Prioritizing CD4 count monitoring in response to ART in resource-constrained settings: a retrospective application of prediction-based classification.

BACKGROUND: Global programs of anti-HIV treatment depend on sustained laboratory capacity to assess treatment initiation thresholds and treatment response over time. Currently, there is no valid alternative to CD4 count testing for monitoring immunologic responses to treatment, but laboratory cost and capacity limit access to CD4 testing in resource-constrained settings. Thus, methods to prioritize patients for CD4 count testing could improve treatment monitoring by optimizing resource allocation. METHODS AND FINDINGS: Using a prospective cohort of HIV-infected patients (n=1,956) monitored upon antiretroviral therapy initiation in seven clinical sites with distinct geographical and socio-economic settings, we retrospectively apply a novel prediction-based classification (PBC) modeling method. The model uses repeatedly measured biomarkers (white blood cell count and lymphocyte percent) to predict CD4(+) T cell outcome through first-stage modeling and subsequent classification based on clinically relevant thresholds (CD4(+) T cell count of 200 or 350 cells/µl). The algorithm correctly classified 90% (cross-validation estimate=91.5%, standard deviation [SD]=4.5%) of CD4 count measurements <200 cells/µl in the first year of follow-up; if laboratory testing is applied only to patients predicted to be below the 200-cells/µl threshold, we estimate a potential savings of 54.3% (SD=4.2%) in CD4 testing capacity. A capacity savings of 34% (SD=3.9%) is predicted using a CD4 threshold of 350 cells/µl. Similar results were obtained over the 3 y of follow-up available (n=619). Limitations include a need for future economic healthcare outcome analysis, a need for assessment of extensibility beyond the 3-y observation time, and the need to assign a false positive threshold. CONCLUSIONS: Our results support the use of PBC modeling as a triage point at the laboratory, lessening the need for laboratory-based CD4(+) T cell count testing; implementation of this tool could help optimize the use of laboratory resources, directing CD4 testing towards higher-risk patients. However, further prospective studies and economic analyses are needed to demonstrate that the PBC model can be effectively applied in clinical settings. Please see later in the article for the Editors' Summary.

Electronic decision protocols for ART patient triaging to expand access to HIV treatment in South Africa: a cross sectional study for development and validation.

BACKGROUND: The shortage of doctors and nurses, along with future expansion into rural clinics, will require that the majority of clinic visits by HIV infected patients on antiretroviral therapy (ART) are managed by non-doctors. The goal of this study was to develop and evaluate a screening protocol to determine which patients needed a full clinical assessment and which patients were stable enough to receive their medications without a doctor's consultation. For this study, we developed an electronic, handheld tool to guide non-physician counselors through screening questions. METHODS: Patients visiting two ART clinics in South Africa for routine follow-up visits between March 2007 and April 2008 were included in our study. Each patient was screened by non-physician counselors using the handheld device and then received a full clinical assessment. Clinicians' report on whether full clinical assessment had been necessary was used as the gold standard for determining "required referral". Observations were randomly divided into two datasets--989 for developing a referral protocol and 200 for validating protocol performance. RESULTS: A third of patients had at least one physical complaint, and 16% had five or more physical complaints. 38% of patients required referral for full clinical assessment. We identify a subset of questions which are 87% sensitive and 47% specific for recommended patient referral. CONCLUSIONS: The final screening protocol is highly sensitive and could reduce burden on ART clinicians by 30%. The uptake and acceptance of the handheld tool to support implementation of the protocol was high. Further examination of the data reveals several important questions to include in future referral algorithms to improve sensitivity and specificity. Based on these results, we identify a refined algorithm to explore in future evaluations.

Clinical and immunological status of a newly diagnosed HIV positive population, in Marrakech, Morocco.

