Impact of differentiated service delivery models on retention in HIV care and viral suppression among people living with HIV in sub-Saharan Africa: A systematic review and meta-analysis of randomised controlled trials.

Differentiated service delivery (DSD) models, such as adherence clubs (ACs), are client-centred approaches where clinically stable people living with HIV (PLHIV) meet to receive various services, including psychosocial support, brief symptoms screening, and refills of antiretroviral medications, among others. We conducted a review to assess the impact of DSD models, including ACs, on sustaining retention in care (RC) and achieving viral suppression (VS) among PLHIV in sub-Saharan Africa. The review protocol was registered in PROSPERO (CRD42023418988). We searched the literature from PubMed, Scopus, Web of Science, Embase and Google Scholar from their inception through May 2023. Eligible randomised controlled trials of adherence clubs were reviewed to assess impact on retention and viral suppression. Random effect models were used to estimate the risk ratios (RR) and 95% confidence intervals (CI). The literature search yielded a total of 1596 records of which 16 randomised clinical trials were determined to be eligible. The trials were conducted in diverse populations among adults and children with a total of 13,886 participants. The RR between any DSD models and standard of care (SoC) was 1.09 (95% CI: 1.08-1.11, I2 : 0%, p: <0.96) and 1.01 (95% CI: 1.00-1.02, I2 : 0%, p: <0.85) for RC and VS, respectively. The RR between ACs and SoC was 1.01 (95% CI: 0.96-1.07, I2 : 84%, p: <0.01) and 1.02 (95% CI: 0.98-1.07, I2 : 77%, p: <0.01) for RC and VS, respectively. DSD models, including ACs, show comparable effectiveness to SoC in maintaining care and achieving viral suppression for stable PLHIV. To maximise adoption, an implementation science approach is crucial for designing effective strategies and overcoming challenges.

The role of community pharmacies in early detection of suspected COVID-19 cases in 2020: lessons from Dar es Salaam, Tanzania.

Tanzania reported its first COVID-19 case on 16 March 2020. We conducted event-based surveillance of COVID-19 suspect cases among pharmacy clients presenting with respiratory symptoms and influenza-like illness to increase early and rapid detection of COVID-19 cases and mitigate transmission. We conveniently sampled 103 pharmacies from Dar es Salaam, the epicentre for the COVID-19 pandemic in Tanzania at the time. Between 23 April 2020 and 18 May 2020, 67% of the pharmacies (69/103) reported an observed increase in the number of clients presenting with respiratory symptoms and influenza-like illness compared with the 1 month before the COVID-19 outbreak. In the 1-month surveillance period, the participating pharmacies recorded 75 alerts of COVID-19 suspect cases and referred all suspected COVID-19 cases to rapid response teams for additional symptomatic screening and SARS-CoV-2 testing. A key implementation challenge was that some clients identified as COVID-19 suspected cases were hesitant to provide follow-up information for linkage to rapid response teams. Addressing concerns among drug dispensers in the participating pharmacies and informing them of the benefits of the surveillance activity were important implementation components. Our approach demonstrates the overall feasibility of rapidly implementing an event-based surveillance system for an emerging health threat through an existing network of pharmacies within the community. The approach and tools used in this surveillance activity could be adapted in similar settings to detect and generate alerts of disease outbreaks in the community that other surveillance systems may otherwise miss.

Awareness, Willingness and Use of HIV Pre-Exposure Prophylaxis Among Female Sex Workers Living in Dar-es-Salaam, Tanzania.

Tanzania is in the final stages to roll out pre-exposure prophylaxis (PrEP) to Female Sex Workers (FSWs) so as to reduce new infections. PrEP demonstration projects support programming through gaining first experiences.We analyzed data from a cohort of 700 HIV negative FSWs in Dar-es-Salaam to determine proportions of FSWs who were aware, willing and used PrEP. We compared proportions at cohort enrolment and after 12 months. Logistic regression was used to determine factors associated with PrEP use. PrEP awareness increased from 67% to 97% after 12 months. Willingness was high at both time points (98% versus 96%). Only 8% (57/700) had used PrEP. Being married/cohabiting or separated/divorced/widowed and having sex with a HIV infected partner were independently associated with PrEP use. The PrEP program should focus on scaling up access as willingness to use PrEP is high.

