Long-term retention on antiretroviral treatment after enrolment in prevention of vertical HIV transmission services: a prospective cohort study in Dar es Salaam, Tanzania.

Introduction: To prevent vertical HIV transmission and ensure healthy mothers and children, pregnant women with HIV must remain on antiretroviral treatment (ART) for life. However, motivation to remain on ART may decline beyond the standard 2-year breastfeeding/postpartum period. We assessed attrition and retention in ART care among women with HIV up to 6 years since enrolment in vertical transmission prevention services in Dar es Salaam, Tanzania.

Effect of peer-mother interactive programme on prevention of mother-to-child HIV transmission outcomes among pregnant women on anti-retroviral treatment in routine healthcare in Dar es Salaam, Tanzania.

Peer support services are increasingly being integrated in programmes for the prevention of mother-to-child HIV transmission (PMTCT). We aimed to evaluate the effect of a peer-mother interactive programme on PMTCT outcomes among pregnant women on anti-retroviral treatment (ART) in routine healthcare in Dar es Salaam, Tanzania. Twenty-three health facilities were cluster-randomized to a peer-mother intervention and 24 to a control arm.

Vertical HIV transmission within 18 months post partum among women on lifelong antiretroviral therapy for HIV in Dar es Salaam, Tanzania: a prospective cohort study.

Background: The UNAIDS estimate of vertical HIV transmission in Tanzania is high (11%), despite 84% uptake of antiretroviral therapy (ART) among pregnant women with HIV. We aimed to evaluate vertical transmission and its determinants by 18 months post partum among women on lifelong ART in routine health-care settings in Tanzania.

Methods: We conducted a prospective cohort study in 226 health facitilies across Dar-es-Salaam, Tanzania.

The Prevalence, Incidence, and Risk Factors for HIV Among Female Sex Workers-A Cohort Being Prepared for a Phase IIb HIV Vaccine Trial in Dar es Salaam, Tanzania.

Background: A cohort of female sex workers (FSWs) was established to determine HIV prevalence and incidence, and associated factors in preparation for a phase IIb HIV vaccine and pre-exposure prophylaxis trial (PrEPVacc).

Setting: A cohort of FSWs in Dar es Salaam, Tanzania.

Methods: FSWs aged 18-45 years were recruited using a respondent-driven sampling method.

Health care costs associated with clinic visits for prevention of mother-to-child transmission of HIV in Dar es Salaam, Tanzania.

Early and appropriate antenatal care (ANC) is key for the effectiveness of prevention of mother-to-child transmission (PMTCT) of human immunodeficiency virus (HIV). We evaluated the importance of ANC visits and related service costs for women receiving option B+ to prevent mother-to-child transmission (MTCT) of HIV in Tanzania.A cost analysis from a health care sector perspective was conducted using routine data of 2224 pregnant women newly diagnosed with HIV who gave birth between August 2014 and May 2016 in Dar es Salaam, Tanzania.

Long-term virological outcomes in women who started option B+ care during pregnancy for prevention of mother-to-child transmission of HIV in Dar es Salaam, Tanzania: a cohort study.

Background: Option B+ marked a milestone in prevention of mother-to-child transmission (PMTCT) of HIV by recommending lifelong antiretroviral therapy (ART) for all pregnant women with HIV. Nevertheless, concerns remain regarding long-term outcomes in settings with a high HIV burden. We analysed long-term virological outcomes in women enrolled on option B+ in Tanzania.

Frequent and Durable Anti-HIV Envelope VIV2 IgG Responses Induced by HIV-1 DNA Priming and HIV-MVA Boosting in Healthy Tanzanian Volunteers.

We evaluated antibody responses to the human immunodeficiency virus (HIV) envelope variable regions 1 and 2 (V1V2) in 29 vaccinees who had received three HIV-1 DNA immunizations and two HIV-modified vaccinia virus Ankara (MVA) boosts in the phase I/II HIVIS03 vaccine trial. Twenty vaccinees received a third HIV-MVA boost after three years in the HIVIS06 trial. IgG and IgG antibody subclasses to gp70V1V2 proteins of HIV-1 A244, CN54, Consensus C, and Case A2 were analysed using an enzyme-linked immunosorbent assay (ELISA).

