HIV Polymerase Chain Reaction Research Articles

Near-real-time tracking of gaps in prevention of mother-to-child transmission of HIV in three districts of KwaZulu-Natal Province, South Africa

Background. Identifying and addressing gaps in the prevention of mother-to-child transmission of HIV (PMTCT) is required if South Africa (SA) is to achieve targets for eliminating MTCT (eMTCT). Potential PMTCT gaps that increase MTCT risk include late maternal HIV diagnosis, lack of or delayed antiretroviral therapy (ART) during pregnancy and breastfeeding, and lack of effective prophylaxis for HIV-exposed infants. Objectives. To investigate, in near real time, PMTCT gaps among HIV-infected infants in three districts of KwaZulu-Natal Province, SA. Methods. Between May and September 2016, PMTCT co-ordinators from eThekwini, uMgungundlovu and uMkhanyakude districts received daily email notification of all HIV polymerase chain reaction (PCR)-positive results. Co-ordinators reviewed facility records for each infant to identify gaps in PMTCT care, including maternal age, timing of maternal HIV diagnosis, maternal treatment history and maternal viral load (VL) monitoring. Data were submitted via the mobile phone SMS (text message) service using Rapid Pro technology and analysed in Stata 14. Results. Data on PMTCT gaps were received for 367 (91.8%) of 400 infants with HIV PCR-positive results, within a median time of 12.5 days (interquartile range (IQR) 6 - 23). The median maternal age was 25 years (IQR 22 - 30), with 48 teenage mothers (15 - 19 years). The sample size was too small to determine whether there were significant differences in PMTCT gaps between the 48 teenage mothers and 293 older (20 - 34 years) mothers. Of the mothers, 220 (60.0%) were first diagnosed prior to conception or at their first antenatal care (ANC) visit, and 127 (34.6%) at or after delivery; 137 (37.3%) transmitted HIV to their infants despite receiving >12 weeks of ART. VL results were unavailable for 70.0% of women. Only 41 (17.5%) of women known to be HIV-positive during ANC had confirmed virological suppression. No statistically significant differences in PMTCT gaps were observed between districts, owing to small sample sizes in uMgungundlovu and uMkhanyakude. Conclusions. The findings highlight the need to improve services during ANC, in particular prioritising maternal VL monitoring. We intend to use improved technology to streamline data collection and reporting towards eMTCT.

Closing the gaps to eliminate mother-to-child transmission of HIV (MTCT) in South Africa: Understanding MTCT case rates, factors that hinder the monitoring and attainment of targets, and potential game changers

Background. Ninety percent of the world’s HIV-positive pregnant women live in 22 countries. These 22 countries, including South Africa (SA) have prioritised the elimination of mother-to-child transmission of HIV (EMTCT). Since 2016 all 22 countries recommend lifelong antiretroviral treatment for all HIV-positive pregnant and lactating women. To measure South African national, provincial and district-level progress towards attaining EMTCT, we analysed the number of in utero (IU) paedatric HIV infections per 100 000 live births (IU case rate), and synthesised factors hindering the monitoring of EMTCT progress and attainment from the viewpoint of provincial and district-level healthcare managers and implementers. We highlight potential innovations to strengthen health systems and improve EMTCT programme delivery. Methods. We reviewed national-, provincial- and district-level birth HIV testing data from routine National Health Laboratory Services (NHLS) records between April 2016 and March 2017. To obtain a qualitative perspective from healthcare managers and implementers, we synthesised information from the nine 2016 provincial-level EMTCT stock-taking workshops. These workshops involve key provincial and district-level staff, mentors and supporting partners. Lastly, we highlight potential innovations presented at these workshops to overcome operational challenges. Results. The national IU mother-to-child transmission (MTCT) rate was 0.9%, which translated to an IU case rate of 245 HIV-positive neonates per 100 000 live births. Provincial IU percent MTCT risk ranged from 0.6% to 1.3%, with IU case rates ranging between 168 and 325 cases per 100 000 live births. District-level IU percent MTCT risk ranged from 0.4% to 1.9%. Potential game changers include: pre-conception counselling to optimise maternal-partner health, weekly dissemination of HIV polymerase chain reaction (PCR) and viral load reports from the NHLS to specific individuals who trace mothers and infants needing care, use of ward-based outreach teams and community caregivers to trace HIV-infected mothers and their infants to link them into care, inclusion of a unique identifier in patient-held infant Road to Health booklets to facilitate infant tracing and continuous quality improvement (CQI) processes within facilities and districts and implementation of an HIV-positive baby tool to understand the characteristics and risks of HIV-positive infants. On an ecological level, provinces and districts using community-based approaches and CQI methodology seemed to have lower MTCT and IU case rates. Conclusions. More quantitative analyses are needed to understand what proportion of the success can be attributed to community-based and CQI approaches and the impact of the potential game changers on progress towards EMTCT.

