Patterns of human herpesvirus-8 oral shedding among diverse cohorts of human herpesvirus-8 seropositive persons.

Background: Human herpesvirus-8 (HHV-8), the etiologic agent of Kaposi sarcoma (KS), establishes lifelong latent infection with periodic lytic replication ("shedding") at mucosal sites, especially the oropharynx. Patterns of HHV-8 shedding are not well understood, and require elucidation to better predict risk of HHV-8 related malignancies in those infected. We sought to characterize patterns of HHV-8 oropharyngeal shedding among diverse cohorts that enrolled HHV-8 seropositive persons.

I Knew I Would Be Safer. Experiences of Kenyan HIV Serodiscordant Couples Soon After Pre-Exposure Prophylaxis (PrEP) Initiation.

Pre-exposure prophylaxis (PrEP) for HIV-uninfected persons is highly efficacious for HIV prevention. Understanding how people at risk for HIV will use PrEP is important to inform PrEP scale-up and implementation. We used qualitative methods to gather insights into couples' early experiences with PrEP use within the Partners Demonstration Project, an open-label implementation study evaluating integrated delivery of PrEP and antiretroviral therapy (ART).

Comparison of subjective and objective adherence measures for preexposure prophylaxis against HIV infection among serodiscordant couples in East Africa.

Background: Preexposure prophylaxis (PrEP) efficacy is highly dependent on adherence. Yet, it is unclear which adherence measures perform best for PrEP.

Methods: We compared three types of self-reported adherence questions (rating of ability to adhere, frequency of doses taken, percentage of doses taken) and three forms of objective adherence measurement [unannounced pill counts (UPC), electronic monitoring, plasma tenofovir levels] using data from an ancillary adherence study within a clinical trial of PrEP among East African serodiscordant couples (Partners PrEP Study).

Preexposure prophylaxis-selected drug resistance decays rapidly after drug cessation.

Objective: Resistance to emtricitabine plus tenofovir disoproxil fumarate (FTC/TDF) or TDF alone used as preexposure prophylaxis (PrEP) has been detected in individuals who initiated PrEP during unrecognized acute HIV infection and, rarely, in PrEP breakthrough infections. PrEP-selected resistance could alter future treatment options, and therefore we sought to determine how long resistance persisted after PrEP cessation.

Methods: The Partners PrEP Study was a randomized placebo-controlled trial of FTC/TDF or TDF as PrEP for HIV prevention.

A Scoring Tool to Identify East African HIV-1 Serodiscordant Partnerships with a High Likelihood of Pregnancy.

Introduction: HIV-1 prevention programs targeting HIV-1 serodiscordant couples need to identify couples that are likely to become pregnant to facilitate discussions about methods to minimize HIV-1 risk during pregnancy attempts (i.e. safer conception) or effective contraception when pregnancy is unintended.

Transient Increase in Herpes Simplex Virus Type 2 (HSV-2)-Associated Genital Ulcers Following Initiation of Antiretroviral Therapy in HIV/HSV-2-Coinfected Individuals.

Background: Immune reconstitution inflammatory syndrome (IRIS) in human immunodeficiency virus (HIV)-infected persons beginning antiretroviral therapy (ART) has been incompletely characterized for herpes simplex virus type 2 (HSV-2).

Methods: We evaluated genital ulcer disease (GUD) and HSV-2-associated GUD at quarterly visits or when spontaneously reported at monthly visits in 3381 HIV/HSV-2-coinfected individuals in a placebo-controlled trial of suppressive acyclovir therapy to prevent HIV transmission, 349 of whom initiated ART during the study. Incidence was calculated for months before and after ART initiation, and incidence rate ratios (IRRs) were calculated.

Younger Age Predicts Failure to Achieve Viral Suppression and Virologic Rebound Among HIV-1-Infected Persons in Serodiscordant Partnerships.

Background: Antiretroviral therapy (ART) markedly reduces the risk of HIV-1 transmission in serodiscordant partnerships. We previously found that younger age and higher CD4 counts were associated with delayed initiation of ART by HIV-1-infected partners in serodiscordant partnerships. Among those initiating ART, we sought to explore whether those same factors were associated with failure to achieve viral suppression.

Regulatory T-Cell Activity But Not Conventional HIV-Specific T-Cell Responses Are Associated With Protection From HIV-1 Infection.

