Prevention of Mother-to-Child HIV Transmission in Nigeria: Six Years Experience from a Tertiary Institution

Background: In line with global standards and progress made in Prevention of Mother-to-Child Transmission (PMTCT), an assessment of the outcome of Early Infant Diagnosis in northern Nigeria is necessary to evaluate progress towards a zero Human immunodeficiency Virus (HIV) infection rate among children. Objectives: This study assessed the infection rate and risk factors for mother-to-child HIV transmission among HIV-exposed children in Kano, northwest Nigeria. Method: Using a retrospective cohort design, pregnant HIV-positive women and their exposed infants were recruited over a period of six years (2010 to 2016). Participants were enrolled during pregnancy or at delivery from the PMTCT clinic of a tertiary health facility in Kano, Nigeria. The main observations of the study were Early infant diagnosis positivity for HIV at 6 weeks and the risk factors for positivity. Results: Of the 1,514 infants studied, Early Infant Diagnosis was positive for HIV among 13 infants (0.86%). Infants whose mothers did not have antiretroviral therapy (adjusted Prevalence Ratio aPR = 2.58, 95%CI [1.85- 3.57]); who had mixed feeding (aPR = 12.06, 95%CI [9.86- 14.70]) and those not on antiretroviral prophylaxis (aPR = 20.39, 95%CI [16.04- 25.71]) were more likely to be infected with HIV. HIV-exposed infants on nevirapine and zidovudine prophylaxis accounted for 95% and 74%, respectively, and were less likely to be infected with HIV. Conclusion: HIV infection rate remains high among HIV-exposed infants whose mothers did not receive PMTCT services. Scaling up proven interventions of early commencement of antiretroviral treatment for mothers, adherence to antiretroviral prophylaxis and avoidance of mixed feeding among HIV-exposed infants would protect future generations from HIV infection.

Safety, Tolerability, and Pharmacokinetics of a Long-Acting Broadly Neutralizing HIV-1 Monoclonal Antibody VRC01LS in HIV-1-Exposed Newborn Infants

Background Perinatal HIV-1 continues to occur due to barriers to effective antiretroviral prevention that might be mitigated by long-acting broadly neutralizing monoclonal antibodies (bNAbs). Methods Extended half-life bNAb, VRC01LS, was administered subcutaneously (SC) at 80 mg/dose after birth to HIV-1-exposed, non-breastfed (Cohort 1, n=10) and breastfed (Cohort 2, n=11) infants. Cohort 2 received a second dose (100mg) at 12 weeks. All received antiretroviral prophylaxis. VRC01LS levels were compared to VRC01 levels determined in a prior cohort. Results Local reactions (all Grade <2) occurred in 67% and 20% after Dose 1 and Dose 2, respectively. The weight-banded dose (mean 28.8 mg/kg) of VRC01LS administrated SC achieved a mean +SD plasma level of 222.3 + 71.6 mcg/mL by 24 hours and 44.0 + 11.6 mcg/mL at week 12, prior to Dose 2. The pre-established target of > 50 mcg/mL was attained in 95% and 32% at week 8 and 12, respectively. The terminal half-life was 37-41 days. VRC01LS level after one dose was significantly greater (p=<0.002) than after a VRC01 dose (20mg/kg). No infants acquired HIV-1. Conclusions VRC01LS was well tolerated with pharmacokinetics that support further studies of more potent long-acting bNAbs as adjunct treatment with ARVs to prevent infant HIV-1 transmission.

Immunization by exposure to live virus (SIVmne/HIV-2287) during antiretroviral drug prophylaxis may reduce risk of subsequent viral challenge

Rationale/Study design A major challenge in the development of HIV vaccines is finding immunogens that elicit protection against a broad range of viral strains. Immunity to a narrow range of viral strains may protect infants of HIV-infected women or partners discordant for HIV. We hypothesized that immunization to the relevant viral variants could be achieved by exposure to infectious virus during prophylaxis with antiretroviral drugs. To explore this approach in an animal model, macaques were exposed to live virus (SIVmne or HIV-2287) during prophylaxis with parenteral tenofovir and humoral and cellular immune responses were quantified. Subsequently, experimental animals were challenged with homologous virus to evaluate protection from infection, and if infection occurred, the course of disease was compared to control animals. Experimental animals uninfected with SIVmne were challenged with heterologous HIV-2287 to assess resistance to retroviral infection. Methodology/Principal findings Juvenile female Macaca nemestrina (N = 8) were given ten weekly intravaginal exposures with either moderately (SIVmne) or highly (HIV-2287) pathogenic virus during tenofovir prophylaxis. Tenofovir protected all 8 experimental animals from infection, while all untreated control animals became infected. Specific non-neutralizing antibodies were elicited in blood and vaginal secretions of experimental animals, but no ELISPOT responses were detected. Six weeks following the cessation of tenofovir, intravaginal challenge with homologous virus infected 2/4 (50%) of the SIVmne-immunized animals and 4/4 (100%) of the HIV-2287-immunized animals. The two SIVmne-infected and 3 (75%) HIV-2287-infected had attenuated disease, suggesting partial protection. Conclusions/Significance Repeated exposure to SIVmne or HIV-2287, during antiretroviral prophylaxis that blocked infection, induced binding antibodies in the blood and mucosa, but not neutralizing antibodies or specific cellular immune responses. Studies to determine whether antibodies are similarly induced in breastfeeding infants and sexual partners discordant for HIV infection and receiving pre-exposure antiretroviral prophylaxis are warranted, including whether these antibodies appear to confer partial or complete protection from infection.