A retrospective cohort study on effect of literacy status of HIV-positive pregnant women on possibility of child getting HIV infected.

Introduction:Prevention of parent-to-child transmission (PPTCT) program aims at reduction of HIV transmission through vertical route. Although medical intervention reduces chance of HIV transmission substantially, several demographic factors are often contributory. Minimum literacy is required for HIV-infected individuals to understand the course of medicine and to ensure compliance to the treatment which may have impact on vertical transmission. The objective of this study is to analyze relationship between maternal education and possibility of her babies to get HIV infected.Materials and Methods:A retrospective cohort study was carried out through analysis of secondary data during the period from April 13 to September 16 from all stand-alone integrated counseling and testing centers in West Bengal. A total number of 326 HIV-exposed babies, whose 6th week HIV-Polymerase Chain Reaction (PCR) reports are available and both the mother-baby received PPTCT services, were recruited in the study, and their maternal literacy status was substantiated and analyzed.Results:HIV positivity among HIV-exposed babies was found to be 6.67% whose mothers were illiterate as compared to 5.55% whose mothers were literate up to primary standard and 3.93% whose mothers were educated up to secondary standard. HIV positivity among the exposed babies whose mothers studied higher secondary standard or above showed zero HIV positivity. Chi-square was done to ascertain statistical significance but result was inconclusive although the trend shows increasing chance of HIV-exposed babies to get infected with decreasing literacy.Conclusion:Maternal literacy status favorably influences vertical transmission of HIV.

Prevalence and outcomes of HIV-1 diagnostic challenges during universal birth testing - an urban South African observational cohort.

Introduction: HIV‐1 polymerase chain reaction (PCR) testing at birth aims to facilitate earlier initiation of antiretroviral therapy (ART) for HIV‐infected neonates. Data from two years of universal birth testing implementation in a high‐burden South African urban setting are presented to demonstrate the prevalence and outcomes of diagnostic challenges in this context. Methods: HIV‐exposed neonates born at Rahima Moosa Mother and Child Hospital between 5 June 2014 and 31 August 2016 were routinely screened at birth for HIV‐1 on whole blood samples using the COBAS® AmpliPrep/COBAS® TaqMan (CAP/CTM) HIV‐1 Qualitative Test, version 2.0 (Roche Molecular Systems, Inc., Branchburg, NJ, USA). Virological results were interpreted according to standard operating procedures with the South African National Health Laboratory Service. All neonates with non‐negative results were actively followed‐up and categorized according to HIV infection status as positive, negative, uncertain and lost to follow‐up (LTFU). Results: 104 (1.8%) of 5743 HIV‐exposed neonates received a non‐negative birth PCR result, for which laboratory data were available for 102 (98%) cases – 78 (76%) tested positive and 24 (24%) indeterminate. HIV infection status was confirmed positive in 83 (81%) infants, negative in 8 (8%), uncertain in 5 (5%) and LTFU in 6 (6%) cases. The positive predictive value (excluding cases of uncertain diagnosis and inadequate testing) following a non‐negative HIV‐1 PCR screening test at birth was 0.91 (83/91; 95% confidence interval: 0.85–0.96). Neonates testing positive at birth had significantly higher viral load (VL) results than those testing indeterminate at birth of 4.5 and 3.0 log copies/ml (p = 0.0007), respectively. Similarly, mothers of neonates with positive as compared to indeterminate birth test results had higher VLs of 4.5 and 2.7 log copies/ml (p = 0.0013), respectively. Half of neonates with an indeterminate birth test were shown to be HIV‐infected on subsequent confirmatory testing, with time to final diagnosis 30 days longer for these neonates (p < 0.0001). Conclusion: Indeterminate HIV‐1 PCR results accounted for a quarter of non‐negative results at birth and were associated with a high risk of infection in comparison to the risk of in utero transmission. Indeterminate birth results with positive HIV PCR results on repeat testing were associated with later final diagnosis. The HIV‐1 status remains uncertain in a minority of cases because of repeatedly indeterminate results, highlighting the need for more sensitive and specific virological tests.

