Pregnancy and contraceptive use among women participating in an HIV prevention trial in Tanzania.

OBJECTIVES: Information on pregnancy rates and factors associated with pregnancy and contraceptive use is important for clinical trials in women in sub-Saharan Africa where withdrawal of investigational products may be required in the event of pregnancy with a consequent effect on sample size and trial power. METHODS: A prospective cohort analysis of pregnancy and contraceptive use was conducted in Tanzanian women enrolled in a randomised placebo-controlled trial of herpes simplex virus-suppressive therapy with acyclovir to measure the effect on HIV incidence in HIV-negative women and on genital and plasma HIV viral load in HIV-positive women. The cohort was followed every 3 months for 12-30 months. Women at each visit were categorised into users or non-users of contraception. Pregnancy rates and factors associated with pregnancy incidence and contraceptive use were measured. RESULTS: Overall 254 of 1305 enrolled women became pregnant at least once during follow-up (pregnancy rate: 12.0/100 person-years). Younger age, being unmarried, higher baseline parity and changes in contraceptive method during follow-up were independently associated with pregnancy. Having paid sex and being HIV positive were associated with lower risk of pregnancy. Uptake of contraception was associated with young age, being unmarried, occupation, parity and the number and type of sexual partners. CONCLUSIONS: Data on use of contraceptive methods and risk factors for pregnancy can help to guide decisions on trial eligibility and the need for additional counselling. Mandatory reliable contraceptive use in study participants may be required to reduce pregnancy rates in studies where pregnancy is contraindicated

HIV Infection among Young People in Northwest Tanzania: The Role of Biological, Behavioural and Socio-Demographic Risk Factors.

BACKGROUND: Young people are at high risk of HIV and developing appropriate prevention programmes requires an understanding of the risk factors for HIV in this age group. We investigated factors associated with HIV among participants aged 15-30 years in a 2007-8 cross-sectional survey nested within a community-randomised trial of the MEMA kwa Vijana intervention in 20 rural communities in northwest Tanzania. METHODS: We analysed data for 7259(53%) males and 6476(47%) females. Using a proximate-determinant conceptual framework and conditional logistic regression, we obtained sex-specific Odds Ratios (ORs) for the association of HIV infection with socio-demographic, knowledge, behavioural and biological factors. RESULTS: HSV-2 infection was strongly associated with HIV infection (females: adjOR 4.4, 95%CI 3.2-6.1; males: adjOR 4.2, 95%CI 2.8-6.2). Several socio-demographic factors (such as age, marital status and mobility), behavioural factors (condom use, number and type of sexual partnerships) and biological factors (blood transfusion, lifetime pregnancies, genital ulcers, Neisseria gonorrhoeae) were also associated with HIV infection. Among females, lifetime sexual partners (linear trend, p<0.001), ≥2 partners in the past year (adjOR 2.0, 95%CI 1.4-2.8), ≥2 new partners in the past year (adjOR 1.9 95%CI 1.2, 3.3) and concurrent partners in the past year (adjOR 1.6 95%CI 1.1, 2.4) were all associated with HIV infection. CONCLUSIONS: Efforts must be intensified to find effective interventions to reduce HSV-2. Effective behavioural interventions focusing on reducing the number of sexual partnerships and risk behaviour within partnerships are also needed. An increase in risky sexual behaviour may occur following marriage dissolution or when a young woman travels outside of her community and interventions addressing the needs of these subgroups of vulnerable women may be important. TRIAL REGISTRATION: ClinicalTrial.gov NCT00248469

Rapid acquisition of HPV around the time of sexual debut in adolescent girls in Tanzania.

BACKGROUND: No reports exist on genotype-specific human papillomavirus (HPV) acquisition in girls after first sex in sub-Saharan Africa, despite high HPV prevalence and cervical cancer incidence. METHODS: We followed 503 HP-unvaccinated girls aged 15-16 years in Mwanza, Tanzania, 3-monthly for 18 months with interviews and self-administered vaginal swabs. Swabs were tested for 13 higHRisk and 24 low-risk HPV genotypes. Incidence, clearance and duration of overall HPV and genotype-specific infections were calculated and associated factors evaluated. RESULTS: A total of 106 participants reported first sex prior to enrolment (N = 29) or during follow-up (N = 77). One was HIV-positive at the final visit. The remaining 105 girls contributed 323 adequate specimens. Incidence of any new HPV genotype was 225/100 person-years (pys), and incidence of vaccine types HPV-6, -11, -16 and -18 were 12, 2, 2 and 7/100 pys, respectively. Reporting sex in the past 3 months and knowing the most recent sexual partner for a longer period before sex were associated with HPV acquisition. Median time from reported sexual debut to first HPVinfection was 5 months, and infection duration was 6 months. CONCLUSION: This is the first description of HPV acquisition after first sex in sub-Saharan Africa where the incidence of cervical cancer is amongst the highest in the world. HPV incidence was very high after first sex, including some vaccine genotypes, and infection duration was short. This very high HPV incidence may help explain high cervical cancer rates, and supports recommendations that the HPV vaccine should be given to girls before first sex

Prevalence of human papillomavirus in adolescent girls before reported sexual debut.

