RESUMEN
BACKGROUND: Transmission through breastfeeding accounts for more than half of the unacceptably high number of new paediatric HIV infections worldwide. We hypothesised that, in addition to maternal antiretroviral therapy (ART), extended postnatal prophylaxis with lamivudine, guided by point-of-care assays for maternal viral load, could reduce postnatal transmission. METHODS: We did a phase 3, open-label, randomised controlled trial at four health-care facilities in Zambia and four health-care facilities in Burkina Faso. Mothers with HIV and their breastfed infants without HIV attending the second visit of the Expanded Programme of Immunisation (EPI-2; infant age 6-8 weeks) were randomly assigned 1:1 to intervention or control groups. In the intervention group, maternal viral load was measured using Xpert HIV viral load assay at EPI-2 and at 6 months, with results provided immediately. Infants whose mothers had a viral load of 1000 copies per mL or higher were started on lamivudine syrup twice per day for 12 months or 1 month after breastfeeding discontinuation. The control group followed national guidelines for prevention of postnatal transmission of HIV. The primary outcome assessed by modified intention to treat was infant HIV infection at age 12 months, with HIV DNA point-of-care testing at 6 months and at 12 months. This trial is registered with ClinicalTrials.gov (NCT03870438). FINDINGS: Between Dec 12, 2019 and Sept 30, 2021, 34 054 mothers were screened for HIV. Among them, 1506 mothers with HIV and their infants without HIV, including 1342 mother and infant pairs from Zambia and 164 from Burkina Faso, were eligible and randomly assigned 1:1 to the intervention (n=753) or control group (n=753). At baseline, the median age of the mothers was 30·6 years (IQR 26·0-34·7), 1480 (98·4%) of 1504 were receiving ART, and 169 (11·5%) of 1466 had a viral load ≥1000 copies/mL. There was one case of HIV transmission in the intervention group and six in the control group, resulting in a transmission incidence of 0·19 per 100 person-years (95% CI 0·005-1·04) in the intervention group and 1·16 per 100 person-years (0·43-2·53) in the control group, which did not reach statistical significance (p=0·066). HIV-free survival and serious adverse events were similar in both groups. INTERPRETATION: Our intervention, initiated at EPI-2 and based on extended single-drug postnatal prophylaxis guided by point-of-care maternal viral load could be an important strategy for paediatric HIV elimination. FUNDING: The EDCTP2 programme with the support of the UK Department of Health & Social Care.
Asunto(s)
Fármacos Anti-VIH , Infecciones por VIH , Adulto , Femenino , Humanos , Lactante , Fármacos Anti-VIH/uso terapéutico , Burkina Faso , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/prevención & control , Infecciones por VIH/epidemiología , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Lamivudine/uso terapéutico , Madres , Zambia/epidemiologíaRESUMEN
OBJECTIVE: Our study aimed to assess the PMTCT indicators in Burkina Faso and Zambia using a patient-orientated innovative strategy based on the second visit in the Expanded Program on Immunization (EPI-2) visit at 6-8âweeks. DESIGN: This was a cross sectional study. METHODS: We assessed women attending EPI-2 at primary healthcare facilities in Burkina Faso and Zambia with their children about their exposure to PMTCT interventions. For women living with HIV (WLHIV), viral load was measured and their children were tested for HIV DNA using point of care devices. RESULTS: Overall, 25â093 were enrolled from Burkina Faso and 8961 women from Zambia. Almost, all women attended at least one antenatal care visit. Among those aware of their HIV-positive status, 95.8 and 99.2% were on antiretroviral therapy (ART) in Burkina Faso and Zambia, respectively. Among WLHIV on ART, 75 and 79.2% achieved a viral load suppression (viral load <1000âcopies/ml) in Burkina Faso and Zambia, respectively. Infant postnatal prophylaxis was administered from birth until EPI-2 to 60.9 and 89.7% of HIV-exposed children in Burkina Faso and Zambia, respectively. In Burkina Faso, only 60 of 192 (31.3%) of HIV-exposed children were sampled at day 42 for early infant diagnosis (EID) and 3 (1.6%) received a result by EPI-2. In Zambia, these figures were 879 of 1465 (64.0%) and 9.9% (145/1465), respectively for HIV-exposed children sampled at birth. CONCLUSION: This evaluation strategy at EPI-2 visit could strengthen program monitoring and help identifying gaps to be addressed on the last mile towards elimination of MTCT of HIV.