Objective: Two distinct hypotheses have been proposed for T-cell involvement in protection from HIV-1 acquisition. First, HIV-1-specific memory T-cell responses generated on HIV-1 exposure could mount an efficient response to HIV-1 and inhibit the establishment of an infection. Second, a lower level of immune activation could reduce the numbers of activated, HIV-1-susceptible CD4 T cells, thereby diminishing the likelihood of infection.

Effect of Condom Use on Per-act HSV-2 Transmission Risk in HIV-1, HSV-2-discordant Couples.

Background: The efficacy of condoms for protection against transmission of herpes simplex virus type 2 (HSV-2) has been examined in a variety of populations with different effect measures. Often the efficacy has been assessed as change in hazard of transmission with consistent vs inconsistent use, independent of the number of acts. Condom efficacy has not previously measured on a per-act basis.

Effectiveness of hormonal contraception in HIV-infected women using antiretroviral therapy.

Objective: The objective of this study is to assess whether antiretroviral therapy (ART) may diminish the effectiveness of hormonal contraceptive methods.

Methods: Using data from 5153 HIV-infected women followed prospectively for 1-3 years in three HIV prevention studies in Africa, we compared incident pregnancy rates by contraceptive method (implant, injectable, oral or none) and ART use. Multivariable Cox regression models were used to determine adjusted hazard ratios (aHRs) and test interactions between each method and ART use.

Estimating efficacy in a randomized trial with product nonadherence: application of multiple methods to a trial of preexposure prophylaxis for HIV prevention.

Antiretroviral preexposure prophylaxis (PrEP) for persons at high risk of human immunodeficiency virus infection is a promising new prevention strategy. Six randomized trials of oral PrEP were recently conducted and demonstrated efficacy estimates ranging from 75% to no effect, with nonadherence likely resulting in attenuated estimates of the protective effect of PrEP. In 1 of these trials, the Partners PrEP Study (Kenya and Uganda, 2008-2011), participants (4,747 serodiscordant heterosexual couples) were randomized to receipt of tenofovir (TDF), coformulated TDF/emtricitabine (FTC), or placebo.

Rapid Antiretroviral Therapy Initiation for Women in an HIV-1 Prevention Clinical Trial Experiencing Primary HIV-1 Infection during Pregnancy or Breastfeeding.

During an HIV-1 prevention clinical trial in East Africa, we observed 16 cases of primary HIV-1 infection in women coincident with pregnancy or breastfeeding. Nine of eleven pregnant women initiated rapid combination antiretroviral therapy (ART), despite having CD4 counts exceeding national criteria for ART initiation; breastfeeding women initiated ART or replacement feeding. Rapid ART initiation during primary HIV-1 infection during pregnancy and breastfeeding is feasible in this setting.

Tenofovir-based oral preexposure prophylaxis prevents HIV infection among women.

Purpose Of Review: Despite tremendous promise as a female-controlled HIV prevention strategy, implementation of preexposure prophylaxis (PrEP) among women has been limited, in part because of disparate efficacy results from randomized trials in this population. This review synthesizes existing evidence regarding PrEP efficacy for preventing HIV infection in women and considerations for delivering PrEP to women.

Recent Findings: In three efficacy trials, conducted among men and women, tenofovir-based oral PrEP reduced HIV acquisition in subgroups of women by 49-79% in intent-to-treat analyses, and by >85% when accounting for PrEP adherence.

Fertility Decision-Making Among Kenyan HIV-Serodiscordant Couples Who Recently Conceived: Implications for Safer Conception Planning.

HIV-serodiscordant couples often choose to attempt pregnancy despite their HIV transmission risk. Optimizing delivery of HIV risk reduction strategies during peri-conception periods (i.e.

Estimating PMTCT's Impact on Heterosexual HIV Transmission: A Mathematical Modeling Analysis.

Introduction: Prevention of mother-to-child HIV transmission (PMTCT) strategies include combined short-course antiretrovirals during pregnancy (Option A), triple-drug antiretroviral treament (ART) during pregnancy and breastfeeding (Option B), or lifelong ART (Option B+). The WHO also recommends ART for HIV treatment and prevention of sexual transmission of HIV. The impact of PMTCT strategies on prevention of sexual HIV transmission of HIV is not known.

Rethinking HIV prevention to prepare for oral PrEP implementation for young African women.

Introduction: HIV incidence remains high among young women in sub-Saharan Africa in spite of scale-up of HIV testing, behavioural interventions, antiretroviral treatment and medical male circumcision. There is a critical need to critique past approaches and learn about the most effective implementation of evidence-based HIV prevention strategies, particularly emerging interventions such as pre-exposure prophylaxis (PrEP).