Humoral Immune Responses following COVID-19 Vaccinations among Adults in Tanzania.

COVID-19 vaccination remains to be the most important intervention in the fight against the pandemic. The immunity among the vaccinated population and its durability can significantly vary due to various factors. This study investigated the humoral immune responses among individuals who received any of the COVID-19 vaccines approved for use in Tanzania. A total of 1048 randomly selected adults who received COVID-19 vaccines at different time points were enrolled and humoral immune responses (IR) were tested at baseline and three months later (960, 91.6%). The level of SARS-CoV-2 anti-spike/receptor binding domain (RBD) IgG, anti-nucleocapsid IgG, and IgM antibodies were determined using a commercially available chemiluminescent microparticle immunoassay. Descriptive data analysis was performed using STATA version 18 and R. At baseline, serum IgG against anti-spike/RBD was detected in 1010/1048 (96.4%) participants (95%CI: 94.9-97.5) and 98.3% (95%CI: 97.3-99) three months later. The IgG against the SARS-CoV-2 nucleocapsid proteins were detected in 40.8% and 45.3% of participants at baseline and follow-up, respectively. The proportion of seroconverters following vaccination and mean titers of anti-spike/RBD antibodies were significantly more among those who had past SARS-CoV-2 infection than in those with no evidence of past infection, (p < 0.001). Only 0.5% of those who had detectable anti-spike/RBD antibodies at baseline were negative after three months of follow-up and 1.5% had breakthrough infections. The majority of participants (99.5%) had detectable anti-spike/RBD antibodies beyond 6 months post-vaccination. The proportion of Tanzanians who mounted humoral IR following COVID-19 vaccination was very high. Seroconversions, as well as the mean titers and durability of humoral IR, were significantly enhanced by exposure to natural SARS-CoV-2 infection. In view of the limited availability of COVID-19 vaccines as well as challenges to completing subsequent doses, booster doses could only be suggested to high-risk groups.

Personal experiences following acquiring HIV infection while volunteering in Phase I/II HIV vaccine trials: A qualitative study from Tanzania.

BACKGROUND: Participation in HIV vaccine trials is an essential step towards development of an effective preventive vaccine. A Phase I/II HIV vaccine trial enrolls volunteers at low risk of acquiring HIV infection, however a few may still become infected. Understanding the experiences of volunteers who acquired HIV infection while participating in such trials is essential for future research. Here, we describe experiences of HIV infected volunteers in Phase I/II HIV vaccine trials conducted in urban Tanzania. MATERIALS AND METHODS: We used a case study design. In-depth interviews were conducted with four participants who became HIV infected during long follow-up visits after completion of vaccination schedules in a Phase I/II trial. Between 3 and 8 years after HIV positive diagnosis, each participant was interviewed at three time points within a two-year interval so as to allow for accumulation of experiences and cross-checking the emerging constructs. Data was analyzed using a qualitative data analysis framework. RESULTS: Analysis revealed that participation in HIV vaccine trials involves balancing controversies and the spirit of informed decision. The participants declared that they did not acquire HIV from the experimental vaccine. Disclosure of HIV status within the family was gender specific. Men were hesitant to disclose their HIV status to their sexual partners fearing for the consequences. Women's attempt to disclose their HIV status yielded negative reactions from the sexual partners. The acquired knowledge from the HIV vaccine research enabled the participants to cope with the uncertainties and their health status. CONCLUSIONS: The knowledge acquired during the Phase I/II HIV vaccine trial appears to be an essential resource to cope with uncertainties post research. The HIV vaccine trial implementers need to understand the challenges the volunteers may confront after the trial while coping with their health status. Longitudinal studies are essential to trace the effects of uncertainties to the individual participants.