Antiretroviral Treatment Initiated in the First Month of Life.

Earlier diagnosis of HIV-infected infants facilitates earlier access to therapy and improved clinical outcomes. The aim of this study was to describe the management of infants who started antiretroviral therapy (ART) in the first month of life. A retrospective review was performed on HIV-infected neonates who started ART within the first month of life between January 2013 and March 2015. A total of 997 neonates had 1 HIV polymerase chain reaction test. Of the 997 neonates, 26 (2.6%) tested positive for HIV and 22 initiated therapy in the first month of life. The median age of first HIV polymerase chain reaction test was 7 days. Neonates were started on ART within a median of 7 days of their first HIV test, which equated to a median age of 13.5 [interquartile range (IQR) 7-20] days of life. Median gestational age was 35 weeks (IQR 33-38 weeks), and birth weight was 2170 g (IQR 1773-2480). Nineteen (86.4%) had low birth weight (<2.5 kg) and 16 (72.7%) were premature. Median baseline HIV viral loads were log 4.444 copies/mL (IQR 3.457-5.125), median CD4 counts were 1338 (IQR 803-1928) and CD4% percentages were 36.1% (22.2-45.4). All children initiated zidovudine and lamivudine, 10 with lopinavir/ritonavir and 12 with nevirapine. All children in care are now receiving lopinavir/ritonavir. Of the 22 neonates initiated on treatment, 11 are in care (mean age, 2.1 years), and 2 of these infants had a viral load of <50 copies/ mL when last measured. Early ART initiation in neonates is feasible. Challenges include safe, palatable regimens and continued close follow-up of mothers and infants.

Birth Point of Care (POC) HIV polymerase chain reaction testing in a primary care setting, South Africa

Birth Point of Care (POC) HIV polymerase chain reaction testing in a primary care setting, South Africa

Detection of human immunodeficiency virus-1 ribonucleic acid in the peritoneal effluent of renal failure patients on highly active antiretroviral therapy.

We evaluated the shedding of human immunodeficiency virus (HIV)-1 particles into continuous ambulatory peritoneal dialysis (CAPD) effluents of HIV-positive patients with end-stage renal disease (ESRD). A total of 58 HIV-positive patients with ESRD on highly active antiretroviral therapy (HAART) who had Tenckhoff catheters inserted between September 2012 and February 2015 were prospectively reviewed and followed for 18 months. Peritoneal dialysis (PD) effluent samples from functioning CAPD catheters and plasma samples were obtained at three points during regular clinic visits on days 45 ± 37, 200 ± 19 and 377 ± 13 after catheter insertion. All specimens were stored at -20°C, and each batch was analysed by Roche quantitative HIV-1 polymerase chain reaction assay to detect HIV-1 particles. Clustered logistic regression was used to test for independent predictors of HIV-1 detection in CAPD effluents. HIV-1 RNA above 20 copies/mL assay limit was detectable in 19% (first batch), 26.3% (second batch) and 20% (third batch) of PD effluent specimens. HIV-1 RNA was detectable in PD fluid, without corresponding detection in the paired plasma in 3.4% (first batch), 5.3% (second batch) and 10% (third batch) of samples. Detection of HIV-1 in plasma sample (odds ratios 3.94; 95% confidence interval 1.14-13.55; P = 0.030), body mass index, serum albumin and HAART regimen were found to be significantly associated with HIV-1 detection in PD effluents. HIV particles are shed in detectable amounts into CAPD effluents even in patients with suppressed plasma viral load, raising concerns of a localized sanctuary site and potential infectivity of HIV-positive CAPD patients on a full complement of HAART.

