HIV-exposed children account for more than half of 24-month mortality in Botswana.

BACKGROUND: The contribution of HIV-exposure to childhood mortality in a setting with widespread antiretroviral treatment (ART) availability has not been determined. METHODS: From January 2012 to March 2013, mothers were enrolled within 48 h of delivery at 5 government postpartum wards in Botswana. Participants were followed by phone 1-3 monthly for 24 months. Risk factors for 24-month survival were assessed by Cox proportional hazards modeling. RESULTS: Three thousand mothers (1499 HIV-infected) and their 3033 children (1515 HIV-exposed) were enrolled. During pregnancy 58 % received three-drug ART, 23 % received zidovudine alone, 11 % received no antiretrovirals (8 % unknown); 2.1 % of children were HIV-infected by 24 months. Vital status at 24 months was known for 3018 (99.5 %) children; 106 (3.5 %) died including 12 (38 %) HIV-infected, 70 (4.7 %) HIV-exposed uninfected, and 24 (1.6 %) HIV-unexposed. Risk factors for mortality were child HIV-infection (aHR 22.6, 95 % CI 10.7, 47.5 %), child HIV-exposure (aHR 2.7, 95 % CI 1.7, 4.5) and maternal death (aHR 8.9, 95 % CI 2.1, 37.1). Replacement feeding predicted mortality when modeled separately from HIV-exposure (aHR 2.3, 95 % CI 1.5, 3.6), but colinearity with HIV-exposure status precluded investigation of its independent effect. Applied at the population level (26 % maternal HIV prevalence), an estimated 52 % of child mortality occurs among HIV-exposed or HIV-infected children. CONCLUSIONS: In a programmatic setting with high maternal HIV prevalence and widespread maternal and child ART availability, HIV-exposed and HIV-infected children still account for most deaths at 24 months. Lack of breastfeeding was a likely contributor to excess mortality among HIV-exposed children.

Birth weight for gestational age norms for a large cohort of infants born to HIV-negative women in Botswana compared with norms for U.S.-born black infants.

BACKGROUND: Standard values for birth weight by gestational age are not available for sub-Saharan Africa, but are needed to evaluate incidence and risk factors for intrauterine growth retardation in settings where HIV, antiretrovirals, and other in utero exposures may impact birth outcomes. METHODS: Birth weight data were collected from six hospitals in Botswana. Infants born to HIV-negative women between 26-44 weeks gestation were analyzed to construct birth weight for gestational age charts. These data were compared with published norms for black infants in the United States. RESULTS: During a 29 month period from 2007-2010, birth records were reviewed in real-time from 6 hospitals and clinics in Botswana. Of these, 11,753 live infants born to HIV-negative women were included in the analysis. The median gestational age at birth was 39 weeks (1st quartile 38, 3rd quartile 40 weeks), and the median birth weight was 3100 grams (1st quartile 2800, 3rd quartile 3400 grams). We constructed estimated percentile curves for birth weight by gestational age which demonstrate increasing slope during the third trimester and leveling off beyond 40 weeks. Compared with black infants in the United States, Botswana-born infants had lower median birth weight for gestational age from weeks 37 through 42 (p < .02). CONCLUSIONS: We present birth weight for gestational age norms for Botswana, which are lower at term than norms for black infants in the United States. These findings suggest the importance of regional birth weight norms to identify and define risk factors for higher risk births. These data serve as a reference for Botswana, may apply to southern Africa, and may help to identify infants at risk for perinatal complications and inform comparisons among infants exposed to HIV and antiretrovirals in utero.

High Proportion of Deaths Attributable to HIV Among Postpartum Women in Botswana Despite Widespread Uptake of Antiretroviral Therapy.

Mortality in the postpartum period may be impacted by antiretroviral therapy (ART) received in pregnancy, and whether ART is continued in the postpartum period. HIV-infected and HIV-uninfected mothers were enrolled within 48 h of delivery at five public hospital maternity wards throughout Botswana and followed for 24 months. Maternal deaths were reported by one of the approved contacts given by the mother at enrollment. Detailed information on the cause of death was not available. Risk factors for 24-month mortality were assessed using Cox proportional hazard models. From February 2012 to March 2013, 3000 mothers (1499 HIV infected and 1501 HIV uninfected) were enrolled, and 2985 (99.5%) were followed to 24 months or death, or until the death of their child. There were 26 total maternal deaths through 24 months postpartum [439 per 100,000 person-years (p-y)], 22 among HIV-infected women (758 per 100,000 p-y) and 4 among HIV-uninfected women (132 per 100,000 p-y). Maternal HIV-infection (aHR 5.0, 95% CI 1.6-15.2) and infant birth injury (aHR 3.8, 95% CI 1.3-11.4) were independent risk factors for maternal death. Universal ART in pregnancy became the standard-of-care after June 2012, and 978 (65%) women received ART in pregnancy; by 24 months postpartum or end of follow-up, 1148 (79%) had started ART overall. There was no significant difference in 24-month mortality among HIV-infected women who took ART in pregnancy and continued throughout the follow-up period compared with HIV-infected women who took ART or zidovudine in pregnancy and stopped postpartum (aHR 0.6, 95% CI 0.2-1.7). Despite high uptake of ART in pregnancy and postpartum, women with HIV infection in Botswana are five times more likely to die than HIV-uninfected women in the 24 months postpartum.