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. Social demographic data, HIV risk behavioral assessments, and blood samples for testing of HIV, syphilis, hepatitis B (HBV), and hepatitis C (HCV) infections were collected at baseline and then at 3, 6, 9, and 12 months. Poisson regressions were used to estimate the prevalence ratios for factors associated with HIV prevalence and to estimate the 12-month HIV incidence rate. RESULTS: Between October and December 2018, a total of 773 FSWs were screened for eligibility and 700 were enrolled. The baseline prevalence of HIV, syphilis, HBV, and HCV was 7.6%, 1.2%, 1.7%, and 1.0%, respectively. HIV prevalence was associated with older age, using illicit drugs, and being infected with syphilis, HBV, or HCV. Attendance at 12 months was 80% (562/700). Twenty-one FSWs seroconverted during follow-up, giving a 12-month HIV incidence rate of 3.45 per 100 person-years at risk (95% CI; 2.25-5.28/100 person-years at risk). The HIV incidence rate was higher among FSWs aged 18-24 years, FSWs who used drugs, and those diagnosed with syphilis, HBV, or HCV. CONCLUSION: The high HIV incidence rate and retention rate among FSWs enrolled into the cohort demonstrate that this population is suitable for participation in HIV prevention trials.

Compliance to infection prevention and control interventions for slowing down COVID-19 in early phase of disease transmission in Dar es Salaam, Tanzania.

Introduction: on 16th March 2020, Tanzania announced its first COVID-19 case. The country had already developed a 72-hour response plan and had enacted three compulsory infection prevention and control interventions. Here, we describe public compliance to Infection Prevention and Control (IPC) public health measures in Dar es Salaam during the early COVID-19 response and testing of the feasibility of an observational method. Methods: a cross sectional study was conducted between April and May 2020 in Dar es Salaam City. At that time, Dar es Salaam was the epi centre of the epidemic. Respondents were randomly selected from defined population strata (high, medium and low). Data were collected using a structured questionnaire and through observations. Results: a total of 390 subjects were interviewed, response rate was 388 (99.5%). Mean age of the respondents was 34.8 years and 168 (43.1%) had primary level education. Out of the 388 respondents, 384 (98.9%) reported to have heard about COVID-19 public health and social measures, 90.0% had heard from the television and 84.6% from the radio. Covering coughs and sneezes using a handkerchief was the most common behaviour observed among 320 (82.5%) respondents; followed by hand washing hygiene practice, 312 (80.4%) and wearing face masks, 240 (61.9%). Approximately 215 (55.4%) adhered to physical distancing guidance. Age and gender were associated with compliance to IPC measures (both, p<0.05). Conclusion: compliance to public health measures during the early phase of COVID-19 pandemic in this urban setting was encouraging. As the pandemic continues, it is critical to ensure compliance is sustained and capitalize on risk communication via television and radio.

Evaluation of a New Field Epidemiology Training Program Intermediate Course to Strengthen Public Health Workforce Capacity in Tanzania.

OBJECTIVES: Sub-Saharan Africa faces a shortage of skilled epidemiologists to prevent, detect, and respond to health threats. Tanzania has implemented one of the first Centers for Disease Control and Prevention Field Epidemiology Training Program (FETP) Intermediate courses in Africa. This course aims to strengthen health workforce capacity in surveillance system assessment, outbreak investigation, and evaluation, prioritizing HIV control. We conducted an outcome evaluation of this new course. METHODS: We used a pre/post evaluation design using data from 4 cohorts of trainees who took the FETP Intermediate course from 2017 to 2020. We conducted knowledge assessments before and after each cohort and combined those results. Outcomes included knowledge and self-rated competency and trends in integrated disease surveillance and response (IDSR) data. We collected data through tests, field assignments, exit interviews, and data audits. We compared the mean change in pre-/posttest scores using linear regression and 95% CIs. We used content analysis to summarize exit interviews. RESULTS: Fifty-three FETP trainees from 10 regions enrolled in the FETP Intermediate course, and 52 (99.0%) completed the course. We found substantial increases in mean knowledge (44.0 to 68.0 points) and self-rated competency (4.14 to 4.43) scores before and after the course. Trainees evaluated 52 surveillance systems and 52 district HIV care programs, and 39 (75.0%) trainees participated in outbreak investigations. From before to after cohort 1, timeliness and completeness of IDSR reports increased from 4.2% to 52.1% and from 27.4% to 76.5%, respectively. Course strengths were quality of instruction, individualized mentoring, and practical skills gained. Challenges were mentor availability, limited time for data analysis practice, and balancing work and field assignments. CONCLUSIONS: The Tanzania FETP Intermediate course substantially improved trainee knowledge and helped to improve local data quality and reporting. This course is a promising model to strengthen subnational capacity to prevent, detect, and respond to public health threats in Africa.