Effectiveness of an SMS-based maternal mHealth intervention to improve clinical outcomes of HIV-positive pregnant women

ABSTRACTWe conducted a retrospective study to investigate the effectiveness of an mHealth messaging intervention aiming to improve maternal health and HIV outcomes. Maternal health SMSs were sent to 235 HIV-infected pregnant women twice per week in pregnancy and continued until the infant’s first birthday. The messages were timed to the stage of the pregnancy/infant age and covered maternal health and HIV-support information. Outcomes, measured as antenatal care (ANC) visits, birth outcomes and infant HIV testing, were compared to a control group of 586 HIV-infected pregnant women who received no SMS intervention. Results showed that intervention participants attended more ANC visits (5.16 vs. 3.95, p < 0.01) and were more likely to attend at least the recommended four ANC visits (relative risk (RR): 1.41, 95% confidence interval (CI): 1.15–1.72). Birth outcomes of intervention participants improved as they had an increased chance of a normal vaginal delivery (RR: 1.10, 95% CI: 1.02–1.19) and a lower risk of delivering a low-birth weight infant (<2500 g) (RR: 0.14, 95% CI: 0.02–1.07). In the intervention group, there was a trend towards higher attendance to infant polymerase chain reaction (PCR) testing within six weeks after birth (81.3% vs. 75.4%, p = 0.06) and a lower mean infant age in weeks at HIV PCR testing (9.5 weeks vs. 11.1 weeks, p = 0.14). These results add to the growing evidence that mHealth interventions can have a positive impact on health outcomes and should be scaled nationally following comprehensive evaluation.

An audit of primary medical conditions in children admitted to the paediatric intensive care unit of Charlotte Maxeke Johannesburg Academic Hospital

Background. There is approximately one paediatric intensive care unit (PICU) bed per 22 800 children in SA, making PICU beds a very limited resource. Objectives. To determine the spectrum of medical conditions in children admitted to a PICU, their outcomes, and to compare the number and outcomes of HIV-exposed/infected children v. HIV-unexposed children. Methods. This was a retrospective chart review of children older than 28 days, admitted to Charlotte Maxeke Johannesburg Academic Hospital (CMJAH) PICU for medical conditions from 1 January 2013 to 31 July 2014. Results. There were 883 admissions; 518 (59%) were neonates and 234 (26.5%) were surgical patients, leaving a final sample of 131 (14.8%) children with medical conditions. The median age of children admitted was 3.8 months. Out of 131 children, 44 (34%) were HIV-exposed and 16 (12.2%) had a positive HIV polymerase chain reaction (PCR) result. Lower respiratory tract infections (LRTIs) accounted for two-thirds of all admissions at 84 (64.1%) and were significantly more common in HIV-exposed children (p=0.0005); 32 (24.4%) patients died. HIV-exposed children stayed 3 days longer (p=0.015), were ventilated for 4 more days (p=0.012) and were three times more likely to require high-frequency oscillatory ventilation (p=0.0005) than HIV-unexposed children. Mortality was similar between these two groups. Children confirmed HIV PCR-positive had a significantly longer duration of ICU stay (p=0.03) and ventilation (p=0.006) than those who were exposed but uninfected. Conclusion. There were 883 children admitted in 19 months to CMJAH PICU. A total of 15% of admissions were for medical conditions, two-thirds of which were for LRTIs. One-third of the children were HIV-exposed and had similar outcomes to their unaffected counterparts, although their duration of ventilation and length of stay were longer.

TRACnet Internet and Short Message Service Technology Improves Time to Antiretroviral Therapy Initiation Among HIV-infected Infants in Rwanda.

Delays in testing HIV-exposed infants and obtaining results in resource-limited settings contribute to delays for initiating antiretroviral therapy (ART) in infants. To overcome this challenge, Rwanda expanded its national mobile and Internet-based HIV/AIDS informatics system, called TRACnet, to include HIV polymerase chain reaction (PCR) results in 2010. This study was performed to evaluate the impact of TRACnet technology on the time to delivery of test results and the subsequent initiation of ART in HIV-infected infants. A retrospective cohort study was conducted on 380 infants who initiated ART in 190 health facilities in Rwanda from March 2010 to June 2013. Program data collected by the TRACnet system were extracted and analyzed. Since the introduction of TRACnet for processing PCR results, the time to receive results has significantly decreased from a median of 144 days [interquartile range (IQR): 121-197 days] to 23 days (IQR: 17-43 days). The number of days between PCR sampling and health facility receipt of results decreased substantially from a median of 90 days (IQR: 83-158 days) to 5 days (IQR: 2-8 days). After receiving PCR results at a health facility, it takes a median of 44 days (IQR: 32-77 days) before ART initiation. Result turnaround time was significantly associated with time to initiating ART (P < 0.001). An increased number of staff trained for HIV care and treatment was also significantly associated with decreased time to ART initiation (P = 0.004). The use of mobile technology for communication of HIV PCR results, coupled with well-trained and skilled personnel, can reduce delays in communicating results to providers. Such reductions may improve timely ART initiation in resource-limited settings.