Reassuring Birth Outcomes With Tenofovir/Emtricitabine/Efavirenz Used for Prevention of Mother-to-Child Transmission of HIV in Botswana.

BACKGROUND: Before introduction of tenofovir/emtricitabine/efavirenz (TDF/FTC/EFV), 3-drug antiretroviral therapy (ART) was associated with increased adverse birth outcomes when used for prevention of mother-to-child HIV transmission (PMTCT) in Botswana. METHODS: We extracted obstetric records from all women at the 2 largest maternities in Botswana from 2009-2011 when Botswana National Guidelines recommended zidovudine (ZDV) from 28 weeks gestational age (GA) for CD4 ≥350 and ART for CD4 <350, and again in 2013-2014 after implementation of TDF/FTC/EFV for prevention of mother-to-child HIV transmission regardless of CD4 or GA. We compared the use of TDF/FTC/EFV in pregnancy with other 3-drug ART regimens, and with initiation of ZDV, among women with similar CD4 cell counts. Outcomes included small for gestational age (SGA), preterm delivery (PTD) (<37 weeks GA), and stillbirths (SB). RESULTS: Among 9445 HIV-infected women delivering during the study period, 170 were on TDF/FTC/EFV at conception and 1468 initiated TDF/FTC/EFV during pregnancy. Adverse birth outcomes were high overall (3% SB, 21% PTD, and 18% SGA) and among women receiving TDF/FTC/EFV (3% SB, 22% PTD, and 12% SGA). There was no difference in PTD or SB among women initiating TDF/FTC/EFV compared with ZDV or other 3-drug ART, but initiating TDF/FTC/EFV was associated with fewer SGA infants than other 3-drug ART (adjusted odds ratio: 0.4, 95% confidence interval: 0.2 to 0.7). CONCLUSIONS: Adverse birth outcomes remain high among HIV-infected women. TDF/FTC/EFV was at least as safe as other ART and associated with fewer SGA infants when initiated during pregnancy. Larger studies are needed to evaluate birth outcomes and congenital abnormalities among women on TDF/FTC/EFV at conception.

High prevalence of hypertension and placental insufficiency, but no in utero HIV transmission, among women on HAART with stillbirths in Botswana.

BACKGROUND: Increased stillbirth rates occur among HIV-infected women, but no studies have evaluated the pathological basis for this increase, or whether highly active antiretroviral therapy (HAART) influences the etiology of stillbirths. It is also unknown whether HIV infection of the fetus is associated with stillbirth. METHODS: HIV-infected women and a comparator group of HIV-uninfected women who delivered stillbirths were enrolled at the largest referral hospital in Botswana between January and November 2010. Obstetrical records, including antiretroviral use in pregnancy, were extracted at enrollment. Verbal autopsies; maternal HIV, CD4 and HIV RNA testing; stillbirth HIV PCR testing; and placental pathology (blinded to HIV and treatment status) were performed. RESULTS: Ninety-nine stillbirths were evaluated, including 62 from HIV-infected women (34% on HAART from conception, 8% on HAART started in pregnancy, 23% on zidovudine started in pregnancy, and 35% on no antiretrovirals) and 37 from a comparator group of HIV-uninfected women. Only 2 (3.7%) of 53 tested stillbirths from HIV-infected women were HIV PCR positive, and both were born to women not receiving HAART. Placental insufficiency associated with hypertension accounted for most stillbirths. Placental findings consistent with chronic hypertension were common among HIV-infected women who received HAART and among HIV-uninfected women (65% vs. 54%, p = 0.37), but less common among HIV-infected women not receiving HAART (28%, p = 0.003 vs. women on HAART). CONCLUSIONS: In utero HIV infection was rarely associated with stillbirths, and did not occur among women receiving HAART. Hypertension and placental insufficiency were associated with most stillbirths in this tertiary care setting.