OBJECTIVE: To evaluate the clinical and the immune status of newly HIV diagnosed patients, in Marrakech city and its neighboring area, in Morocco. METHODS: We performed a retrospective study on 235 patients who have been previously confirmed for HIV infection, and underwent a CD4 T cells using flow cytometry (FacsCount, Becton Dickinson®). RESULTS: The mean age of patients was 34,3 ± 8,4 years (range: 14-55), with a male predominance (sex-ratio M/F=1.4). On basis of clinical data of the patients, 62% (n=146) of them were categorized as "category C", 18.4% (n=43) as "category B", and 19.6% (n=46) as "category A" according to CDC (Center for Disease Control) HIV classification. Among all of them, 60.4% (n=142) had less than 200 CD4T cells, 26% (n=61) had between 200 and 499 CD4T cells, and only 13.6% (n=32) showed a number of CD4T cells less or equal to 500/mm(3). CONCLUSION: The results of this study reflect a significant delay in the diagnosis of HIV infected patients. Therefore, this delay may compromise timely management of HIV infected individuals and enhances propagation of the epidemic in our country. These data confirm the need for intensifying prevention efforts among high-risk population. Moreover, continuing education in HIV/AIDS among healthcare providers should be reinforced.

HIV: medical milestones and clinical challenges.

Since its discovery in the 1980s, HIV has infected every continent on the globe by crossing socioeconomic, racial, ethnic, and gender barriers, and it continues to contribute to human morbidity and mortality. Advances in medicine and technology have led to new combination medications for HIV-positive patients, early HIV testing methodologies, and potential for an HIV vaccine, and they have given researchers and clinicians a larger armamentarium with which to treat and prevent the disease. Even with these vast improvements in HIV prevention, detection, and treatment, scientists have been unsuccessful in developing its vaccine. Therefore, the search for a cure for HIV remains the marathon of the millennium.

HIV symptoms.

People with HIV/AIDS are a vulnerable group whose symptoms can seriously affect their quality of life. HIV/AIDS symptoms can result from the disease itself, from secondary complications of the disease, or from side-effects of highly active antiretroviral therapy (HAART) and other medications related to comorbidities. HIV symptoms are the single most important indicators for patients and practitioners. Symptoms prompt patients to seek medical attention and provide health care providers with essential clues about changes in health status and quality of life. Despite increased recognition of the importance of addressing symptoms among people with HIV/AIDS, few studies have examined the management of HIV symptoms. This chapter introduces HIV symptoms, reports on the methods of review, provides an overview of contextual issues including the literature on symptoms, issues related to symptom measures, theoretical foundations on symptom management, HIV-specific measures, non-HIV-specific measures, translation of findings into practice, and implications for future research and policy.

HIV antiretroviral therapy in resource-limited settings: experiences from Haiti.

An unprecedented international effort to expand high activity antiretroviral therapy (HAART) to resource-poor nations has been launched. The World Health Organization (WHO) has created antiretroviral (ARV) treatment guidelines adapted to resource-poor settings. The first-line regimen is two nucleoside reverse transcriptase inhibitors (NsRTIs) and one nonnucleoside reverse transcriptase inhibitor (NNRTI). Therapy is initiated by clinical staging and CD4 T-cell counts when available. Adherence is the responsibility of health care workers. The use of ARV therapy in resource-poor settings faces several challenges, including the poverty of patients, political and social upheavals and violence, social stigma associated with HIV/AIDS, unreliable pharmacy systems, tuberculosis, and lack of trained health care workers. Using our experience in Haiti, we describe how we have addressed these challenges with the goal of increasing access to care for the poor with HIV/AIDS.

Mental health status and use of general medical services for persons with human immunodeficiency virus.