Asunto(s)
Fármacos Anti-VIH , Infecciones por VIH , Lactante , Recién Nacido , Humanos , Embarazo , Femenino , Fármacos Anti-VIH/uso terapéutico , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Burkina Faso , Zambia , Estudios Transversales , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/prevención & control , InmunizaciónRESUMEN
Background: Infant post-natal prophylaxis (PNP) is used to prevent HIV transmission through breastfeeding. The WHO edited recommendations but so far there is no consensus on the duration of prophylaxis and the type of drug used depends on national guidelines. In Zambia, the national recommendations include a three-drug prophylaxis, composed of a dispersible combined tablet of zidovudine (AZT) and lamivudine (3TC) and an oral suspension of nevirapine (NVP) for 12 weeks or until the mother's viral load is <1,000 cp/mL. The PROMISE-EPI study, modified the PNP regimen to lamivudine only, initiated at 6 weeks and continued until 12 months to all HIV exposed uninfected infants of virally unsuppressed mothers. Our aim in this analysis was to identify barriers and facilitators to this extended PNP, the keystone toward an effective prevention. Methods: Individual interviews and focus group discussion (FGD) were conducted with PROMISE-EPI participants who had received prophylaxis for their children from the national program up to 6 weeks and then lamivudine oral solution in PROMISE-EPI study. Health care providers and PROMISE-EPI staff were also interviewed. Sessions were recorded, transcribed verbatim and translated from local languages into English. An initial code-book was designed and then adapted on the basis of the emerging themes, to allow a descriptive thematic analysis. Results: More barriers to PNP adherence were identified with triple drug prophylaxis than with lamivudine. These barriers were related to the formulation and bitter taste of AZT/3TC tablets. The ready to use formulation and sweet taste of lamivudine syrup were appreciated by mothers. Extended PNP proposed in the PROMISE-EPI study was globally well accepted and strategies were found to increase adherence. Adherence to lamivudine appeared to be better than the mothers' adherence to their own antiretroviral therapy. Conclusion: Accompanying mothers living with HIV and giving them the choice of the PNP to prevent transmission via breastfeeding (type of PNP regimen and extended PNP in non-adherent mothers), may be one of the keys to reducing the burden of pediatric HIV acquisition in low and middle income countries.
Asunto(s)
Infecciones por VIH , Transmisión Vertical de Enfermedad Infecciosa , Lamivudine , Profilaxis Posexposición , Femenino , Humanos , Lactante , Grupos Focales , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/prevención & control , Lamivudine/uso terapéutico , Investigación Cualitativa , Zambia , Transmisión Vertical de Enfermedad Infecciosa/prevención & controlRESUMEN
The number of children newly infected with HIV dropped by 50%, from 320â 000 in 2010 to 160â 000 in 2021. Despite progress, ongoing gaps persist in diagnosis, continuity of care, and treatment optimization. In response, the United States President's Emergency Plan for AIDS Relief created the Faith-based Action for Scaling-Up Testing and Treatment for Epidemic Response (FASTER). Faith-based Action for Scaling-Up Testing and Treatment for Epidemic Response addressed gaps in countries with the highest unmet need by working with government to operationalize innovative interventions and ensure alignment with national priorities and with communities living with HIV to ensure the change was community-led. Between 2019 and 2021, FASTER's interventions were incorporated into national policies, absorbed by Ministries of Health, and taken up in subsequent awards and country operating plans. Continued effort is needed to sustain gains made during the FASTER initiative and to continue scaling evidence-based interventions to ensure that children and adolescents are not left behind in the global HIV response.
Asunto(s)
Infecciones por VIH , Humanos , Niño , Adolescente , Estados Unidos , Zambia , Uganda/epidemiología , Infecciones por VIH/epidemiología , Infecciones por VIH/terapia , Infecciones por VIH/diagnóstico , Tanzanía , Nigeria , Accesibilidad a los Servicios de SaludRESUMEN
Subclinical mastitis (SCM) is an important risk factor of postnatal HIV-1 transmission that is still poorly understood. A longitudinal sub-study of the ANRS12174 trial including 270 breastfeeding mothers in Lusaka, Zambia measured sodium (Na+) and potassium (K+) in archived paired breast milk samples collected at week 14, 26 and 38 postpartum to determine cumulative incidence of SCM and the effects of recurrent severe SCM on HIV-1 shedding in breast milk. A nested retrospective cohort study including 112 mothers was also done to determine longitudinal effects of SCM on four pro-inflammatory cytokines; IL6, IL8, IP10 and RANTES. The cumulative incidence for any SCM (Na + /K + ratio > 0.6) and severe SCM (Na + /K + ratio > 1) were 58.6% (95%CI: 52.7 - 64.5) and 27.8% (95%CI: 22.5 - 33.1), respectively. In majority of affected mothers (51.4%) severe SCM was recurrent. Both breasts were involved in 11.1%, 33.3% and 70% of the mothers with a single episode, 2 and 3 episodes respectively. In affected breasts, an episode of severe SCM resulted in steep upregulation of the four cytokines considered (IL8, IP10, RANTES and IL6) compared to: before and after the episode; contralateral unaffected breasts; and SCM negative control mothers. Recurrent severe SCM significantly increased the odds of shedding cell-free HIV-1 in breast milk (OR: 5.2; 95%CI: 1.7 - 15.6) whereas single episode of severe SCM did not (OR: 1.8; 95%CI: 0.8 - 4.2). A Na+/K+ ratio > 1 indicative of severe SCM is an excellent indicator of breast inflammation characterized by a steep, localized and temporal upregulation of several pro-inflammatory cytokines that favor HIV-1 shedding in mature breast milk and may facilitate postnatal HIV-1 transmission through breastfeeding.
