BACKGROUND: We reviewed the impact of HIV, HIV exposure, and antiretroviral therapy/prophylaxis on neurodevelopmental outcomes of HIV-infected and HIV-exposed-uninfected infants and children. METHODS: A literature search of Medline, Embase, PsychINFO, Web of Science, PubMed, and conference Web sites (1990–March 2011) using the search terms, infant, child, HIV, neurodevelopment, cognition, language, and antiretroviral therapy, identified 31 studies of HIV/antiretroviral exposure using standardized tools to evaluate infant/child development as the main outcome. Articles were included if results were reported in children RESULTS: Infants who acquired HIV during fetal and early life tended to display poorer mean developmental scores than HIV-unexposed children. Mean motor and cognitive scores were consistently 1 to 2 SDs below the population mean. Mean scores improved if the infant received treatment before 12 weeks and/or a more complex antiretroviral regimen. Older HIV-infected children treated with highly active antiretroviral therapy demonstrated near normal global mean neurocognitive scores; subtle differences in language, memory, and behavior remained. HIV-exposed-uninfected children treated with antiretrovirals demonstrated subtle speech and language delay, although not universally. CONCLUSIONS: In comparison with resource-rich settings, HIV-infected and HIV-exposed-uninfected infants/children in resource-poor settings demonstrated greater neurodevelopmental delay compared with HIV-unexposed infants. The effects on neurodevelopment in older HIV-infected children commenced on antiretroviral therapy from an early age and HIV-exposed-uninfected children particularly in resource-poor settings remain unclear.

Neurodevelopment in Children Born to HIV-Infected Mothers by Infection and Treatment Status

Objective To examine whether or not self-sampled cervical screening for human papillomavirus (HPV) DNA is acceptable and if women prefer self-sampling to clinician-based sampling. Design Systematic review and meta-analysis. Data sources Thirty-seven primary studies obtained through a comprehensive search of six electronic bibliographic databases from 1986 to 2014 and other sources. Search keywords included HPV, screening, DNA testing, vaginal testing, self-collected specimen, self-collected sample, self-sampling, self-screening, preferences and acceptability. Review methods Studies eligible for analysis included those that had participants perform self-sampling, evaluated participant acceptance of or preference for self-sampled vaginal HPV DNA and reported data to calculate an effect size. There were no exclusion criteria for publication status or geographical location. Meta-analytic methods were used to quantitatively synthesise effect sizes across studies. Results The 37 studies included 18 516 female participants from 24 countries across five continents. Overall, there was a high level of acceptability of self-sampling among the participants. Participants reported preference for self-sampling over clinician sampling due to attractive characteristics such as ease and privacy. Conclusions The overall acceptability of self-sampled cervical screening, coupled with economic and effective care, provides opportunities for expanding screening services. Importantly, this can provide a creative screening alternative for women who do not participate in traditional cytological screening, and may ultimately reduce health disparities and prevent cervical disease.

https://sti.bmj.com/content/sextrans/early/2016/10/19/sextrans-2016-052609.full.pdf

The acceptability of self-sampled screening for HPV DNA: a systematic review and meta-analysis

BACKGROUND: Dried blood spots (DBS) have been used as alternative specimens to plasma to increase access to HIV viral load (VL) monitoring and early infant diagnosis (EID) in remote settings. We systematically reviewed evidence on the performance of DBS compared to plasma for VL monitoring and EID. METHODS AND FINDINGS: Thirteen peer reviewed HIV VL publications and five HIV EID papers were included. Depending on the technology and the viral load distribution in the study population, the percentage of DBS samples that are within 0.5 log of VL in plasma ranged from 52-100%. Because the input sample volume is much smaller in a blood spot, there is a risk of false negatives with DBS. Sensitivity of DBS VL was found to be 78-100% compared to plasma at VL below 1000 copies/ml, but this increased to 100% at a threshold of 5000 copies/ml. Unlike a plasma VL test which measures only cell free HIV RNA, a DBS VL also measures proviral DNA as well as cell-associated RNA, potentially leading to false positive results when using DBS. The systematic review showed that specificity was close to 100% at DBS VL above 5000 copies/ml, and this threshold would be the most reliable for predicting true virologic failure using DBS. For early infant diagnosis, DBS has a sensitivity of 100% compared to fresh whole blood or plasma in all studies. CONCLUSIONS: Although limited data are available for EID, DBS offer a highly sensitive and specific sampling strategy to make viral load monitoring and early infant diagnosis more accessible in remote settings. A standardized approach for sampling, storing, and processing DBS samples would be essential to allow successful implementation. TRIAL REGISTRATION: PROSPERO Registration #: CRD42013003621.

