Extending HIV care in resource-limited settings

Despite the clear benefits of antiretroviral therapy (ART), only three countries in sub-Saharan Africa have achieved the "3 by 5" goal of treating at least half of the persons living with HIV/AIDS who need it. A major obstacle faced by many lower income countries is the establishment of treatment programs in rural areas where there is a scarcity of trained health care providers and infrastructure. This paper reviews published data on rural ART programs in lower income countries to identify necessary components of such a program. No clearly superior model for rural ART delivery has emerged. All programs document the need for expanded physical infrastructure, laboratory development, recruitment/ training of additional health care providers, and/or the introduction of new technologies in order to effectively support the needs of ART roll-out.     

Home testing for HIV infection in resource-limited settings

Among an estimated 33 million individuals who are infected with HIV worldwide, only 10% are aware of their status. HIV testing is the cornerstone to preventing further transmission and to caring for those infected, particularly as access to treatment improves in resource-limited settings. However, efforts to expand testing through facilities-based testing have not achieved adequate testing coverage, prompting efforts to reach more individuals through strategies such as home-based HIV testing. Home testing is showing promising early results in some high-prevalence, resource-limited settings. This article reviews the mechanisms and literature to date of this door-to-door approach.     

Managing HIV/AIDS in correctional settings

Approximately one quarter of people living with HIV/AIDS in the United States pass through the correctional system, resulting in a burden of infection on the correctional health care system that has challenged correctional and public health officials. The HIV epidemic behind bars results from the high prevalence of HIV risk behaviors among those incarcerated: illicit drug use, untreated mental illness, prostitution, homelessness, and poverty. Challenges to HIV care in correctional settings include management of comorbid conditions, remoteness from HIV care sites, organizational constraints, and access to effective therapies. Despite these challenges, prisoners with HIV have derived considerable benefit from HIV detection and treatment. In order to achieve parity in HIV outcomes among vulnerable populations, effective prison-release programs that incorporate effective case management with effective drug treatment and adherence strategies are required to extend the benefit of highly active antiretroviral therapy as prisoners transition back to community settings.     

Immune status monitoring of HIV/AIDS patients in resource-limited settings: a review with an emphasis on CD4+ T-lymphocyte determination

CD4 T-lymphocytes play a vital role in maintaining the integrity of the human immune system. They are also the primary target cells for human immunodeficiency virus (HIV). The progressive depletion of these cells eventually results in weakening of the host's immune ability to fight against any pathogen, thus rendering the host susceptible to infections and leading ultimately to death of patients in the terminal stage of acquired immune deficiency syndrome (AIDS). Although several clinical and laboratory parameters have been used for monitoring disease progression and the effectiveness of HIV antiretroviral therapy (ART), it is the simple measurement of CD4+ T-lymphocytes that remains the single and most important parameter for management of HIV-infected patients in resource-limited settings. To date, flow cytometer is considered to be the most accepted technology for both percentage and absolute CD4+ T-lymphocyte determination because of its accuracy, precision and reproducibility. However, flow cytometer based CD4 testing is relatively expensive, complex and thus technically demanding. Simple innovative approaches applicable to the conventional flow cytometric system and new technologies have been successfully developed to increase cost saving especially for use in resource-challenged settings. Principles of the existing dual- and single-platform approaches as well as several affordable CD4 measurement technologies are discussed along with both internal and external quality control systems in the management of laboratories performing CD4 testing.     

A non-specific biomarker of disease activity in HIV/AIDS patients from resource-limited environments

Background

A general non-specific marker of disease activity that could alert the clinician and prompt further investigation would be of value in patients with HIV/AIDS, especially in resource limited environments.

Objective

To investigate the potential of neopterin as non-specific biomarker in patients with advanced HIV/AIDS.

Methods

Cross-sectional study in 105 HIV positive patients (75 on highly active antiretroviral treatment (HAART). Neopterin was assessed by enzyme linked immune-absorbent assay and cytokines by flow cytometry.

Results

Neopterin levels were significantly higher (p<0.001) for the total patient than for the control group. Significant correlations between neopterin and plasma indicators of inflammation showed neopterin to be a good indicator of active inflammatory status and of the effect of HAART on the immune system. Neopterin was superior to C-reactive protein and to individual cytokines as indicator of immune deficiency. Increased neopterin levels were associated with a decline in albumin, haemoglobin and the albumin/globulin ratio, and with increases in red cell distribution width.

Conclusions

Plasma neopterin is a good non-specific biomarker of disease activity in HIV/AIDS patients. It is a good indicator of inflammatory activity, perpetuation of inflammation-associated co-morbidities, degree of immune deficiency and has predictive value for underlying disease, and for monitoring the HAART response.     

