20 July 2016 Authors Rebecca Zash Sajini Souda Jean Leidner Kelebogile Binda Chazha Hick Kathleen Powis Joseph Makhema Mompati Mmalane Max Essex ID: 639885
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High proportion of deaths attributable to HIV among post-partum women in Botswana despite widespread uptake of ART
20 July, 2016Authors: Rebecca Zash, Sajini Souda, Jean Leidner, Kelebogile Binda, Chazha Hick, Kathleen Powis, Joseph Makhema, Mompati Mmalane, Max Essex, Shahin Lockman and Roger L Shapiro Funding: CDC U2GPS000941 and NIH/NIAID T32 5T32AI007433-21 Slide2
Author DisclosuresNo author reports any conflict of interestSlide3
BackgroundThe contribution of HIV-infection to post-partum mortality is not well characterized in the antiretroviral therapy (ART) era
Post-partum is a vulnerable time for mothersOutcomes expected to improve with increasing number of women on 3-drug ART during pregnancy and prior to conceptionSlide4
Study aimsTo determine the 24-month mortality rate among HIV-infected and HIV-uninfected postpartum women in Botswana
To evaluate risk factors for mortality among HIV-infected women in a setting with widespread uptake of ART and PMTCT servicesSlide5
EnrollmentMothers recruited at one of 5 public hospital maternity wards
Inclusion criteria:
<48 hours post-partum
>
18 years old
Reside <100km away
Exclusion criteria:
unable to provide a telephone
contact
for herself,
a family member, or friend
Slide6
Antiretroviral UseAntiretrovirals
(ARVs) received from the government system according to national guidelinesFree for citizensPMTCT in BotswanaPrior to June 2012: WHO Option AZDV/3TC/NVP for pregnant women with CD4 <250ZDV-monotherapy during pregnancy for women with CD4 >250June 2012: WHO Option B with TDF/FTC/EFVMoved CD4 count cutoff for adult ART from 250350Pregnant women with CD4 >350 stopped ART after delivery or breastfeedingSlide7
Follow-upPrimary means of contact was by cell phoneAt
1, 3, 6, 9, 12, 15, 18, and 24m post-partumScripted interview using EDCIf participant could not be reached, home visits were attemptedIf home visit not successful, attempted to confirm vital status (alive/dead) with family memberSlide8
ResultsFeb 2012-March 20131499 HIV-infected and 1501 HIV-uninfected mothers enrolled
Complete follow-up on 2979 (96%)106 (3.5%) not followed after the death of their child9 (0.3%) withdrew6 (0.2%) LTFUSlide9
Baseline Characteristics
HIV-Infected Mothers (N=1499)HIV-Uninfected Mothers (N=1501)Age, median [IQR]29 [25,34]24 [21,28]Primigravid244 (16%)675 (45%)
Gravida >4
545 (36%)199 (13%)
No or Primary Education
197 (13%)77 (5%)
Drinking water piped directly into the home
209 (14%)
317 (21%)
No latrine facilities in the compound
107 (7%)
60 (4%)
Electricity in the home
799 (53%)
987 (66%)
Any smoking or alcohol
during pregnancy
168 (12%)
200 (13%)
Any hospitalization during pregnancy204 (14%)192 (13%)Mode of Delivery
Vaginal Scheduled C-section Emergency C-section1334 (88%)21 (1%)160 (11%)1387 (91%)16 (1%)115 (8%)Slide10
Baseline Characteristics
HIV-Infected Mothers (N=1499)HIV-Uninfected Mothers (N=1501)Age, median [IQR]29 [25,34]24 [21,28]Primigravid244 (16%)675 (45%)
Gravida >4545 (36%)
199 (13%)
No or Primary Education197 (13%)
77 (5%)
Drinking water piped directly into the home
209 (14%)
317 (21%)
No latrine facilities
107 (7%)
60 (4%)
Electricity in the home
799 (53%)
987 (66%)
Any smoking or alcohol
during pregnancy
168 (12%)
200 (13%)
Any hospitalization during pregnancy204 (14%)192 (13%)Mode of Delivery
Vaginal Scheduled C-section Emergency C-section1334 (88%)21 (1%)160 (11%)1387 (91%)16 (1%)115 (8%)Slide11
Baseline Characteristics
HIV-Infected Mothers (N=1499)HIV-Uninfected Mothers (N=1501)Age, median [IQR]29 [25,34]24 [21,28]Primigravid244 (16%)675 (45%)
Gravida >4545 (36%)
199 (13%)
No or Primary Education197 (13%)
77 (5%)
Drinking water piped directly into the home
209 (14%)
317 (21%)
No latrine facilities in the compound
107 (7%)
60 (4%)
Electricity in the home
799 (53%)
987 (66%)
Any smoking or alcohol
during pregnancy
168 (12%)
200 (13%)
Any hospitalization during pregnancy204 (14%)192 (13%)Mode of Delivery
Vaginal Scheduled C-section Emergency C-section1334 (88%)21 (1%)160 (11%)1387 (91%)16 (1%)115 (8%)Slide12
Antiretroviral Use
Pre-Conception34% on ARTN=511 (34%)N=307 (20%)N=106 (7%)
N=54 (4%)
N=225 (15%)
N=185 (12%)
N=41 (3%)
N=70 (5%)
Pregnancy
92% on ARVs
71% ART, 29% ZDV
24m follow-up
79% on ART
No ARVs
ART
ART
ART
ART
ART
ART
ART
ZDV
ZDVSlide13
24-month mortality
Number of DeathsMortality rate (per 100,000 p-y)Total26439HIV-infected22758HIV-uninfected4
138
HIV-infected women were 5-times more
likely than HIV-uninfected women to die:
aHR 5.0 (95% CI 1.6, 15.2)Slide14
ART and mortality
Number of Deaths (%)aHR (95% CI)ART in pregnancy and throughout follow-up13 (59%)refStopped ART/ZDV post-partum but initiated ART during follow up2 (9%)0.9 (0.3, 6.4)Received ART/ZDV in pregnancy and stopped post-partum4 (18%)
1.7 (0.6, 5.1)
No ART during pregnancy or follow up3 (14%)
1.6 (0.2, 15.2)
Median CD4= 421 cells/mm
3
CD4 in pregnancy unrelated to mortality (p=0.20)Slide15
Strengths/LimitationsLarge, representative sample with minimal LTFUMay underestimate mortality in immediate post-partum period
Sickest women less likely to agree to enrollmentLack of information on cause of deathLimited power to detect differences by ART status post-partumMinimal information regarding ART adherenceSlide16
ConclusionsEven with high uptake of 3-drug ART in pregnancy and post-partum, HIV-infected women are at increased risk of death within 24-months after delivery
Closer clinical monitoring of post-partum women could improve maternal outcomesFurther study needed to understand the cause of death and potential risk factors specific to the post-partum periodSlide17
Thanks!CDC/PEPFARNIH/NIAID
MOHOnkabetse MokgosiJudith MabutaDaphne SegobyeGosego LegasePatricia MophuthegiRosemary MoremiEdith MosekiCynthia DubeChazha HickGloria MayondiBHP Data CenterBHP Lab personnelSuperintendents and Doctors at participating hospitalsMaternity Matrons and Midwives at participating hospitalsAll the women and children who participated in our study