Discussion: Women in sub-Saharan Africa are at increased risk of HIV during adolescence and into their 20s, in part due to contextual factors including gender norms and relationship dynamics, and limited access to reproductive and sexual health services.

Cost-effectiveness of pre-exposure prophylaxis targeted to high-risk serodiscordant couples as a bridge to sustained ART use in Kampala, Uganda.

Introduction: Despite scale-up of antiretroviral therapy (ART) for treating HIV-positive persons, HIV incidence remains elevated among those at high risk such as persons in serodiscordant partnerships. Antiretrovirals taken by HIV-negative persons as pre-exposure prophylaxis (PrEP) has the potential to avert infections in individuals in serodiscordant partnerships. Evaluating the cost-effectiveness of implementing time-limited PrEP as a short-term bridge during the first six months of ART for the HIV-positive partner to prevent HIV transmission compared to increasing ART coverage is crucial to informing policy-makers considering PrEP implementation.

Acyclovir Prophylaxis Reduces the Incidence of Herpes Zoster Among HIV-Infected Individuals: Results of a Randomized Clinical Trial.

Human immunodeficiency virus (HIV)-infected persons have higher rates of herpes zoster than HIV-uninfected individuals. We assessed whether twice daily treatment with 400 mg of oral acyclovir reduces the incidence of herpes zoster in a randomized, double-blind, placebo-controlled trial among 3408 persons coinfected with HIV and herpes simplex virus type 2. During 5175 person-years of follow-up, 26 cases of herpes zoster occurred among those assigned acyclovir, compared with 69 cases among those assigned placebo (rates, 1.

Biomedical HIV Prevention Including Pre-exposure Prophylaxis and Opiate Agonist Therapy for Women Who Inject Drugs: State of Research and Future Directions.

Women who inject drugs (WWID) are at higher risk of HIV compared with their male counterparts as a result of multiple factors, including biological, behavioral, and sociostructural factors, yet comparatively little effort has been invested in testing and delivering prevention methods that directly target this group. In this article, we discuss the need for expanded prevention interventions for WWID, focusing on 2 safe, effective, and approved, yet underutilized biomedical prevention methods: opiate agonist therapy (OAT) and oral pre-exposure prophylaxis (PrEP). Although both interventions are well researched, they have not been well examined in the context of gender.

Toll-like receptor gene variants and bacterial vaginosis among HIV-1 infected and uninfected African women.

Bacterial vaginosis (BV) is a common vaginal syndrome associated with altered microflora that increases the risk of preterm delivery and acquisition of sexually transmitted diseases. The cause of BV is unknown although toll-like receptors (TLRs), that are central to innate immune responses, may be important. We evaluated associations between TLR SNPs and BV among HIV-1 infected and uninfected African women.

Empowering patients to link to care and treatment: qualitative findings about the role of a home-based HIV counselling, testing and linkage intervention in South Africa.

To explore the barriers and facilitators of linkage to and retention in care amongst persons who tested positive for HIV, qualitative research was conducted in a home-based HIV counselling and testing (HBCT) project with interventions to facilitate linkages to HIV care in rural KwaZulu-Natal, South Africa. The intervention tested 1272 adults for HIV in Vulindlela of whom 32% were HIV positive, received point-of-care (POC) CD4 testing and referral to local HIV clinics. Those testing positive also received follow-up visits from a counsellor to evaluate linkages to care.

Frequency of false positive rapid HIV serologic tests in African men and women receiving PrEP for HIV prevention: implications for programmatic roll-out of biomedical interventions.

Background: Rapid HIV assays are the mainstay of HIV testing globally. Delivery of effective biomedical HIV prevention strategies such as antiretroviral pre-exposure prophylaxis (PrEP) requires periodic HIV testing. Because rapid tests have high (>95%) but imperfect specificity, they are expected to generate some false positive results.

Cost-effectiveness of community-based strategies to strengthen the continuum of HIV care in rural South Africa: a health economic modelling analysis.

Background: Home HIV counselling and testing (HTC) achieves high coverage of testing and linkage to care compared with existing facility-based approaches, particularly among asymptomatic individuals. In a modelling analysis we aimed to assess the effect on population-level health and cost-effectiveness of a community-based package of home HTC in KwaZulu-Natal, South Africa.

Methods: We parameterised an individual-based model with data from home HTC and linkage field studies that achieved high coverage (91%) and linkage to antiretroviral therapy (80%) in rural KwaZulu-Natal, South Africa.