Study inclusion criteria.

<p>Study inclusion criteria.</p

Retention of HIV-Infected Children in the First 12 Months of Anti-Retroviral Therapy and Predictors of Attrition in Resource Limited Settings: A Systematic Review

<div><p>Current UNAIDS goals aimed to end the AIDS epidemic set out to ensure that 90% of all people living with HIV know their status, 90% initiate and continue life-long anti-retroviral therapy (ART), and 90% achieve viral load suppression. In 2014 there were an estimated 2.6 million children under 15 years of age living with HIV, of which only one-third were receiving ART. Little literature exists describing retention of HIV-infected children in the first year on ART. We conducted a systematic search for English language publications reporting on retention of children with median age at ART initiation less than ten years in resource limited settings. The proportion of children retained in care on ART and predictors of attrition were identified. Twelve studies documented retention at one year ranging from 71–95% amongst 31877 African children. Among the 5558 children not retained, 4082 (73%) were reported as lost to follow up (LFU) and 1476 (27%) were confirmed to have died. No studies confirmed the outcomes of children LFU. Predictors of attrition included younger age, shorter duration of time on ART, and severe immunosuppression. In conclusion, significant attrition occurs in children in the first 12 months after ART initiation, the majority attributed to LFU, although true outcomes of children labeled as LFU are unknown. Focused efforts to ensure retention and minimize early mortality are needed as universal ART for children is scaled up.</p></div

Reported predictors of mortality in children on ART in resource limited settings.

<p>Reported predictors of mortality in children on ART in resource limited settings.</p

Identification and selection of studies.

<p>Fig 1 shows the studies identified and reasons for inclusion or exclusion.</p

Retention of children initiating ART at median age <10 years by overall follow up time.

<p>Retention of children initiating ART at median age <10 years by overall follow up time.</p

Retention at 12 months on ART amongst HIV-infected children.

<p>Retention at 12 months on ART amongst HIV-infected children.</p

Serious Adverse Events Are Uncommon with Combination Neonatal Antiretroviral Prophylaxis: A Retrospective Case Review

<div><p>Six weeks of zidovudine (ZDV) is recommended for postnatal prophylaxis of HIV-exposed infants, but combination antiretrovirals are indicated if HIV transmission risk is increased. We investigated the frequency and severity of adverse events (AE) in infants receiving multiple drug prophylaxis compared to ZDV alone. In this retrospective review of 148 HIV-exposed uninfected infants born between 1997–2009, we determined clinical and laboratory AE that occurred between days of life 8–42. Thirty-six infants received combination prophylaxis; among those, a three-drug regimen containing ZDV, lamivudine, and nevirapine was most common (53%). Rates of laboratory AE grade ≥1 were as follows for the combination prophylaxis and ZDV alone groups, respectively: neutropenia 55% and 39%; anemia 50% and 39%; thrombocytopenia 0 and 3%; elevated aspartate aminotransferase 3% and 3%; elevated alanine aminotransferase 0 and 1%; hyperbilirubinemia 19% and 42%. Anemia occurred more frequently in infants who received three-drug prophylaxis compared to infants who received ZDV alone (63% vs. 39%, p = 0.04); all anemia AE were grade 1 or 2 in the three-drug prophylaxis group. Overall, 75% of infants on combination prophylaxis and 66% of infants on ZDV alone developed grade ≥1 AE (p = 0.32), and 17% of infants in either group developed grade ≥3 AE. Stavudine was substituted for ZDV in 23 infants due to anemia or neutropenia. After this antiretroviral change, 50% of evaluable infants demonstrated improvement in AE grade, and 25% had no change. In conclusion, low grade anemia, neutropenia, and hyperbilirubinemia occurred frequently regardless of the prophylactic regimen, but serious AE were uncommon. Although most AE were typical of ZDV toxicity, the combination of ZDV with lamivudine and nevirapine resulted in an increased frequency of low-grade anemia. Further studies are needed to identify prophylactic regimens with less toxicity for infants born to HIV-infected mothers.</p></div

Infant demographics and maternal HIV characteristics.

<p>^a Infant race and ethnicity determined by maternal self-report.</p><p>^b From earliest known maternal laboratory values during pregnancy.</p><p>^c From last known maternal laboratory values within 28 days prior to and including the date of delivery.</p><p>Infant demographics and maternal HIV characteristics.</p

Infant prophylaxis.

<p>^a The substitution of stavudine occurred at a median age of 30 days (range, 8–40 days)</p><p>^b Zidovudine was administered for at least 6 weeks in all infants.</p><p>^c One infant also received 1 week of ritonavir.</p><p>^d Treatment prescribed prior to warnings from the Food and Drug Administration against use of ritonavir-boosted lopinavir in infants younger than age 14 days.</p><p>^e This infant received stavudine rather than zidovudine due to maternal receipt of stavudine antenatally.</p><p>Infant prophylaxis.</p

Frequency and severity of laboratory adverse events for infants exposed to zidovudine alone, combination prophylaxis, or three-drug prophylaxis.

<p>The maximum grade adverse event within each laboratory test (hemoglobin, Hgb; absolute neutrophil count, ANC; platelets, plts; aspartate aminotransferase, AST; alanine aminotransferase, ALT; total bilirubin, tB) that occurred between days of life 8 through 42 is shown for infants exposed postnatally to zidovudine alone (ZDV), combination antiretroviral prophylaxis (combo), and three-drug prophylaxis containing zidovudine (or stavudine), lamivudine, and nevirapine (3ARV). Significant differences are denoted by p-values.</p