Modeling the Impact of HIV-1 Nucleic Acid Testing Among Symptomatic Adult Outpatients in Kenya.

BACKGROUND: Up to 69% of adults who acquire HIV in Kenya seek care before seroconversion, providing an important opportunity for early diagnosis and treatment. The Tambua Mapema Plus (TMP) trial tested a combined HIV-1 nucleic acid testing, linkage, treatment, and partner notification intervention for adults aged 18-39 years with symptoms of acute HIV infection presenting to health facilities in coastal Kenya. We estimated the potential impact of TMP on the Kenyan HIV epidemic. METHODS: We developed an agent-based network model of HIV-1 transmission using TMP data and Kenyan statistics to estimate potential population-level impact of targeted facility-based testing over 10 years. Three scenarios were modeled: standard care [current use of provider-initiated testing and counseling (PITC)], standard HIV rapid testing scaled to higher coverage obtained in TMP (scaled-up PITC), and the TMP intervention. RESULTS: Standard care resulted in 90.7% of persons living with HIV (PLWH) knowing their status, with 67.5% of those diagnosed on treatment. Scaled-up PITC resulted in 94.4% of PLWH knowing their status and 70.4% of those diagnosed on treatment. The TMP intervention achieved 97.5% of PLWH knowing their status and 80.6% of those diagnosed on treatment. The percentage of infections averted was 1.0% (95% simulation intervals: -19.2% to 19.9%) for scaled-up PITC and 9.4% (95% simulation intervals: -8.1% to 24.5%) for TMP. CONCLUSION: Our study suggests that leveraging new technologies to identify acute HIV infection among symptomatic outpatients is superior to scaled-up PITC in this population, resulting in >95% knowledge of HIV status, and would reduce new HIV infections in Kenya.

High patient acceptability but low coverage of provider-initiated HIV testing among adult outpatients with symptoms of acute infectious illness in coastal Kenya.

BACKGROUND: Only approximately one in five adults are offered HIV testing by providers when seeking care for symptoms of acute illness in Sub-Saharan Africa. Our aims were to estimate testing coverage and identify predictors of provider-initiated testing and counselling (PITC) and barriers to PITC implementation in this population. METHODS: We assessed HIV testing coverage among adult outpatients 18-39 years of age at four public and two private health facilities in coastal Kenya, during a 3- to 6-month surveillance period at each facility. A subset of patients who reported symptoms including fever, diarrhoea, fatigue, body aches, sore throat or genital ulcers were enrolled to complete a questionnaire independently of PITC offer. We assessed predictors of PITC in this population using generalised estimating equations and identified barriers to offering PITC through focus group discussion with healthcare workers (HCW) at each facility. RESULTS: Overall PITC coverage was 13.7% (1600 of 11,637 adults tested), with 1.9% (30) testing positive. Among 1,374 participants enrolled due to symptoms, 378 (27.5%) were offered PITC and 352 (25.6%) were tested, of whom 3.7% (13) tested positive. Among participants offered HIV testing, 93.1% accepted it; among participants not offered testing, 92.8% would have taken an HIV test if offered. The odds of completed PITC were increased among older participants (adjusted odds ratio [aOR] 1.7, 95% confidence interval [CI] 1.4-2.1 for 30-39 years, relative to 18-24 years), men (aOR 1.3, 95% CI 1.1-1.7); casual labourers (aOR 1.3, 95% CI 1.0-1.7); those paying by cash (aOR 1.2, 95% CI 1.0-1.4) or insurance (aOR 3.0, 95% CI 1.5-5.8); participants with fever (aOR 1.5, 95% CI 1.2-1.8) or genital ulcers (aOR 4.0, 95% CI 2.7-6.0); and who had tested for HIV >1 year ago (aOR 1.4, 95% CI 1.0-2.0) or had never tested (aOR 2.2, 95% CI 1.5-3.1). Provider barriers to PITC implementation included lack of HCW knowledge and confidence implementing guidelines, limited capacity and health systems constraints. CONCLUSION: PITC coverage was low, though most patients would accept testing if offered. Missed opportunities to promote testing during care-seeking were common and innovative solutions are needed.