Uptake of early infant diagnosis in Thailand's national program for preventing mother-to-child HIV transmission and linkage to care, 2008-2011.

IntroductionEarly infant diagnosis (EID) has been a component of Thailand's prevention of mother-to-child HIV transmission (PMTCT) programme since 2007. This study assessed the uptake, EID coverage, proportion of HIV-exposed infants receiving a definitive HIV diagnosis, mother-to-child transmission (MTCT) rates and linkage to HIV care and treatment.MethodsInfant polymerase chain reaction (PCR) testing data from the National AIDS Program database were analyzed. EID coverage was calculated as the percentage of number of HIV-exposed infants receiving ≥1 HIV PCR test divided by the number of HIV-exposed infants estimated from HIV prevalence and live-birth registry data. Definitive HIV diagnosis was defined as having two concordant PCR results. MTCT rates were calculated based on infants tested with PCR and applied as a best-case scenario, and a sensitivity analysis was used to adjust these rates in average and worst scenarios. We defined linkage to HIV care as infants with at least one PCR-positive test who were registered with Thailand's National AIDS Program. Chi-squared tests for linear trend were used to analyze changes in programme coverage.ResultsFor 2008 to 2011, the average EID coverage rate increased from 54 to 76% (p<0.001), with 65% coverage (13,761/21,099) overall. The number of hospitals submitting EID samples increased from 458 to 645, and the percentage of community hospitals submitting samples increased from 75 to 78% (p=0.044). A definitive HIV diagnosis was made for 10,854 (79%) infants during this period. The adjusted MTCT rates had significantly decreasing trends in all scenarios. Overall, an estimated 53% (429/804) of HIV-infected infants were identified through the EID programme, and 80% (341/429) of infants testing positive were linked to care. The overall rate of antiretroviral treatment (ART) initiation within one year of age was 37% (157/429), with an increasing trend from 28 to 52% (p<0.001).ConclusionsEID coverage increased and MTCT rates decreased during 2008 to 2011; however, about half of HIV-infected infants still did not receive EID. Most HIV-infected infants were linked to care but less than half initiated ART within one year of age. Active follow-up of HIV-exposed infants to increase early detection of HIV infection and early initiation of ART should be more widely implemented.

A matter of context – time to clinically validate 9-month infant HIV testing in South Africa(?)

The author discusses a recent article (Fairlie et al.) about the need for increased identification and early treatment of postnatally HIV-infected infants and suggests that testing at 9 months of age using HIV rapid tests (HRTs) will assist in this regard. While agreeing on this point the author is less certain that such a practice will reduce the number of HIV polymerase chain reaction (PCR) tests done with resultant cost savings as the original article concluded.

False-negative HIV-1 polymerase chain reaction in a 15-month-old boy with HIV-1 subtype C infection.

Polymerase chain reaction (PCR) testing is the gold standard for determining the HIV status in children <18 months of age. However, when clinical manifestations are not consistent with laboratory results, additional investigation is required. We report a 15-month-old HIV-exposed boy referred to our hospital after he had been admitted several times for infectious diseases. A rapid antibody test on the child was positive, while routine diagnostic HIV PCRs using the Roche COBAS Ampliprep/COBAS TaqMan HIV Qual Test were negative at 6 weeks, 6 months, 7 months and 15 months. In addition, the same PCR test performed on the HIV-infected mother was also negative. Alternative PCR and viral load assays using different primer sets detected HIV RNA or proviral DNA in both child and mother. Gag sequences from the child and his mother classified both infections as HIV-1 subtype C, with very rare mutations that may have resulted in PCR assay primer/probe mismatch. Consequently, the child was commenced on antiretroviral therapy and made a remarkable recovery. These findings indicate that more reliable PCR assays capable of detecting a wide range of HIV subtypes are desirable to circumvent the clinical problems created by false-negative PCR results.

Time to implement 9-month infant HIV testing in South Africa.