Frequent Anti-V1V2 Responses Induced by HIV-DNA Followed by HIV-MVA with or without CN54rgp140/GLA-AF in Healthy African Volunteers.

Antibody responses that correlated with reduced risk of HIV acquisition in the RV144 efficacy trial were assessed in healthy African volunteers who had been primed three times with HIV-DNA (subtype A, B, C) and then randomized into two groups; group 1 was boosted twice with HIV-MVA (CRF01_AE) and group 2 with the same HIV-MVA coadministered with subtype C envelope (Env) protein (CN54rgp140/GLA-AF). The fine specificity of plasma Env-specific antibody responses was mapped after the final vaccination using linear peptide microarray technology. Binding IgG antibodies to the V1V2 loop in CRF01_AE and subtype C Env and Env-specific IgA antibodies were determined using enzyme-linked immunosorbent assay.

Induction of Identical IgG HIV-1 Envelope Epitope Recognition Patterns After Initial HIVIS-DNA/MVA-CMDR Immunization and a Late MVA-CMDR Boost.

In the RV144 trial, to date the only HIV-1 vaccine efficacy trial demonstrating a modestly reduced risk of HIV-1 acquisition, antibody responses toward the HIV Envelope protein (Env) variable (V) 2 and V3 regions were shown to be correlated with a reduced risk of infection. These potentially protective antibody responses, in parallel with the vaccine efficacy, however, waned quickly. Dissecting vaccine-induced IgG recognition of antigenic regions and their variants within the HIV-1 Env from different vaccine trials will aid in designing future HIV-1 immunogens and vaccination schedules.

Engaging community leaders to improve male partner participation in the prevention of mother-to-child transmission of HIV in Dar es Salaam, Tanzania.

Background: Male partner participation improves uptake, retention and outcomes of prevention of mother-to-child transmission of HIV (PMTCT) services. However, in patriarchal settings few men accompany their partners to antenatal care (ANC) and PMTCT services. We explored whether community leaders can improve male partner participation in ANC and PMTCT.

Optimizing the immunogenicity of HIV prime-boost DNA-MVA-rgp140/GLA vaccines in a phase II randomized factorial trial design.

Background: We evaluated the safety and immunogenicity of (i) an intradermal HIV-DNA regimen given with/without intradermal electroporation (EP) as prime and (ii) the impact of boosting with modified vaccinia virus Ankara (HIV-MVA) administered with or without subtype C CN54rgp140 envelope protein adjuvanted with Glucopyranosyl Lipid A (GLA-AF) in volunteers from Tanzania and Mozambique.

Methods: Healthy HIV-uninfected adults (N = 191) were randomized twice; first to one of three HIV-DNA intradermal priming regimens by needle-free ZetaJet device at weeks 0, 4 and 12 (Group I: 2x0.1mL [3mg/mL], Group II: 2x0.

Intradermal HIV-1 DNA Immunization Using Needle-Free Zetajet Injection Followed by HIV-Modified Vaccinia Virus Ankara Vaccination Is Safe and Immunogenic in Mozambican Young Adults: A Phase I Randomized Controlled Trial.

We assessed the safety and immunogenicity of HIV-DNA priming using Zetajet™, a needle-free device intradermally followed by intramuscular HIV-MVA boosts, in 24 healthy Mozambicans. Volunteers were randomized to receive three immunizations of 600 μg (n = 10; 2 × 0.1 ml) or 1,200 μg (n = 10; 2 × 0.

Job satisfaction and turnover intentions among health care staff providing services for prevention of mother-to-child transmission of HIV in Dar es Salaam, Tanzania.

Background: Option B+ for the prevention of mother-to-child transmission (PMTCT) of HIV (i.e., lifelong antiretroviral treatment for all pregnant and breastfeeding mothers living with HIV) was initiated in Tanzania in 2013.

HIVIS-DNA or HIVISopt-DNA priming followed by CMDR vaccinia-based boosts induce both humoral and cellular murine immune responses to HIV.