BACKGROUND: Serious medical illness often is accompanied by psychological distress. Individuals experiencing mental disorders or symptoms have higher rates of morbidity and mortality, worse social functioning, and use of general medical services. OBJECTIVES: We sought to examine the association between mental health and use of general medical services for persons in care for HIV. DESIGN AND PARTICIPANTS: We used longitudinal data from the HIV Cost and Services Utilization Study (HCSUS), a nationally representative sample of 2267 HIV+ adults receiving care and who completed all 3 interviews during an 18-month period. MAIN OUTCOME MEASURES: Probability of use and general medical expenditures, by type of service. RESULTS: HIV+ individuals who screened positive for depression or had 5 or more mental health symptoms at baseline spent 20% to 25% more for general medical services in the following 12 months than HIV+ adults without mental health symptoms, after adjusting for disease severity and patient characteristics. Higher spending was largely the result of greater use of inpatient and emergency services. CONCLUSIONS: Psychological distress remains an independent predictor of general medical service use, although the magnitude of effect diminishes with better controls for physical well-being and previous service use. Identifying HIV patients with symptoms of affective or anxiety disorders may reduce overall treatment costs modestly.

The relationship between prevention of mother to child transmission of HIV and stakeholder decision making in Uganda: implications for health policy.

OBJECTIVES: To explore a selection of stakeholders' use of evidence and other reasons in the relative ranking of the prevention of mother to child HIV transmission with nevirapine in a setting of extreme resource scarcity. DESIGN: Group interviews using nominal group technique with provision of evidence. SETTING: One rural and one urban district in Uganda. PARTICIPANTS: People living with HIV/AIDS, people from the general population, planners, health workers and people with hypertension. MAIN OUTCOME MEASURE: relative ranking of prevention of vertical HIV transmission with nevirapine compared to nine other interventions for different conditions and evaluation of participants' use of evidence in the ranking. RESULTS: In the overall final ranking, prevention of vertical HIV transmission with nevirapine was ranked as number five compared to the other eight conditions. Treatment for childhood diseases and highly active anti retroviral treatment (HAART) for HIV/AIDS were ranked higher. Group specific ranking followed the same pattern, although the people living with HIV-group ranked HAART consistently as number one. CONCLUSIONS: Stakeholders seem to rank prevention of vertical HIV transmission lower than treatment for malaria, pneumonia and diarrhoea. Policies considering prevention of vertical transmission of HIV should consider its implications. This study shows that stakeholders are open to considering evidence in assessing the relative priority of different interventions competing for scarce resources. More research is needed to develop methods that can involve representative stakeholders, including the public, in good and legitimate decisions on priorities.

HIV serostatus and factors related to physical and mental well-being in Latina family AIDS caregivers.

In a survey of 154 Latina AIDS caregivers living in Los Angeles, we examined differences in the stress process for those who were HIV seropositive, seronegative, and those with an unknown serostatus. Most caregivers were monolingual, poor, suffered from chronic physical illness unrelated to HIV, and received few services. All three subsamples reached clinical cut-off levels for depression on the brief symptom inventory. In the sample as a whole and in all three groups we examined differences in primary and secondary stressors as predictors of mental and physical well-being; differences in background factors as they relate to mental and physical well-being; and differences in predictive value of various factors that may attenuate the relationship between stress and mental and physical well-being. Models predicting both mental and physical well-being differ across subsamples divided on the basis of serostatus. Based on these findings, we discuss implications for service provision designed to target these underserved Latina AIDS caregivers.

Analyses of nursing home residents with HIV and dementia using the minimum data set.

OBJECTIVE: The objective of this paper is to profile nursing home residents with HIV who also have dementia at the time of admission, using the Minimum Data Set (MDS). In addition, this paper compares HIV residents with dementia with other residents with HIV. These resident profiles contain sociodemographic characteristics, health status measures, treatments, and procedures. STUDY SUBJECTS: There are 1,074 admission assessments for HIV residents with dementia and 4,040 admission assessments for other residents with HIV in the MDS between June 22, 1998 and January 17, 2000; these were analyzed for this study. RESULTS: Other residents with HIV were twice as likely to be physically independent as HIV residents with dementia. Only 1 of 5 HIV residents with dementia was independent in cognitive skills for daily decision making compared with 3 of 5 other residents with HIV who were independent in these skills. Significantly greater percentages of HIV residents with dementia also had anemia, depression, schizophrenia, cognitive and memory problems, hepatitis, renal failure, and cancer than other residents with HIV. CONCLUSIONS: These analyses demonstrate that HIV residents with dementia were significantly more likely to have other diseases, infections, and health care conditions than other residents with HIV.