"I did not plan to have a baby. This is the outcome of our work": a qualitative study exploring unintended pregnancy among female sex workers.

BACKGROUND: High number of unintended pregnancies-often leading to induced abortions-are reported among female sex workers (FSWs), highlighting a major unmet need for contraception. To better understand barriers to contraceptive use, we explored FSW's pregnancy perceptions and experiences of unintended pregnancy. We hypothesized that sex work exacerbates barriers to contraceptive use and that FSW's pregnancy perceptions and experiences of unintended pregnancy influence future commitment to contraceptive use. METHODS: We conducted in-depth interviews with 11 FSWs (January-June 2019) in Dar es Salaam, Tanzania. We purposively sampled FSWs with a positive pregnancy test from those participating in a HIV vaccine preparedness cohort. We used open ended questions to explore how FSWs make decisions when facing barriers to contraceptive use, dealing with unintended pregnancy and adhering to contraceptive use after experiencing unintended pregnancy. All interviews were conducted in Kiswahili, audio-recorded, transcribed and translated into English. Grounded theory approach was used to analyse transcripts. Open and selective coding was performed using Nvivo software. RESULTS: FSWs reported that sex work impedes good contraceptive behaviour because sex workers felt unable to negotiate consistent condom use, avoided health services due to stigma, missed monthly contraceptive supplies because of inconvenient clinic operating hours or skipped contraceptive pills when intoxicated after taking alcohol. FSWs who perceived pregnancy to be a burden terminated the pregnancy because of fear of loss of income during pregnancy or child rearing expenses in case child support was not assured by their partners. FSWs who perceived pregnancy to be a blessing decided to keep the pregnancy because they desired motherhood and hoped that children would bring prosperity. Family planning counselling and availability of contraceptives during postpartum care influenced the initiation of contraception among FSWs. Financial hardships related to childrearing or painful abortion experiences influenced FSWs' commitment to good contraceptive practices. CONCLUSION: Our results demonstrate that FSWs face barriers to initiating and adhering to contraceptive use because of sex work stigma, inability to negotiate condoms and failure to access medical services at their convenience. Our findings underscore the need to integrate contraceptive services with HIV programs serving FSWs in their areas of work.

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. Functional antibody-dependent cellular cytotoxicity (ADCC)-mediating antibody responses were measured using luciferase assay. Mapping of linear epitopes within HIV-1 Env demonstrated strong targeting of the V1V2, V3, and the immunodominant region in gp41 in both groups, with additional recognition of two epitopes located in the C2 and C4 regions in group 2. A high frequency of V1V2-specific binding IgG antibody responses was detected to CRF01_AE (77%) and subtype C antigens (65%). In conclusion, coadministration of CN54rgp140/GLA-AF with HIV-MVA did not increase the frequency, breadth, or magnitude of anti-V1V2 responses or ADCC-mediating antibodies induced by boosting with HIV-MVA alone.

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). Cyclic V2 peptides of A244, Consensus C, and MN were used in a surface plasmon resonance (SPR) assay. Four weeks after the second HIV-MVA, anti-V1V2 IgG antibodies to A244 were detected in 97% of HIVIS03 vaccinees, in 75% three years later, and in 95% after the third HIV-MVA. Anti-CN54 V1V2 IgG was detectable in 48% four weeks after the second HIV-MVA. The SPR data supported the findings. The IgG response was predominantly IgG1. Four weeks after the second HIV-MVA, 85% of vaccinees had IgG1 antibodies to V1V2 A244, which persisted in 25% for three-years. IgG3 and IgG4 antibodies to V1V2 A244 were rare. In conclusion, the HIV-DNA/MVA vaccine regimen induced durable V1V2 IgG antibody responses in a high proportion of vaccinees.

