Outcomes in a cohort of women who discontinued maternal triple-antiretroviral regimens initially used to prevent mother-to-child transmission during pregnancy and breastfeeding--Kenya, 2003-2009.
ABSTRACT: BACKGROUND:In 2012, the World Health Organization (WHO) amended their 2010 guidelines for women receiving limited duration, triple-antiretroviral drug regimens during pregnancy and breastfeeding for prevention of mother-to-child transmission of HIV (tARV-PMTCT) (Option B) to include the option to continue lifelong combination antiretroviral therapy (cART) (Option B+). We evaluated clinical and CD4 outcomes in women who had received antiretrovirals for prevention of mother-to-child transmission and then discontinued antiretrovirals 6-months postpartum. METHODS AND FINDINGS:The Kisumu Breastfeeding Study, 2003-2009, was a prospective, non-randomized, open-label clinical trial of tARV-PMTCT in ARV-naïve, Kenyan women. Women received tARV-PMTCT from 34 weeks' gestation until 6-months postpartum when women were instructed to discontinue breastfeeding. Women with CD4 count (CD4) <250cells/mm3 or WHO stage III/IV prior to 6-months postpartum continued cART indefinitely. We estimated the change in CD4 after discontinuing tARV-PMTCT and the adjusted relative risk [aRR] for factors associated with declines in maternal CD4. We compared maternal and infant outcomes following weaning-when tARV-PMTCT discontinued-by maternal ARV status through 24-months postpartum. Compared with women who continued cART, discontinuing antiretrovirals was associated with infant HIV transmission and death (10.1% vs. 2.4%; P?=?0.03). Among women who discontinued antiretrovirals, CD4<500 cells/mm3 at either initiation (21.8% vs. 1.5%; P?=?0.002; aRR: 9.8; 95%-confidence interval [CI]: 2.4-40.6) or discontinuation (36.9% vs. 8.3%; P<0.0001; aRR: 4.4; 95%-CI: 1.9-5.0) were each associated with increased risk of women requiring cART for their own health within 6 months after discontinuing. CONCLUSIONS:Considering the serious health risks to the woman's infant and the brief reprieve from cART gained by stopping, every country should evaluate the need for and feasibility to implement WHO Option B+ for PMTCT. Evaluating CD4 at antiretroviral initiation or 6-months postpartum can identify pregnant women who would most benefit from continuing cART in settings unable to implement WHO Option B+.
Project description:<h4>Background</h4>Since 2012, WHO guidelines for the prevention of mother-to-child transmission (PMTCT) of HIV-1 in resource-limited settings recommend the initiation of lifelong antiretroviral combination therapy (cART) for all pregnant HIV-1 positive women independent of CD4 count and WHO clinical stage (Option B+). However, long-term outcomes regarding development of drug resistance are lacking until now. Therefore, we analysed the emergence of drug resistance mutations (DRMs) in women initiating Option B+ in Fort Portal, Uganda, at 12 and 18 months postpartum (ppm).<h4>Methods and findings</h4>124 HIV-1 positive pregnant women were enrolled within antenatal care services in Fort Portal, Uganda. Blood samples were collected at the first visit prior starting Option B+ and postpartum at week six, month six, 12 and 18. Viral load was determined by real-time RT-PCR. An RT-PCR covering resistance associated positions in the protease and reverse transcriptase HIV-1 genomic region was performed. PCR-positive samples at 12/18 ppm and respective baseline samples were analysed by next generation sequencing regarding HIV-1 drug resistant variants including low-frequency variants. Furthermore, vertical transmission of HIV-1 was analysed. 49/124 (39.5%) women were included into the DRM analysis. Virological failure, defined as >1000 copies HIV-1 RNA/ml, was observed in three and seven women at 12 and 18 ppm, respectively. Sequences were obtained for three and six of these. In total, DRMs were detected in 3/49 (6.1%) women. Two women displayed dual-class resistance against all recommended first-line regimen drugs. Of 49 mother-infant-pairs no infant was HIV-1 positive at 12 or 18 ppm.<h4>Conclusion</h4>Our findings suggest that the WHO-recommended Option B+ for PMTCT is effective in a cohort of Ugandan HIV-1 positive pregnant women with regard to the low selection rate of DRMs and vertical transmission. Therefore, these results are encouraging for other countries considering the implementation of lifelong cART for all pregnant HIV-1 positive women.
