Refocussing on STI management to impact HIV prevention

Refocussing on STI management to impact HIV prevention Koleka Mlisana Head: Medical Microbiology (UKZN & NHLS) 14 June 2017: SA AIDS Conference

NSP 2017 2022 Objectives Goal 1:Accelerate preventioninorder toreduce new HIVand TB infections and new STIs. Breaking the cycle of transmission Goal 2: Reduce morbidity and mortality by providing treatment, care and adherencesupportforall. Reaching909090ineverydistrict Goal 3: Reach all key and vulnerable populations with customised and targeted interventions. Nobody left behind Goal4:AddressthesocialandstructuraldriversofHIV,TBandSTIs,andlink these efforts to the NDP. A multi-department, multisector approach Goal 5: Ground the response to HIV, TB and STIs in human rights principles and approaches. Equal treatment and social justice Goal 6: Promote leadership at all levels and shared accountability for a sustainable response to HIV, TB and STIs. Mutual accountability

Facts Sheet >1milSTIsareacquiredeverydayworldwide. 357milnewinfxwith1of4STIs:CT,NG,TV&TP/year Except for viral causes, sexually transmitted infections are curable!!! Generally,>65%ofSTIsareasymptomatic!!!! Condoms prevent STIs including HIV, only when used properly at every sex act!!! It takes two to tango, treating one partner is inadequate (for both the symptomatic and the asymptomatic)!!!

Syndromic vs Diagnostic Management Less Expertise required Immediate Treatment Lower Cost Diagnostic Accuracy Monitor Treatment response Reduce HIV Risk STI & Resistance surveillance

STI prevalence in women at acute HIV infection CAPRISA 002 (N=160) Total % Asymptomatic % Chlamydia 15.4 79.2 Gonorrhoea 8.3 76.9 Mycoplasma 8.3 76.9 Trichomonas 10.9 88.2 HSV-2 serology 84.2 N/A HSV-2 PCR 8.3 84.6 Syphilis 5.0 75.0 Bacterial vaginosis 62.6 78.4

Limitations of syndromic management Under-diagnosis and over-treatment Lab Diagnosis Clinical Diagnosis + - + 25 48-179 723 Sensitivity = 12.3 % Specificity = 93.8% PPV = 34.2% NPV = 80.2% Only 1 of 8 women with an STI is diagnosed. 2 of 3 women receive unnecessary treatment.

Genital Inflammation and the risk of HIV infection Genital Inflammation is associated with HIV risk, but the causes are poorly understood. STIs, asymptomatic or symptomatic, are associated with increased inflammation. Masson et al, CID, 2015

Genital Inflammation and the risk of HIV infection Elevated genital concentrations of HIV target cell recruiting chemokines and a genital inflammatory profile contributes to the high risk of HIV acquisition in these African women. Lindi Masson et al, Clin Infect Dis. 2015;61(2):260-269.

STIs and HIV acquisition

Contribution of Genital Tract Infections to HIV acquisition among Kenyan High-Risk Women Population attributable risk (PAR) % of STIs to HIV acquisition Masese et al. AIDS. 2015 Jun 1; 29(9): 1077 1085.

STIs in key/vulnerable populations in SA Hi risk Pregnancy 2 MSM 3 FSW 4 Asymptomatic PLHIV 5 Women 1 Any STI 31.3 32.2 42.0 18.9 N. gonorrhoeae 5.4 6.4 3 10.3 5.4 C. trachomatis 4.2 17.8 10 11.8 2.1 T. vaginalis 20.3 15.3 35.7 7.6 Syphilis 2.9 18.0 31.4 2.4 (RPR); 21.4 (TP) HSV-2 86.0 84.0 85.2 Candidiasis 14.0 18.3 Bacterial vaginosis 52.7 28.0 1 Mlisana K, et al, JID 2012:206 (1): 6-14 2 Moodley, D., Sexually transmitted diseases, 42(1), pp.43-47. 3 Zahn R., SA AIDS 2016 MSMs in PE and CPT 4 Ramjee G., JAIDS 39.3 (2005): 333-339. 5 Lewis DA., Sexually Transmitted Diseases. 39(7):531-536, July 2012

WHO STIs 2030 TARGETS 90% reduction of T. pallidum incidence globally (2018 global baseline). 90% reduction in N. gonorrhoea incidence globally (2018 global baseline). 50 cases of congenital syphilis per 100 000 live births in 80% of countries. Sustain 90% national coverage and at least 80% in every district (or equivalent administrative unit) in countries with the human papillomavirus vaccine in their national immunization programme.