Acute and early HIV infection screening among men who have sex with men, a systematic review and meta-analysis.

INTRODUCTION: Screening for acute and early HIV infections (AEHI) among men who have sex with men (MSM) remains uncommon in sub-Saharan Africa (SSA). Yet, undiagnosed AEHI among MSM and subsequent failure to link to care are important drivers of the HIV epidemic. We conducted a systematic review and meta-analysis of AEHI yield among MSM mobilized for AEHI testing; and assessed which risk factors and/or symptoms could increase AEHI yield in MSM. METHODS: We systematically searched four databases from their inception through May 2020 for studies reporting strategies of mobilizing MSM for testing and their AEHI yield, or risk and/or symptom scores targeting AEHI screening. AEHI yield was defined as the proportion of AEHI cases among the total number of visits. Study estimates for AEHI yield were pooled using random effects models. Predictive ability of risk and/or symptom scores was expressed as the area under the receiver operator curve (AUC). RESULTS: Twenty-two studies were identified and included a variety of mobilization strategies (eight studies) and risk and/or symptom scores (fourteen studies). The overall pooled AEHI yield was 6.3% (95% CI, 2.1 to 12.4; I2  = 94.9%; five studies); yield varied between studies using targeted strategies (11.1%; 95% CI, 5.9 to 17.6; I2  = 83.8%; three studies) versus universal testing (1.6%; 95% CI, 0.8 to 2.4; two studies). The AUC of risk and/or symptom scores ranged from 0.69 to 0.89 in development study samples, and from 0.51 to 0.88 in validation study samples. AUC was the highest for scores including symptoms, such as diarrhoea, fever and fatigue. Key risk score variables were age, number of sexual partners, condomless receptive anal intercourse, sexual intercourse with a person living with HIV, a sexually transmitted infection, and illicit drug use. No studies were identified that assessed AEHI yield among MSM in SSA and risk and/or symptom scores developed among MSM in SSA lacked validation. CONCLUSIONS: Strategies mobilizing MSM for targeted AEHI testing resulted in substantially higher AEHI yields than universal AEHI testing. Targeted AEHI testing may be optimized using risk and/or symptom scores, especially if scores include symptoms. Studies assessing AEHI yield and validation of risk and/or symptom scores among MSM in SSA are urgently needed.

Point-of-care HIV RNA testing and immediate antiretroviral therapy initiation in young adults seeking out-patient care in Kenya.

: We evaluated outcomes of an HIV-1-testing intervention using rapid HIV tests followed by point-of-care Xpert Qual testing for HIV-1 RNA. Of 706 young urgent-care seeking participants evaluated, 24 (3.4%) had chronic HIV (antibody-positive), 3 (0.4%) acute HIV-1 (Qual-positive, antibody-negative), and 3 (0.4%) early HIV-1 infection (Qual-positive, antibody-discordant). Overall, 21 (70.0%) diagnosed patients started antiretroviral therapy after a median of 4 days (range 0-71). HIV-1 RNA testing led to an increase in confirmed diagnoses by 25%.

Pilot testing of an online training module about screening for acute HIV infection in adult patients seeking urgent healthcare.

BACKGROUND: Acute HIV infection (AHI) is the phase of HIV infection immediately after acquisition, during which many patients develop symptoms and often seek healthcare. However, clinicians in sub-Saharan Africa are not currently taught about AHI. METHODS: This study pilot-tested a self-directed AHI training module among clinical officers (COs) in coastal Kenya and assessed knowledge gained and challenges to instituting screening. The training module included four domains: AHI definition and importance of AHI recognition; symptoms and screening algorithms; diagnostic strategies; and management. AHI knowledge was assessed before and immediately after training. Participants' ability to utilize an AHI screening algorithm was evaluated with a case-based exercise. RESULTS: Self-directed training was completed by 45 COs. Pre-test scores were low (median score 35% IQR 30-45%), but improved significantly after training (median post-test score 75%, IQR 70-85%, Wilcoxon signed-rank test p<0.0001). Participants had challenges in understanding the utility and application of a screening algorithm to identify patients for whom AHI testing would be indicated. Knowledge of AHI was poor at baseline, but improved with self-directed learning. Based on these findings, we revised and improved the AHI training module and pre- and post-assessments, which are now freely available online at www.marps-africa.org. CONCLUSIONS: Guidelines on AHI screening and diagnosis are urgently needed in high HIV transmission areas.

