfinavir-based regimen to 43%; 29% changed one nucleoside reverse transcriptase inhibitor and 71% changed two nucleoside reverse transcriptase inhibitors. Median follow-up on second-line antiretroviral therapy was 8 months, and probability of remaining in care at 12 months was 0.86. Median CD4 gains were 90 at 6 months and 135 at 12 months. Death rates were higher in patients in World Health Organization stage 4 at antiretroviral therapy initiation and in those with CD4 nadir count less than 50 cells/microl. The rate of switch to second-line treatment in antiretroviral therapy-naive adults on non-nucleoside reverse transcriptase inhibitor-based first-line antiretroviral therapy was relatively low, with good early outcomes observed in protease inhibitor-based second-line regimens. Severe immunosuppression was associated with increased mortality on second-line treatment.