Background: In order to develop a more effective prophylactic HIV-1 vaccine it is important optimize the components, improve Envelope glycoprotein immunogenicity as well as to explore prime-boost immunization schedules. It is also valuable to include several HIV-1 subtype antigens representing the world-wide epidemic.

Methods: HIVIS-DNA plasmids which include Env genes of subtypes A, B and C together with Gag subtypes A and B and RTmut/Rev of subtype B were modified as follows: the Envelope sequences were shortened, codon optimized, provided with an FT4 sequence and an immunodominant region mutated.

Preferential Targeting of Conserved Gag Regions after Vaccination with a Heterologous DNA Prime-Modified Vaccinia Virus Ankara Boost HIV-1 Vaccine Regimen.

Prime-boost vaccination strategies against HIV-1 often include multiple variants for a given immunogen for better coverage of the extensive viral diversity. To study the immunologic effects of this approach, we characterized breadth, phenotype, function, and specificity of Gag-specific T cells induced by a DNA-prime modified vaccinia virus Ankara (MVA)-boost vaccination strategy, which uses mismatched Gag immunogens in the TamoVac 01 phase IIa trial. Healthy Tanzanian volunteers received three injections of the DNA-SMI vaccine encoding a subtype B and AB-recombinant Gag and two vaccinations with MVA-CMDR encoding subtype A Gag Gag-specific T-cell responses were studied in 42 vaccinees using fresh peripheral blood mononuclear cells.

The potential of task-shifting in scaling up services for prevention of mother-to-child transmission of HIV: a time and motion study in Dar es Salaam, Tanzania.

Background: In many African countries, prevention of mother-to-child transmission of HIV (PMTCT) services are predominantly delivered by nurses. Although task-shifting is not yet well established, community health workers (CHWs) are often informally used as part of PMTCT delivery. According to the 2008 World Health Organization (WHO) Task-shifting Guidelines, many PMTCT tasks can be shifted from nurses to CHWs.

Three-Year Durability of Immune Responses Induced by HIV-DNA and HIV-Modified Vaccinia Virus Ankara and Effect of a Late HIV-Modified Vaccinia Virus Ankara Boost in Tanzanian Volunteers.

We explored the duration of immune responses and the effect of a late third HIV-modified vaccinia virus Ankara (MVA) boost in HIV-DNA primed and HIV-MVA boosted Tanzanian volunteers. Twenty volunteers who had previously received three HIV-DNA and two HIV-MVA immunizations were given a third HIV-MVA immunization 3 years after the second HIV-MVA boost. At the time of the third HIV-MVA, 90% of the vaccinees had antibodies to HIV-1 subtype C gp140 (median titer 200) and 85% to subtype B gp160 (median titer 100).

Predictors of Patient Dissatisfaction with Services for Prevention of Mother-To-Child Transmission of HIV in Dar es Salaam, Tanzania.

Background: Mother-to-child transmission (MTCT) of HIV remains a major source of new HIV infections in children. Prevention of mother-to-child transmission of HIV (PMTCT) using lifelong antiretroviral treatment (ART) for all pregnant and breastfeeding women living with HIV (Option B+) is the major strategy for eliminating paediatric HIV. Ensuring that patients are satisfied with PMTCT services is important for optimizing uptake, adherence and retention in treatment.

Boosting with Subtype C CN54rgp140 Protein Adjuvanted with Glucopyranosyl Lipid Adjuvant after Priming with HIV-DNA and HIV-MVA Is Safe and Enhances Immune Responses: A Phase I Trial.

Background: A vaccine against HIV is widely considered the most effective and sustainable way of reducing new infections. We evaluated the safety and impact of boosting with subtype C CN54rgp140 envelope protein adjuvanted in glucopyranosyl lipid adjuvant (GLA-AF) in Tanzanian volunteers previously given three immunizations with HIV-DNA followed by two immunizations with recombinant modified vaccinia virus Ankara (HIV-MVA).

Methods: Forty volunteers (35 vaccinees and five placebo recipients) were given two CN54rgp140/GLA-AF immunizations 30-71 weeks after the last HIV-MVA vaccination.