Urogenital pathogens, associated with Trichomonas vaginalis, among pregnant women in Kilifi, Kenya: a nested case-control study.

BACKGROUND: Screening of curable sexually transmitted infections is frequently oriented towards the diagnosis of chlamydia, gonorrhea, syphilis and trichomoniasis, whereas other pathogens, sometimes associated with similar urogenital syndromes, remain undiagnosed and/or untreated. Some of these pathogens are associated with adverse pregnancy outcomes. METHODS: In a nested case-control study, vaginal swabs from 79 pregnant women, i.e., 28 T. vaginalis-positive (cases) and 51 T. vaginalis-negative (controls), were screened by quantitative PCR for Adenovirus 1 and 2, Cytomegalovirus, Herpes Simplex Virus 1 and 2, Chlamydia trachomatis, Escherichia coli, Haemophilus ducreyi, Mycoplasma genitalium, M. hominis, candidatus M. girerdii, Neisseria gonorrhoeae, Streptococcus agalactiae, Treponema pallidum, Ureaplasma parvum, U. urealyticum, and Candida albicans. Additionally, we determined whether women with pathogens highly associated with T. vaginalis had distinct clinical signs and symptoms compared to women with T. vaginalis mono-infection. RESULTS: M. hominis was independently associated with T. vaginalis (adjusted odds ratio = 6.8, 95% CI: 2.3-19.8). Moreover, M. genitalium and Ca M. girerdii were exclusively detected in women with T. vaginalis (P = 0.002 and P = 0.001), respectively. Four of the six women co-infected with T. vaginalis and Ca M. girerdii complained of vaginal itching, compared to only 4 out of the 22 women infected with T. vaginalis without Ca M. girerdii (P = 0.020). CONCLUSION: We confirm M. hominis as a correlate of T. vaginalis in our population, and the exclusive association of both M. genitalium and Ca. M. girerdii with T. vaginalis. Screening and treatment of these pathogens should be considered.

HIV care engagement and ART adherence among Kenyan gay, bisexual, and other men who have sex with men: a multi-level model informed by qualitative research.

Gay, bisexual, and other men who have sex with men (GBMSM) are highly stigmatized and male-male sex is often criminalized in sub-Saharan Africa, impeding access to quality care for sexual health, HIV prevention, and treatment. To better understand HIV care engagement and antiretroviral therapy (ART) adherence among GBMSM in this context, a conceptual model incorporating sociocultural factors is needed. We conducted a qualitative study of barriers to and facilitators of HIV care engagement and ART adherence among Kenyan GBMSM, informed by a conceptual model based on an access, information, motivation, and behavioral skills (access-IMB) model, with trust in providers and stigma and discrimination as a priori factors of interest. We conducted 30 semi-structured interviews with HIV-positive Kenyan GBMSM, of whom 20 were taking ART and 10 had not yet initiated treatment. A deductive approach was used to confirm the relevance of basic concepts of the access-IMB model, while an inductive approach was used to identify content that emerged from men's lived experiences. Access-related information, motivation, and behavioral skills appeared relevant to HIV care engagement and ART adherence, with stigma and discrimination appearing consistently across discourse exploring facilitators and barriers. Trusted providers and supportive family and friends helped many men, and resilience-related concepts such as selective disclosure of GBMSM status, connection to lesbian, gay, bisexual, and transgender (LGBT) organizations, self-acceptance, goal-setting, social identity and altruism emerged as important facilitators. Findings suggest a need to increase support from providers and peers for Kenyan GBMSM living with HIV infection. In addition, they point toward the potential value of interventions that provide opportunities to build or enhance one's sense of community belonging in order to improve HIV care engagement and promote ART adherence for this vulnerable population.