Asunto(s)
Infecciones por VIH , VIH-1 , Mastitis , Lactancia Materna , Quimiocina CCL5 , Quimiocina CXCL10 , Citocinas , Femenino , Infecciones por VIH/epidemiología , Humanos , Interleucina-6 , Interleucina-8 , Mastitis/epidemiología , Estudios Retrospectivos , Sodio , ZambiaRESUMEN
Post-natal HIV infection through breastfeeding remains a challenge in many low and middle-income countries, particularly due to non-availability of alternative infant feeding options and the suboptimal Prevention of Mother to Child Transmission of HIV-1 (PMTCT) cascade implementation and monitoring. The PROMISE-EPI study aims to address the latter by identifying HIV infected mothers during an almost never-missed visit for their infant, the second extended program on immunization visit at 6-8 weeks of age (EPI-2). The study is divided into 3 components inclusive of an open-label randomized controlled trial aiming to assess the efficacy of a responsive preventive intervention compared to routine intervention based on the national PMTCT guidelines for HIV-1 uninfected exposed breastfeeding infants. The preventive intervention includes: a) Point of care testing for early infant HIV diagnosis and maternal viral load; b) infant, single-drug Pre-Exposure Prophylaxis (PrEP) (lamivudine) if mothers are virally unsuppressed. The primary outcome is HIV-transmission rate from EPI-2 to 12 months. The study targets to screen 37,000 mother/infant pairs in Zambia and Burkina Faso to identify 2000 mother/infant pairs for the clinical trial. The study design and challenges faced during study implementation are described, including the COVID-19 pandemic and the amended HIV guidelines in Zambia in 2020 (triple-drug PrEP in HIV exposed infants guided by quarterly maternal viral load). The changes in the Zambian guidelines raised several questions including the equipoise of PrEP options, the standard of care-triple-drug (control arm in Zambia) versus the study-single-drug (intervention arm). Trial registration number (www.clinicaltrials.gov): NCT03869944. Submission category: Study Design, Statistical Design, Study Protocols.
Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Lactancia Materna , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/transmisión , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Lamivudine/uso terapéutico , Adolescente , Adulto , Fármacos Anti-VIH/administración & dosificación , Fármacos Anti-VIH/efectos adversos , Burkina Faso , COVID-19/epidemiología , Estudios Transversales , Femenino , Infecciones por VIH/diagnóstico , Humanos , Lactante , Lamivudine/administración & dosificación , Lamivudine/efectos adversos , Pandemias , Profilaxis Pre-Exposición/métodos , Proyectos de Investigación , SARS-CoV-2 , Carga Viral , Adulto Joven , ZambiaRESUMEN
In the ANRS 12174 trial, HIV-exposed uninfected African neonates who received lopinavir-ritonavir (LPV/r) prophylaxis for 1 year exhibited slower growth from birth to week 50 compared with those receiving lamivudine (3TC). We assessed whether this difference in growth persisted over time, and was accompanied by differences in neuropsychological and clinical outcomes. Between February 2017 and February 2018, we conducted a cross-sectional clinical evaluation among former trial participants who completed the 50-week follow-up and who were not HIV-infected. In addition to clinical examination, neuropsychological outcomes were assessed using the tests Kaufman-ABCII, Test of Variables of Attention, Movement Assessment Battery for Children and the Strengths and Difficulties questionnaire, parent version. Of 1101 eligible children, aged 5-7 years, 553 could be traced and analysed (274 in the LPV/r and 279 in the 3TC groups). Growth, clinical and neuropsychological outcomes did not differ between treatment groups. At school age, children exposed to LPV/r and 3TC at birth for 1 year had comparable growth and neuropsychological outcomes without evidence of long-term side-effects of LPV/r. It provides reassuring data on clinical outcomes for all HIV-infected children treated with this antiretroviral drug in early life.
Asunto(s)
Fármacos Anti-VIH/administración & dosificación , Quimioprevención/métodos , Infecciones por VIH/prevención & control , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Lamivudine/administración & dosificación , Lopinavir/administración & dosificación , Ritonavir/administración & dosificación , Burkina Faso , Niño , Desarrollo Infantil/efectos de los fármacos , Desarrollo Infantil/fisiología , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Lactante , Masculino , Pruebas Neuropsicológicas , Sudáfrica , Encuestas y Cuestionarios , Uganda , ZambiaRESUMEN
BACKGROUND: Perinatal treatment with lopinavir boosted by ritonavir (LPV/r) is associated with steroidogenic abnormalities. Long-term effects in infants have not been studied. METHODS: Adrenal-hormone profiles were compared at weeks 6 and 26 between human immunodeficiency virus (HIV)-1-exposed but uninfected infants randomly assigned at 7 days of life to prophylaxis with LPV/r or lamivudine (3TC) to prevent transmission during breastfeeding. LPV/r in vitro effect on steroidogenesis was assessed in H295R cells. RESULTS: At week 6, 159 frozen plasma samples from Burkina Faso and South Africa were assessed (LPV/r group: n = 92; 3TC group: n = 67) and at week 26, 95 samples from Burkina Faso (LPV/r group: n = 47; 3TC group: n = 48). At week 6, LPV/r-treated infants had a higher median dehydroepiandrosterone (DHEA) level than infants from the 3TC arm: 3.91 versus 1.48 ng/mL (P < .001). Higher DHEA levels (>5 ng/mL) at week 6 were associated with higher 17-OH-pregnenolone (7.78 vs 3.71 ng/mL, P = .0004) and lower testosterone (0.05 vs 1.34 ng/mL, P = .009) levels in LPV/r-exposed children. There was a significant correlation between the DHEA and LPV/r AUC levels (ρ = 0.40, P = .019) and Ctrough (ρ = 0.40, P = .017). At week 26, DHEA levels remained higher in the LPV/r arm: 0.45 versus 0.13 ng/mL (P = .002). Lopinavir, but not ritonavir, inhibited CYP17A1 and CYP21A2 activity in H295R cells. CONCLUSIONS: Lopinavir was associated with dose-dependent adrenal dysfunction in infants. The impact of long-term exposure and potential clinical consequences require evaluation. CLINICAL TRIALS REGISTRATION: NCT00640263.
