Patterns of prevalent HPV and STI co-infections and associated factors among HIV-negative young Western Cape, South African women: the EVRI trial.

OBJECTIVE: To estimate the prevalence and describe the patterns of concurrent human papillomavirus (HPV) and STIs and associated factors among HIV-negative young Western Cape, South African women participating in the Efficacy of HPV Vaccine to Reduce HIV Infection (EVRI) trial. METHODS: HIV-negative women aged 16-24 years old were enrolled in the EVRI trial (NCT01489527) and randomised to receive the licensed four-valent HPV vaccine or placebo. At study entry, participants were clinically evaluated for five STIs: herpes simplex virus type 2 (HSV-2), chlamydia, gonorrhoea, syphilis and disease-causing HPV genotypes (6/11/16/18/31/33/35/39/45/51/52/56/58/59/68). Demographic and sexual history characteristics were compared among women with STI co-infections, single infection and no infection using Pearson χ2 and Mann-Whitney tests. ORs were calculated to evaluate factors associated with STI co-infection prevalence. RESULTS: Among 388 young women, STI co-infection prevalence was high: 47% had ≥2 concurrent STIs, 36% had a single STI and 17% had none of the five evaluated STIs. HPV/HSV-2 (26%) was the most prevalent co-infection detected followed by HPV/HSV-2/Chlamydia trachomatis (CT) (17%) and HPV/CT (15%). Co-infection prevalence was independently associated with alcohol use (adjusted OR=2.01, 95% CI 1.00 to 4.06) and having a sexual partner with an STI (adjusted OR=6.96, 95% CI 1.53 to 30.08). CONCLUSIONS: Among high-risk young women from underserved communities such as in Southern Africa, a multicomponent prevention strategy that integrates medical and behavioural interventions targeting both men and women is essential to prevent acquisition of concurrent STI infections and consequent disease. TRIAL REGISTRATION NUMBER: NCT01489527; Post-results.

HPV SEROSTATUS PRE- AND POST-VACCINATION IN A RANDOMIZED PHASE II PREPAREDNESS TRIAL AMONG YOUNG WESTERN CAPE, SOUTH AFRICAN WOMEN: THE EVRI TRIAL.

BACKGROUND: HPV antibodies are a marker of past exposure to the virus. Our objective was to assess HPV serostatus pre- and post-vaccination among HIV-negative women. METHODS: Women aged 16-24 years old were randomized in a placebo controlled trial utilizing the 4-valent HPV (4vHPV) vaccine (NCT01489527, clinicaltrials.gov). Participants (n=389) received the 4vHPV vaccine or placebo following a three dose schedule. Sera were collected at Day 1 and Month 7 for assessment of HPV 6, 11, 16, and 18 neutralizing antibody levels using a multiplex competitive Luminex immunoassay (Merck) based on detecting the L1 capsid antigen for each HPV type. RESULTS: Seroprevalence was 73% for HPV6, 47% for HPV11, 33% for HPV16, and 44% for HPV18. Seroprevalence for any HPV type did not significantly differ by age or lifetime number of partners. The majority of participants (64%) had two or more 4vHPV antibodies present at enrollment and 12% had antibodies to all four. Among women in the vaccine arm, those that were seropositive for HPV16 at enrollment had higher titers at month 7 compared to women that were seronegative for HPV16 at enrollment; this trend holds for the other HPV types as well. Seroconversion among baseline seronegative participants in the placebo group ranged from 5% for HPV16 to 23% for HPV6. CONCLUSION: HPV seroprevalence was high in this population, emphasizing the need to vaccinate prior to sexual debut.

Cervical HPV natural history among young Western Cape, South African women: The randomized control EVRI Trial.

OBJECTIVE: The objective of this analysis was to assess human papillomavirus (HPV) infection persistence and incidence 7-months post-enrollment by HPV vaccine study arm (vaccine or placebo). METHODS: HIV-negative, sexually active women aged 16-24 years in the Western Cape, South Africa, were enrolled in the EVRI Trial and were randomized to receive 4-valent HPV vaccine or placebo. Cervical specimens were collected at enrollment and at the 7-month visit and were genotyped for HPV. HPV prevalence, persistence, and incidence were calculated. Prevalence ratios and odds ratios were calculated to assess factors associated with a prevalent and incident HPV infection. RESULTS: HPV incidence rates were marginally higher for the placebo group (n = 163) compared to the vaccine group (n = 169). A large proportion of the prevalent high-risk (HR-HPV) HPV types (49%) persisted over the 7-month period in both arms. Prevalent HR-HPV infection was significantly associated with a prevalent gonorrhea infection and detection of Herpes simplex type 2 antibodies. Incident HR-HPV infection was significantly associated with abnormal cervical cytology at enrollment and younger age. CONCLUSIONS: Women living in geographic areas, such as southern Africa, at high-risk for HPV need to receive HPV vaccination at a very young age to maximally prevent infection and subsequent disease.

High HIV, HPV, and STI prevalence among young Western Cape, South African women: EVRI HIV prevention preparedness trial.

BACKGROUND: This study sought to assess the feasibility of conducting a phase III HIV prevention trial using a multivalent human papillomavirus (HPV) vaccine (Gardasil; Merck, Whitehouse Station, NJ). METHODS: A total of 479 sexually active women aged 16-24 years in the Western Cape, South Africa, were enrolled in the Efficacy of HPV Vaccine to Reduce HIV Infection (EVRI) Trial. Of these, 402 were HIV negative, nonpregnant, and randomized 1:1 to receive Gardasil or a saline placebo vaccine. Vaccine doses were administered at enrollment, month 2, and month 6, and participants were followed for 1 month after the third dose. Enrollment HIV, HPV, other sexually transmitted infections (STIs), and cervical cytology were evaluated. Rates of accrual, vaccine compliance, and adherence to protocol were monitored. RESULTS: High rates of accrual of eligible females to study (93%) and completion of the 3-dose vaccine series (91%) were noted, with few protocol violations. Ineligibility due to reported HIV positivity was 19%, and another 12% of those enrolled tested HIV positive. STI prevalence was high, with 6.2%, 10.9%, and 32.8% testing positive for syphilis, gonorrhea, and chlamydia, respectively. Cervical prevalence of ≥1 of 37 HPV types was 71%. STI and HPV prevalence was highest among the youngest women (<19 years). CONCLUSIONS: Feasibility (successful accrual, retention, and vaccination) of conducting randomized placebo-controlled trials of HPV vaccines among HIV high-risk women in South Africa was demonstrated. This work demonstrates that phase III HIV prevention trials need to intervene at young ages and screen and treat multiple STIs concurrently to have a measurable impact on HIV acquisition.