Role of HIV exposure and infection in relation to neonatal GBS disease and rectovaginal GBS carriage: a systematic review and meta-analysis.

Streptococcus agalactiae (GBS) is the leading cause worldwide of neonatal sepsis. We sought to assess to which extent HIV exposure of neonates is associated with GBS neonatal disease. Furthermore, we assessed to which extent HIV infection in women is associated with maternal rectovaginal GBS carriage, the single most important risk factor for GBS neonatal disease. We searched Pubmed, Embase, and Web of Science for studies assessing the association between neonatal GBS disease and HIV-status of the mother and studies that assessed the association between rectovaginal GBS colonization and HIV status in women. HIV-exposed uninfected neonates were more than twice as likely to have neonatal GBS disease compared to unexposed neonates. HIV-exposed neonates were not at increased risk for early-onset neonatal disease, but were 4.43 times more likely to have late-onset neonatal GBS disease. There was no significant association between HIV infection status and rectovaginal GBS carriage. Public health interventions preventing neonatal GBS disease are urgently needed for the increasing group of HIV-exposed neonates. A framework integrating and explaining our findings highlights opportunities for the clinical practice and global health policy to prevent disease. Well-designed studies should clarify the relation between HIV-status and GBS carriage.

Uptake and Acceptability of Oral HIV Self-Testing among Community Pharmacy Clients in Kenya: A Feasibility Study.

BACKGROUND: While HIV testing and counselling is a key entry point for treatment as prevention, over half of HIV-infected adults in Kenya are unaware they are infected. Offering HIV self-testing (HST) at community pharmacies may enhance detection of undiagnosed infections. We assessed the feasibility of pharmacy-based HST in Coastal Kenya. METHODS: Staff at five pharmacies, supported by on-site research assistants, recruited adult clients (≥18 years) seeking services indicative of HIV risk. Participants were offered oral HST kits (OraQuick®) at US$1 per test. Within one week of buying a test, participants were contacted for post-test data collection and counselling. The primary outcome was test uptake, defined as the proportion of invited clients who bought tests. Views of participating pharmacy staff were solicited in feedback sessions during and after the study. RESULTS: Between November 2015 and April 2016, 463 clients were invited to participate; 174 (38%) were enrolled; and 161 (35% [95% Confidence Interval (CI) 31-39%]) bought a test. Uptake was higher among clients seeking HIV testing compared to those seeking other services (84% vs. 11%, adjusted risk ratio 6.9 [95% CI 4.9-9.8]). Only 4% of non-testers (11/302) stated inability to pay as the reason they did not take up the test. All but one tester reported the process was easy (29%) or very easy (70%). Demand for HST kits persisted after the study and participating service providers expressed interest in continuing to offer the service. CONCLUSIONS: Pharmacy HST is feasible in Kenya and may be in high demand. The uptake pattern observed suggests that a client-initiated approach is more feasible compared to pharmacy-initiated testing. Price is unlikely to be a barrier if set at about US$1 per test. Further implementation research is required to assess uptake, yield, and linkage to care on a larger scale.

The plasma virome of febrile adult Kenyans shows frequent parvovirus B19 infections and a novel arbovirus (Kadipiro virus).

Viral nucleic acids present in the plasma of 498 Kenyan adults with unexplained fever were characterized by metagenomics analysis of 51 sample pools. The highest to lowest fraction of plasma pools was positive for parvovirus B19 (75 %), pegivirus C (GBV-C) (67 %), alpha anellovirus (59 %), gamma anellovirus (55 %), beta anellovirus (41 %), dengue virus genotype 2 (DENV-2) (16 %), human immunodeficiency virus type 1 (6 %), human herpesvirus 6 (6 %), HBV (4 %), rotavirus (4 %), hepatitis B virus (4 %), rhinovirus C (2 %), Merkel cell polyomavirus (MCPyV; 2 %) and Kadipiro virus (2 %). Ranking by overall percentage of viral reads yielded similar results. Characterization of viral nucleic acids in the plasma of a febrile East African population showed a high frequency of parvovirus B19 and DENV infections and detected a reovirus (Kadipiro virus) previously reported only in Asian Culex mosquitoes, providing a baseline to compare with future virome studies to detect emerging viruses in this region.