South Africa (SA) is likely to meet the National Strategic Plan target of &lt;2% mother-to-child HIV transmission at 6 weeks of age in 2015. Children infected with HIV after 6 weeks often remain undiagnosed because of poor implementation of post-weaning and final outcome 18-month HIV testing. The World Health Organization recommends a screening HIV rapid test (HRT) in HIV-exposed infants at the 9-month immunisation visit to exclude postnatal infection, with a confirmatory HIV polymerase chain reaction (PCR) test if the HRT is positive. To evaluate the impact of substituting this recommendation for the post-weaning HIV testing recommended by SA guidelines. Rates of seroreversion and probability of infection at 9 months of age were applied to a theoretical population of 100 HIV-exposed infants, uninfected at birth and breastfed for 1 year with antiretroviral prophylaxis. Nine scenarios were developed and the number of HIV PCRs saved compared with current guidelines was calculated. Nine-month testing using the HRT reduced the number of follow-up PCR tests done in all scenarios by &gt;50%, with differences ranging from 51% to 59% and 81% to 89% for low and high seroreversion rates, respectively. Nine-month testing using HRT would increase identification and early treatment of HIV-infected infants, improve monitoring of postnatal transmission rates, and reduce the number of HIV PCR tests done with resultant cost saving. Training of healthcare workers implementing HRT would be required. Ongoing efforts to improve implementation and monitoring of testing at 9 and 18 months will be essential.

Absence of Detectible HIV-1 Viremia After Treatment Cessation in an Infant.

Until very recently, the only patient “cured” of HIV was the “Berlin patient,” an adult male treated for HIV-associated acute myeloid leukemia with stem cell transplantation from a donor who was intrinsically resistant to HIV. The donor carried homozygous mutations (delta32) in the chemokine receptor 5 gene, which is an essential co-receptor for HIV entry into most target cells. The present study reports on an infant who also may be cured with early, highly active antiretroviral therapy (ART) after documented perinatal infection.A 35-week gestational age infant was born by normal vaginal delivery to an HIV-infected woman who received no prenatal care and who was not taking ART. ART was initiated in the infant at 30 hours of age with zidovudine, lamivudine, and nevirapine. At 1 week of age, this regimen was adjusted to zidovudine, lamivudine, and ritonavir-boosted lopinavir. The infant remained on ART for 18 months and was then lost to follow-up until 23 months of age. ART has been discontinued and, because of results from subsequent studies, has not been restarted.Standard HIV polymerase chain reaction (PCR) assays and HIV antibody testing were used to diagnose and monitor the HIV-exposed infant. Peripheral blood mononuclear cell cultures were analyzed with PCR for virus DNA and with co-culture techniques for replication-competent virus. Lymphocyte subset analysis was conducted with standard flow cytometry, and HIV-specific T-cell responses were evaluated with intracellular cytokine generation assays.During the first month of life and while receiving ART, the infant had elevated quantitative HIV RNA PCR measurements that declined to undetectable levels and remained there. Subsequently, although proviral DNA was detected at the limits of the assay at 26 months of age, plasma viral RNA was undetectable, and replication-competent virus could not be cultured at age 24 months. HIV antibody assays were not detected in the infant at or after 24 months of age, when maternal antibody would not confound the assays, and HIV-specific T-cell responses were not detected at age 28 months. CD4+ T-cell counts remain normal throughout the study.Very early ART therapy in infants born at risk may abort HIV infection.In patients with established HIV infection, effective ART drives the virus to “undetectable” levels, usually defined as <20/copies of viral RNA/mL of plasma. However, viremia persists in such patients at very low levels and as DNA pro-virus in peripheral blood mononuclear cells. Was this infant cured of HIV? According to the Centers for Disease Control and Prevention definition, the infant was “infected”: 2 positive PCR test results on at least 2 different blood specimens. The data presented demonstrated that after unintended discontinuation of therapy, the infant remained free of replication-competent HIV from at least 12 months of age. As the authors conclude, “very early ART in infants may alter the establishment and long term persistence of HIV-infection.” But why might this happen in a newborn when it has not been demonstrated in older patients except under the unique circumstances of the Berlin patient? HIV persistence depends on the establishment of a reservoir of infected cells. Recent studies suggest that this condition involves a specific population of “central memory T cells.” Perhaps very early therapy aborts or inhibits establishment of this reservoir or perhaps these cells have not fully matured to be infected in newborns. In any case, the present report suggests that very early therapy may prevent establishment of HIV in high-risk infants, and certainly this possibility is being studied intensively.