Asunto(s)
Fármacos Anti-VIH , Infecciones por VIH , Fármacos Anti-VIH/efectos adversos , Burkina Faso , Niño , Femenino , Infecciones por VIH/tratamiento farmacológico , Humanos , Lactante , Lopinavir/uso terapéutico , Embarazo , Ritonavir/efectos adversos , Sudáfrica , Esteroide 21-HidroxilasaRESUMEN
The risk of postnatal HIV transmission exists throughout the breastfeeding period. HIV shedding in breast milk beyond six months has not been studied extensively. The aim of this study was to determine prevalence and determinants of HIV shedding in breast milk during continued breastfeedingA cross-sectional study was nested in the PROMISE-PEP trial in Lusaka, Zambia to analyze breast milk samples collected from both breasts at week 38 post-partum (mid-way during continued breastfeeding). We measured concurrent HIV deoxyribonucleic acid (DNA) and HIV ribonucleic acid (RNA) as proxies for cell-associated HIV (CAV) and cell-free HIV (CFV) shedding in breast milk respectively. Participants' socio-demographic date, concurrent blood test results, sub clinical mastitis test results and contraceptive use data were available. Logistic regression models were used to identify determinants of HIV shedding in breast milk (detecting either CAV or CFV).The prevalence of HIV shedding in breast milk at 9 months post-partum was 79.4% (95%CI: 74.0 - 84.0). CAV only, CFV only and both CAV and CFV were detectable in 13.7%, 17.3% and 48.4% mothers, respectively. The odds of shedding HIV in breast milk decreased significantly with current use of combined oral contraceptives (AOR: 0.37; 95%CI: 0.17 - 0.83) and increased significantly with low CD4 count (AOR: 3.47; 95%CI: 1.23 - 9.80), unsuppressed plasma viral load (AOR: 6.27; 95%CI: 2.47 - 15.96) and severe sub-clinical mastitis (AOR: 12.56; 95%CI: 2.48 - 63.58).This study estimated that about 80% of HIV infected mothers not on ART shed HIV in breast milk during continued breastfeeding. Major factors driving this shedding were low CD4 count, unsuppressed plasma viral load and severe sub-clinical mastitis. The inverse relationship between breast milk HIV and use of combined oral contraceptives needs further clarification. Continued shedding of CAV may contribute to residual postnatal transmission of HIV in mothers on successful ART.
Asunto(s)
Infecciones por VIH/epidemiología , Infecciones por VIH/transmisión , Leche Humana/virología , Adulto , Antirretrovirales , Lactancia Materna , Recuento de Linfocito CD4 , Ácidos Nucleicos Libres de Células , Anticonceptivos Orales Combinados/administración & dosificación , Estudios Transversales , ADN Viral , Femenino , Humanos , Transmisión Vertical de Enfermedad Infecciosa , Modelos Logísticos , Mastitis/epidemiología , Madres , Prevalencia , ARN Viral , Factores Socioeconómicos , Carga Viral , Esparcimiento de Virus/fisiología , Adulto Joven , ZambiaRESUMEN
BACKGROUND: The tolerance of antiretroviral drugs in infants must be carefully evaluated. In previous studies of children with HIV type 1 (HIV-1) less weight gain was observed in children given lopinavir-ritonavir-based combinations than those given nevirapine. We aimed to compare the effects of lopinavir-ritonavir and lamivudine on growth in HIV-exposed uninfected infants included in the ANRS 12174 trial. METHODS: ANRS 12174 was a multicentre, randomised, controlled trial of infant prophylaxis to prevent HIV-1 transmission by breastfeeding done at four antenatal clinics in Burkina Faso, South Africa, Uganda, and Zambia. HIV-exposed uninfected infants born to asymptomatic mothers not eligible for antiretroviral therapy (CD4 count >350 cells per µL) were randomly assigned (1:1) to receive lopinavir-ritonavir or lamivudine 7 days after birth, with stratification by country. In a prespecified secondary analysis, we assessed the effect of lopinavir-ritonavir and lamivudine on the growth of these infants from day 7 until cessation of breastfeeding (maximum treatment time 12 months) in the modified intention-to-treat population, which included all children correctly enrolled with at least one follow-up anthropometric measurement. We compared the growth of infants, defined as children's WHO-defined length-for-age Z score (LAZ), weight-for-length Z score (WAZ), and weight-for-age Z score (WLZ). We used linear mixed effect and ß spline-regression models to compare growth between the treatment groups. The trial is registered with ClinicalTrials.gov, number NCT00640263. FINDINGS: 1273 HIV-exposed uninfected infants and their mothers were enrolled between Nov 16, 2009, and May 7, 2013, of whom 1266 (99%) infants were included in the modified intention-to-treat analysis (630 assigned to lopinavir-ritonavir, 636 assigned to lamivudine). Baseline characteristics of the infants and mothers were similar across the two treatment groups. No differences in least-squares (LS) mean LAZ were identified between the treatment groups at any timepoint. LS mean WLZ was significantly lower in the lopinavir-ritonavir group than the lamivudine group at 26 weeks (difference -0·22 [95% CI -0·34 to -0·09], p=0·0006) and 50 weeks (-0·25 [-0·47 to -0·04], p=0·02). LS mean WAZ was also significantly lower in the lopinavir-ritonavir group than the lamivudine group at 26 weeks (difference -0·18 [95% CI -0·30 to -0·05], p=0·01) and 50 weeks (-0·24 [-0·45 to -0·05], p=0·02). Linear mixed models showed that lopinavir-ritonavir was associated with decreases in WLZ and WAZ over time (p<0·0001 and p=0·002), whereas spline regression models indicated that these reductions occurred early and remained constant thereafter (p<0·0001 with a knot at 44 days for WLZ; p=0·02 with a knot at 118 days for WAZ). The difference in LS mean WLZ at 50 weeks between the treatment groups was higher among girls than boys (difference -0·29 [95% CI -0·58 to 0·01], p=0·05 for girls; -0·22 [-0·53 to 0·09], p=0·18 for boys). INTERPRETATION: Less weight gain was observed in infants given lopinavir-ritonavir than those given lamivudine, which is indicative of a persistent effect that could have long-term deleterious effects. This finding merits attention considering the recommendations for early and lifelong treatment of infants with HIV. FUNDING: French National Agency for Research on AIDS and Viral Hepatitis, the Total Foundation, the European Developing Countries Clinical Trials Partnership, and the Research Council of Norway.
