Antiretrovirals for HIV prevention: when should they be recommended?

Since the introduction of the first antiretroviral agent for HIV treatment, information on antiretroviral therapy (ART) effectiveness has grown continuously. In recent years, there has also been a growth of interest in use of ART for the prevention of HIV transmission, either by reducing the infectivity of the infected person or by protecting the uninfected individuals from HIV acquisition. The purpose of this review is to summarize the body of evidence available for treatment as prevention and pre-exposure prophylaxis and their effectiveness in prevention of infection. In addition, our aim is to discuss the operational aspects of both prevention strategies and to provide commentary for future HIV prevention programs.

Mortality and associated factors after initiation of pediatric antiretroviral treatment in the Democratic Republic of the Congo.

OBJECTIVE: We aimed to describe factors associated with mortality among children receiving antiretroviral treatment (ART) at a pediatric hospital in Kinshasa, Democratic Republic of the Congo. RESULTS: Two hundred ninety-nine children, <18 years old, were followed for a median of 77 weeks (interquartile range: 61-103) post-ART initiation. Survival probability was 89.6% [95% confidence interval (CI): 85.5-92.6%] at 12 months; 24 of 31 deaths (77.4%) occurred within 2 months of ART initiation. Predictors of mortality in bivariate analysis were >/=2 opportunistic infections before ART initiation, severe immunosuppression as defined by age-specific CD4 count or percentage criteria, hemoglobin <9 g/dL, oral candidiasis, and severe malnutrition. In multivariate analysis, weight for age z-score [hazard ratio (HR): 0.39; 95% CI: 0.27-0.61; P < 0.001] and oral candidiasis (HR: 5.86; 95% CI: 2.34-14.65; P = 0.0002) were independent predictors of mortality. Suspected septic shock was the most common cause of death (n = 12/31, 38.7%). CONCLUSIONS: Children receiving ART in this resource-poor setting were at the highest risk of dying in the first 2 months of ART, particularly when they presented with malnutrition or oral candidiasis. Optimal timing of ART initiation during nutritional rehabilitation should be determined. Promotion of early care seeking, strengthened health care, and prevention services are important to further improve outcome of pediatric ART in resource-poor settings.

A visual dosing aid for first-line pediatric antiretroviral treatment in resource-poor settings.

The visual dosing aid (VDA) was developed to facilitate dosing calculations in response to children's; growth and weight during antiretroviral treatment. The theoretical accuracy of the VDA was assessed using anthropometric data from 55 children receiving care in the USA and 324 children in the Democratic Republic of the Congo. The VDA dose was similar to the WHO recommended dose. A potentially significant relative dosing difference of >or=20% occurred in <3% of children for NVP, AZT and d4T, but was observed in 20% for 3TC, overdosing being more frequent. The VDA compared well with generic pediatric fixed dose combination tablets. Results did not differ between sites. The VDA enables accurate dosing of pediatric ART in distinct populations and could facilitate roll-out of pediatric ART in resource-poor settings.

Pediatric HIV infection: the state of antiretroviral therapy.

Pediatric HIV/AIDS has become less of a problem in resource-rich countries as the number of perinatal infections has reduced dramatically since the advent of antiretrovirals, resulting in the effective prevention of mother-to-child transmission. In resource-limited settings, however, pediatric HIV infection remains a colossal problem; a separate review in this same issue of Expert Review of Anti-Infective Therapy examines the international aspects of pediatric HIV/AIDS. Treatment of HIV infection in children differs from that in adults in the use of immunologic markers and owing to drug pharmacokinetics and age-related adherence issues. This review, geared for the general pediatrician or family practitioner who may see the HIV-positive child in the clinic or the hospital, summarizes the most recent pediatric data and guidelines for the testing and treatment of HIV, including the US NIH guidelines released in February 2008. Treatment-experienced patients, who should be cared for by pediatric HIV specialists, are not addressed here specifically. Adolescents, infected either perinatally or sexually, with their own unique issues, deserve a separate review.

HIV care and treatment for children in resource-limited settings.

Although efforts to combat the HIV epidemic have focused on the perinatal reduction of HIV transmission, many children are still being infected with HIV in resource-limited settings. Access to HIV care, cotrimoxazole and antiretroviral therapy (ART) for HIV-infected children has greatly improved in recent years, and has proven to be very effective in reducing mortality in all age categories. Many challenges remain to be resolved, such as the retention in care of children born to HIV-infected mothers, the lack of pharmacokinetic data on ART in malnourished children, optimum timing of ART, treatment and diagnosis of concomitant tuberculosis, and the effects of ART and HIV on the child's development. In the long term, treatment success might be negated due to lower rates of viral suppression in children and the accumulation of resistance mutations. Evidenced-based comprehensive care models should allow for decentralizing care up to the level of the community, allowing larger numbers of children to receive HIV care.

Computed CD4 percentage as a low-cost method for determining pediatric antiretroviral treatment eligibility.

BACKGROUND: The performance of the WHO recommendations for pediatric antiretroviral treatment (ART) in resource poor settings is insufficiently documented in routine care. METHODS: We compared clinical and immunological criteria in 366 children aged 0 to 12 years in Kinshasa and evaluated a simple computation to estimate CD4 percent, based on CD4 count, total white blood cell count and percentage lymphocytes. Kappa (kappa) statistic was used to evaluate eligibility criteria and linear regression to determine trends of CD4 percent, count and total lymphocyte count (TLC). RESULTS: Agreement between clinical and immunological eligibility criteria was poor (kappa = 0.26). One third of children clinically eligible for ART were ineligible using immunological criteria; one third of children immunologically eligible were ineligible using clinical criteria. Among children presenting in WHO stage I or II, 54 (32%) were eligible according to immunological criteria. Agreement with CD4 percent was poor for TLC (kappa = 0.04), fair for total CD4 count (kappa = 0.39) and substantial for CD4 percent computational estimate (kappa = 0.71). Among 5 to 12 years old children, total CD4 count was higher in younger age groups (-32 cells/mm3 per year older), CD4 percent was similar across age groups. CONCLUSION: Age-specific thresholds for CD4 percent optimally determine pediatric ART eligibility. The use of CD4 percent computational estimate may increase ART access in settings with limited access to CD4 percent assays.

Pulmonary Sporothrix schenckii infection in a HIV positive child.

Sporothrix schenckii is a ubiquitous fungus, causing mostly non life-threatening localized infections of the skin and subcutaneous tissues that can be treated with oral antifungal agents. Meningeal, pulmonary and osteoarticular dissemination occur mainly in immunosuppressed patients. Pulmonary sporotrichosis is rare and responds poorly to treatment. Cases of disseminated sporotrichosis have most frequently been reported in patients residing in South America and Asia, and have increasingly been reported in AIDS patients. The distribution and pathogenicity of S. schenckii in Sub-Saharan Africa is not well known. We report a case of invasive pulmonary sporotrichosis in an eleven year old HIV-infected boy in Kinshasa, Democratic Republic of the Congo, successfully treated with oral fluconazole.