Assessing the effectiveness of prevention of mother-to-child HIV transmission

Aim. To analyze the outcomes of a set of interventions to prevent vertical transmission of the human immunodeficiency virus (HIV) in the Republic of Mari El. Methods. A retrospective analysis of temporary registration forms Notifications of the termination of pregnancy in an HIV-infected woman and Notifications of a newborn born by an HIV-infected mother, case histories and outpatient medical records of HIV-infected women who gave birth in 20002018 was carried out. The study included all children born in the Republic of Mari El to HIV-positive women registered with the Republican Center for the Prevention and Control of AIDS and Infectious Diseases, as well as children whose HIV status is detected after birth as a result of epidemiological investigations. The assessment of the risks of transmission as an outcome of the three-step preventive interventions has been carried out. A comparative analysis of the results of perinatal prevention of HIV transmission in the Republic of Mari El and other regions of the Russian Federation was performed. Results. A total of 299 HIV-infected pregnant women and 368 children born to these women during the study period were registered in the region; 63 (21.7%) of these women had more than one child. Over the entire study period, 18 (4.8%) children with confirmed HIV infection were registered. The most common factor associated with infant HIV infection is late maternal HIV diagnosis: (1) several years after childbirth in the absence of antiretroviral (ARV) prophylaxis and the infants were breastfeeding (11 cases, 64.7%); (2) during or shortly after childbirth, when the patient did not receive entire three-step antiretroviral prophylaxis during pregnancy and childbirth (6 cases, 29.4%); (3) in the third trimester of pregnancy (1 case, 5.5%). An important limitation for the successful prevention of vertical transmission of HIV was the lack of routine HIV testing, which is required by women and their partners before and at various stages during pregnancy. A single case of self-infection indicates the need to introduce preventive measures from early adolescence among children. Conclusion. Due to the late maternal HIV diagnosis, during or after delivery, HIV transmission events occurred either with limited or no limited antiretroviral prophylaxis.

Prevention of Mother-to-Child Transmission of HIV: Data Analysis Based on Pregnant Women Population from 2012 to 2018, in Nantong City, China

Background: China has implemented a nation-wide policy to control mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV) since 2011, yet the efficacy of the control policy is less studied. The aim of the present study was to report the data in the prevention of MTCT of HIV in Nantong city, China. Methods: The screening and prevalence of HIV in pregnant women and the efficacy of prophylaxis in Nantong city, China, January 2012 through December 2018, were analyzed. Results: Among a total population of 410,044 pregnant women, anti-HIV was tested prenatally in 393,658 (96.0%) women and in 16,287 (3.97%) women at delivery. In total, 51 women were confirmed with HIV infection. After exclusion of repeat pregnancies, the overall prevalence of HIV infection was 1.20/10 000 (48/400,377). The prevalence (6.75/10,000) in women tested at delivery was >5-fold higher than that (1.02/10,000) in prenatally screened women. Of 48 HIV-infected women, 12 terminated their pregnancies and 36 others delivered 36 neonates, of whom 35 were followed up. No HIV infection occurred in 24 children born to mothers with antiretroviral therapy (ART) during pregnancy along with other preventive measures. Among 11 children born to mothers who did not receive ART during pregnancy because of the absence of prenatal anti-HIV test, none of the 6 children who were delivered by cesarean section and timely administered neonatal antiretroviral prophylaxis was infected, but 2 (40%) of 5 children who were spontaneously delivered and administered delayed antiretroviral prophylaxis were infected. Conclusions: Prenatal identification of HIV infection and timely administration of all preventive measures can completely block MTCT of HIV. The data indicate that more efforts must be taken to ensure that all pregnant women are tested for anti-HIV during pregnancy. For pregnant women who missed prenatal screening, a positive result in rapid anti-HIV test at delivery should be sufficient to take preventive measures to prevent MTCT of HIV.