Remote consultations and HIV/AIDS continuing education in low-resource settings

BACKGROUND: Telemedicine is a way to support physicians working in resource-poor settings, providing remote consultations and continuing medical education on HIV/AIDS care. METHODS: A hybrid E-mail/web support telemedicine service was created in 2003 at the Institute of Tropical Medicine, Antwerp, Belgium, with a discussion forum hosting more than 170 healthcare professionals from 40 different countries, generally resource constrained. Interesting posts and recurring questions from this discussion forum have been elaborated as case studies or frequently asked questions, available on the website for consultation. Education and support are also provided through interactive quizzes, user-friendly guidelines, and policy documents with a particular focus on HIV/AIDS care in developing countries. RESULTS: From April 2003 to March 2005, 342 questions were sent from over 17 countries in Africa, Asia, and South America. The vast majority of these questions (93%) were patient-oriented, with only 7% being general questions. Of the patient-oriented questions, 49% were related to antiretroviral therapy, and 44% were related to the diagnosis and treatment of opportunistic infections. CONCLUSIONS: Telemedicine is a cheap and effective method of providing clinical support and continuing education to healthcare workers treating HIV-positive patients in resource-poor settings.     

Integrating multidimensional HIV prevention programs into healthcare settings

Effective secondary prevention programs to reduce HIV transmission risk-relevant behaviors among HIV-infected individuals must go beyond the traditional, common sense prevention components to develop biomedically and epidemiologically informed behavioral interventions as part of comprehensive, integrated, multidisciplinary HIV care. Incorporating and expanding on the Serostatus Approach to Fighting the Epidemic, a five-pronged strategy set forth by the Centers for Disease Control and Prevention in 2001, we discuss recent findings from the biomedical sciences on viral and host factors that influence infectiousness to support the idea that the most proactive prevention programs will explicitly integrate biomedical interventions and approaches designed to reduce infectiousness, and thus the sexual transmission of HIV. Based on studies of emerging and spreading drug-resistant HIV variants, we have posited the potential development of biodisparity as the biological entrenchment of disparities in socioeconomic status, access to care, and HIV risk-relevant behaviors that differentially affect minorities living with HIV in the US. It is clear that creative approaches based on an expanded behavioral medicine interface with the latest HIV biomedical and epidemiological research are needed to enhance the efficacy of HIV secondary prevention.     

Antiretroviral treatment strategies in resource-limited settings

To date, a minority of persons living with HIV worldwide has benefited from the advances in HIV therapeutics fueled by the scientific community, policy-makers, advocates, and the pharmaceutical industry in the global North. A growing body of evidence demonstrates that access to highly active antiretroviral therapy can be successfully scaled-up in less wealthy nations in the South. High rates of adherence correspond with clinical, immunologic, and virologic outcomes similar to those seen in wealthier nations. Recent reports of successful programs highlight the provision of free care, reliance on the international funding sources, and proactive adherence counseling. As access to antiretroviral therapy has improved, there is an urgent need to develop better strategies for initiating and monitoring therapy, including the scale-up of viral load testing.     

IRB/FDA requirements relevant to HIV/AIDS clinical trials in correctional settings

Federally funded research involving inmates in US correctional facilities requires the approval of the Office for Protection from Research Risks (now called the Office for Human Research Protections [OHRP] and located in the Office of the Secretary of the Department of Health and Human Services). Trials that are carried out by pharmaceutical companies (not federally funded) fall under the jurisdiction of the FDA. This article reviews OHRP and FDA guidelines relevant to the conduct of HIV/AIDS clinical trials in correctional settings.     

Simple Pediatric AIDS Severity Score (PASS): a pediatric severity score for resource-limited settings

BACKGROUND: A multidimensional pediatric AIDS severity score (PASS) has been developed for severity adjustment and as a predictive model for mortality in a pediatric HIV-infected population. While the prognostic value of PASS is relevant in the US setting, there is a need to develop a simpler model of PASS for use in resource-limited settings where CD4% values and HIV RNA levels may not be available to assess prognosis and guide treatment decisions. METHODS: A Simple PASS model was developed including baseline weight percentile, WHO stage, symptoms, a general health rating, total lymphocyte count, packed-cell volume, and albumin measures from 1178 perinatally HIV-infected children enrolled into a prospective cohort study (PACTG 219). This prognostic model was then validated among 952 perinatally HIV-infected children enrolled in other PACTG research studies at the same sites. Survival estimates and Hazard Ratios (HR) were obtained using the Kaplan-Meier method and proportional hazards models, respectively. The predictive ability of the models was determined using Harrell's "C" statistic. RESULTS: Of the clinical measures and assays considered in this study, weight percentile, WHO stage, symptomatology, general health rating, total lymphocyte count, packed-cell volume, and albumin were found to be predictive of mortality. The simple PASS model including only the simple clinical measures and assays was found to be predictive of mortality (C statistic = 0.852). Its discriminative ability for mortality was comparable to a model consisting of the Simple PASS plus CD4% (C statistic = 0.871). CONCLUSION: The Simple PASS scoring system provides a reasonable alternative to CD4% values and HIV viral-load levels to assess prognosis and guide decisions about antiretroviral therapy initiation in resource-limited settings.     