HIV-DNA Given with or without Intradermal Electroporation Is Safe and Highly Immunogenic in Healthy Swedish HIV-1 DNA/MVA Vaccinees: A Phase I Randomized Trial.

Background: We compared safety and immunogenicity of intradermal (ID) vaccination with and without electroporation (EP) in a phase I randomized placebo-controlled trial of an HIV-DNA prime HIV-MVA boost vaccine in healthy Swedish volunteers.

Methods: HIV-DNA plasmids encoding HIV-1 genes gp160 subtypes A, B and C; Rev B; Gag A and B and RTmut B were given ID at weeks 0, 6 and 12 in a dose of 0.6 mg.

Virologic and immunologic failure, drug resistance and mortality during the first 24 months postpartum among HIV-infected women initiated on antiretroviral therapy for life in the Mitra plus Study, Dar es Salaam, Tanzania.

Background: In the Mitra plus study of prevention of mother-to-child transmission of HIV-1, which included 501 women in Dar es Salaam, Tanzania, triple antiretroviral therapy (ART) was given from late pregnancy throughout breastfeeding up to 6 months postnatally. Here we report findings in a sub-cohort of women with ≤200 CD4cells/μL at enrolment who were continued on ART for life and followed up during 24 months after delivery to determine virologic and immunologic responses, drug resistance and mortality.

Methods: Blood samples for viral load and CD4 counts testing were collected at enrolment and at 3, 6, 12 and 24 months postpartum.

Priming with a simplified intradermal HIV-1 DNA vaccine regimen followed by boosting with recombinant HIV-1 MVA vaccine is safe and immunogenic: a phase IIa randomized clinical trial.

Background: Intradermal priming with HIV-1 DNA plasmids followed by HIV-1MVA boosting induces strong and broad cellular and humoral immune responses. In our previous HIVIS-03 trial, we used 5 injections with 2 pools of HIV-DNA at separate sites for each priming immunization. The present study explores whether HIV-DNA priming can be simplified by reducing the number of DNA injections and administration of combined versus separated plasmid pools.

Potent functional antibody responses elicited by HIV-I DNA priming and boosting with heterologous HIV-1 recombinant MVA in healthy Tanzanian adults.

Unlabelled: Vaccine-induced HIV antibodies were evaluated in serum samples collected from healthy Tanzanian volunteers participating in a phase I/II placebo-controlled double blind trial using multi-clade, multigene HIV-DNA priming and recombinant modified vaccinia Ankara (HIV-MVA) virus boosting (HIVIS03). The HIV-DNA vaccine contained plasmids expressing HIV-1 gp160 subtypes A, B, C, Rev B, Gag A, B and RTmut B, and the recombinant HIV-MVA boost expressed CRF01_AE HIV-1 Env subtype E and Gag-Pol subtype A. While no neutralizing antibodies were detected using pseudoviruses in the TZM-bl cell assay, this prime-boost vaccination induced neutralizing antibodies in 83% of HIVIS03 vaccinees when a peripheral blood mononuclear cell (PBMC) assay using luciferase reporter-infectious molecular clones (LucR-IMC) was employed.

Incidence of HIV and the prevalence of HIV, hepatitis B and syphilis among youths in Maputo, Mozambique: a cohort study.

Background: Prevalence of HIV in Mozambique among individuals aged 15-49 years is 11.5%. The HIV prevalence is higher in women than in men across the country, peaking at ages 25-29 years and 35-39 years, respectively.

Women's preferences regarding infant or maternal antiretroviral prophylaxis for prevention of mother-to-child transmission of HIV during breastfeeding and their views on Option B+ in Dar es Salaam, Tanzania.

Background: The WHO 2010 guidelines for prevention of mother-to-child transmission (PMTCT) of HIV recommended prophylactic antiretroviral treatment (ART) either for infants (Option A) or mothers (Option B) during breastfeeding for pregnant women with a CD4 count of >350 cell/µL in low-income countries. In 2012, WHO proposed that all HIV-infected pregnant women should receive triple ART for life (B+) irrespective of CD4 count. Tanzania has recently switched from Option A to B+, with a few centers practicing B.