BACKGROUND: Human papillomavirus (HPV) vaccines are recommended for girls prior to sexual debut because they are most effective if administered before girls acquire HPV. Little research has been done on HPV prevalence in girls who report not having passed sexual debut in high HPV-prevalence countries. METHODS: Using attendance registers of randomly selected primary schools in the Mwanza region of Tanzania, we enrolled girls aged 15-16 years who reported not having passed sexual debut. A face-to-face interview on sexual behavior and intravaginal practices, and a nurse-assisted self-administered vaginal swab were performed. Swabs were tested for 13 high-risk and 24 low-risk HPV genotypes. RESULTS: HPV was detected in 40/474 (8.4%; 95% confidence interval [CI], 5.9-11.0) girls. Ten different high-risk and 21 different low-risk genotypes were detected. High-risk genotypes were detected in 5.3% (95% CI, 3.5-7.8). In multivariable analysis, only intravaginal cleansing (practiced by 20.9%) was associated with HPV detection (adjusted odds ratio = 2.19, 95% CI, 1.09-4.39). CONCLUSION: This cohort of adolescent Tanzanian girls had a high HPV prevalence prior to self-reported sexual debut, and this was associated with intravaginal cleansing. This most likely reflects underreporting of sexual activity, and it is possible that intravaginal cleansing is a marker for unreported sexual debut or nonpenetrative sexual behaviors

Linkage to primary care after home-based blood pressure screening in rural KwaZulu-Natal, South Africa: a population-based cohort study

Objectives: The expanding burden of non-communicable diseases (NCDs) globally will require novel public health strategies. Community-based screening has been promoted to augment efficiency of diagnostic services, but few data are available on the downstream impact of such programmes. We sought to assess the impact of a home-based blood pressure screening programme on linkage to hypertension care in rural South Africa.  Setting: We conducted home-based blood pressure screening withinin a population cohort in rural KwaZulu-Natal, using the WHO Stepwise Approach to Surveillance (STEPS) protocol.  Participants: Individuals meeting criteria for raised blood pressure (≥140 systolic or ≥90 diastolic averaged over two readings) were referred to local health clinics and included in this analysis. We defined linkage to care based on self-report of presentation to clinic for hypertension during the next 2 years of cohort observation. We estimated the population proportion of successful linkage to care with inverse probability sampling weights, and fit multivariable logistic regression models to identify predictors of linkage following a positive hypertension screen.  Results: Of 11 694 individuals screened, 14.6% (n=1706) were newly diagnosed with elevated pressure. 26.9% (95% CI 24.5% to 29.4%) of those sought hypertension care in the following 2 years, and 38.1% (95% CI 35.6% to 40.7%) did so within 5 years. Women (adjusted OR (aOR) 2.41, 95% CI 1.68 to 3.45), those of older age (aOR 11.49, 95% CI 5.87 to 22.46, for 45–59 years vs <30) and those unemployed (aOR 1.71, 95% CI 1.10 to 2.65) were more likely to have linked to care.  Conclusions: Linkage to care after home-based identification of elevated blood pressure was rare in rural South Africa, particularly among younger individuals, men and the employed. Improved understanding of barriers and facilitators to NCD care is needed to enhance the effectiveness of blood pressure screening in the region

Suitability of simple human immunodeficiency virus rapid tests in clinical trials in community-based clinic settings