90% reduction of syphilis incidence Identify those at risk ANC screening Laboratory testing Appropriate treatment Partner therapy

90% reduction of gonorrhoea incidence Symptomatic vs asymptomatic Regular screening (key pops) NAAT ; POCT; home testing Surveillance for drug resistance Treatment to include?expedited partner therapy Testing for cure

CDC Recommendations: STI screening Women Sexually active women under 25 yrs of age 25 yrs if @ increased risk screened at least, annually Retest 3 months after treatment Men Who have Sex With Men (MSM) & FSW At least annually for sexually active MSM at sites of contact (urethra, rectum, pharynx) regardless of condom use Every 3 to 6 months if at increased risk Persons with HIV For sexually active individuals, screen at first HIV evaluation, and at least annually thereafter More frequent screening might be appropriate depending on individual risk behaviours and the local epidemiology

Diagnosis and screening recommendations for common STIs. Yarbrough ML;TheABCs of STIs: Clinical chemistry. 2016 Jun 1;62(6):811-23. Disease Chlamydia and gonorrhea Syphilis Symptoms Cervical inflammation, dysuria, pruritus, and discharge Primary: painless ulcer on genitals, rectum, or mouth; secondary: rash, wart-like sores, systemic symptoms; latent: symptomless stage of untreated syphilis; tertiary: organ damage Screening recommendations Females 25 years old, annually; MSM or young males in high-prevalence areas, annually No routine screening; pregnant women: first prenatal visit; MSM: annually Optimal testing method NAAT RPR; confirmation: FTA-Abs or TP- PA Optimal specimen type Females: provider/selfcollected vaginal swab, first-void urine; males: urethral, rectal, or throat swab, first-void urine Serum CDC Reference CDC ; US Preventive Services Task Force HSV Ulcers on the mouth, genitals, or rectum; may present with systemic symptoms No routine screening; testing to be considered in men or women who present with STI NAAT Swab from the leading edge of active lesion LeGoff et al. Virol J 2014;11:83. HBV HPV Bacterial vaginosis Trichomoniasis Abdominal pain, malaise, jaundice, and dark urine Usually asymptomatic and self-limiting; high-risk subtypes linked to cervical and rectal neoplasias Abnormal vaginal discharge, itching, or odor No routine screening; pregnant women: first prenatal visit; MSM and others at increased risk Females: begin screening at 21 years of age No routine screening HBsAg Serum Cervical cytology by Pap smear; Cervical HPV NAAT (>30 years of age) Optimal testing method is evolving Vaginal Asymptomatic; may have diffuse yellow-green No routine screening NAAT Vaginal, cervical, or urine Workowski and Bolan; MMWR 2015 LeFevre Ann Intern Med 2014;161:58 66. Moyer; Ann Intern Med 2012;156:880 91 Workowski and Bolan; MMWR 2015, Brotman et al. JID 2010;202:1907 15. Van Der Pol; JCM 2015;54:7 12

Multipurpose prevention technologies (MPTs): Ideal Qualities New all-in-one tools being explored to protect vs HIV, other STIs and even unintended pregnancy. Represent the next generation of measures for STI control. Be customized for the infections in a targeted geographic area. Result in multi-faceted, positive outcomes Trends in Microbiology 2015 23, 429-436DOI: (10.1016/j.tim.2015.02.006

STI Management overhaul NSP 2017-2022 Strengthen proper implementation of syndromic management! Physical examination and clear referral pathways Drug availability Regular surveillance to monitor aetiologies and drug susceptibility patterns Focus on asymptomatic infections Targeted screening? Presumptive treatment of vulnerable/key populations Regular testing -? Annually Upscaling laboratory expertise To be intentional about treating partners Financial/Resources commitment!!!!

Acknowledgements Nigel Garrett Ravesh Singh Nireshni Naidoo

Table 1 Etiology and STI/HIV Coinfections Among Patients With Urethral and Vaginal Discharge Syndromes in South Africa Mhlongo, Sakhile; Magooa, Precious; Müller, Etienne E.; Nel, Noel; Radebe, Frans; Wasserman, Elizabeth; Lewis, David A. Sexually Transmitted Diseases. 37(9):566-570, September 2010. doi: 10.1097/OLQ.0b013e3181d877b7 TABLE 1. Etiology and Seroprevalence of Syphilis, HSV-2 and HIV Among Patients With Male Urethral and Vaginal Discharge Syndromes in Cape Town and Johannesburg Copyright 2017 American Sexually Transmitted Diseases Association 22