Asunto(s)
Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , Inhibidores de la Proteasa del VIH/uso terapéutico , VIH-1/efectos de los fármacos , Adulto , Terapia Antirretroviral Altamente Activa , Recuento de Linfocito CD4 , Femenino , Infecciones por VIH/diagnóstico , Infecciones por VIH/inmunología , Inhibidores de la Proteasa del VIH/farmacología , VIH-1/inmunología , Humanos , Lamivudine/administración & dosificación , Lopinavir/administración & dosificación , Masculino , Ritonavir/administración & dosificación , Resultado del Tratamiento , Carga Viral , Adulto JovenRESUMEN
BACKGROUND: Adolescents living with HIV face challenges, such as disclosure of HIV status, adherence to antiretroviral therapy, mental health, and sexual and reproductive health (SRH). These challenges affect their future quality of life. However, little evidence is available on their sexual behaviors and SRH needs in Zambia. This study aimed at assessing their sexual behaviors and SRH needs and identifying factors associated with marriage concerns and a desire to have children. METHODS: This cross-sectional study was conducted at the University Teaching Hospital from April to July 2014. We recruited 200 adolescents aged 15-19 years who were aware of their HIV-positive status. We collected data on their first and recent sexual behavior, concerns about marriage, and desire to have children. We used the Generalized Linear Model to identify factors associated with having concerns about marriage and desire to have children. We performed thematic analysis with open-ended data to determine their perceptions about marriage and having children in the future. RESULTS: Out of 175 studied adolescents, 20.6% had experienced sexual intercourse, and only 44.4% used condoms during the first intercourse. Forty-eight percent had concerns about marriage, and 87.4% desired to have children. Marriage-related concerns were high among those who desired to have children (adjusted relative risk [ARR] = 2.51, 95% CI = 1.02 to 6.14). Adolescents who had completed secondary school were more likely to desire to have children (ARR = 1.35, 95% CI = 1.07 to 1.71). Adolescents who had lost both parents were less likely to want children (ARR = 0.80, 95% CI = 0.68 to 0.95). Thematic analysis identified that major concerns about future marriage were fear of disclosing HIV status to partners and risk of infecting partners and/or children. The reasons for their willingness to have children were the desire to be a parent, having children as family assets, a human right, and a source of love and happiness. CONCLUSIONS: Zambian adolescents living with HIV are at risk of engaging in risky sexual relationships and have difficulties in meeting needs of SRH. HIV care service must respond to a wide range of needs.
Asunto(s)
Conducta del Adolescente , Seropositividad para VIH , Conducta Reproductiva , Conducta Sexual , Adolescente , Conducta del Adolescente/etnología , Antirretrovirales/uso terapéutico , Estudios Transversales , Escolaridad , Salud de la Familia/etnología , Femenino , Seropositividad para VIH/tratamiento farmacológico , Seropositividad para VIH/epidemiología , Seropositividad para VIH/etnología , Seropositividad para VIH/transmisión , Conductas Relacionadas con la Salud/etnología , Encuestas Epidemiológicas , Hospitales de Enseñanza , Humanos , Intención , Masculino , Evaluación de Necesidades , Investigación Cualitativa , Conducta Reproductiva/etnología , Salud Reproductiva/etnología , Riesgo , Autorrevelación , Conducta Sexual/etnología , Zambia/epidemiologíaRESUMEN
Physical and psychosocial changes during adolescence could influence the psychological well-being and adherence to antiretroviral therapy (ART) of adolescents living with HIV. However, few studies have assessed these two important issues in Zambia. This study aimed at addressing this gap by examining adolescents' depressive symptoms and ART adherence. This was a mixed-methods study conducted from April to July 2014. We recruited 200 adolescents, ages 15 to 19, who were already aware of their HIV status. We measured depressive symptoms using the short form of the Center for Epidemiologic Studies Depression Scale, and self-reported three-day adherence to ART. We performed logistic regression analysis to identify factors associated with depressive symptoms and non-adherence to ART. For qualitative data, we examined challenges over ART adherence using thematic analysis. Out of 190 adolescents, 25.3% showed high scores of depressive symptoms. Factors associated with depressive symptoms were unsatisfactory relationships with family (Adjusted Odds Ratio [AOR] 3.01; 95% Confidence Interval [CI] 1.20-7.56); unsatisfactory relationships with health workers (AOR 2.68; 95% CI 1.04-6.93); and experience of stigma (AOR 2.99; 95% CI 1.07-8.41). Of all participants, 94.2% were taking ART, but 28.3% were non-adherent. Factors associated with non-adherence to ART were loss of a mother (AOR 3.00; 95% CI 1.05-8.58) and lack of basic knowledge about HIV (AOR 3.25; 95% CI 1.43-7.40). Qualitative data identified the following challenges to ART adherence: management of medication, physical reactions to medicine, and psychosocial distress. The evidence suggests that depressive symptoms and non-adherence to ART were priority issues in late adolescence in Zambia. Health workers should be aware of these issues, and the care and treatment services should be tailored to respond to age-specific needs.