Immunization by exposure to live virus (SIVmne/HIV-2287) during antiretroviral drug prophylaxis reduces risk of subsequent viral challenge

Rationale/Study DesignA major challenge in the development of HIV vaccines is finding immunogens that elicit protection against a broad range of viral strains. Immunity to a narrow range of viral strains may protect infants of HIV-infected women or partners discordant for HIV. We hypothesized that immunization to the relevant viral variants could be achieved by exposure to infectious virus during prophylaxis with antiretroviral drugs. To explore this approach in an animal model, macaques were exposed to live virus (SIVmne or HIV-2287) during prophylaxis with parenteral tenofovir. The humoral and cellular immune responses were quantified. Subsequently, experimental animals were challenged with homologous virus to evaluate protection from infection, and if infection occurred, the course of disease was compared to control animals. Experimental animals uninfected with SIVmne were challenged with heterologous HIV-2287 to assess resistance to retroviral infection.Methodology/Principal FindingsJuvenile Macaca nemestrina (N=8) were given ten weekly intravaginal exposures with either moderately (SIVmne) or highly (HIV-2287) pathogenic virus during tenofovir prophylaxis. Tenofovir protected all 8 experimental animals from infection, while all untreated control animals became infected. Specific non-neutralizing antibodies were elicited in blood and vaginal secretions of experimental animals, but no ELISPOT responses were detected. Six weeks following the cessation of tenofovir, intravaginal challenge with homologous virus infected 2/4 (50%) of the SIVmne-immunized animals and 4/4 (100%) of the HIV-2287-immunized animals. The two SIVmne-infected and 3 (75%) HIV-2287-infected had attenuated disease, suggesting partial protection.Conclusions/SignificanceRepeated exposure to SIVmne or HIV-2287 during antiretroviral prophylaxis blocked infection induced binding antibodies in the blood and mucosa, but not neutralizing antibodies or specific cellular immune responses. Studies to determine whether antibodies are similarly induced in breastfeeding infants and sexual partners discordant for HIV infection and receiving pre-exposure antiretroviral prophylaxis are warranted, including whether these antibodies appear to confer partial or complete protection from infection.

Mobile application development structured in self-care for occupational post-exposure prophylaxis to biological material

ABSTRACT Objective: to develop and validate an application for cellphones structured in self-care to encourage adherence to antiretroviral prophylaxis after occupational exposure to biological material. Methods: phase 1 - descriptive study to identify characteristics of occupational exposure; phase 2 - methodological study to construct and validate an application content aiming to increase adherence to antiretrovirals. Results: phase 1 - 55 occupational exposures were recorded; 32 (58.2%) antiretroviral indication. Blood was present in 96.9% of exposures; most professionals have insufficient knowledge about exposure risks. A statistical relationship was identified between self-care and adherence (p<0.001). Phase 2 - application was constructed, validated by 11 experts, and considered appropriate to encourage health professionals for self-care and adherence to antiretrovirals. Conclusion: the application “Exposição Ocupacional ao HIV” was considered adequate to expand self-care and adherence of professionals to prophylactic treatment to occupational infections arising from biological risks.

Implementation of prevention of mother-to-child transmission (PMTCT) in South Africa: outcomes from a population-based birth cohort study in Paarl, Western Cape

ObjectivesThe coverage of prevention of mother-to-child transmission (PMTCT) services in South Africa is variable. Identifying gaps in the implementation of these services is necessary to isolate steps needed to further reduce paediatric infections and eliminate transmission.SettingTwo primary care clinics in Paarl, South Africa.Participants1225 pregnant women; inclusion criteria were 18 years or older, clinic attendance and remaining in area for at least 1 year.MethodsData were collected through the Drakenstein Child Health Study, a population-based birth cohort in a periurban area of the Western Cape, South Africa. A combination of clinic records, hospital records, national database searches and maternal self-report were collected during the study.ResultsOf the 1225 mothers enrolled in the cohort between 2012 and 2015, 260 (21%) were confirmed HIV infected antenatally and 1 mother tested positive in the postnatal period. Of those with documentation (n=250/260, 96%), the majority (99%) received antiretroviral prophylaxis or therapy (ART) before labour; however, there was a high rate of defaulting from ART noted during pregnancy (20%). All HIV-exposed infants with data received antiretroviral prophylaxis, 35% were exclusively breast fed until 6 weeks and 16% for 6 months. There were two cases of infant HIV infection (0.8%) who were initiated on ART but had complicated histories.ConclusionDespite the low transmission rate in this cohort, reaching elimination will require further work, and this study illustrates several areas to improve implementation of PMTCT services and reduce paediatric infections including retesting at-risk HIV-negative mothers through the duration of breast feeding, infant HIV testing at any admission in addition to routine testing and improved counselling to prevent defaulting from treatment. Better data surveillance systems are essential for determining the implementation of PMTCT guidelines.