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.

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.

"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.

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.

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 Gagp37 and two vaccinations with MVA-CMDR encoding subtype A Gagp55 Gag-specific T-cell responses were studied in 42 vaccinees using fresh peripheral blood mononuclear cells. After the first MVA-CMDR boost, vaccine-induced gamma interferon-positive (IFN-γ+) Gag-specific T-cell responses were dominated by CD4+ T cells (P < 0.001 compared to CD8+ T cells) that coexpressed interleukin-2 (IL-2) (66.4%) and/or tumor necrosis factor alpha (TNF-α) (63.7%). A median of 3 antigenic regions were targeted with a higher-magnitude median response to Gagp24 regions, more conserved between prime and boost, compared to those of regions within Gagp15 (not primed) and Gagp17 (less conserved; P < 0.0001 for both). Four regions within Gagp24 each were targeted by 45% to 74% of vaccinees upon restimulation with DNA-SMI-Gag matched peptides. The response rate to individual antigenic regions correlated with the sequence homology between the MVA- and DNA Gag-encoded immunogens (P = 0.04, r2 = 0.47). In summary, after the first MVA-CMDR boost, the sequence-mismatched DNA-prime MVA-boost vaccine strategy induced a Gag-specific T-cell response that was dominated by polyfunctional CD4+ T cells and that targeted multiple antigenic regions within the conserved Gagp24 protein.IMPORTANCE Genetic diversity is a major challenge for the design of vaccines against variable viruses. While including multiple variants for a given immunogen in prime-boost vaccination strategies is one approach that aims to improve coverage for global virus variants, the immunologic consequences of this strategy have been poorly defined so far. It is unclear whether inclusion of multiple variants in prime-boost vaccination strategies improves recognition of variant viruses by T cells and by which mechanisms this would be achieved, either by improved cross-recognition of multiple variants for a given antigenic region or through preferential targeting of antigenic regions more conserved between prime and boost. Engineering vaccines to induce adaptive immune responses that preferentially target conserved antigenic regions of viral vulnerability might facilitate better immune control after preventive and therapeutic vaccination for HIV and for other variable viruses.

Neuropsychiatric manifestations among HIV-1 infected African patients receiving efavirenz-based cART with or without tuberculosis treatment containing rifampicin.

PURPOSE: Efavirenz-based combination antiretroviral therapy (cART) is associated with neuropsychiatric adverse events. We investigated the time to onset, duration, clinical implications, impact of pharmacogenetic variations, and anti-tuberculosis co-treatment on efavirenz-associated neuropsychiatric manifestations. METHODS: Prospective cohort study of cART naïve HIV patients with or without tuberculosis (HIV-TB) co-infection treated with efavirenz-based cART. Rifampicin-based anti-tuberculosis therapy was initiated 4 weeks prior to efavirenz-based cART in HIV-TB patients. Data on demographic, clinical, laboratory, and a 29-item questionnaire on neuropsychiatric manifestations were collected for 16 weeks after cART initiation. Genotyping for CYP2B6, CYP3A5, SLCO1B1, and ABCB1 and quantification of efavirenz plasma concentration were done on the 4th and 16th week. RESULTS: Data from 458 patients (243 HIV-only and 215 HIV-TB) were analyzed. Overall incidence of neuropsychiatric manifestations was 57.6% being higher in HIV-only (66.7%) compared to HIV-TB patients (47.4%) (p < 0.01). HIV-only patients were more symptomatic, with proportionately higher grades of manifestations compared to HIV-TB patients. Median time to manifestations was 1 week after cART initiation in HIV-only and 6 weeks after anti-TB (i.e., 2 weeks after cART initiation) in HIV-TB patients. HIV-only patients had significantly higher efavirenz plasma concentrations at 4 weeks after cART compared to HIV-TB patients. No association of sex or genotype was seen in relation to neuropsychiatric manifestations. Risk for neuropsychiatric manifestations was three times more in HIV-only patients compared to HIV-TB (p < 0.01). CONCLUSIONS: Incidence of neuropsychiatric manifestations during early initiation of efavirenz-based cART is high in Tanzanian HIV patients. Risk of neuropsychiatric manifestations is lower in HIV patients co-treated with rifampicin containing anti-TB compared to those treated with efavirenz-based cART only.

Gender aspects on HIV prevention efforts and participation in HIV vaccine trials among Police officers in Dar es Salaam, Tanzania.