A mathematical model evaluating the timing of early diagnostic testing in HIV-exposed infants in South Africa.

Antiretroviral therapy is often initiated too late to impact early HIV-related infant mortality. Earlier treatment requires an earlier diagnosis, and the currently recommended 6-week HIV polymerase chain reaction (PCR) test needs reconsideration. This study aims to identify (1) optimal testing intervals to maximize the number of perinatal HIV infections diagnosed and (2) programmatic issues that impact diagnosis. A mathematical model was developed to simulate antiretroviral prophylaxis uptake and health outcomes in 240,000 HIV-exposed South African infants. The model considered routine early testing with 1 PCR (at birth, 6, 10, or 14 weeks of age) and with 2 PCR tests (at birth and at 6, 10, or 14 weeks of age). A single 6-week test would diagnose the same number of perinatal HIV infections as birth testing (P = 0.92) but fewer infections than a 10-week test (P < 0.01). Ten-week testing identifies the highest number of perinatally infected infants (P < 0.01 compared with a single test at all other ages) but does not save additional life years compared with birth testing (P = 0.27). Performing 2 PCR tests (at birth and 10 weeks) would identify the highest number of perinatal infections (P < 0.01 versus a second 6- or 14-week test). However, 25% of perinatal HIV infections would remain undiagnosed, largely because of failure to return PCR test results to caregivers. Six weeks may no longer be the optimal age to diagnose perinatal HIV infections. Two early PCR tests (at birth and 10 weeks) would likely be the ideal diagnostic algorithm, but must be coupled with improved program coverage.

Infections in HIV-exposed uninfected children with focus on sub-Saharan Africa.

Infections in HIV-exposed uninfected children with focus on sub-Saharan Africa.

An Unusual Cause of Odynophagia in a Patient With Eosinophilic Esophagitis

Question: An 18-year-old white man presented with 3 days of epigastric pain, odynophagia, vomiting, and fevers. He also reported 4 months of dysphagia with solids. His history included heartburn, allergic rhinitis, and wheat allergy. There was no personal or family history of recent infection. On admission, he was febrile (101.8°F) and tachycardic (110 bpm). Physical examination revealed a 2-mm ulcer in the lower lip and epigastric tenderness. Blood counts, biochemistry, and liver function tests were normal. Esophagogastroduodenoscopy (EGD) revealed esophagitis with multiple discrete shallow round, 3- to 4-mm ulcers starting in upper esophagus and distributed throughout its circumference (Figure A, B). Histopathology revealed necroinflammatory tissue and squamous epithelium with intercellular edema, basal zone hyperplasia, and up to 56 eosinophils per high-power field (Figure C). Immunoperoxidase staining was negative for herpes simplex virus (HSV) and cytomegalovirus. Serum HSV antibodies, HIV, and cytomegalovirus polymerase chain reaction were negative. The histologic findings were interpreted as eosinophilic esophagitis (EoE) and treatment with pantoprazole was administered. Odynophagia persisted and repeated EGD at day 5 showed persistent coalescent esophageal ulcers along with white exudates and erythema (Figure D). Several specimens were obtained from the edge of the biopsy. A representative histopathology is shown (Figure E, F). What is the diagnosis? Look on page 38 for the answer and see the Gastroenterology web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI. Histopathology revealed marked inflammation and viral cytopathic changes. Immunohistochemistry showed broad reactivity for HSV types I and II (Figure G). Further investigation of cell and humoral immunity was normal. The patient was treated with intravenous acyclovir with resolution of odynophagia within 3 days and then completed 14 days with valacyclovir. At 3 months on therapy with pantoprazol, dysphagia had improved and further endoscopy was normal but random biopsies revealed persistence of mucosal eosinophilia. A final diagnosis of herpetic esophagitis (HE) with concurrent EoE was made. Since its first description in 1940, close to 60 cases of HE have been well-documented in immunocompetent adults and adolescents.1Canalejo Castrillero E. Garcia Duran F. Cabello N. et al.Herpes esophagitis in healthy adults and adolescents: report of 3 cases and review of the literature.Medicine (Baltimore). 2010; 89: 204-210Crossref PubMed Scopus (77) Google Scholar HE usually affects young men. Prodromal symptoms of upper respiratory tract infection and concurrent orolabial lesions can be present. The most common clinical manifestations include acute onset of odynophagia, retrosternal pain, fever, and dysphagia. EGD reveals multiple, coalescent or discrete, small ulcers in most patients. The diagnosis can be confirmed by histopathology, viral culture, or polymerase chain reaction detection of biopsies taken from the edge of the ulcers or esophageal brush. Despite the initial negative histopathology in our patient, high clinical suspicion prompted further endoscopic evaluation, which led to the final diagnosis. Antiviral therapy on immunocompetent patients remains debatable. The pathogenesis of HE in the immunocompetent host is not entirely understood. EoE has been linked to the occurrence of HSV esophagitis in previous case reports.2Squires K.A. Cameron D.J. Oliver M. et al.Herpes simplex and eosinophilic oesophagitis: the chicken or the egg?.J Pediatr Gastroenterol Nutr. 2009; 49: 246-250Crossref PubMed Scopus (37) Google Scholar, 3Zaja Franulovic O. Lesar T. Busic N. et al.Herpes simplex primo-infection in an immunocompetent host with eosinophilic esophagitis.Pediatr Int. 2013; 55: e38-e41Crossref PubMed Scopus (20) Google Scholar In addition to local mucosal injury, dysregulation of T-helper 2 response in EoE may lead to a breakdown in barrier function and increase susceptibility to infection with swallowed virus. Future studies are needed to clarify the apparent link between these 2 entities.