The suitability and accuracy of using simple human immunodeficiency virus (HIV) rapid (SR) tests in community-based clinics in northwest Tanzania were determined to assess eligibility for participation in clinical trials. The HIV rapid and ELISA test results for 789 women aged 16 to 54 who were screened for two clinical trials of HIV prevention were compared. Women were offered voluntary HIV counseling and testing (VCT) at screening; those who accepted were tested with the Abbott Determine and Trinity Biotech Capillus SR tests in parallel. The results were confirmed by two parallel HIV enzyme-linked immunosorbent assay (ELISA) tests (Abbott Murex HIV Ag/Ab combination and Vironostika Uniform II HIV Ag/Ab) to determine eligibility. Positive samples for any of the four assays were confirmed by a line immunoassay and p24 testing. The parallel SR tests had high concordance (96.2%) with the parallel ELISA algorithm. The sensitivities of the SR tests were 98.6% for Capillus (95% confidence interval [CI], 95.1 to 99.8%), 99.3% for Determine (95% CI, 96.2 to 100%), and 98.6% for the parallel SR (95% CI, 95.1 to 99.8%). The specificities were 99.7% for Capillus (95% CI, 98.9 to 100%), 99.7% for Determine (95% CI, 98.9 to 100%), and 100% for the parallel SR (95% CI, 99.4 to 100%). SR tests are suitable for use in community-based clinical research settings to assess eligibility both for trial participation and for the provision of on-site VCT services. Copyrigh

Early impact of the DREAMS partnership on young women's knowledge of their HIV status: causal analysis of population-based surveys in Kenya and South Africa.

BACKGROUND: Knowledge of one's HIV status is the gateway to treatment and prevention, but remains low among young people. We investigated the early impact (2016-2017) of Determined, Resilient, Empowered, AIDS-free, Mentored and Safe (DREAMS), a multisectoral HIV prevention package, on knowledge of HIV status among adolescent girls and young women (AGYW). METHODS: In 2017, randomly selected AGYW were enrolled into surveys, N=1081 aged 15-22 years in Nairobi slum settlements, and N=2174 aged 13-22 years in rural KwaZulu-Natal. We estimated the causal effect of being a DREAMS beneficiary on knowledge of HIV status (those who self-reported as HIV-positive or tested HIV-negative in the past year), accounting for an AGYW's propensity to be a DREAMS beneficiary. RESULTS: In Nairobi, knowledge of HIV status was higher among DREAMS beneficiaries compared with non-beneficiaries (92% vs 69%, adjusted OR=8.7; 95% CI 5.8 to 12.9), with DREAMS predicted to increase the outcome by 28%, from 65% if none were a DREAMS beneficiary to 93% if all were beneficiaries. The increase attributable to DREAMS was larger among younger participants: 32% and 23% among those aged 15-17 and 18-22 years, respectively. In KwaZulu-Natal, knowledge of status was higher among DREAMS beneficiaries aged 13-17 years (37% vs 26% among non-beneficiaries), with a 9% difference due to DREAMS (95% CI 4.8% to 14.4%), and no evidence of effect among 18-22 years (-2.8%; 95% CI -11.1% to 5.7%). CONCLUSION: DREAMS substantially increased knowledge of HIV status among AGYW in Nairobi, and among younger but not older AGYW in KwaZulu-Natal. Adolescent girls can be reached early (before age 18) with community-based HIV testing programmes in diverse high-prevalence settings, with a large impact on the proportion who know their HIV status

A dose-reduction HPV vaccine immunobridging trial of two HPV vaccines among adolescent girls in Tanzania (the DoRIS trial) - Study protocol for a randomised controlled trial.

BACKGROUND: Human papillomavirus (HPV) infection is the primary cause of cervical cancer. In 2018, the World Health Organization (WHO) Director General announced his commitment to eliminate cervical cancer, with HPV vaccination as a priority. However, the costs of setting up a multi-dose HPV vaccination programme remain a barrier to its introduction. METHODS/DESIGN: We are conducting a randomised-controlled trial of reduced dose schedules of HPV vaccine in Tanzania to establish whether a single dose produces immune responses that will be effective in preventing cervical cancer. 930 girls aged 9-14 years in Mwanza, Tanzania, were randomised to one of 6 arms, comprising 3 different dose schedules of the 2-valent (Cervarix) and 9-valent (Gardasil-9) HPV vaccines: 3 doses; 2 doses given 6 months apart; or a single dose. All participants will be followed for 36 months; those in the 1 and 2 dose arms will be followed for 60 months. Trial outcomes focus on vaccine immune responses including HPV 16/18-specific antibody levels, antibody avidity, and memory B cell responses. Results will be immunobridged to historical cohorts of girls and young women in whom efficacy has been demonstrated. DISCUSSION: This is the first randomised trial of the single dose HPV vaccine schedule in the target age group. The trial will allow us to examine the quality and durability of immune responses of reduced dose schedules in a population with high burden of malaria and other infections that may affect vaccine immune responses. Initial results (24 months) are expected to be published in early 2021

HPV prevalence around the time of sexual debut in adolescent girls in Tanzania.