BACKGROUND: For more than three decades, Human Immunodeficiency Virus (HIV) infection and Acquired Immune Deficiency Syndrome (AIDS) continue to dominate the health agenda. In sub-Saharan African countries, women are at more risk of contracting HIV and AIDS compared with men due to biological, social, economic, socio-economic and cultural factors. Women in the uniformed services may be more vulnerable to HIV/AIDS because of their work context, mobility, age and other factors that expose them to a higher risk of infection than women in the general population. This article describes gender dimensions, motives and challenges towards HIV prevention amongst Police officers (POs) in Dar es Salaam, Tanzania. METHODS: This was a descriptive qualitative study conducted at Police stations in Dar es Salaam, Tanzania. Fifteen in-depth interviews were conducted on POs; seven men, and eight women. Content analysis approach was used to analyze data. RESULTS: Participants' self-descriptions shed light on gender differences in relation to self -perceptions, job contexts, sexual relationships and HIV prevention. Both men and women perceived themselves as role models, and believed that the surrounding community perceived the same. Safe sexual behavior appeared crucial to avoid undesirable health outcomes. Risky sexual practices were considered avoidable. Under unavoidable sexual temptations, women in particular would be keen to avoid risky sexual practices. Some participants expressed positive views towards condoms use during extra-marital sexual relationships, while others had negative opinions. Early phases of HIV vaccine trials appeared to gain support from sexual partners. However, condom use during phase I/II HIV vaccine trials was deemed as difficult. Support from the spouse was reported to influence condom use outside the wedlock. However, religious beliefs, socio-cultural issues and individual reasons were perceived as difficulties to promote condoms use. CONCLUSIONS: These findings increase understanding of gender differences and context specific efforts towards HIV prevention. Individuals' assertiveness against risky sexual practices and the intention to participate in HIV vaccine trials to develop an effective vaccine are worth noting. Nevertheless, uncertainties towards condoms use underscore the importance of condoms' marketing particularly in extra marital sexual relationships and during early HIV vaccine trials.

Cost-Effectiveness of isoniazid preventive therapy among HIV-infected patients clinicaly screened for latent tuberculosis infection in Dar es Salaam, Tanzania: A prospective Cohort study.

BACKGROUND: One of the reasons why Isoniazid preventive therapy (IPT) for Tuberculosis (TB) is not widely used in low income countries is concerns on cost of excluding active TB. We analyzed the cost-effectiveness of IPT provision in Tanzania having ruled out active TB by a symptom-based screening tool. METHODS: Data on IPT cost-effectiveness was prospectively collected from an observational cohort study of 1283 HIV-infected patients on IPT and 1281 controls; followed up for 24 months. The time horizon for the analysis was 2 years. Number of TB cases prevented and deaths averted were used for effectiveness. A micro costing approach was used from a provider perspective. Cost was estimated on the basis of clinical records, market price or interviews with medical staff. We annualized the cost at a discount of 3%. A univariate sensitivity analysis was done. Results are presented in US$ at an average annual exchange rate for the year 2012 which was Tanzania shillings 1562.4 for 1 US $. RESULTS: The number of TB cases prevented was 420/100,000 persons receiving IPT. The number of deaths averted was 979/100,000 persons receiving IPT. Incremental cost due to IPT provision was US$ 170,490. The incremental cost effective ratio was US $ 405.93 per TB case prevented and US $ 174.15 per death averted. These costs were less than 3 times the 768 US $ Gross Domestic Product (GDP) per capita for Tanzania in the year 2014, making IPT provision after ruling out active TB by the symptom-based screening tool cost-effective. The results were robust to changes in laboratory and radiological tests but not to changes in recurrent, personnel, medication and utility costs. CONCLUSION: IPT should be given to HIV-infected patients who screen negative to symptom-based TB screening questionnaire. Its cost-effectiveness supports government policy to integrate IPT to HIV/AIDS care and treatment in the country, given the availability of budget and the capacity of health facilities.

Auditory Impairments in HIV-Infected Children.