Project description:BACKGROUND:Universal antiretroviral treatment (ART) for pregnant women with HIV, Option B+, has been adopted widely for prevention of mother-to-child HIV transmission (PMTCT). Some evidence shows high loss to follow-up (LTF) under this model. However, gaps in data systems limit this evidence. We collected additional information for women and infants LTF from Option B+ in Eswatini to assess more accurate outcomes. METHODS:LTF at 6-months postpartum was assessed using facility data. Additional data was gathered from: 1) the national ART database and paper records; 2) patient tracing; and 3) interviews and abstraction from patient-held records. Engagement in care was defined as any clinic visit within 91 days before or after 6-months postpartum or completion of a documented transfer; or, for those traced but not completing study interviews, visits at 6-months postpartum or later (for infants), or visits within 3-months of tracing (for women). Multivariable loglinear models were used to identify correlates of engagement. RESULTS:One-hundred-ninety-four (44.7%) of 434 LTF women had outcomes ascertained, including 122 (62.9%) women engaged in care. Among 510 LTF infants, 265 (52.0%) had ascertained outcomes, including 143 (54.0%) engaged in care, 47 (17.7%) pregnancy losses, and 18 (6.8%) deaths. Seventy-two of 189 live infants (38.1%) with ascertained outcomes had a 6-week early infant diagnostic (EID) test. Among women with ascertained outcomes, gestational age of 20+ weeks (vs. fewer than 20 weeks, aRR 0.80; 95% CI 0.68-0.94) and age 25-29 years (vs. 15-24 years, aRR 0.81; 95% CI 0.67-0.97), were associated with lower engagement; initiating ART after first ANC visit was associated with higher engagement (vs. at first ANC visit, aRR 1.12; 95% CI 1.04-1.21). Among infants with ascertained outcomes, mother not initiating ART was associated with lower engagement (vs. ART at first ANC visit, aRR 0.71; 95% CI 0.54-0.91). CONCLUSION:Substantial numbers of women and infants classified as LTF under Option B+ were engaged in care, though a suboptimal level of 6-week EID testing was observed. These findings highlight a need to improve coverage of routine EID testing, and improve data systems to better capture PMTCT patient outcomes.
Project description:Maternal administration of the acyclovir prodrug valacyclovir is compatible with pregnancy and breastfeeding. However, the safety profile of prolonged infant and maternal exposure to acyclovir in the context of antiretrovirals (ARVs) for prevention of mother-to-child HIV-1 transmission (PMTCT) has not been described.Pregnant Kenyan women co-infected with HIV-1/HSV-2 with CD4 counts > 250 cells/mm(3) were enrolled at 34 weeks gestation and randomized to twice daily 500 mg valacyclovir or placebo until 12 months postpartum. Women received zidovudine from 28 weeks gestation and single dose nevirapine was given to women and infants at the time of delivery for PMTCT. Infant blood was collected at 6 weeks for creatinine and ALT. Breast milk specimens were collected at 2 weeks postpartum from 71 women in the valacyclovir arm; acyclovir levels were determined for a random sample of 44 (62%) specimens. Fisher's Exact and Wilcoxon rank-sum tests were used for analysis.One hundred forty-eight women were randomized and 146 mother-infant pairs were followed postpartum. PMTCT ARVs were administered to 98% of infants and all mothers. Valacyclovir was not associated with infant or maternal toxicities or adverse events, and no congenital malformations were observed. Infant creatinine levels were all normal (< 0.83 mg/dl) and median creatinine (median 0.50 mg/dl) and infant growth did not differ between study arms. Acyclovir was detected in 35 (80%) of 44 breast milk samples collected at 2 weeks postpartum. Median and maximum acyclovir levels were 2.62 and 10.15 mg/ml, respectively (interquartile range 0.6-4.19).Exposure to PMTCT ARVs and acyclovir after maternal administration of valacyclovir during pregnancy and postpartum to women co-infected with HIV-1/HSV-2 was not associated with an increase in infant or maternal toxicities or adverse events.ClinicalTrials.gov NCT00530777.