PrEP implementation research in Africa: what is new?

INTRODUCTION: Of the two million new HIV infections in adults in 2014, 70% occurred in sub-Saharan Africa. Several African countries have already approved guidelines for pre-exposure prophylaxis (PrEP) for individuals at substantial risk of HIV as part of combination HIV prevention but key questions remain about how to identify and deliver PrEP to those at greatest need. Throughout the continent, individuals in sero-discordant relationships, and members of key populations (sex workers, men who have sex with men (MSM), transgender women and injection drug users) are likely to benefit from the availability of PrEP. In addition, adolescent girls and young women (AGYW) are at substantial risk in some parts of the continent. It has been estimated that at least three million individuals in Africa are likely to be eligible for PrEP according to WHO's criteria. Tens of demonstration projects are planned or underway across the continent among a range of countries, populations and delivery settings. DISCUSSION: In each of the target populations, there are overarching issues related to (i) creating demand for PrEP, (ii) addressing supply-side issues and (iii) providing appropriate and tailored adherence support. Critical for creating demand for PrEP is the normalization of HIV prevention. Community-level interventions which engage opinion leaders as well as empowerment interventions for those at highest risk will be key. Critical to supply of PrEP is that services are accessible for all, including for stigmatized populations. Establishing accessible integrated services provides the opportunity to address other public health priorities including the unmet need for HIV testing, contraception and sexually transmitted infections treatment. National policies need to include minimum standards for training and quality assurance for PrEP implementation and to address supply chain issues. Adherence support needs to recognize that social and structural factors are likely to have an important influence. Combining interventions that build self-efficacy, empowerment and social cohesion, with evidence-based individualized adherence support for PrEP, are most likely to be effective. CONCLUSIONS: Efficacy of tenfovir-based PrEP is proven but many issues related to implementation remain unclear. Here, we have summarized some of the important implementation questions that need to be assessed as PrEP is rolled out across Africa.

Effect of Text Message, Phone Call, and In-Person Appointment Reminders on Uptake of Repeat HIV Testing among Outpatients Screened for Acute HIV Infection in Kenya: A Randomized Controlled Trial.

BACKGROUND: Following HIV-1 acquisition, many individuals develop an acute retroviral syndrome and a majority seek care. Available antibody testing cannot detect an acute HIV infection, but repeat testing after 2-4 weeks may detect seroconversion. We assessed the effect of appointment reminders on attendance for repeat HIV testing. METHODS: We enrolled, in a randomized controlled trial, 18-29 year old patients evaluated for acute HIV infection at five sites in Coastal Kenya (ClinicalTrials.gov NCT01876199). Participants were allocated 1:1 to either standard appointment (a dated appointment card) or enhanced appointment (a dated appointment card plus SMS and phone call reminders, or in-person reminders for participants without a phone). The primary outcome was visit attendance, i.e., the proportion of participants attending the repeat test visit. Factors associated with attendance were examined by bivariable and multivariable logistic regression. PRINCIPAL FINDINGS: Between April and July 2013, 410 participants were randomized. Attendance was 41% (85/207) for the standard group and 59% (117/199) for the enhanced group, for a relative risk of 1.4 [95% Confidence Interval, CI, 1.2-1.7].Higher attendance was independently associated with older age, study site, and report of transactional sex in past month. Lower attendance was associated with reporting multiple partners in the past two months. CONCLUSIONS: Appointment reminders through SMS, phone calls and in-person reminders increased the uptake of repeat HIV test by forty percent. This low-cost intervention could facilitate detection of acute HIV infections and uptake of recommended repeat testing. TRIAL REGISTRATION: Clinicaltrials.gov NCT01876199.

Targeted screening of at-risk adults for acute HIV-1 infection in sub-Saharan Africa.