OBJECTIVES: In a cross-sectional study of human immunodeficiency virus (HIV)-infected adults, the authors showed lower distortion product otoacoustic emissions (DPOAEs) in HIV+ individuals compared with controls as well as findings consistent with a central auditory processing deficit in HIV+ adults on antiretroviral therapy. The authors hypothesized that HIV+ children would also have a higher prevalence of abnormal central and peripheral hearing test results compared with HIV- controls. DESIGN: Pure-tone thresholds, DPOAEs, and tympanometry were performed on 244 subjects (131 HIV+ and 113 HIV- subjects). Thirty-five of the HIV+, and 3 of the HIV- subjects had a history of tuberculosis treatment. Gap detection results were available for 18 HIV- and 44 HIV+ children. Auditory brainstem response results were available for 72 HIV- and 72 HIV+ children. Data from ears with abnormal tympanograms were excluded. RESULTS: HIV+ subjects were significantly more likely to have abnormal tympanograms, histories of ear drainage, tuberculosis, or dizziness. All audiometric results were compared between groups using a two-way ANOVA with HIV status and ear drainage history as grouping variables. Mean audiometric thresholds, gap detection thresholds, and auditory brainstem response latencies did not differ between groups, although the HIV+ group had a higher proportion of individuals with a hearing loss >25 dB HL in the better ear. The HIV+ group had reduced DPOAE levels (p < 0.05) at multiple frequencies compared with HIV- subjects. No relationships were found between treatment regimens or delay in starting treatment and audiological parameters. CONCLUSIONS: As expected, children with HIV+ were more likely to have a history of ear drainage, and to have abnormal tympanograms. Similar to the adult findings, the HIV+ group did not show significantly reduced audiometric thresholds, but did have significantly lower DPOAE magnitudes. These data suggest that (1) HIV+ children often have middle ear damage which complicates understanding the direct effects of HIV on the hearing system, and (2) even when corrected for confounders DPOAEs were lower in the HIV+ group. Previous studies suggest ototoxicity from antiretroviral drugs is an unlikely cause of the reduced DPOAE magnitudes. Other possibilities include effects on efferent pathways connecting to outer hair cells or a direct effect of HIV on the cochlea.

Acceptability and adherence to Isoniazid preventive therapy in HIV-infected patients clinically screened for latent tuberculosis in Dar es Salaam, Tanzania.

BACKGROUND: Proper adherence to isoniazid preventive therapy (IPT) may depend upon the results of tuberculosis (TB) screening test and patients' understanding of their risk of developing active TB. We conducted a study to assess the acceptability, adherence and completion profile of IPT among HIV-infected patients who were clinically screened for latent TB Infection (LTBI). METHODS: A multicenter observational study was conducted in Dar es Salaam, Tanzania between February 2012 and March 2014. HIV-infected patients 10 years or older were clinically screened using a validated symptom-based screening tool to rule out active TB. Patients found to have no symptoms in the screening tool were given 300 mg of isoniazid (INH) daily for 6 months. Patients were followed up monthly at the National and Municipal hospital HIV clinics for INH refill and assessment of treatment adherence. Adherence was defined as consumption of 90 % or more of the monthly prescription of INH. RESULTS: All 1303 invited patients agreed to participate in the study. Of 1303 invited HIV-infected patients, 1283 (98.5 %) were recruited into the study. Twenty eight (2.2 %) did not complete treatment. Those who did not complete the treatment were exclusively adults aged 18 years or older, p = 0.302. The overall mean (±SD) adherence was 98.9 % (±2.9). Adherence level among children aged <18 years (92.2 %) was significantly lower than adherence level among patients aged 18-29 years (98.3 %), 30-49 years (98.8 %) and ≥ 50 years (98.5), p-value = 0.011. Sex, occupation, socio-economic status, duration of HIV infection, being on antiretroviral drugs (ARV) and duration of ARV use were not associated with adherence. CONCLUSION: IPT is highly accepted by HIV infected patients. Patients demonstrated high level of adherence to IPT. The level of adherence among children was slightly lower than that among adults. IPT non-completers were exclusively adults. Children might need adult supervision in taking IPT.

Symptom-based screening tool in ruling out active tuberculosis among HIV-infected patients eligible for isoniazid preventive therapy in Tanzania.