Potential impact of antiretroviral therapy on HIV-1 transmission and AIDS mortality in resource-limited settings

OBJECTIVE: To estimate the potential impact of antiretroviral therapy on the heterosexual spread of HIV-1 infection and AIDS mortality in resource-limited settings. METHODS: A mathematic model of HIV-1 disease progression and transmission was used to assess epidemiologic outcomes under different scenarios of antiretroviral therapy, including implementation of World Health Organization guidelines. RESULTS: Implementing antiretroviral therapy at 5% HIV-1 prevalence and administering it to 100% of AIDS cases are predicted to decrease new HIV-1 infections and cumulative deaths from AIDS after 10 years by 11.2% (inter-quartile range [IQR]: 1.8%-21.4%) and 33.4% (IQR: 26%-42.8%), respectively. Later implementation of therapy at endemic equilibrium (40% prevalence) is predicted to be less effective, decreasing new HIV-1 infections and cumulative deaths from AIDS by 10.5% (IQR: 2.6%-19.3%) and 27.6% (IQR: 20.8%-36.8%), respectively. Therapy is predicted to benefit the infected individual and the uninfected community by decreasing transmission and AIDS deaths. The community benefit is greater than the individual benefit after 25 years of treatment and increases with the proportion of AIDS cases treated. CONCLUSIONS: Antiretroviral therapy is predicted to have individual and public health benefits that increase with time and the proportion of infected persons treated. The impact of therapy is greater when introduced earlier in an epidemic, but the benefit can be lost by residual infectivity or disease progression on treatment and by sexual disinhibition of the general population.     

Sensitization and training for health promotion on HIV / AIDS and STDS

Many people are loathe to confront the issues of HIV/AIDS, sexually transmitted diseases, and sexual behavior. Health planners, administrators, and personnel, must, however, courageously confront such issues as they plan and implement programs to help populations in need. The sensitization and training of people who could be or are involved in health promotion/education is an ongoing process. People must consciously confront their values, norms, and attitudes on factors associated with the HIV/AIDS epidemic so that they can learn to teach others in an unbiased and nondiscriminatory manner. On that note, a better understanding is needed of how what is undertaken in health promotion is connected to the larger whole of HIV/AIDS and STD activities. A strategic approach is called for.     

Complete blood cell count as a surrogate CD4 cell marker for HIV monitoring in resource-limited settings

BACKGROUND: A total lymphocyte count (TLC) of 1200 cells/mL has been used as a surrogate for a CD4 count of 200 cells/microL in resource-limited settings with varying results. We developed a more effective method based on a decision tree algorithm to classify subjects. METHODS: A decision tree was used to develop models with the variables TLC, hemoglobin, platelet count, gender, body mass index, and antiretroviral treatment status of subjects from the University of Alabama at Birmingham (UAB) observational database. Models were validated on data from the Birmingham Veterans Affairs Medical Center (BVAMC) and Zambia, with primary decision trees also generated from these data. RESULTS: A total of 1189 patients from the UAB observational database were included. The UAB decision tree classified a CD4 count < or =200 cells/microL as better than a TLC cut-point of 1200 cells/mL, based on the area under the curve of the receiver-operator characteristic curve (P < 0.0001). When applied to data from the BVAMC and Zambia, the UAB-based decision tree performed better than the TLC cut-point of 1200 cells/mL (BVAMC: P < 0.0001; Zambia: P = 0.0009) but worse than a decision tree based on local data (BVAMC: P < or = 0.0001; Zambia: P < or = 0.0001). CONCLUSION: A decision tree algorithm based on local data identifies low CD4 cell counts better than one developed from a different population or a TLC cut-point of 1200 cells/mL.     

HIV-associated tuberculosis and cryptococcosis in resource-limited settings

Tuberculosis (TB) and cryptococcosis are common infectious complications in HIV in resource-limited settings and contribute substantial morbidity and mortality. The increasing access to highly active antiretroviral treatment (HAART) has invited numerous challenges such as timing of HAART, cotreatment (drug dosages and interaction), immune reconstitution syndromes, and withdrawal of chemoprophylaxis. Numerous small studies propose the feasibility of concomitant TB/HIV treatment that needs to be confirmed in large, randomized trials. Treatment of acute cryptococcocal meningo-encephalitis with amphoterecin B is fraught with logistic problems in resource-limited settings. An effective safe dose of fluconazole as monotherapy needs to be determined in phase II studies. Current management guidelines extrapolated from developed countries may not necessarily apply and need validation in resource-limited settings.