Systematic review of the use of dried blood spots for monitoring HIV viral load and for early infant diagnosis.

Objective To evaluate the accuracy of a point-of-care (POC) nucleic acid-based test (NAT) for early infant HIV diagnosis (EID) in primary health clinics in Mozambique. Methods POC and laboratory NAT EID tests were conducted on matched blood samples collected from 827 HIV-exposed infants younger than 18 months who were enrolled consecutively at 4 periurban primary health clinics and the central hospital in Maputo. Lancet heel draw blood collected by nurses was tested on site for HIV-1/-2 RNA on the Alere HIV NAT POC device and also used to create dried blood spots for later laboratory EID testing on the Roche Cobas Taqman/Ampliprep instrument. Results were used to determine the sensitivity, specificity, and agreement between the POC and laboratory NAT EID tests. Results The sensitivity and specificity of POC NAT EID testing were 98·5% (95% confidence interval (CI): 91.7 to 99.9, n = 65) and 99·9% (95% CI: 99.3 to 100, n = 762), respectively, compared with laboratory EID tests. Overall agreement was high (Cohen kappa = 0·981; 95% CI: 0.96 to 1.00). Positive (98·5%; 95% CI: 96·3 to 100) and negative 99.9% (95% CI: 99.7 to 100) test agreement was also high. Conclusions Primary health care nurses accurately performed POC NAT EID testing within primary health care clinics. On-site nucleic acid-based EID testing is technically feasible in clinic settings and could be used in efforts to improve access to pediatric HIV antiretroviral treatment.

Accurate early infant HIV diagnosis in primary health clinics using a point-of-care nucleic acid test.

Tropical infectious diseases diagnosis and surveillance are often hampered by difficulties of sample collection and transportation. Filter paper potentially provides a useful medium to help overcome such problems. We reviewed the literature on the use of filter paper, focusing on the evaluation of nucleic acid and serological assays for diagnosis of infectious diseases using dried blood spots (DBS) compared with recognized gold standards. We reviewed 296 eligible studies and included 101 studies evaluating DBS and 192 studies on other aspects of filter paper use. We also discuss the use of filter paper with other body fluids and for tropical veterinary medicine. In general, DBS perform with sensitivities and specificities similar or only slightly inferior to gold standard sample types. However, important problems were revealed with the uncritical use of DBS, inappropriate statistical analysis, and lack of standardized methodology. DBS have great potential to empower healthcare workers by making laboratory-based diagnostic tests more readily accessible, but additional and more rigorous research is needed.

An Overview of the Clinical Use of Filter Paper in the Diagnosis of Tropical Diseases

Worldwide, in 2008, an estimated 430 000 [240 000–610 000] new infections due to the human immunodeficiency virus (HIV) occurred in children, of which 90% were acquired through motherto-child transmission (MTCT) of HIV. Of the 430 000 new infections, between 280 000 and 360 000 were acquired during labour and in the pre-partum period. Of the remaining new infections, the majority were acquired during breastfeeding.
In infantsi who acquire HIV around the time of delivery, disease progression occurs very rapidly in the first few months of life, often leading to death. To enable antiretroviral (ARV) prophylaxis to be given to infants as soon as possible after birth, all infants should have their HIV exposure status known at birth. As not all mothers are given HIV tests, very few HIV-exposed infants are
identified and very few infants are known to be gaining access to early diagnosis, the necessary prerequisite to ‘timely’ initiation of antiretroviral therapy (ART). Currently, only an estimated 15% of HIV-exposed infants needing testing are tested in the first two months of life.
Recently published data confirming dramatic survival benefits for infants started on ART as early as possible after the diagnosis of HIV, prompted a review of the World Health Organization(WHO) paediatric treatment guidelines. In June 2008, new guidance was issued, which recommends prompt initiation of ART in infants diagnosed with HIV infection. In order to identify those infants who will need immediate ART, early confirmation of HIV infection is required. In November 2008, a meeting was convened to review recommendations by WHO for the diagnostic testing of HIV infection in infants and children. The meeting brought together the guideline review group that had developed the initial recommendations in 2005.
The guideline review group followed the grading of recommendations assessment, development and evaluation (GRADE) approach in reviewing the recommendations for early detection of HIV infection according to the current WHO Guidelines for Guidelines. This document contains the new recommendations. The full document, including GRADE evidence profiles and the factors that have been taken into account in the group's decision-making with respect to the strength of the recommendations, is available in annexes which are posted online at http://www.who.int/
hiv/topics/paediatric/en/

Artur Ramos

Papers

WHO recommendations on the diagnosis of HIV infection in infants and children