Laboratory information system data demonstrate successful implementation of the prevention of mother-to-child transmission programme in South Africa.

Monitoring the prevention of mother-to-child transmission (PMTCT) programme to identify gaps for early intervention is essential as South Africa progresses from prevention to elimination of HIV infection in children. Early infant diagnosis (EID) by an HIV polymerase chain reaction (PCR) test is recommended at 6 weeks of age for all HIV-exposed infants. The National Health Laboratory Service (NHLS) performs the PCR tests for the public health sector and stores test data in a corporate data warehouse (CDW). To demonstrate the utility of laboratory data for monitoring trends in EID coverage and early vertical transmission rates and to describe the scale-up of the EID component of the PMTCT programme. HIV PCR test data from 2003 to 2012 inclusive were extracted from the NHLS CDW by year, province, age of infant tested and test result and used to calculate EID coverage and early vertical transmission rates to provincial level. Rapid scale-up of EID over the first decade of the PMTCT programme was evident from the 100-fold increase in PCR tests to 350 000 by 2012. In 2012, 73% of the estimated 270 000 HIV-exposed infants requiring an early PCR were tested and the early vertical transmission rate had fallen to 2.4% as a result of successful implementation of the PMTCT programme. Laboratory data can provide real time, affordable monitoring of aspects of the PMTCT programme and assist in achieving virtual elimination of paediatric HIV infection in South Africa.

Reduction in Perinatal HIV Infections in KwaZulu-Natal, South Africa, in the Era of More Effective Prevention of Mother to Child Transmission Interventions (2004–2012)

To describe a trend in perinatal HIV transmission associated with the implementation of rapidly changing prevention of mother to child transmission (PMTCT) interventions from 2004 to 2012. Retrospective analysis of infant HIV polymerase chain reaction results of infants from 2004 to 2012 archived from a Laboratory Information System. KwaZulu-Natal, South Africa. HIV infection in infants aged 4-8 weeks. The proportion of 4- to 8-week-old infants who tested HIV polymerase chain reaction positive decreased significantly (P < 0.0001) from 27.5% in 2004 to 2.9% in 2012. The reduction rates in perinatal HIV infections in 4- to 8-week-old HIV-exposed infants decreased significantly (P < 0.0001) by 48.7% following single-dose nevirapine (sdNVP) (2005 to April 2008), 68.4% with zidovudine from 28 weeks and sdNVP together with triple antiretroviral therapy for women with CD4 cell count < 200 cells/mm³ (May 2008-April 2010), and 89.5% with zidovudine from 14 weeks, sdNVP, and triple antiretroviral therapy for women with CD4⁺ cell count < 350 cells/mm³ (May 2010-December 2012). We show an almost 10-fold reduction in mother to child transmission from 2004 to 2012 in infants aged 4-8 weeks during a rapid implementation of more complex and robust PMTCT interventions. The significant reductions in mother to child transmission in the South African PMTCT program are encouraging for a middle-income country with the second highest antenatal HIV prevalence in the world.