Secular trends in the survival of HIV-infected homosexual men in Amsterdam and Vancouver estimated from a death-included CD4-staged Markov model.

BACKGROUND: The purpose of this study was to investigate secular trends in waiting times in CD4-based stages of human immunodeficiency virus (HIV) disease progression in two cohorts of homosexual men, one in Vancouver and one in Amsterdam. All HIV-positive men with two or more CD4 counts in their AIDS-free period between 1 January 1985 and 1 January 1997 were included in this study. Data regarding clinical AIDS diagnoses (using the 1987 Centers for Disease Control and Prevention [CDC] AIDS case definition) and death were collected through active follow-up, review of hospital records, and municipal/national registries. The Vancouver Lymphadenopathy-AIDS Study (VLAS), was started in November 1982 and had enrollment until December 1984. Both HIV-negative and HIV-positive men were followed at intervals of 3-6 months until 1986 and annually thereafter. The Amsterdam cohort study on HIV and AIDS (ACS) started in December 1984, has ongoing enrollment and follow-up of both HIV-negative and HIV-positive homosexual men. The HIV-positive men were followed at intervals of 3 months. METHODS: The CD4-based stage of an individual at each visit was determined using smoothed data. For each cohort and in each calendar time period, a CD4-based Markov model with death as the absorbing stage was fitted to the data. The parameters in this model were estimated using the method of maximum likelihood and confidence intervals were calculated using bootstrap methods. RESULTS: A total of 509 homosexual men participating in the VLAS were included in this study, providing 5356 visits. Some 292 men developed AIDS before 1 January 1997 and 239 died before this date. In all, 232 of the 239 deaths were AIDS related. Thirty-seven per cent of all visits were related to treatment. A total of 543 homosexual men participating in the ACS were included in this study, providing 10 043 visits; 277 men developed AIDS before 1 January 1997 and 250 died before this date. The date of AIDS diagnosis was known for 225 of the 250 deaths. Twenty per cent of all visits were related to treatment. We found that in both cohort studies the stage-specific waiting times were longer in the low CD4-based stages (stages 4, 5 and 6: i.e. CD4 count <500 cells per mm(3)) after March 1990 compared to waiting times before March 1990. The increase in mean waiting time in these stages with low CD4 count was 21%, 33% and 53%, respectively in the ACS and 20%, 2% and 29% in the VLAS. Because waiting times alone are not exclusive for progression in a reversible model we also calculated the stage-specific median incubation periods till death. Men spent considerably longer in these CD4-based stages after March 1990 compared to before March 1990. CONCLUSIONS: Data from these population-based cohort studies showed that HIV disease progression in the calendar period where treatment was administered was slower for individuals in stages with low CD4 counts. We found no evidence for shortening of the incubation period that may have appeared from increasing virulence of the HIV in the population.

What is the cost of getting the price wrong?