Asunto(s)
Depresión/epidemiología , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/psicología , Cumplimiento de la Medicación/psicología , Salud Mental , Adolescente , Fármacos Anti-VIH/uso terapéutico , Depresión/diagnóstico , Relaciones Familiares/psicología , Femenino , Conocimientos, Actitudes y Práctica en Salud , Humanos , Masculino , Relaciones Profesional-Paciente , Escalas de Valoración Psiquiátrica , Autoinforme , Estigma Social , Adulto Joven , ZambiaRESUMEN
BACKGROUND: HIV serostatus disclosure is an immense challenge for adolescents living with HIV, their caregivers, and health workers. In Zambia, however, little guidance is available from the adolescents' point of view on the HIV disclosure process. OBJECTIVE: This study aimed to examine the setting of HIV serostatus disclosure for adolescents, its impacts on them, and their suggestions on the best practice of HIV disclosure. METHODS: We conducted a mixed-methods study at the University Teaching Hospital in Zambia from April to July 2014. We recruited 200 adolescents living with HIV, aged 15-19 years. We collected data using a structured questionnaire including two open-ended questions. We excluded two adolescents due to withdrawal during the survey, and eight from the data set due to out-of-eligibility criteria in age. Eventually, we included 190 in the analysis. We performed descriptive analysis to calculate the distributions of basic characteristics of the adolescents, their experience and preference on HIV serostatus disclosure, its emotional and behavioral impacts, and health education topics they had ever learned at hospital. We performed thematic analysis with open-ended data to explain first impressions upon disclosure in detail and to determine perceived advantages of HIV serostatus disclosure. RESULTS: The majority of adolescents recommended the age of 12 as appropriate for adolescents to learn about their HIV serostatus and preferred disclosure by both parents. Out of 190 adolescents, 73.2% had negative or mixed feelings about HIV serostatus disclosure, while 86.2% reported that disclosure was beneficial. Thematic analyses showed that the adolescents reacted emotionally due to an unexpected disclosure and a belief of imminent death from HIV. However, they improved adherence to treatment (84.7%), limited self-disclosure of their HIV serostatus to others (81.1%), and felt more comfortable in talking about HIV with their caregivers (54.2%). Thematic analysis identified perceived benefits of disclosure as follows: better understanding of their sickness and treatment, and improved self-care and treatment adherence. Lower percentage of the adolescents have learned about psychosocial well-being, compared to facts about HIV and treatment. CONCLUSION: Despite initial emotional distress experienced after the disclosure, knowing one's own HIV serostatus was found to be a crucial turning point for adolescents to improve motivation for self-care. HIV serostatus disclosure to adolescents requires follow-up support involving parents/primary caregivers, health workers, and peers.
RESUMEN
Epstein-Barr virus (EBV) in breast milk and subclinical mastitis (SCM) are both associated with human immunodeficiency virus (HIV) shedding and possibly with postnatal HIV transmission. The objective of this nested case-control study was to investigate the interplay between SCM and EBV replication in breast milk of HIV-infected mothers.The relationships between EBV deoxyribonucleic acid (DNA) shedding, HIV-1 ribonucleic acid (RNA) level, and SCM were explored in breast milk samples of Zambian mothers participating in the ANRS 12174 trial. Mammary gland inflammation was defined as a breast milk sodium to potassium ratio (Na/K) greater than 0.6 and further subclassified as either "possible SCM" (Na/K ratio 0.6-1.0) or SCM (Na/K ratioâ≥â1.0). Breast milk interleukin 8 (IL-8) was measured as a surrogate marker of mammary gland inflammation.EBV DNA was detected in breast milk samples from 42 out of 83 (51%) participants and was associated with HIV-1 shedding in breast milk (P = 0.006). EBV DNA levels were higher in samples with SCM and "possible SCM" compared to non-SCM breast milk samples (P = 0.06; P = 0.007). An EBV DNA level of >200âcopies/mL was independently associated with SCM and "possible SCM" (OR: 2.62; 95%: 1.13-6.10). In patients with SCM, higher EBV replication in the mammary gland was associated with a lower induction of IL-8 (P = 0.013). Resistance to DNase treatment suggests that EBV DNA in lactoserum is encapsidated.SCM and decreased IL-8 responses are associated with an increased EBV shedding in breast milk which may in turn facilitate HIV replication in the mammary gland.
