The recent Ebola virus outbreak in West Africa clearly demonstrated the critical role of laboratory systems and networks in responding to epidemics. Because of the huge challenges in establishing functional laboratories at all tiers of health systems in developing countries, strengthening specimen referral networks is critical. In this review article, we propose a platform strategy for developing specimen referral networks based on 2 models: centralized and decentralized laboratory specimen referral networks. These models have been shown to be effective in patient management in programs in resource-limited settings. Both models lead to reduced turnaround time and retain flexibility for integrating different specimen types. In Haiti, decentralized specimen referral systems resulted in a 182% increase in patients enrolling in human immunodeficiency virus treatment programs within 6 months. In Uganda, cost savings of up to 62% were observed with a centralized model. A platform strategy will create a network effect that will benefit multiple disease programs.

BACKGROUND: During 2004-2009, >12,000 children (<15 years old) initiated antiretroviral therapy (ART) in Mozambique. Nationally representative outcomes and temporal trends in outcomes were investigated. METHODS: Rates of death, loss to follow-up (LTFU), and attrition (death or LTFU) were evaluated in a nationally representative sample of 1,054 children, who initiated ART during 2004-2009 at 25 facilities randomly selected using probability-proportional-to-size sampling. RESULTS: At ART initiation during 2004-2009, 50% were male, median age was 3.3 years, median CD4% was 13%, median CD4 count was 375 cells/microL, and median weight-for-age z-score was -2.1. During 2004-2009, median time from HIV diagnosis to care initiation declined from 33 to 0 days (p=0.001), median time from care to ART declined from 93 to 62 days (p=0.004), the percentage aged <2 at ART initiation increased from 16% to 48% (p=0.021), the percentage of patients with prior tuberculosis declined from 50% to 10% (p=0.009), and the percentage with prior lymphocytic interstitial pneumonia declined from 16% to 1% (p<0.001). Over 2,652 person-years of ART, 183 children became LTFU and 26 died. Twelve-month attrition was 11% overall, but increased from 3% to 22% during 2004-2009, due mainly to increases in 12-month LTFU (from 3% to 18%). CONCLUSION: Declines in the prevalence of markers of advanced HIV disease at ART initiation probably reflect increasing ART access. However, 12-month LTFU increased during program expansion, and this negated any program improvements in outcomes that might have resulted from earlier ART initiation.

Guidelines for antiretroviral (ARV) prophylaxis following high-risk exposure (postexposure prophylaxis—PEP) to human immunodeficiency virus (HIV) date to 1990, when the US Centers for Disease Control and Prevention (CDC) first considered such recommendations for persons with occupational exposures to HIV [1]. The US Public Health Service also issued recommendations focused on occupational exposures in 1996 [2]; these recommendations have been updated 5 times [3–7]. Prophylaxis after non-occupational exposures to HIV (via sexual contact and sharing of drug-using paraphernalia) was first addressed by the CDC in 1998 [8] and updated in 2005 [9]. The World Health Organization (WHO) first considered PEP in 2007 and included PEP recommendations in the 2013 consolidated guidelines; both documents focused on occupational exposures [10, 11]. The most recently published WHO guidelines on PEP recommend that a PEP regimen be administered as soon as possible within the 72-hour window period after an HIV-related exposure and that whereas a 2-drug antiretroviral regimen is acceptable, a 3-drug regimen is preferred [12].

BACKGROUND: Measurement of CD4+ T-lymphocytes (CD4) is a crucial parameter in the management of HIV patients, particularly in determining eligibility to initiate antiretroviral treatment (ART). A number of technologies exist for CD4 enumeration, with considerable variation in cost, complexity, and operational requirements. We conducted a systematic review of the performance of technologies for CD4 enumeration. METHODS AND FINDINGS: Studies were identified by searching electronic databases MEDLINE and EMBASE using a pre-defined search strategy. Data on test accuracy and precision included bias and limits of agreement with a reference standard, and misclassification probabilities around CD4 thresholds of 200 and 350 cells/mul over a clinically relevant range. The secondary outcome measure was test imprecision, expressed as % coefficient of variation. Thirty-two studies evaluating 15 CD4 technologies were included, of which less than half presented data on bias and misclassification compared to the same reference technology. At CD4 counts <350 cells/mul, bias ranged from -35.2 to +13.1 cells/mul while at counts >350 cells/mul, bias ranged from -70.7 to +47 cells/mul, compared to the BD FACSCount as a reference technology. Misclassification around the threshold of 350 cells/mul ranged from 1-29% for upward classification, resulting in under-treatment, and 7-68% for downward classification resulting in overtreatment. Less than half of these studies reported within laboratory precision or reproducibility of the CD4 values obtained. CONCLUSIONS: A wide range of bias and percent misclassification around treatment thresholds were reported on the CD4 enumeration technologies included in this review, with few studies reporting assay precision. The lack of standardised methodology on test evaluation, including the use of different reference standards, is a barrier to assessing relative assay performance and could hinder the introduction of new point-of-care assays in countries where they are most needed.

In the article by Greig et al1 from Médecins sans Frontières, the authors compared data from their supported HIV/AIDS care and treatment programs at 17 sites in 9 countries in sub-Saharan Africa. Initially, their support began as vertical programs, but later they changed to an integrated model that incorporated HIV treatment into general health care services. In this retrospective study (2003–2010), they compared a number of clinical indicators of antiretroviral treatment (ART) outcome, although controlling for a variety of potential confounders. However, a major potential confounder, CD4 count at initiation of ART, was not included due to 30% with missing data. The study included 14,124 patients at 7 vertical program sites and 1279 at 10 integrated sites. All of the integrated sites were rural, whereas 4 of 7 vertical sites were urban. Programs were standardized across both program types. Training and advisory staff were similar for both. A standardized electronic database containing routinely collected data facilitated this study. Follow-up data were censored at 30 months on ART to make the follow-up time equal between the 2 programs. | Although the authors used data collected from a large number of sites in multiple countries, they examined only retrospective data and were unable to address specific country contexts and the relative costs of the 2 approaches. However, the study results add useful information to the small body of studies that evaluate the utility of integrated programs compared with vertical programs.