OBJECTIVES: We assessed the usefulness of the National TB and Leprosy Control Program (NTLP) symptom-based tuberculosis (TB) screening tool in identifying HIV-infected patients eligible for isoniazid preventive therapy in Muhimbili National Hospital, Dar es Salaam Tanzania. METHODS: Descriptive cross-sectional study. Data collected included socio-demographic and clinical data. Chest X-ray, sputum for acid-fast bacilli (AFB) microscopy, mycobacterial culture, CD4 + count and complete blood count were performed. Patients were considered not having active TB if they presented with no symptom in the screening tool, which comprised these symptoms: cough, fever and excessive night sweats for ≥2 weeks; weight loss of ≥3 kg in 4 weeks and haemoptysis of any duration. The reference standard was a negative culture for Mycobacterium tuberculosis. RESULTS: We enroled 373 patients, of whom 72.1% were females. Active pulmonary TB was found in 4.1% (14/338) of the participants as defined by a positive culture. The sensitivity and specificity of the NTLP screening tool were 71.4% (10/14) and 75.9% (246/324), respectively. False-negative rate was 28.6% (4/10). Cough, fever for ≥2 weeks and weight loss were independent predictors of NTLP-defined TB. Cough ≥2 weeks predicted TB when a positive culture was used to define TB. CONCLUSION: The screening tool had fairly good sensitivity and specificity for TB screening; however, there is a possibility that about 29% of the screened population will be given IPT while they are supposed to receive a full course of TB treatment.

Auditory impairments in HIV-infected individuals in Tanzania.

OBJECTIVES: Abnormal hearing tests have been noted in human immunodeficiency virus (HIV)-infected patients in several studies, but the nature of the hearing deficit has not been clearly defined. The authors performed a cross-sectional study of both HIV+ and HIV- individuals in Tanzania by using an audiological test battery. The authors hypothesized that HIV+ adults would have a higher prevalence of abnormal central and peripheral hearing test results compared with HIV- controls. In addition, they anticipated that the prevalence of abnormal hearing assessments would increase with antiretroviral therapy (ART) use and treatment for tuberculosis (TB). DESIGN: Pure-tone thresholds, distortion product otoacoustic emissions (DPOAEs), tympanometry, and a gap-detection test were performed using a laptop-based hearing testing system on 751 subjects (100 HIV- in the United States, plus 651 in Dar es Salaam, Tanzania, including 449 HIV+ [130 ART- and 319 ART+], and 202 HIV-, subjects. No U.S. subjects had a history of TB treatment. In Tanzania, 204 of the HIV+ and 23 of the HIV- subjects had a history of TB treatment. Subjects completed a video and audio questionnaire about their hearing, as well as a health history questionnaire. RESULTS: HIV+ subjects had reduced DPOAE levels compared with HIV- subjects, but their hearing thresholds, tympanometry results, and gap-detection thresholds were similar. Within the HIV+ group, those on ART reported significantly greater difficulties understanding speech in noise, and were significantly more likely to report that they had difficulty understanding speech than the ART- group. The ART+ group had a significantly higher mean gap-detection threshold compared with the ART- group. No effects of TB treatment were seen. CONCLUSIONS: The fact that the ART+/ART- groups did not differ in measures of peripheral hearing ability (DPOAEs, thresholds), or middle ear measures (tympanometry), but that the ART+ group had significantly more trouble understanding speech and had higher gap-detection thresholds indicates a central processing deficit. These data suggest that: (1) hearing deficits in HIV+ individuals could be a CNS side effect of HIV infection, (2) certain ART regimens might produce CNS side effects that manifest themselves as hearing difficulties, and/or (3) some ART regimens may treat CNS HIV inadequately, perhaps due to insufficient CNS drug levels, which is reflected as a central hearing deficit. Monitoring of central hearing parameters could be used to track central effects of either HIV or ART.

Greater preexisting interferon γ responses to mycobacterial antigens and lower bacillary load during HIV-associated tuberculosis.

The role of preexisting interferon (IFN) γ responses in controlling bacillary burden in human immunodeficiency virus (HIV)-associated tuberculosis is not known. Among BCG-immunized HIV-infected adults who developed tuberculosis in a phase III trial of an investigational tuberculosis vaccine, greater baseline IFN-γ responses to early secretory antigenic target 6 and Mycobacterium tuberculosis whole-cell lysate were associated with reduced bacillary burden on sputum smear grade, days to culture positivity on agar, and sputum culture grade during subsequent tuberculosis. This association was most consistent among recipients of the investigational vaccine. When HIV-associated tuberculosis develops, greater preexisting IFN-γ responses to mycobacterial antigens are associated with reduced tuberculosis bacillary burden. ClinicalTrials.gov Identifier. NCT0052195.

Recurrent tuberculosis risk among HIV-infected adults in Tanzania with prior active tuberculosis.