Asunto(s)
Infecciones por VIH/transmisión , VIH-1/fisiología , Herpesvirus Humano 4/fisiología , Transmisión Vertical de Enfermedad Infecciosa , Mastitis/virología , Leche Humana/virología , Esparcimiento de Virus , Adulto , Recuento de Linfocito CD4 , ADN Viral/análisis , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Recién Nacido , ARN Viral/análisis , ZambiaRESUMEN
BACKGROUND: Strategies to prevent postnatal mother-to-child transmission of HIV-1 in Africa, including infant prophylaxis, have never been assessed past 6 months of breastfeeding, despite breastfeeding being recommended up to 12 months after birth. We aimed to compare the efficacy and safety of infant prophylaxis with the two drug regimens (lamivudine or lopinavir-ritonavir) to prevent postnatal HIV-1 transmission up to 50 weeks of breastfeeding. METHODS: We did a randomised controlled trial in four sites in Burkina Faso, South Africa, Uganda, and Zambia in children born to HIV-1-infected mothers not eligible for antiretroviral therapy (CD4 count >350 cells per µL). An independent researcher electronically generated a randomisation schedule; we then used sequentially numbered envelopes to randomly assign (1:1) HIV-1-uninfected breastfed infants aged 7 days to either lopinavir-ritonavir or lamivudine (paediatric liquid formulations, twice a day) up to 1 week after complete cessation of breastfeeding or at the final visit at week 50. We stratified the randomisation by country and used permuted blocks of four and six. We used a study label on drug bottles to mask participants, study physicians, and assessors to the treatment allocation. The primary outcome was infant HIV-1 infection between age 7 days and 50 weeks, diagnosed every 3 months with HIV-1 DNA PCR, in the modified intention-to-treat population (all who attended at least one follow-up visit). This trial is registered with ClinicalTrials.gov, number NCT00640263. FINDINGS: Between Nov 16, 2009, and May 7, 2012, we enrolled and randomised 1273 infants and analysed 1236; 615 assigned to lopinavir-ritonavir or 621 assigned to lamivudine. 17 HIV-1 infections were diagnosed in the study period (eight in the lopinavir-ritonavir group and nine in the lamivudine group), resulting in cumulative HIV-1 infection of 1.4% (95% CI 0.4-2.5) and 1.5% (0.7-2.5), respectively. Infection rates did not differ between the two drug regimens (hazard ratio [HR] of lopinavir-ritonavir versus lamivudine of 0.90, 95% CI 0.35-2.34; p=0.83). Clinical and biological severe adverse events did not differ between groups; 251 (51%) infants had a grade 3-4 event in the lopinavir-ritonavir group compared with 246 (50%) in the lamivudine group. INTERPRETATION: Infant HIV-1 prophylaxis with lopinavir-ritonavir was not superior to lamivudine and both drugs led to very low rates of HIV-1 postnatal transmission for up to 50 weeks of breastfeeding. Infant pre-exposure prophylaxis should be extended until the end of HIV-1 exposure and mothers should be informed about the persistent risk of transmission throughout breastfeeding. FUNDING: INSERM/National Agency for Research on AIDS and Viral Hepatitis (including funds from the Total Foundation), European Developing Countries Clinical Trials Partnership, Research Council of Norway.
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Fármacos Anti-VIH/administración & dosificación , Lactancia Materna , Infecciones por VIH/prevención & control , VIH-1 , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Profilaxis Pre-Exposición/métodos , África del Sur del Sahara , Esquema de Medicación , Quimioterapia Combinada , Femenino , Infecciones por VIH/transmisión , Humanos , Lactante , Recién Nacido , Lamivudine/administración & dosificación , Lopinavir/administración & dosificación , Ritonavir/administración & dosificaciónRESUMEN
BACKGROUND: Human milk oligosaccharides (HMOs) have multiple immunomodulatory functions that influence child health. OBJECTIVE: In this study we investigated whether HMO composition influences survival to 2 y of age in HIV-infected and HIV-exposed, uninfected (HEU) children during and after breastfeeding. METHODS: In the context of an early weaning trial in 958 HIV-infected women in Lusaka, Zambia, we conducted a nested case-cohort analysis of mortality to 2 y of age among 103 HIV-infected and 143 HEU children. Breast-milk samples collected at 1 mo postpartum were analyzed for HMO content. Samples were selected to include mothers of all HIV-infected children detected by 6 wk of age, of whom 63 died at <2 y of age; mothers of all HEU children who died at <2 y of age (n = 66); and a random sample of 77 HEU survivors. Associations before and after weaning in HIV-infected and HEU infants separately were investigated by using Cox models. RESULTS: Among HEU children, higher maternal breast-milk concentrations of 2-linked fucosylated HMOs [2'-fucosyllactose and lacto-N-fucopentaose (LNFP) I] (HR: 0.33; 95% CI: 0.14, 0.74) as well as non-2-linked fucosylated HMOs (3-fucosyllactose and LNFP II/III; HR: 0.28; 95% CI: 0.13, 0.67) were significantly associated with reduced mortality during, but not after, breastfeeding after adjustment for confounders. Breastfeeding was protective against mortality only in HEU children with high concentrations of fucosylated HMOs. Among HIV-infected children, no consistent associations between HMOs and mortality were observed, but breastfeeding was protective against mortality. CONCLUSIONS: The oligosaccharide composition of breast milk may explain some of the benefits of breastfeeding in HEU children. HIV infection may modulate some of the consequences of HMOs on child survival.