Addressing the workforce capacity for public health surveillance through field epidemiology and laboratory training program: the need for balanced enhanced skill mix and distribution, a case study from Tanzania.

INTRODUCTION: Skill mix refers to the range of professional development and competencies, skills and experiences of staff within a particular working environment that link with specific outcome while responding to client needs. A balanced skill-mix and distribution of core human resources is important to strengthen decision-making process and rapid responses. We analysed graduates´ information of the Tanzania Field Epidemiology and Laboratory Training Program (TFELTP) between 2008-2016, distribution of skill-mix and the surveillance workforce-gaps within regions. METHODS: Trainees´ data of nine cohorts enrolled between 2008 and 2016 were extracted from the program database. Distribution by sex, region and cadres/profession was carried out. An indicator to determine enhanced-skill mix was established based on the presence of a clinician, nurse, laboratory scientist and environmental health officer. A complete enhanced skill-mix was considered when all four were available and have received FELTP training. RESULTS: The TFELTP has trained 113 trainees (male=71.7%), originated from 17 regions of Tanzania Mainland (65.4% of all) and Zanzibar. Clinicians (34.5%) and laboratory scientists (38.1%) accounted for the most recruits, however, the former were widely spread in regions (83% vs. 56%). Environmental health officers (17.7%) were available in 39% of regions. The nursing profession, predominantly lacking (6.2%) was available in 22% of regions. Only two regions (11.7%) among 17 covered by TFELTP presented complete skill-mix, representing 7.7% of Tanzanian regions. Seven regions (41%) had an average of one trainee. CONCLUSION: The TFELTP is yet to reach the required skill-mix in many regions within the country. The slow fill-rate for competent and key workforce cadres might impede effective response. Strategies to increase program awareness at subnational levels is needed to improve performance of surveillance and response system in Tanzania.

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. We, therefore, analyzed the IgG response toward linear HIV-1 Env epitopes elicited by a multi-clade, multigene HIVIS-DNA priming, and heterologous recombinant modified vaccinia virus Ankara (MVA-CMDR) boosting regimen (HIVIS03) and assessed whether a late MVA-CMDR boost 3 years after completion of the initial vaccination schedule (HIVIS06) restored antibody responses toward these epitopes. Here we report that vaccination schedule in the HIVIS03 trial elicited IgG responses against linear epitopes within the V2 and V3 tip as well as against the gp41 immunodominant region in a high proportion of vaccinees. Antibodies against the V2 and gp41 Env regions were restricted to variants with close homology to the MVA-CMDR immunogen sequence, while V3 responses were more cross-reactive. Boosting with a late third MVA-CMDR after 3 years effectively restored waned IgG responses to linear Env epitopes and induced targeting of identical antigenic regions and variants comparable to the previous combined HIVIS-DNA/MVA-CMDR regimen. Our findings support the notion that anti-HIV-1 Env responses, associated with a reduced risk of infection in RV144, could be maintained by regular boosting with a single dose of MVA-CMDR.

Skin disorders among children living in orphanage centres in Dar es Salaam, Tanzania.