BACKGROUND: Active tuberculosis is common among human immunodeficiency virus (HIV)-infected persons living in tuberculosis-endemic areas, but the hazard of subsequent tuberculosis disease has not been quantified in a single prospective cohort. METHODS: Among HIV-infected, BCG-immunized adults with CD4 counts ≥200 cells/µL who received placebo in the DarDar tuberculosis vaccine trial in Tanzania, we compared the prospective risk of active tuberculosis between subjects who did and who did not report prior active tuberculosis. All subjects with a positive tuberculin skin test without prior active tuberculosis were offered isoniazid preventive treatment. Definite or probable tuberculosis was diagnosed during active follow-up using rigorous published criteria. RESULTS: We diagnosed 52 cases of definite and 92 cases of definite/probable tuberculosis among 979 subjects during a median follow-up of 3.2 years. Among the 80 subjects who reported prior active tuberculosis, 11 (13.8%) subsequently developed definite tuberculosis and 17 (21.3%) developed definite/probable tuberculosis, compared with 41 (4.6%) and 75 (8.3%), respectively, of 899 subjects without prior active tuberculosis (definite tuberculosis risk ratio [RR], 3.01; 95% confidence interval [CI], 1.61-5.63, P < .001; definite/probable tuberculosis RR, 2.55; 95% CI, 1.59-4.09, P < .001). In a Cox regression model adjusting for age, CD4 count, and isoniazid receipt, subjects with prior active tuberculosis had substantially greater hazard of subsequent definite tuberculosis (hazard radio [HR], 3.69; 95% CI, 1.79-7.63, P < .001) and definite/probable tuberculosis (HR, 2.78; 95% CI, 1.58-4.87, P < .001). CONCLUSIONS: Compared to subjects without prior tuberculosis, the hazard of active tuberculosis is increased 3-fold among HIV-infected adults with prior active tuberculosis. Clinical Trials Registration. NCT0052195.

A qualitative study of perceived risk for HIV transmission among police officers in Dar es Salaam, Tanzania.

BACKGROUND: Understanding people's views about HIV transmission by investigating a specific population may help to design effective HIV prevention strategies. In addition, knowing the inherent sexual practices of such a population, as well as the risky circumstances that may facilitate HIV transmission, is crucial for the said strategies to become effective. In this article, we report how police officers in Dar es Salaam, Tanzania, perceived the problem of HIV and AIDS in their local context, particularly in relation to unsafe sexual practices. The study was done with the view to recommending ways by which HIV transmission could be minimised within the police force. METHODS: The study was conducted among members of the police force in Dar es Salaam, Tanzania. Eight focus group discussions (FGDs) were conducted, with a total of 66 participants who were mixed in terms of age, gender, and marital status. Some of these were caregivers to patients with AIDS. Data were analysed using the interpretive description approach. RESULTS: The participants believed that both individual sexual behaviour and work-related circumstances were sources of HIV infection. They also admitted that they were being tempted to engage in risky sexual practices because of the institutional rules that prohibit officers from getting married during their training and for three years after. Nevertheless, as members of the Police Force, they stressed the fact that the risky sexual behaviour that exposes them to HIV is not limited to the force; it is rather a common problem that is faced by the general population. However, they complained, the nature of their job exposes them to road accident victims, subjecting them further to possible infection, especially when they have to handle these road accident casualties without proper protective gear. CONCLUSION: Individual sexual behaviour and job-related circumstances are worth investigating if proper advice is to be given to the police regarding HIV prevention strategies. In order to improve the lives of these police officers, there is a need to review the existing institutional rules and practices to accommodate individual sexual needs. In addition, improving their working environment may minimize the risk of HIV transmission from handling casualties in emergency situations.

Declining HIV-1 prevalence and incidence among Police Officers - a potential cohort for HIV vaccine trials, in Dar es Salaam, Tanzania.

BACKGROUND: A safe effective and affordable HIV vaccine is the most cost effective way to prevent HIV infection worldwide. Current studies of HIV prevalence and incidence are needed to determine potentially suitable cohorts for vaccine studies. The prevalence and incidence of HIV-1 infection among the police in Dar es Salaam in 1996 were 13.8% and 19.6/1000 PYAR respectively. This study aimed at determining the current prevalence and incidence of HIV in a police cohort 10 years after a similar study was conducted. METHODS: Police officers in Dar es Salaam, Tanzania were prospectively enrolled into the study from 2005 and followed-up in an incidence study three years later. HIV infection was determined by two sequential enzyme linked immunosorbent assays (ELISAs) in the prevalence study and discordant results between two ELISAs were resolved by a Western blot assay. Rapid HIV assays (SD Bioline and Determine) were used for the incidence study. RESULTS: A total of 1,240 police participated in the HIV prevalence study from August 2005 to November 2008. Of these, 1101 joined the study from August 2005-September 2007 and an additional 139 were recruited between October 2007 to November 2008 while conducting the incidence study. A total of 726 (70%) out of the 1043 eligible police participated in the incidence study.The overall HIV-1 prevalence was 65/1240 (5.2%). Females had a non-statistically significant higher prevalence of HIV infection compared to males 19/253, (7.5%) vs. 46/987 (4.7%) respectively (p=0.07). The overall incidence of HIV-1 was 8.4 per 1000 PYAR (95% CI 4.68-14.03), and by gender was 8.8 and 6.9 per 1000 PYAR, among males and females respectively, (p=0.82). CONCLUSIONS: The HIV prevalence and incidence among the studied police has declined over the past 10 years, and therefore this cohort is better suited for phase I/II HIV vaccine studies than for efficacy trials.