Project description:BACKGROUND:Despite the success of prevention of mother to child transmission (PMTCT) program in South Africa, the 30% HIV prevalence among women of childbearing age requires the PMTCT program to be maximally efficient to sustain gains in the prevention of vertical HIV transmission. We aimed to determine the immunologic and virologic status at entry into antenatal care (ANC) and at childbirth among HIV positive women who conceived under the CD4<500 cells/?l antiretroviral therapy (ART) eligibility threshold and universal test and treat (UTT) policies in the Gauteng province of South Africa. METHOD:We conducted a retrospective cohort study of 692 HIV positive adult (>18 years) postpartum women who gave birth between September 2016 and December 2017. Demographic, viral load (VL) and CD4 data at ANC start (3-9 months before delivery) and delivery (3 months before/after) were obtained from medical records of consenting women. We compared CD4?500 cell/?l and viral load (VL) suppression (<400 copes/ml) rates at ANC start and delivery among women with a pre-pregnancy ART, women known HIV positive but with in-pregnancy ART and newly diagnosed women with in-pregnancy ART. Predictors of having a high CD4 and suppressed VL were assessed by log-binomial regression. RESULTS:Of the 692 participants, 394 (57.0%) had CD4 data and 326 (47.1%) had VL data. Overall women with a pre-pregnancy ART were more likely to start ANC with CD4 count?500 cell/?l (46.3% vs 24.8%, adjusted risk ratio (aRR) = 1.9; 95% confidence interval (95% CI): 1.4-2.5), compared to newly diagnosed women. This difference was no longer apparent at the time of delivery (aRR 1.2 95% CI: 0.4-3.7). Similarly, viral suppression at delivery was higher among women with pre-pregnancy ART (87.2% vs 69.3%, aRR 1.3, 95% CI: 1.1-1.6) as compared to the newly diagnosed women. Viral suppression rate among newly diagnosed women increased substantially by the time of delivery from 43.5% to 69.3% (p = 0.001). CONCLUSION:These results show that pre-pregnancy ART improves immunologic and virologic control during pregnancy and call for renewed efforts in HIV testing, linkage to ART and viral monitoring.
Project description:<h4>Background</h4>The success of prevention of mother-to-child transmission (PMTCT) programmes depends on retention of mothers throughout the PMTCT cascade.<h4>Methods</h4>In a clinical trial of short-course combination antiretroviral therapy (cART) for PMTCT in Tanzania, senior nurses were employed to reduce the substantial loss-to-follow up (LTFU) rate.<h4>Results</h4>Following intervention, the relative risk (RR) of receiving a CD4 count result and antiretroviral therapy was 1.16 (95% confidence interval [CI], 1.05 to 1.27), the RR of delivery at clinic was 2.51 (95% CI, 2.06 to 3.06), the RR for reporting for follow-up at 6 to 8 weeks postpartum was 4.63 (95% CI, 3.41 to 6.27), and the RR for being retained until 9 months postpartum was 28.19 (95% CI, 11.81 to 67.28). No significant impact on transmission was found.<h4>Conclusion</h4>Significantly higher retention was found after senior nurses were employed. No impact on transmission was found. Relatively low transmission was found in both study arms.