BACKGROUND: Skin conditions contribute significantly to the global burden of diseases and are among the leading causes of non-fatal disease burden. Children living in orphanage centres are vulnerable to several conditions including dermatological disorders, and there is limited data on the burden of these conditions among orphans in Tanzania. This study was carried out to determine the pattern of dermatological conditions and contributing factors among orphans in Dar es Salaam, Tanzania. METHODOLOGY: A cross-sectional study was conducted among 420 children aged less than 18 years from 12 orphanage centres in Dar es Salaam. Guided interviews using structured questionnaires were carried out to obtain socio-demographic and clinical data from participants. Clinical examination was performed for each participant and whenever indicated skin scrapings and biopsy were obtained. RESULTS: Four hundred and twenty participants were recruited out of which 281 (66.9%) were male, mean and median ages of participants were 11 ± 3.7 and 12 years, respectively. Two hundred and twenty-five (53.6%) participants were aged between 6 and12 years. Proportion of children with dermatological manifestations among participants was 57.4%. Two hundred and ninety-six diagnoses were made comprising of 192 (64.9%) infections and 104 (35.1%) non-infectious conditions. Tinea capitis was the commonest infection while acne vulgaris was the most common non-infectious condition. Proportionately more male children were affected as compared to female ones, p = 0.006. CONCLUSION: Skin conditions are common among children living in orphanage centres in Dar es Salaam. Infectious conditions were predominant conditions and male children were more affected than female children. Reducing crowding and improving hygienic practices in these centres will be important in reducing the burden of these conditions.

Recruitment using respondent driven sampling, risk behaviors assessment and willingness of young female sex workers (18-25 years) in Dar Es Salaam, Tanzania to participate in HIV vaccine trials.

BACKGROUND: Despite the present HIV preventive and treatment programs, the prevalence of HIV is still high in eastern and southern Africa, among young women and populations at high. risk for HIV transmission such as sex workers. There is a need to prepare a suitable population that will participate in efficacy HIV vaccine trials to determine the efficacy of HIV vaccines that had proven to be safe and immune potent. METHODS: It was a cross-sectional study that recruited 600 female sex workers using respondent-driven sampling in Dar es Salaam. The study examined recruitment approaches, risk behaviors and willingness of young female sex workers to participate in an HIV vaccine trial. Descriptive statistics described risk behaviors and willingness of the participants to participate in efficacy HIV vaccine trials. The logistic regression model computed the likelihood of willingness to participate in the trials with selected variables. RESULTS: The study demonstrated 53% were less than 20 years old, 96% were single, and 22% lived in brothels. Eighty percent of the participants started selling sex at the age between 15 and 19 years old, 61% used illicit drugs for the first time when they were less than 20 years old, 24% had anal sex ever. Eighty-nine percent had more than 20-lifetime sexual partners, and 56% had unprotected sexual intercourse with sex clients. Ninety-one percent expressed a willingness to participate in the HIV vaccine trial. Sixty-one percent did not need permission from anyone for participating in a trial. Ninety-one percent expressed willingness to participate in the efficacy of HIV vaccine trial. In the logistic regression model, willingness was significantly associated with the need to ask permission for participation in HIV vaccine trial from sex agent. CONCLUSION: Respondent-driven sampling provided a rapid means of reaching young female sex workers who reported high-risk behaviors. The majority expressed a high level of willingness to participate in the HIV vaccine trial which was marginally correlated to the need to seek consent for participation in the trial from the sex brokers. Future HIV vaccine trials involving this population should consider involving the brokers in the trials because they form an essential part of the community for the participants.

Perception of potential harm and benefits of HIV vaccine trial participation: A qualitative study from urban Tanzania.

BACKGROUND: The development of an effective preventive HIV vaccine is the best-known option to halt incident HIV infections. Participants in HIV vaccine trials may possess expectations shaped by existing socio-cultural contexts that are important to understand to allow for improved trial design. Here, we describe post-phase I/II HIV vaccine trial perceptions within participating communities in Dar es Salaam, Tanzania. MATERIALS AND METHODS: This descriptive qualitative study was conducted in May 2016. We conducted eight focus group discussions, each consisting of 5 to 12 participants. Four groups comprised of the past phase I/II HIV vaccine trial participants and four groups involved those who did not participate. We used a thematic analysis approach. RESULTS: Ongoing concerns existed among non-vaccine trial participants who believed that those who participated in HIV vaccine trials were infected with HIV. Limited post-HIV vaccine trial result dissemination, the pre-existing negative beliefs about vaccines, and experiences from other previous medical experiments fueled these concerns. The participants anticipated that broader dissemination of facts regarding HIV vaccine trials using media, former volunteers, and flyers would reduce the reported concerns. In contrast, some participants embraced the benefits gained through participating in HIV vaccine trials. HIV vaccine trial participants appreciated trial interventions, such as health status check-ups, knowledge acquisition, and facilitation of access to medical services. They envisioned mutual benefits in the form of community protection and capacity building among the local scientists. CONCLUSIONS: The future conduct of HIV vaccine trials in Tanzania requires wider community dissemination of information and post-trial feedback to alleviate concerns among the participating communities. Interventions such as medical services may represent essential incentives to the HIV vaccine trial volunteers. In future HIV vaccine trials, it is crucial to boost individual and perceived mutual benefits.

