Vaccine and Non-Vaccine HPV Types Presence in Adolescents with Vertically Acquired HIV Five Years Post Gardasil Quadrivalent Vaccination: The ZIMGARD Cohort.

BACKGROUND: Human papillomavirus (HPV) vaccination programs are a key intervention in protecting individuals against HPV-related disease. HIV1-infected individuals are at increased risk of HPV-associated cancers. This study was conducted to evaluate the potential role of prophylactic HPV vaccines in preventing new HPV infections among participants with perinatally acquired HIV who received the quadrivalent HPV vaccine at least five years before this study. METHODS: This cross-sectional study was conducted at Newlands Clinic, Harare, Zimbabwe. The clinic provided the Gardasil quadrivalent HPV vaccine (4vHPV) to 624 adolescents living with HIV starting in December 2015. Vaginal and penile swabs were collected and tested for HPV types from the study participants who had received the 4vHPV vaccine 5-6 years before enrolment. RESULTS: We present the results of 98 participants (44.6% female) vaccinated at a median age of 15 years (IQR 12-16). The mean amount of time since vaccination was 6 years (SD: ±0.4). The HPV-positive rate amongst the analyzed swabs was 69% (68/98). Among 30/98 (31%) HPV-positive participants, 13/98 (13%) had low-risk HPV types, and 17/98 (17%) had high-risk HPV types. Twelve participants tested positive for HPV18, only one participant tested positive for HPV16, and an additional four (4.3%) tested positive for either type 6 or 11, with respect to vaccine-preventable low-risk HPV types. CONCLUSION: The Gardasil quadrivalent HPV vaccine (4vHPV) was expected to protect against infection with HPV types 16, 18, 6, and 11. We demonstrated a possible waning of immunity to HPV18 in 17% of the participants, and an associated loss in cross-protection against HPV45. We observed a relatively high prevalence of 'opportunistic non-vaccine HPV types' or 'ecological niche occupiers' in this cohort, and suggest further research on the involvement of these types in cervical and other genital cancers. Our study is one of the few, if not the first, to report on HPV vaccine immunoprotection among people living with HIV (PLWH), thereby setting a baseline for further studies on HPV vaccine effectiveness among PLWH.

Group counselling for adherence support among young people failing first-line antiretroviral therapy in Zimbabwe.

BACKGROUND: Sub-optimal adherence to antiretroviral therapy (ART) is reportedly worse amongst young people living with HIV (YPLHIV). Group adherence counselling can be useful to improve adherence. OBJECTIVES: We evaluated an enhanced adherence counselling group intervention (EACGI) amongst YPLHIV failing a non-nucleoside reverse transcriptase (NNRTI)-based first-line ART regimen. METHOD: This was a retrospective cohort study using routinely collected data of YPLHIV failing NNRTI-based first-line ART. Patients with confirmed virological failure were referred for EACGI, a 12-week curriculum of weekly, 1.5-h sessions accommodating 8-15 people per group. It aimed to facilitate readiness to switch to second-line ART and improve adherence through a mental health intervention. Viral loads of HIV were measured pre-EACGI; at baseline; 3, 6 and 12 months post switch. RESULTS: Fifty-seven patients aged 13-25 years were invited to EACGI and followed for up to 48 weeks. Thirty-three (58%) patients attended at least four sessions, whilst 24 (42%) attended none. Amongst those who attended none, two (8%) were transferred out, three (13%) were lost to follow-up and two (8%) had died by week 48 of follow-up, whilst all who attended were still in care. By week 48, amongst patients still in care, 29%, 44% and 67% of those who attended no sessions, 4-9 and 10-12 sessions, respectively, had viral loads of < 50 copies/mL. CONCLUSION: An EACGI is a promising intervention for YPLHIV failing ART prior to treatment switch, leading to improved adherence. This study's findings support the need for further enquiry into rigorous, evidence-based multilevel adherence interventions that are acceptable and effective for YPLHIV.

Sexually transmitted infections, the silent partner in HIV-infected women in Zimbabwe.