BACKGROUND: Patients with acute HIV-1 infection (AHI) have elevated infectivity, but cannot be diagnosed using antibody-based testing. Approaches to screen patients for AHI are urgently needed to enable counselling and treatment to reduce onward transmission. METHODS: We pooled data from four African studies of high-risk adults that evaluated symptoms and signs compatible with acute retroviral syndrome and tested for HIV-1 at each visit. AHI was defined as detectable plasma viral load or p24 antigen in an HIV-1-antibody-negative patient who subsequently seroconverted. Using generalized estimating equation, we identified symptoms, signs, and demographic factors predictive of AHI, adjusting for study site. We assigned a predictor score to each statistically significant predictor based on its beta coefficient, summing predictor scores to calculate a risk score for each participant. We evaluated the performance of this algorithm overall and at each site. RESULTS: We compared 122 AHI visits with 45 961 visits by uninfected patients. Younger age (18-29 years), fever, fatigue, body pains, diarrhoea, sore throat, and genital ulcer disease were independent predictors of AHI. The overall area under the receiver operating characteristics curve (AUC) for the algorithm was 0.78, with site-specific AUCs ranging from 0.61 to 0.89. A risk score of at least 2 would indicate AHI testing for 5-50% of participants, substantially decreasing the number needing testing. CONCLUSION: Our targeted risk score algorithm based on seven characteristics reduced the number of patients needing AHI testing and had good performance overall. We recommend this risk score algorithm for use by HIV programs in sub-Saharan Africa with capacity to test high-risk patients for AHI.

Prevalence, Incidence, and Clearance of Anogenital Warts in Kenyan Men Reporting High-Risk Sexual Behavior, Including Men Who Have Sex With Men.

Background. Human papillomavirus (HPV) causes a spectrum of disease, ranging from warts to cancer. Prevalence, incidence, and factors associated with anogenital warts in East African men are unknown. Methods. Kenyan men reporting high-risk sexual behavior were inspected for anogenital warts at enrollment and follow-up visits. Logistic regression was performed to identify associations with anogenital warts at baseline. Cox regression was performed to analyze predictors of incident anogenital warts, and Kaplan-Meier curves were used to estimate clearance. Results. Baseline anogenital wart prevalence in 1137 men was 2.9% (95% confidence interval [CI], 2.0%-4.0%) overall, 2.0% in human immunodeficiency virus (HIV)-uninfected men, and 9.4% in HIV-1-infected men (adjusted odds ratio, 5.43; 95% CI, 2.03-11.29). Over a median of 1.4 years, anogenital wart incidence among 1104 men was 5.3 (95% CI, 4.3-6.5) per 100 person-years. Having HIV-1 infection at baseline (adjusted hazard ratio [aHR], 1.66; 95% CI, 1.01-2.72) or a genital syndrome during follow-up (aHR, 4.78; 95% CI, 3.03-7.56) was associated with increased wart incidence. Wart clearance was lower in HIV-1-infected men (log-rank P<.001). Conclusions. Anogenital wart prevalence and incidence were increased in HIV-1-infected men, and anogenital warts co-occurred with other genital syndromes. Quadrivalent HPV vaccination should be recommended for young men in settings with high HIV-1 prevalence.

Engaging young adult clients of community pharmacies for HIV screening in Coastal Kenya: a cross-sectional study.

