Effectiveness of Community-Based Support for Pregnant Women Living with HIV: A Cohort Study in South Africa

Antiretroviral treatment (ART) initiation in HIV-infected pregnant women in sub-Saharan Africa (SSA) remains inadequate, and there is a severe shortage of professional healthcare workers in the region. The effectiveness of community support programmes for HIV-infected pregnant women and their infants in SSA is unclear. 

This study compared initiation of maternal antiretrovirals and infant outcomes amongst HIV-infected pregnant women and their infants who received and did not receive community-based support (CBS) in a high HIV-prevalence setting in South Africa. A cohort study, including HIV-infected pregnant women and their infants, was conducted at three sentinel surveillance facilities between January 2009 and June 2012, utilising enhanced routine clinical data. 

Through home visits, CBS workers encouraged uptake of interventions in the ART cascade, provided HIV-related education, ART initiation counselling and psychosocial support. Outcomes were compared using Kaplan-Meier analyses and multivariable Cox and log-binomial regression. Amongst 1105 mother-infant pairs included, 264 (23.9%) received CBS. Amongst women eligible to start ART antenatally, women who received CBS had a reduced risk of not initiating antenatal ART, 5.4% vs. 30.3%; adjusted risk ratio (aRR) = 0.18 (95% CI: 0.08-0.44; P < .0001). Women who received CBS initiated antenatal ART with less delay after the first antenatal visit, median 26 days vs. 39 days; adjusted hazard ratio (aHR) = 1.57 (95% CI: 1.15-2.14; P = .004). Amongst women who initiated antenatal zidovudine (ZDV) to prevent vertical transmission, women who received CBS initiated ZDV with less delay, aHR = 1.52 (95% CI: 1.18-2.01; P = .001). Women who received CBS had a lower risk of stillbirth, 1.5% vs. 5.4%; aRR = 0.24 (95% CI: 0.07-1.00; P = .050). 

Pregnant women living with HIV who received CBS had improved antenatal triple ART initiation in eligible women, women initiated ART and ZDV with shorter delays, and had a lower risk of stillbirth. CBS is an intervention that shows promise in improving maternal and infant health in high HIV-prevalence settings.

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By:  Fatti G1, Shaikh N1, Eley B2, Grimwood A1.

• 1 Kheth'Impilo , Cape Town , South Africa.
• 2 Department of Paediatrics and Child Health , Red Cross War Memorial Children's Hospital, University of Cape Town , Cape Town , South Africa. 

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Maternal Tenofovir Disoproxil Fumarate Use in Pregnancy and Growth Outcomes among HIV-Exposed Uninfected Infants in Kenya

Background. 

Tenofovir disoproxil fumarate (TDF) is commonly used in antiretroviral treatment (ART) and preexposure prophylaxis regimens. We evaluated the relationship of prenatal TDF use and growth outcomes among Kenyan HIV-exposed uninfected (HEU) infants. Materials and 

Methods. 

We included PCR-confirmed HEU infants enrolled in a cross-sectional survey of mother-infant pairs conducted between July and December 2013 in Kenya. Maternal ART regimen during pregnancy was determined by self-report and clinic records. Six-week and 9-month z-scores for weight-for-age (WAZ), weight-for-length (WLZ), length-for-age (LAZ), and head circumference-for-age (HCAZ) were compared among HEU infants with and without TDF exposure using t-tests and multivariate linear regression models. 

Results. 

Among 277 mothers who received ART during pregnancy, 63% initiated ART before pregnancy, of which 89 (32%) used TDF. No differences in birth weight (3.0 kg versus 3.1 kg, p = 0.21) or gestational age (38 weeks versus 38 weeks, p = 0.16) were detected between TDF-exposed and TDF-unexposed infants. At 6 weeks, unadjusted mean WAZ was lower among TDF-exposed infants (-0.8 versus -0.4, p = 0.03), with a trend towards association in adjusted analyses (p = 0.06). There were no associations between prenatal TDF use and WLZ, LAZ, and HCAZ in 6-week or 9-month infant cohorts. 

Conclusion. 

Maternal TDF use did not adversely affect infant growth compared to other regimens.

Full article at:   http://goo.gl/WcUCw4

By:  Pintye J¹, Langat A², Singa B³, Kinuthia J⁴, Odeny B⁵, Katana A², Nganga L², John-Stewart G⁶, McGrath CJ⁷.

¹Department of Global Health, University of Washington, Seattle, WA 98104, USA; Department of Nursing, University of Washington, Seattle, WA 98195, USA.

²United States Centers for Disease Control and Prevention (CDC), Nairobi 00202, Kenya.

³Center for Microbiology Research and Center for Clinical Research, Kenya Medical Research Institute, Nairobi 00202, Kenya.

⁴Department of Global Health, University of Washington, Seattle, WA 98104, USA; Department of Obstetrics & Gynecology, Kenyatta National Hospital, Nairobi 00202, Kenya.