Project description:Prevention of mother-to-child transmission of HIV (PMTCT) is a foundational component of a comprehensive HIV treatment program. In addition to preventing vertical transmission to children, PMTCT is an important catch-point for universal test-and-treat strategies that can reduce community viral load and slow the epidemic. However, systematic reviews suggest that care engagement in PMTCT programs is sub-optimal. This study enrolled a cohort of 200 women initiating PMTCT in Kilimanjaro, Tanzania, and followed them to assess HIV care engagement and associated factors. Six months after delivery, 42/200 (21%) of participants were identified as having poor care engagement, defined as HIV RNA >200?copies/mL or, if viral load was unavailable, being lost-to-follow-up in the clinical records or self-reporting being out of care. In a multivariable risk factor analysis, younger women were more likely to have poor postpartum care engagement; with each year of age, women were 7% less likely to have poor care engagement (aRR: 0.93; 95% CI: 0.89, 0.98). Additionally, women who had told at least one person about their HIV status were 47% less likely to have poor care engagement (aRR: .53; 95% CI: 0.29, 0.97). Among women who entered antenatal care with an established HIV diagnosis, those who were pregnant for the first time had increased risk of poor care engagement (aRR 4.16; 95% CI 1.53, 11.28). The findings suggest that care engagement remains a concern in PMTCT programs, and must be addressed to realize the goals of PMTCT. Comprehensive counseling on HIV disclosure, along with community-based stigma reduction programs to provide a supportive environment for people living with HIV, are crucial to address barriers to care engagement and support long-term treatment. Women presenting to antenatal care with an established HIV status require support for care engagement during the crucial period surrounding childbirth, particularly those pregnant for the first time.
Project description:BACKGROUND:Novel strategies are needed to increase retention in prevention of mother-to-child HIV transmission (PMTCT) services. We have recently shown that small, incremental cash transfers conditional on attending clinic resulted in increased retention along the PMTCT cascade. However, whether women who receive incentives to attend clinic visits are as adherent to antiretrovirals (ARV) as those who do not was unknown. OBJECTIVE:To determine whether HIV-infected women who received incentives to remain in care were as adherent to antiretroviral treatment and achieved the same level of viral suppression at 6 weeks postpartum as those who did not receive incentives but also remained in care. METHODS:Newly diagnosed HIV-infected women at ?32 weeks gestational age were recruited at antenatal care clinics in Kinshasa, Democratic Republic of Congo. Women were randomized in a 1:1 ratio to an intervention or control group. The intervention group received compensation ($5, plus $1 increment at each subsequent visit) conditional on attending scheduled clinic visits and accepting offered PMTCT services, whereas the control group received usual care. The proportion of participants who remained in care, were fully adherent (took all their pills at each visit) or with undetectable viral load at 6 weeks postpartum were compared across group. RESULTS:Among 433 women randomized (216 in intervention group and 217 in control group), 332 (76.7%) remained in care at 6 weeks postpartum, including 174 (80.6%) in the intervention group and 158 (72.8%) in the control group, (P = 0.04). Data on pill count were available for 297 participants (89.5%), including 156 (89.7%) and 141 (89.2%) in the intervention and control groups, respectively; 69.9% (109/156) and 68.1% (96/141) in the intervention and control groups had perfect adherence [risk difference, 0.02; 95% CI: -0.06 to 0.09]. Viral load results were available for 171 (98.3%) and 155 (98.7%) women in the intervention and control groups, respectively; 66.1% (113/171) in the intervention group and 69.7% (108/155) in the control group had an undetectable viral load (risk difference, -0.04; 95% CI: -0.14 to 0.07). Results were similar after adjusting for marital status, age, education, baseline CD4 count, viral load, gestational age, and initial ARV regimen. CONCLUSIONS:Although the provision of cash incentives to HIV-infected pregnant women led to higher retention in care at 6 weeks postpartum, among those retained in care, adherence to ARVs and virologic suppression did not differ by study group.