BACKGROUND: The objective of this study was to compare differences in cost estimates for paediatric HIV hospital service provision based on hospital prices with cost estimates obtained through a research-based service-specific costing exercise. METHODS: Activity data on the use of hospital services of children by stage of HIV infection were collected from case-notes for 118 HIV antibody positive children, managed at St Mary's Hospital NHS Trust, London, 1 January 1986-31 December 1994. Hospital unit prices were obtained from the Hospital Trust Finance Department; unit cost estimates were obtained from relevant hospital departments through a research-based service-specific costing exercise. Financial data related to the 1993-1994 financial year, and were indexed to 1995-1996 prices. The main outcome measures were cost estimates per patient-year by stage of HIV infection. Three cost scenarios were calculated: first by linking activity data with hospital prices (Trust Prices); second by linking activity data with routinely available hospital prices plus units costs from the costing exercise where no relevant hospital prices existed (Supplemented Trust Prices); third, by linking activity data exclusively with unit costs from the hospital-specific costing exercise (Unit Costs). RESULTS: There were substantial differences between unit cost estimates per patient-year based on Trust Prices and Supplemented Trust Prices compared with those based on Unit Costs. Differences increased with more intense use of services. The deficit based on Trust Prices compared with Unit Costs ranged from Pound Sterling 432 per patient-year for HIV negative children, Pound Sterling 574 for asymptomatic HIV-infected children, Pound Sterling 1288 for indeterminate children, Pound Sterling 1814 for children with symptomatic non-AIDS to Pound Sterling 7418 per patient-year for children with AIDS. CONCLUSIONS: In this hospital, reliance on generic hospital prices to derive cost estimates for paediatric HIV services produced considerable underestimates of the cost of service provision compared with data derived through the costing exercise. If this occurs across all or most areas of service provision, this can lead to substantial financial deficits, which in turn may mean that the needs of specific client populations may not be met.

Access and use of medications in HIV disease.

OBJECTIVE: To examine if measures of access to medical care are associated with outpatient use of antiretroviral and Pneumocystis carinii pneumonia (PCP) medications among a cohort of individuals with HIV disease. DATA SOURCES: Adults who participated in a series of up to six interviews as part of the AIDS Costs and Services Utilization Survey (ACSUS). ACSUS, a panel survey of persons with HIV disease, was undertaken from 1991 through 1992. STUDY DESIGN: The Andersen Behavioral Model of Health Services Use provided the conceptual framework for the study. Logistic regression analyses with generalized estimating equations were conducted to determine the effects of predisposing, enabling, and need-for-care factors on the odds of antiretroviral or PCP medication use. The analytic sample consisted of 1,586 respondents whose 7,652 interviews provided the data. PRINCIPAL FINDINGS: The multivariate analysis showed that being female (OR = 0.76; 95% C.I. = 0.60-0.95), ages 15 to 24 years (OR = 0.64; 95% C.I. = 0.44-0.92), and having a hospitalization (OR = 0.73; 95% C.I. = 0.63-0.84) were associated with lower odds of using antiretrovirals. African American race (OR = 1.30; 95% C.I. = 1.04-1.62), having both public and private insurance (OR = 2.11; 95% C.I. = 1.47-3.03), attending counseling (OR = 1.17; 95% C.I. = 1.02-1.34), having a usual source of care (OR = 1.70; 95% C.I. = 1.38-2.11), and clinical trials participation (OR = 1.52; 95% C.I. = 1.23-1.87) were associated with a higher odds of use. Similar results were obtained for analyses of PCP medication use. CONCLUSIONS: Sociodemographic differences exist in access and use of prescription drugs within the ACSUS cohort. The results suggest that women and those ages 15 to 24 years have poor access to some medications that improve survival in HIV disease.

[Prevention of wasting and opportunistic infections in HIV-infected patients in West Africa: a realistic and necessary strategy before antiretroviral treatment]. / Prévention de la dénutrition et des infections opportunistes chez lespatients infectés par le VIH en Afrique de l'Ouest: une démarche réaliste, nécessaire, préalabe aux antirétroviraux.