BACKGROUND: Adults in developing countries frequently use community pharmacies as the first and often only source of care. The objective of this study was to assess the success of pharmacy referrals and uptake of HIV testing by young adult clients of community pharmacies in the context of a screening programme for acute HIV-1 infection (AHI). METHODS: We requested five pharmacies to refer clients meeting predefined criteria (ie, 18-29 years of age and requesting treatment for fever, diarrhoea, sexually transmitted infection (STI) symptoms or body pains) for HIV-1 testing and AHI screening at selected clinics. Using multivariable logistical regression, we determined client characteristics associated with HIV-1 test uptake. RESULTS: From February through July 2013, 1490 pharmacy clients met targeting criteria (range of weekly averages across pharmacies: 4-35). Of these, 1074 (72%) accepted a referral coupon, 377 (25%) reported at a study clinic, 353 (24%) were HIV-1 tested and 127 (9%) met criteria for the AHI study. Of those tested, 14 (4.0%) were HIV-1 infected. Test uptake varied significantly by referring pharmacy and was higher for clients who presented at the pharmacy without a prescription versus those with a prescription, and for clients who sought care for STI symptoms. CONCLUSIONS: About a quarter of targeted pharmacy clients took up HIV-1 testing. Clients seeking care directly at the pharmacy (ie, without a prescription) and those with STI symptoms were more likely to take up HIV-1 testing. Engagement of adult pharmacy clients for HIV-1 screening may identify undiagnosed individuals and offers opportunities for HIV-1 prevention research.

Evaluation of WHO screening algorithm for the presumptive treatment of asymptomatic rectal gonorrhoea and chlamydia infections in at-risk MSM in Kenya.

OBJECTIVES: The WHO recommends that men who have sex with men (MSM) reporting unprotected receptive anal intercourse (RAI) and either multiple partners or a partner with a sexually transmitted infection (STI) in the past 6 months should be presumptively treated for asymptomatic rectal Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) infections. We evaluated this recommendation in a cohort of 'high-risk' MSM in Coastal Kenya. METHODS: We assessed presence of genitourinary and rectal symptoms, and determined prevalence and 3-month incidence of rectal NG and CT infections. We performed nucleic acid amplification testing of urine and rectal swab samples collected from MSM followed prospectively, and assessed predictive values of the WHO algorithm at baseline screening. RESULTS: Of 244 MSM screened, 240 (98.4%) were asymptomatic, and 147 (61.3%) reported any RAI in the past 6 months. Among 85 (35.4%) asymptomatic MSM meeting criteria for the WHO presumptive treatment (PT) recommendation, we identified 20 with rectal infections (six NG, 12 CT and two NG-CT co-infections). Among 62 asymptomatic MSM who did not meet criteria, we identified seven who were infected. The sensitivity and specificity of the WHO algorithm were 74.1% (95% CI 53.7% to 88.9%) and 45.8% (95% CI 36.7% to 55.2%), respectively. The 3-month incidence of any rectal NG or CT infection in asymptomatic men reporting any RAI was 39.7 (95% CI 24.3 to 64.8) per 100 person-years. CONCLUSIONS: About one-third of asymptomatic MSM were eligible to receive PT for NG and CT infections. Among MSM who would qualify for PT of rectal STIs, the number needed to treat in order to treat one infection was four. Our results support the value of the WHO screening algorithm and recommended PT strategy in this population.

Emergence of fluoroquinolone resistance in Neisseria gonorrhoeae isolates from four clinics in three regions of Kenya.

We have recently reported high levels of fluoroquinolone resistance in a single region of Kenya. In this article, we report high prevalence of fluoroquinolone resistance (53.2%) in Neisseria gonorrhoeae isolates from 4 clinics in 3 additional regions of Kenya. These findings highlight the need to change first-line treatment in these settings and the need to evaluate empirical management guidelines for treatment of gonococcal infection in Kenya.

Men who have sex with men and HIV/AIDS in sub-Saharan Africa.

Globally, men who have sex with men (MSM) continue to bear a high burden of HIV infection. In sub-Saharan Africa, same-sex behaviours have been largely neglected by HIV research up to now. The results from recent studies, however, indicate the widespread existence of MSM groups across Africa, and high rates of HIV infection, HIV risk behaviour, and evidence of behavioural links between MSM and heterosexual networks have been reported. Yet most African MSM have no safe access to relevant HIV/AIDS information and services, and many African states have not begun to recognise or address the needs of these men in the context of national HIV/AIDS prevention and control programmes. The HIV/AIDS community now has considerable challenges in clarifying and addressing the needs of MSM in sub-Saharan Africa; homosexuality is illegal in most countries, and political and social hostility are endemic. An effective response to HIV/AIDS requires improved strategic information about all risk groups, including MSM. The belated response to MSM with HIV infection needs rapid and sustained national and international commitment to the development of appropriate interventions and action to reduce structural and social barriers to make these accessible.