Experiences on recruitment and retention of volunteers in the first HIV vaccine trial in Dar es Salam, Tanzania - the phase I/II HIVIS 03 trial.

BACKGROUND: Eventual control of HIV/AIDS is believed to be ultimately dependent on a safe, effective and affordable vaccine. Participation of sub-Saharan Africa in the conduct of HIV trials is crucial as this region still experiences high HIV incidences. We describe the experience of recruiting and retaining volunteers in the first HIV vaccine trial (HIVIS03) in Tanzania. METHODS: In this trial enrolled volunteers from amongst Police Officers (POs) in Dar es Salaam were primed with HIV-1 DNA vaccine at months 0, 1 and 3; and boosted with HIV-1 MVA vaccine at months 9 and 21. A stepwise education provision/sensitization approach was employed to eventual recruitment. Having identified a "core" group of POs keen on HIV prevention activities, those interested to participate in the vaccine trial were invited for a first screening session that comprised of provision of detailed study information and medical evaluation. In the second screening session results of the initial assessment were provided and those eligible were assessed for willingness to participate (WTP). Those willing were consented and eventually randomized into the trial having met the eligibility criteria. Voluntary participation was emphasized throughout. RESULTS: Out of 408 POs who formed the core group, 364 (89.0%) attended the educational sessions. 263 out of 364 (72.2%) indicated willingness to participate in the HIV vaccine trial. 98% of those indicating WTP attended the pre-screening workshops. 220 (85.0%) indicated willingness to undergo first screening and 177 POs attended for initial screenings, of whom 162 (91.5%) underwent both clinical and laboratory screenings. 119 volunteers (73.5%) were eligible for the study. 79 were randomized into the trial, while 19 did not turn up, the major reason being partner/family advice. 60 volunteers including 15 females were recruited during a one-year period. All participated in the planned progress updates workshops. Retention into the schedule was: 98% for the 3 DNA/placebo vaccinations, while it was 83% and 73% for the first and second MVA/placebo vaccinations respectively. CONCLUSION: In this first HIV vaccine trial in Tanzania, we successfully recruited the volunteers and there was no significant loss to follow up. Close contact and updates on study progress facilitated the observed retention rates. TRIAL REGISTRATION NUMBERS: ISRCTN90053831 ISRNCT01132976 and ATMR2009040001075080.

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.

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.

Molecular epidemiology of HIV-associated tuberculosis in Dar es Salaam, Tanzania: strain predominance, clustering, and polyclonal disease.

Molecular typing of Mycobacterium tuberculosis can be used to elucidate the epidemiology of tuberculosis, including the rates of clustering, the frequency of polyclonal disease, and the distribution of genotypic families. We performed IS6110 typing and spoligotyping on M. tuberculosis strains isolated from HIV-infected subjects at baseline or during follow-up in the DarDar Trial in Tanzania and on selected community isolates. Clustering occurred in 203 (74%) of 275 subjects: 124 (80%) of 155 HIV-infected subjects with baseline isolates, 56 (69%) of 81 HIV-infected subjects with endpoint isolates, and 23 (59%) of 39 community controls. Overall, 113 (41%) subjects had an isolate representing the East Indian "GD" family. The rate of clustering was similar among vaccine and placebo recipients and among subjects with or without cellular immune responses to mycobacterial antigens. Polyclonal disease was detected in 6 (43%) of 14 patients with multiple specimens typed. Most cases of HIV-associated tuberculosis among subjects from this study in Dar es Salaam resulted from recently acquired infection. Polyclonal infection was detected and isolates representing the East Indian GD strain family were the most common.