Project description:BACKGROUND:Women with HIV and prior exposure to combination antiretroviral therapy (cART) solely for prevention of mother-to-child transmission (pMTCT) need to know whether they can later be treated successfully with a commonly used regimen of efavirenz (EFV) and coformulated emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF). METHODS:Nonpregnant women with plasma HIV-1 RNA of ?500 copies per milliliter, previously cART exposed for pMTCT only, were eligible if they were off ART for ?24 weeks before entry, were without evidence of drug resistance on standard genotyping, and were ready to start EFV plus FTC/TDF. The primary endpoint was virologic response (defined as plasma HIV RNA <400 copies/mL) at 24 weeks. RESULTS:Fifty-four women were enrolled between October 2007 and December 2009; 52 of 54 completed 24 weeks of follow-up. Median baseline CD4 T-cell count was 265/mm and baseline plasma HIV-1 RNA was 4.6 log10 copies per milliliter. Median prior cART duration was 14 weeks, and median time elapsed from the last pMTCT dose to entry was 22 months. Virologic response at 24 weeks was observed in 42 of 52 women or 81% (exact 95% confidence interval: 68% to 90%). There were no differences in response by country, by number, or class of prior pMTCT exposures. Although confirmed virologic failure occurred in 8 women, no virologic failures were observed in women reporting perfect early adherence. CONCLUSIONS:In this first prospective clinical trial studying combination antiretroviral retreatment in women with a history of pregnancy-limited cART, the observed virologic response to TDF/FTC and EFV at 24 weeks was 81%. Virologic failures occurred and correlated with self-reported nonadherence.
Project description:To determine magnitude and reasons of loss to program and poor antiretroviral prophylaxis coverage in prevention of mother-to-child transmission (PMTCT) programs in sub-Saharan Africa.Systematic review and meta-analysis.We searched PubMed and Embase databases for PMTCT studies in sub-Saharan Africa published between January 2002 and March 2012. Outcomes were the percentage of pregnant women tested for HIV, initiating antiretroviral prophylaxis, having a CD4 cell count measured, and initiating antiretroviral combination therapy (cART) if eligible. In children outcomes were early infant diagnosis for HIV, and cART initiation. We combined data using random-effects meta-analysis and identified predictors of uptake of interventions.Forty-four studies from 15 countries including 75,172 HIV-infected pregnant women were analyzed. HIV-testing uptake at antenatal care services was 94% [95% confidence intervals (CIs) 92-95%] for opt-out and 58% (95% CI 40-75%) for opt-in testing. Coverage with any antiretroviral prophylaxis was 70% (95% CI 64-76%) and 62% (95% CI 50-73%) of pregnant women eligible for cART received treatment. Sixty-four percent (95% CI 48-81%) of HIV exposed infants had early diagnosis performed and 55% (95% CI 36-74%) were tested between 12 and 18 months. Uptake of PMTCT interventions was improved if cART was provided at the antenatal clinic and if the male partner was involved.In sub-Saharan Africa, uptake of PMTCT interventions and early infant diagnosis is unsatisfactory. An integrated family-centered approach seems to improve retention.
Project description:In 2013, Tanzania adopted the World Health Organization's Option B+ guidelines for prevention of mother-to-child transmission of HIV (PMTCT), whereby all HIV-infected pregnant women initiate lifelong antiretroviral therapy. This study examined retention in PMTCT across critical junctures in the care continuum. This was a retrospective study of patient-level data for a cohort of women enrolled in PMTCT during the first year of Option B+ in Tanzania. Retention in care was described across three periods: (1) the first month of antenatal care (ANC), (2) pregnancy, and (3) the postpartum period. Logistic regression was used to identify factors associated with loss to follow up (LTFU) during the first month of ANC. Survival analyses were used to identify factors associated with LTFU during pregnancy and the postpartum periods. 650 participants were included in the cohort; 262 (40.3%) were newly diagnosed with HIV. Two years after delivery, 383/650 (58.7%) were LTFU. Of the 383 LTFU, 73 (19.1%) were lost during the first month of ANC, 44 (11.5%) during pregnancy, and 266 (69.5%) after delivery. Being newly diagnosed with HIV predicted higher LTFU during the first month of ANC (aOR 1.76; 95% CI 1.06-2.94) and faster time to LTFU during the postpartum period (adjusted relative time, 0.68; 95% CI 0.51-0.89). High LTFU occurred across the PMTCT continuum, including immediately after enrollment into ANC and the postpartum period. Ongoing research is needed to encourage treatment uptake and sustained engagement after delivery.