Envelope-Specific Recognition Patterns of HIV Vaccine-Induced IgG Antibodies Are Linked to Immunogen Structure and Sequence.

Background: A better understanding of the parameters influencing vaccine-induced IgG recognition of individual antigenic regions and their variants within the HIV Envelope protein (Env) can help to improve design of preventive HIV vaccines. Methods: Env-specific IgG responses were mapped in samples of the UKHVC003 Standard Group (UK003SG, n = 11 from UK) and TaMoVac01 (TMV01, n = 17 from Tanzania) HIV vaccine trials. Both trials consisted of three immunizations with DNA, followed by two boosts with recombinant Modified Vaccinia Virus Ankara (MVA), either mediating secretion of gp120 (UK003SG) or the presentation of cell membrane bound gp150 envelopes (TMV01) from infected cells, and an additional two boosts with 5 µg of CN54gp140 protein adjuvanted with glucopyranosyl lipid adjuvant (GLA). Env immunogen sequences in UK003SG were solely based on the clade C isolate CN54, whereas in TMV01 these were based on clades A, C, B, and CRF01AE. The peptide microarray included 8 globally representative Env sequences, CN54gp140 and the MVA-encoded Env immunogens from both trials, as well as additional peptide variants for hot spots of immune recognition. Results: After the second MVA boost, UK003SG vaccinees almost exclusively targeted linear, non-glycosylated antigenic regions located in the inter-gp120 interface. In contrast, TMV01 recipients most strongly targeted the V2 region and an immunodominant region in gp41. The V3 region was frequently targeted in both trials, with a higher recognition magnitude for diverse antigenic variants observed in the UK003SG (p < 0.0001). After boosting with CN54gp140/GLA, the overall response magnitude increased with a more comparable recognition pattern of antigenic regions and variants between the two trials. Recognition of most immunodominant regions within gp120 remained significantly stronger in UK003SG, whereas V2-region recognition was not boosted in either group. Conclusions: IgG recognition of linear antigenic Env regions differed between the two trials particularly after the second MVA boost. Structural features of the MVA-encoded immunogens, such as secreted, monomeric gp120 vs. membrane-anchored, functional gp150, and differences in prime-boost immunogen sequence variability most probably contributed to these differences. Prime-boosting with multivalent Env immunogens during TMV01 did not improve variant cross-recognition of immunodominant peptide variants in the V3 region.

Sialic acid levels in breast milk from HIV-positive Tanzanian women and impact of maternal diet.

OBJECTIVE: To quantify total sialic acid in milk from HIV-positive Tanzanian mothers and to determine the impact of maternal diet on milk sialic acid levels. DESIGN: Milk samples were analyzed from 74 HIV-positive, Tanzanian women enrolled in a randomized, controlled clinical study of a dietary macronutrient supplement. Women were provided with a daily protein-calorie supplement and a micronutrient supplement or micronutrient supplement only during the last trimester of pregnancy and up to the first 6 months of breastfeeding. METHODS: Milk samples were collected at approximately 2 weeks and at least 3 months postpartum and assayed for total sialic acid. Milk sialic acid was assessed relative to maternal macronutrient intake, age, BMI, CD4+ cell count and infant birth weight. RESULTS: The mean concentration of milk sialic acid was highest in the first 2 weeks postpartum (6.89 ±â€Š2.79 mmol/l) and declined rapidly by 3 months (2.49 ±â€Š0.60 mmol/l). Sialic acid content in milk was similar between both treatment arms of the study, and did not correlate with maternal macronutrient intake. No correlation was found between maternal age, BMI, CD4+ cell count or infant birth weight and total milk sialic acid concentration. CONCLUSION: Milk sialic acid levels in HIV-positive, Tanzanian women without malnutrition are comparable with reported values for women of European descent and show a similar temporal decline during early lactation. These findings suggest that total milk sialic acid is maintained despite macronutrient deficiencies in maternal diet and support a conserved role for milk sialic acid in neonatal development.