⁵Department of Global Health, University of Washington, Seattle, WA 98104, USA.

⁶Department of Global Health, University of Washington, Seattle, WA 98104, USA; Department of Medicine, University of Washington, Seattle, WA 98195, USA; Department of Epidemiology, University of Washington, Seattle, WA 98195, USA.

⁷Department of Global Health, University of Washington, Seattle, WA 98104, USA; University of Texas Medical Branch, Galveston, TX 77555, USA

Infect Dis Obstet Gynecol. 2015;2015:276851. doi: 10.1155/2015/276851. Epub 2015 Dec 28.

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Growth Patterns in the First Year of Life Differ in Infants Born to Perinatally vs Nonperinatally HIV-Infected Women

Objective: To compare the growth patterns in the first year of life between children born to perinatally HIV-infected (PHIV) vs. nonperinatally HIV-infected (NPHIV) women in the United States.

Design: Retrospective cohort study of HIV-infected pregnant women who received care and delivered a live-born at two urban tertiary centers from January 2004 to March 2012.

Methods: We collected data via chart review on demographics, behavioral risk factors, HIV clinical markers, combination antiretroviral therapy (cART), mode of HIV acquisition, pregnancy outcomes, and infant anthropometrics on study participants. Mixed-effects models were used to assess the association between maternal mode of HIV acquisition and weight-for-age z-score (WAZ), length-for-age z-score (LAZ), and weight-for-length z-score (WLZ).

Results: Of the 152 pregnancies evaluated, 32 and 120 infants were born to 25 PHIV and 99 NPHIV women, respectively. Infants of PHIV women exhibited lower mean WAZ and LAZ throughout the first year of life in unadjusted analyses. After adjusting for potential confounders, the relationship between PHIV women and LAZ persisted (β = −0.54, P = 0.026). Small-for-gestational age for each birth anthropometric parameter (birth length, birth weight, and both birth length and weight) was associated with decreased LAZ (β = −0.48, P = 0.007), WAZ (β = −0.99, P < 0.001), and WLZ (β = −0.36, P = 0.027), respectively. A delivery HIV RNA level below 400 copies/ml was associated with increased WAZ and WLZ (β = 0.43, P = 0.015 and β = 0.38, P = 0.021, respectively).

Conclusions: Infants of PHIV women may remain at persistently decreased lengths throughout the first year of life. Further studies aimed at understanding intrauterine and environmental factors in PHIV women are warranted.

Below:  Loess Plots of Mean Weight for Age (WAZ), Length for Age (LAZ), and Weight for Length (WLZ) Z-scores by Maternal Mode of HIV Acquisition

Full article at:  http://goo.gl/ffy9Kb

By:  Jao J1, Agwu A, Mhango G, Kim A, Park K, Posada R, Abrams EJ, Hutton N, Sperling RS.

• 1aDepartment of Medicine, Department of Obstetrics, Gynecology and Reproductive Science, Icahn School of Medicine at Mount Sinai, New York bDepartment of Pediatrics, Division of Infectious Diseases, Johns Hopkins University School of Medicine c Department of Medicine dDepartment of Pediatrics, Icahn School of Medicine at Mount Sinai eICAP, Mailman School of Public Health and College of Physicians & Surgeons, Columbia University, New York fDepartment of Pediatrics, Johns Hopkins University School of Medicine gDepartment of Obstetrics, Gynecology and Reproductive Science, Icahn School of Medicine at Mount Sinai, New York, USA.

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Antiretroviral Exposure During Pregnancy & Adverse Outcomes in HIV-Exposed Uninfected Infants & Children Using a Trigger-Based Design

Objective: To evaluate the safety of in-utero antiretroviral exposure in children born to mothers with HIV, using a trigger-based design.

Design: The Surveillance Monitoring of ART Toxicities Study is a prospective cohort study conducted at 22 US sites to evaluate safety of in-utero antiretroviral drug exposure in HIV-uninfected children born to HIV-infected mothers. Children meeting predefined clinical or laboratory thresholds have more intensive evaluations to determine whether they meet criteria for adverse events.

Methods: Adverse event “cases” were defined for the following domains: growth, hearing, language, neurology, neurodevelopment, metabolic, hematologic/clinical chemistry and blood lactate. We used adjusted log-binomial models to calculate relative risks (RR) of case status overall and within individual domains for various antiretroviral exposures during pregnancy.

Results: Among 2680 youth enrolled between 2007 and 2012 (48% female, 66% black, 33% Hispanic), 48% met a trigger and 25% were defined as a case in at least one domain. Language (13.2%) and metabolic (11.4%) cases were most common. After adjustment for birth cohort and other factors, there was no association of any antiretroviral regimen, drug class, or individual drug with meeting overall case criteria (case in any domain). Within individual domains, zidovudine (74% exposed) was associated with increased risk of metabolic case [RR = 1.69, 95%confidence interval (CI) 1.08–2.64] and didanosine plus stavudine (<1% exposed) with increased risk of both neurodevelopmental (RR = 12.40, 95%CI 5.29–29.08) and language (RR = 4.84, 95%CI 1.14–20.51) cases.