OBJECTIVES: Cervical cancer is the leading cause of cancer-related mortality among women in sub-Saharan Africa (SSA). Data on human papillomavirus (HPV) epidemiology in adolescent girls in SSA are essential to inform HPV vaccine policy recommendations for cervical cancer prevention. We assessed the burden of HPV infection, and risk factors for infection, among adolescent girls around the time of sexual debut. METHODS: Cross-sectional study of secondary school girls aged 17-18 years in Tanzania. Consenting participants provided samples for HPV and STI testing. Vaginal swabs were tested for 37 HPV genotypes by Roche Linear Array. Logistic regression was used to identify factors associated with HPV infection. Y chromosome was tested as a marker of recent condomless sex. RESULTS: 163/385 girls (42.3%) reported previous penetrative sex. HPV was detected in 125/385 (32.5%) girls, including 84/163 (51.5%) girls reporting previous sex and 41/222 (18.5%) reporting no previous sex. High-risk (HR) genotypes were detected in 70/125 (56.0%) girls with HPV infection. The most common HR genotype was HPV-16 (15/385; 3.9%). The prevalence of other HR HPV vaccine genotypes was between 0.8% and 3.1%. Among 186 girls who reported no previous sex, were negative for Y chromosome, and had no STI, 32 (17%) had detectable HPV. Lactobacillus sp and bacterial vaginosis-associated bacteria were negatively and positively associated, respectively, with HPV. CONCLUSIONS: HPV prevalence among adolescent girls around the time of sexual debut was high. However, prevalence of most vaccine genotypes was low, indicating that extending the age range of HPV vaccination in this region may be cost-effective

Long-term biological and behavioural impact of an adolescent sexual health intervention in Tanzania: follow-up survey of the community-based MEMA kwa Vijana Trial.

BACKGROUND: The ability of specific behaviour-change interventions to reduce HIV infection in young people remains questionable. Since January 1999, an adolescent sexual and reproductive health (SRH) intervention has been implemented in ten randomly chosen intervention communities in rural Tanzania, within a community randomised trial (see below; NCT00248469). The intervention consisted of teacher-led, peer-assisted in-school education, youth-friendly health services, community activities, and youth condom promotion and distribution. Process evaluation in 1999-2002 showed high intervention quality and coverage. A 2001/2 intervention impact evaluation showed no impact on the primary outcomes of HIV seroincidence and herpes simplex virus type 2 (HSV-2) seroprevalence but found substantial improvements in SRH knowledge, reported attitudes, and some reported sexual behaviours. It was postulated that the impact on "upstream" knowledge, attitude, and reported behaviour outcomes seen at the 3-year follow-up would, in the longer term, lead to a reduction in HIV and HSV-2 infection rates and other biological outcomes. A further impact evaluation survey in 2007/8 ( approximately 9 years post-intervention) tested this hypothesis. METHODS AND FINDINGS: This is a cross-sectional survey (June 2007 through July 2008) of 13,814 young people aged 15-30 y who had attended trial schools during the first phase of the MEMA kwa Vijana intervention trial (1999-2002). Prevalences of the primary outcomes HIV and HSV-2 were 1.8% and 25.9% in males and 4.0% and 41.4% in females, respectively. The intervention did not significantly reduce risk of HIV (males adjusted prevalence ratio [aPR] 0.91, 95%CI 0.50-1.65; females aPR 1.07, 95%CI 0.68-1.67) or HSV-2 (males aPR 0.94, 95%CI 0.77-1.15; females aPR 0.96, 95%CI 0.87-1.06). The intervention was associated with a reduction in the proportion of males reporting more than four sexual partners in their lifetime (aPR 0.87, 95%CI 0.78-0.97) and an increase in reported condom use at last sex with a non-regular partner among females (aPR 1.34, 95%CI 1.07-1.69). There was a clear and consistent beneficial impact on knowledge, but no significant impact on reported attitudes to sexual risk, reported pregnancies, or other reported sexual behaviours. The study population was likely to have been, on average, at lower risk of HIV and other sexually transmitted infections compared to other rural populations, as only youth who had reached year five of primary school were eligible. CONCLUSIONS: SRH knowledge can be improved and retained long-term, but this intervention had only a limited effect on reported behaviour and no significant effect on HIV/STI prevalence. Youth interventions integrated within intensive, community-wide risk reduction programmes may be more successful and should be evaluated. TRIAL REGISTRATION: ClinicalTrials.gov NCT0024846