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Infecciones por VIH/mortalidad , Infecciones por VIH/transmisión , Leche Humana/química , Oligosacáridos/análisis , Complicaciones Infecciosas del Embarazo , Adulto , Animales , Lactancia Materna , Estudios de Cohortes , Femenino , Infecciones por VIH/prevención & control , Humanos , Factores Inmunológicos , Lactante , Mortalidad Infantil , Recién Nacido , Transmisión Vertical de Enfermedad Infecciosa , Masculino , Leche , Prebióticos/análisis , Embarazo , Trisacáridos/análisis , ZambiaRESUMEN
Analysis of milk from 247 HIV-infected Zambian mothers showed that galectin-3 binding protein concentrations were significantly higher among HIV-infected mothers who transmitted HIV through breast-feeding (6.51 ± 2.12 µg/mL) than among nontransmitters but were also correlated with higher milk and plasma HIV RNA copies/mL and lower CD4+ cell counts. The association between galectin-3 binding protein and postnatal transmission was attenuated after adjustment for milk and plasma HIV load and CD4+ cell counts. This suggests that although milk galectin-3 binding protein is a marker of advanced maternal disease, it does not independently modify transmission risk.
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Antígenos de Neoplasias/análisis , Biomarcadores de Tumor/análisis , Lactancia Materna , Proteínas Portadoras/análisis , Glicoproteínas/análisis , Infecciones por VIH/transmisión , Transmisión Vertical de Enfermedad Infecciosa , Leche Humana/química , Leche Humana/virología , Estudios de Casos y Controles , Femenino , Infecciones por VIH/epidemiología , Infecciones por VIH/metabolismo , Humanos , Factores de Riesgo , Carga Viral , Zambia/epidemiologíaRESUMEN
Concentrations of HIV-1 RNA and DNA in mucosal compartments influence the risk of sexual transmission and mother-to-child transmission of HIV-1. Breast milk production is physiologically regulated such that supply is a function of infant demand, but whether demand also influences HIV-1 dynamics in breast milk is unknown. We tested whether minor and major changes in feeding frequency influence breast milk viral concentrations in 958 HIV-1-infected women and their infants followed, for 24 months during a trial in Lusaka, Zambia. Women were randomized to wean abruptly at 4 months or to continue breast-feeding for a duration of their own choosing. Two weeks after breast-feeding cessation (4.5 months), HIV-1 concentrations in breast milk were substantially higher (median RNA, 2708 copies/ml; DNA, 14 copies/ml) than if breast-feeding continued (median RNA, <50 copies/ml; DNA, <1 copy/ml; P < 0.0001). Among those continuing breast-feeding, HIV-1 concentrations in milk were higher if breast-feeding was nonexclusive (median RNA, 293 copies/ml; DNA, 2 copies/ml; P = 0.0006). Elevated milk viral concentrations after stopping breast-feeding explained higher than expected rates of late postnatal HIV transmission in those who weaned early. Changes in the frequency of breast-feeding peri-weaning and with nonexclusive breast-feeding influenced milk viral concentrations. This may explain the reduced risk of HIV-1 transmission associated with exclusive breast-feeding and why early weaning does not achieve the magnitude of HIV prevention predicted by models. Our results support continuation of maternal antiretroviral drug interventions over the full duration of time when any breast milk exposures may occur after planned weaning.
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VIH-1/aislamiento & purificación , Leche Humana/virología , Destete , Mama/patología , Lactancia Materna , Femenino , Infecciones por VIH/epidemiología , Infecciones por VIH/prevención & control , Infecciones por VIH/transmisión , Infecciones por VIH/virología , Humanos , Recién Nacido , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , ARN Viral/análisis , Factores de Riesgo , Factores de Tiempo , Zambia/epidemiologíaRESUMEN
BACKGROUND: HIV-infected women, particularly those with advanced disease, may have higher rates of pregnancy loss (miscarriage and stillbirth) and neonatal mortality than uninfected women. Here we examine risk factors for these adverse pregnancy outcomes in a cohort of HIV-infected women in Zambia considering the impact of infant HIV status. METHODS: A total of 1229 HIV-infected pregnant women were enrolled (2001-2004) in Lusaka, Zambia and followed to pregnancy outcome. Live-born infants were tested for HIV by PCR at birth, 1 week and 5 weeks. Obstetric and neonatal data were collected after delivery and the rates of neonatal (<28 days) and early mortality (<70 days) were described using Kaplan-Meier methods. RESULTS: The ratio of miscarriage and stillbirth per 100 live-births were 3.1 and 2.6, respectively. Higher maternal plasma viral load (adjusted odds ratio [AOR] for each log10 increase in HIV RNA copies/ml = 1.90; 95% confidence interval [CI] 1.10-3.27) and being symptomatic were associated with an increased risk of stillbirth (AOR = 3.19; 95% CI 1.46-6.97), and decreasing maternal CD4 count by 100 cells/mm3 with an increased risk of miscarriage (OR = 1.25; 95% CI 1.02-1.54). The neonatal mortality rate was 4.3 per 100 increasing to 6.3 by 70 days. Intrauterine HIV infection was not associated with neonatal morality but became associated with mortality through 70 days (adjusted hazard ratio = 2.76; 95% CI 1.25-6.08). Low birth weight and cessation of breastfeeding were significant risk factors for both neonatal and early mortality independent of infant HIV infection. CONCLUSIONS: More advanced maternal HIV disease was associated with adverse pregnancy outcomes. Excess neonatal mortality in HIV-infected women was not primarily explained by infant HIV infection but was strongly associated with low birth weight and prematurity. Intrauterine HIV infection contributed to mortality as early as 70 days of infant age. Interventions to improve pregnancy outcomes for HIV-infected women are needed to complement necessary therapeutic and prophylactic antiretroviral interventions.