The medical inequalities between countries of the North and South (infrastructure, drug availability, medical techniques) are particularly marked in terms of the challenge posed by HIV infection. We propose a strategy for monitoring adult patients in West Africa that is appropriate to the situation in the field and to economic constraints. The aim of this strategy is to increase the quality of life and the life expectancy of HIV-infected adults and to prevent the overcrowding of hospital departments with patients in the terminal phase of AIDS. We analyzed the biological and clinical spectrum of HIV infection before the onset of the diseases that define AIDS (excluding pulmonary tuberculosis). We found that it was particularly important to diagnose B-stage diseases early, especially atypical chronic cutaneous and mucous diseases. Careful analysis of data from a routine hemogram (total lymphocyte count 2500/ml; paradoxical eosinopenia), even in the absence of a CD4 lymphocyte count, should also enable clinicians from a wide variety of health structures to identify the HIV-infected patients most likely to benefit from more detailed clinical follow up, prophylaxis of opportunistic infections using cotrimoxazole, nutritional checkups and prevention of wasting. Cachexia is the most common AIDS-associated disease in West African patients. It involves an overall decrease in calorific intake, diarrhea, immune system activation, an increase in TNFalpha production and greater energy expenditure when resting. Recent nutritional studies have shown that it is vital to optimize the calorific intake of HIV-infected patients presenting with chronic diarrhea, before the onset of severe immune deficiency, to prevent wasting. So, spontaneous calorific intake should de routinely determined in HIV-infected patients and an optimal diet provided. Specific training in nutrition is required for doctors and nurses, as is consideration of the logistic organization required to provide nutritional support to HIV-infected adults. Despite the large number of individuals infected and the lack of sophisticated paraclinical facilities, we feel that it is possible to establish rational management "a minima" of HIV infection in West Africa, whilst waiting for antiretroviral drugs to become more widely available. This strategy could be of direct benefit to patients without swallowing up the financial resources of the health system in expensive biological follow up. Such basic management is also required before the new antiretroviral drugs become widely available. Research should be carried out in parallel in several reference centers in West Africa to determine the most effective associations of antiretroviral drugs and the optimal timing of treatment during the course of infection and to assess the potential side effects of these drugs in HIV patients exposed to recurrent antigenic stimulation by a wide diversity of pathogens.

Heterogeneity in the relationship between the time tradeoff and Short Form-36 for HIV-infected and primary care patients.

OBJECTIVES: Evidence in the literature suggests that the overall correlation between descriptive and valuational measures of health are weak to moderate. In this study, the relationship between descriptive health status measures, obtained using the Short-Form 36, and health values, measured with the time tradeoff, was explored. METHODS: Two groups of patients matched for age and gender were interviewed. One group comprised 139 human immunodeficiency virus (HIV)-infected patients; the other group comprised 124 primary care patients. The relationship between the SF-36 and the time tradeoff was estimated, assuming homogeneity across patients, using multiple regression analysis. Subsequently, the relationship was examined assuming heterogeneity across patients and using the expectation maximization algorithm in a maximum likelihood context (latent class analysis). RESULTS: Four classes, representing 47%, 13%, 8%, and 32% of the population, respectively, were found. The overall percentage of variation explained under the assumption of a homogeneous relationship was only 33% as compared with 85% when heterogeneity was accounted for. Only three characteristics (educational level, employment status, and the SF-36 social functioning score) sufficed to generate a nearly perfect classification of the patients. CONCLUSIONS: Heterogeneity across subjects should be taken into account in describing the relationship between health values and health status dimensions.

Predicting outcomes in HIV-infected veterans: I. Progression to AIDS.

This article and the following article (Parts I and II) report the development of two clinical staging systems for HIV-infected individuals. The objective of the research reported here (Part I) was to construct a clinical staging system to predict progression to AIDS. We analyzed data from VA Cooperative Study Number 298, a multicenter, double-blind, randomized trial that compared immediate versus deferred zidovudine therapy in 338 HIV-infected individuals who did not have AIDS at enrollment. Baseline variables were tested in univariate Cox regression for their relationship to progression to AIDS, and those that appeared predictive were examined in multivariable analysis. Based on these analyses, we constructed a new clinical staging system based on CD4+ cell count, age, hemoglobin, oral hairy leukoplakia or oral thrush, and fever. The stages of the system were significant predictors of progression to AIDS (p = 0.0001, log-rank test). In conclusion, simple, valid, clinical staging systems for HIV-infected patients can be constructed using information that is readily available in clinical practice settings. Such systems provide better prognostic distinction than CD4+ cell count alone by taking into account the known prognostic effects of other variables.