Conclusion: Our findings support current recommendations for combination antiretroviral therapy during pregnancy, although higher risk of metabolic disorder with zidovudine exposure warrants further study.

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By:  Williams, Paige L.^a,b,f; Hazra, Rohan^c; Van Dyke, Russell B.^d; Yildirim, Cenk^a; Crain, Marilyn J.^e; Seage, George R. III^a,f; Civitello, Lucy^g; Ellis, Angela^h; Butler, Laurie^h; Rich, Kennethⁱ; for the Pediatric HIVAIDS Cohort Study

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Breastfeeding Is Associated with Decreased Risk of Hospitalization among HIV-Exposed, Uninfected Kenyan Infants

Human immunodeficiency virus (HIV)-exposed uninfected (HEU) infants are a growing population in sub-Saharan Africa, with higher morbidity and mortality than HIV-unexposed infants. HEU infants may experience increased morbidity due to breastfeeding avoidance.

We sought to describe the burden and identify predictors of hospitalization among HEU infants in the first year of life.

Using a retrospective cohort of HIV-infected mothers and their HEU infants in Nairobi, Kenya, we identified infants who were HIV-uninfected at birth and were followed monthly until their last negative HIV test, death, loss to follow-up, or study exit at 1 year of age. Incidence, timing, and reason for hospitalization was assessed overall as well as stratified by feeding method. Predictors of first infectious disease hospitalization were identified using competing risk regression, with HIV acquisition and death as competing risks.

Among 388 infants, 113 hospitalizations were reported (35/100 infant-years [the combined years of observation contributed by all infants in the study]; 95% confidence interval [CI], 29-42). Ninety hospitalizations were due to 1 or more infectious diseases (26/100 infant-years; 95% CI, 21-32)-primarily pneumonia (n = 40), gastroenteritis (n = 17), and sepsis (n = 14). Breastfeeding was associated with decreased risk of infectious disease hospitalization (subhazard ratio = 0.39; 95% CI, 0.24-0.64), as was time-updated nutrition status (subhazard ratio = 0.73; 95% CI, 0.61-0.89). Incidence of infectious disease hospitalization among formula-fed infants was 51/100 infant-years (95% CI, 37-70) compared to 19/100 infant-years (95% CI, 14-25) among breastfed infants.

Among HEU infants, breastfeeding and nutrition status were associated with reduced hospitalization during the first year of life.

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By: Ásbjörnsdóttir KH1, Slyker JA2, Maleche-Obimbo E3, Wamalwa D3, Otieno P4, Gichuhi CM5, John-Stewart G6.

• 1Department of Epidemiology, University of Washington, Seattle, WA, USA
• 2Department of Global Health, University of Washington, Seattle, WA, USA.
• 3Department of Paediatrics & Child Health, University of Nairobi, Nairobi, Kenya.
• 4Kenya Medical Research Institute, Nairobi, Kenya.
• 5Department of Clinical Medicine and Therapeutics, University of Nairobi, Nairobi, Kenya.
• 6Department of Epidemiology, University of Washington, Seattle, WA, USA Department of Global Health, University of Washington, Seattle, WA, USA Department of Medicine, University of Washington, Seattle, WA, USA Department of Pediatrics, University of Washington, Seattle, WA, USA. 

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Severe Infections in HIV-Exposed Uninfected Infants Born in a European Country

Below:  Occurrence of severe infections during the first year of life according to period of birth & exposure to ARV during pregnancy, Kaplan-Meier survival analysis (N = 537 infants)

The incidence rate of severe infections during the first year of life was 16.8/100 HEU infant-years. The rates of invasive S. pneumoniae (0.62/100 infant-years) and GBS infections (1.05/100 infant-years) were, respectively, 4 and 13-fold higher in HEU infants than in the general infant population. Preterm birth was a risk factor for severe infections in the neonatal period (aOR = 21.34, 95%CI:7.12–63.93) and post-neonatal period (aHR = 3.00, 95%CI:1.53–5.88). As compared to the pre-ARV prophylaxis era, infants born in the ARV prophylaxis era (i.e., after April 1994) had a greater risk of severe infections (aHR = 2.93; 95%CI:1.07–8.05). This risk excess was present in those who received ARV prophylaxis (aHR 2.01, 95%CI 0.72–5.65) and also in those born in the ARV prophylaxis era who did not benefit from ARV prophylaxis as a result of poor access to antenatal care or lack of compliance (aHR 3.06, 95%CI 0.88–10.66).

In HEU infants born in an industrialized country, preterm birth and being born during the ARV prophylaxis era were risk factors of severe infections throughout the first year of life. These observations have important implications for the clinical management of HIV-infected mothers and their infants.

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