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: 2x0.1mL [3mg/mL] plus EP, Group III: 1x0.1mL [6mg/mL] plus EP). Second the same volunteers received 108 pfu HIV-MVA twice, alone or combined with CN54rgp140/GLA-AF, intramuscularly by syringe, 16 weeks apart. Additionally, 20 volunteers received saline placebo. RESULTS: Vaccinations and electroporation did not raise safety concerns. After the last vaccination, the overall IFN-γ ELISpot response rate to either Gag or Env was 97%. Intradermal electroporation significantly increased ELISpot response rates to HIV-DNA-specific Gag (66% group I vs. 86% group II, p = 0.026), but not to the HIV-MVA vaccine-specific Gag or Env peptide pools nor the magnitude of responses. Co-administration of rgp140/GLA-AF with HIV-MVA did not impact the frequency of binding antibody responses against subtype B gp160, C gp140 or E gp120 antigens (95%, 99%, 79%, respectively), but significantly enhanced the magnitude against subtype B gp160 (2700 versus 300, p<0.001) and subtype C gp140 (24300 versus 2700, p<0.001) Env protein. At relatively low titers, neutralizing antibody responses using the TZM-bl assay were more frequent in vaccinees given adjuvanted protein boost. CONCLUSION: Intradermal electroporation increased DNA-induced Gag response rates but did not show an impact on Env-specific responses nor on the magnitude of responses. Co-administration of HIV-MVA with rgp140/GLA-AF significantly enhanced antibody responses.

Pre- and post-natal macronutrient supplementation for HIV-positive women in Tanzania: Effects on infant birth weight and HIV transmission.

OBJECTIVE: To determine if a protein-calorie supplement (PCS) plus a micronutrient supplement (MNS) improves outcomes for HIV-infected lactating women and their infants. DESIGN: Randomized, controlled trial. SETTING: Dar es Salaam, Tanzania. SUBJECTS, PARTICIPANTS: Pregnant HIV-infected women enrolled in PMTCT programs who intended to breastfeed for 6 months. INTERVENTION: Randomization 1:1 to administration of a PCS plus MNS versus MNS alone among 96 eligible women beginning in the third trimester and continuing for 6 months of breast-feeding. MAIN OUTCOME MEASURE(S): Primary: infant weight at 3 months. Secondary: maternal BMI at 6 months. RESULTS: PCS resulted in significant increases in daily energy intake compared to MNS at all time points (range of differences: +388-719 Kcal); and increases in daily protein intake (range of differences: +22-33 gm). Infant birth weight (excluding twins) was higher in the PCS than MNS groups: 3.30 kg vs 3.04 kg (p = 0.04). Infant weight at 3 months did not differ between PCS and MNS groups: 5.63 kg vs 5.99 kg (p = 0.07). Maternal BMI at 6 months did not differ between PCS and MNS groups: 24.3 vs 23.8 kg/m2 (p = 0.68). HIV transmission occurred in 0 infants in the PCS group vs 4 in the MNS group (p = 0.03). CONCLUSIONS: In comparison to MNS the PCS + MNS intervention was well tolerated, increased maternal energy and protein intake, and increased infant birth weight, but not weight at 3 months or maternal BMI at 6 months. Reduced infant HIV transmission in the PCS + MNS group was observed. TRIAL REGISTRATION: Clinical Trials.Gov NCT01461863.