Baseline morbidity in 2,990 adult African volunteers recruited to characterize laboratory reference intervals for future HIV vaccine clinical trials.

BACKGROUND: An understanding of the health of potential volunteers in Africa is essential for the safe and efficient conduct of clinical trials, particularly for trials of preventive technologies such as vaccines that enroll healthy individuals. Clinical safety laboratory values used for screening, enrolment and follow-up of African clinical trial volunteers have largely been based on values derived from industrialized countries in Europe and North America. This report describes baseline morbidity during recruitment for a multi-center, African laboratory reference intervals study. METHODS: Asymptomatic persons, aged 18-60 years, were invited to participate in a cross-sectional study at seven sites (Kigali, Rwanda; Masaka and Entebbe, Uganda; Kangemi, Kenyatta National Hospital and Kilifi, Kenya; and Lusaka, Zambia). Gender equivalency was by design. Individuals who were acutely ill, pregnant, menstruating, or had significant clinical findings were not enrolled. Each volunteer provided blood for hematology, immunology, and biochemistry parameters and urine for urinalysis. Enrolled volunteers were excluded if found to be positive for HIV, syphilis or Hepatitis B and C. Laboratory assays were conducted under Good Clinical Laboratory Practices (GCLP). RESULTS AND CONCLUSIONS: Of the 2990 volunteers who were screened, 2387 (80%) were enrolled, and 2107 (71%) were included in the analysis (52% men, 48% women). Major reasons for screening out volunteers included abnormal findings on physical examination (228/603, 38%), significant medical history (76, 13%) and inability to complete the informed consent process (73, 13%). Once enrolled, principle reasons for exclusion from analysis included detection of Hepatitis B surface antigen (106/280, 38%) and antibodies against Hepatitis C (95, 34%). This is the first large scale, multi-site study conducted to the standards of GCLP to describe African laboratory reference intervals applicable to potential volunteers in clinical trials. Approximately one-third of all potential volunteers screened were not eligible for analysis; the majority were excluded for medical reasons.

Investigating the utility of the HIV-1 BED capture enzyme immunoassay using cross-sectional and longitudinal seroconverter specimens from Africa.

BACKGROUND: The identification of populations at risk of HIV infection is a priority for trials of preventive technologies, including HIV vaccines. To quantify incidence traditionally requires laborious and expensive prospective studies. METHODS: The BED IgG-Capture enzyme immunoassay (EIA) was developed to estimate HIV-1 incidence using cross-sectional data by measuring increasing levels of HIV-specific IgG as a proportion of total IgG. To evaluate this assay, we tested 189 seroconversion samples taken at 3-monthly intervals from 15 Rwandan and 26 Zambian volunteers with known time of infection and cross-sectional specimens from 617 Kenyan and Ugandan volunteers with prevalent infection. RESULTS: The BED-EIA-estimated incidence in Uganda was unexpectedly high, at 6.1%/year [95% confidence interval (CI) 4.2-8.0] in Masaka and 6.0%/year (95% CI 4.3-7.7) in Kakira. Prospective incidence data in Masaka from the same population was 1.7%/year before and 1.4%/year after the study. Kenyan estimates were 3.5%/year in Kilifi (95% CI 2.1-4.9) and 3.4%/year in Nairobi (95% CI 1.5-5.3). From the Rwandan and Zambian data, the sensitivity of the assay was 81.2% and the specificity was 67.8%. After approximately one year, subjects misclassified as recently infected tended to have lower plasma viral loads compared with those not misclassified as recent (median copies/ml 14 773 versus 93 560; P = 0.02). Clinical presentation, sex and HIV subtype were not significantly associated with BED-EIA misclassification in seroconverter samples. CONCLUSION: These data suggest that this assay does not perform reliably in all populations. Further research is warranted before using this assay to estimate incidence from prevalent HIV samples.