BACKGROUND: Coinfection rates of HIV and sexually transmitted infections (STIs) are not widely reported in Zimbabwe and no local guidelines regarding the screening of STIs in people living with HIV exist. OBJECTIVES: This cross-sectional study was conducted to determine the prevalence and associated risk factors for STI coinfection in a cohort of HIV-infected women. METHODS: Between January and June 2016, 385 HIV-infected women presenting for routine cervical cancer screening were tested for five STIs: Neisseria gonorrhoeae (NG), Chlamydia trachomatis (CT), Trichomonas vaginalis (TV), Herpes Simplex Virus (HSV) type 2 and Treponema pallidum (TP). Socio-demographic characteristics and sexual history were recorded. Multiple logistic regression was used to identify factors associated with the diagnosis of non-viral STIs. RESULTS: Two hundred and thirty-three participants (60.5%) had a confirmed positive result for at least one STI: HSV 2 prevalence 52.5%, TV 8.1%, CT 2.1%, NG 1.8% and TP 11.4%. Eighty-seven per cent of the women were asymptomatic for any STI; 62.3% of women with a non-viral STI were asymptomatic. Women who had attended tertiary education were 90% less likely to have a non-viral STI (adjusted odds ratio [aOR]: 0.10, 95% confidence interval [CI]: 0.03-0.39, p < 0.01). Having more than three lifetime sexual partners was a significant predictor for a non-viral STI diagnosis (aOR: 3.3, 95% CI: 1.5-7.2, p < 0.01). CONCLUSION: A high prevalence of predominantly asymptomatic STIs is reported in a cohort of HIV-infected women. Syndromic management results in underdiagnosis of asymptomatic patients. More than three lifetime sexual partners and less formal education are risk factors for coinfection with non-viral STI. High-risk women should be screened using aetiological methods.

HIV drug resistance testing among patients failing second line antiretroviral therapy. Comparison of in-house and commercial sequencing.

INTRODUCTION: HIV genotyping is often unavailable in low and middle-income countries due to infrastructure requirements and cost. We compared genotype resistance testing in patients with virologic failure, by amplification of HIV pol gene, followed by "in-house" sequencing and commercial sequencing. METHODS: Remnant plasma samples from adults and children failing second-line ART were amplified and sequenced using in-house and commercial di-deoxysequencing, and analyzed in Harare, Zimbabwe and at Stanford, U.S.A, respectively. HIV drug resistance mutations were determined using the Stanford HIV drug resistance database. RESULTS: Twenty-six of 28 samples were amplified and 25 were successfully genotyped. Comparison of average percent nucleotide and amino acid identities between 23 pairs sequenced in both laboratories were 99.51 (±0.56) and 99.11 (±0.95), respectively. All pairs clustered together in phylogenetic analysis. Sequencing analysis identified 6/23 pairs with mutation discordances resulting in differences in phenotype, but these did not impact future regimens. CONCLUSIONS: The results demonstrate our ability to produce good quality drug resistance data in-house. Despite discordant mutations in some sequence pairs, the phenotypic predictions were not clinically significant.

HIV infection presenting in older children and adolescents: a case series from Harare, Zimbabwe.

BACKGROUND: Symptomatic human immunodeficiency virus (HIV) infection during late childhood and adolescence may be an emerging problem in southern Africa, but it is one that is poorly described. We investigated social and clinical features in patients of this age group presenting to a HIV treatment clinic with special adolescent services in Harare, Zimbabwe. METHODS: All patients aged 8-19 years and their guardians who attended an adolescent HIV treatment clinic were asked to consent to an interview and a review of medical notes. RESULTS: Of 32 patients, 17 (53%) were male. The median CD4 cell count at presentation was 101 cells/microL (interquartile range, 35-197 cells/microL). Sixty-two percent experienced stunting (mean Z score for height-for-age, -2.55; 95% CI, -2.00 to -3.10), and all presented with World Health Organization stage 3 or 4 HIV infection. The median age at the first HIV test was 11 years, with a median of 3.5 years delay since the first HIV-related illness. Recurrent respiratory tract infections, skin complaints, diarrhea, and past tuberculosis were the most common HIV-related complaints. Seventeen patients (55%) were double orphans, and 10 (62%) surviving parents were known to be HIV positive. CONCLUSIONS: In this small study, HIV-infected adolescents were profoundly immunosuppressed, with characteristics suggesting long-standing HIV infection. The equal sex distribution and high incidence of parental and sibling mortality were consistent; the majority of children had HIV-infected parents and, therefore, were potentially long-term survivors of HIV infection due to mother-to-child transmission. Greater recognition of the substantial burden of undiagnosed HIV infection and acquired immunodeficiency syndrome in this age group is needed, together with services aimed at reducing barriers to earlier diagnosis and initiation of treatment.