Empiric antimicrobial treatment for asymptomatic sexual contacts of sexually transmitted infection in the era of antimicrobial resistance: time to rethink?

Prudent prescribing of antimicrobials is essential in ameliorating the public health problem of antimicrobial resistance. This retrospective audit assesses whether empiric antimicrobial treatment for asymptomatic sexual contacts of sexually transmitted infection is appropriate based on laboratory confirmation.

Non-AIDS complexity amongst patients living with HIV in Sydney: risk factors and health outcomes.

OBJECTIVE: To assess the prevalence of non-AIDS co-morbidities (NACs) and predictors of adverse health outcomes amongst people living with HIV in order to identify health needs and potential gaps in patient management. DESIGN: Retrospective, non-consecutive medical record audit of patients attending a publicly funded HIV clinic in metropolitan Sydney analysed for predictors of adverse health outcomes. We developed a scoring system based on the validated Charlson score method for NACs, mental health and social issues and confounders were selected using directed acyclic graph theory under the principles of causal inference. RESULTS: 211 patient files were audited non-consecutively over 6 weeks. 89.5% were male; 41.8% culturally and linguistically diverse and 4.1% were of Aboriginal/Torres Strait Islander origin. Half of patients had no general practitioner and 25% were ineligible for Medicare subsidised care. The most common NACs were: cardiovascular disease (25%), hepatic disease (21%), and endocrinopathies (20%). One-third of patients had clinical anxiety, one-third major depression and almost half of patients had a lifetime history of tobacco smoking. Five predictors of poor health outcomes were identified: (1) co-morbidity score was associated with hospitalisation (odds ratio, OR 1.58; 95% CI 1.01-2.46; p = 0.044); (2) mental health score was associated with hospitalisation (OR 1.79; 95% CI 1.22-2.62; p = 0.003) and poor adherence to ART (OR 2.34; 95% CI 1.52-3.59; p = 0.001); (3) social issues score was associated with genotypic resistance (OR 2.61; 95% CI 1.48-4.59; p = 0.001), co-morbidity score (OR 1.69; 95% CI 1.24-2.3; p = 0.001) and hospitalisation (OR 1.72; 95% CI 1.1-2.7; p = 0.018); (4) body mass index < 20 was associated with genotypic resistance (OR 6.25; 95% CI 1.49-26.24; p = 0.012); and (5) Medicare eligibility was associated with co-morbidity score (OR 2.21; 95% CI 1.24-3.95; p = 0.007). CONCLUSION: Most HIV patients are healthy due to effective antiretroviral therapy; however, NACs and social/mental health issues are adding to patient complexity. The current findings underpin the need for multidisciplinary management beyond routine viral load and CD4 count monitoring.

Impact of Allogeneic Hematopoietic Stem Cell Transplantation on the HIV Reservoir and Immune Response in 3 HIV-Infected Individuals.

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (HSCT) can lead to significant changes to the HIV reservoir and HIV immune responses, indicating that further characterization of HIV-infected patients undergoing HSCT is warranted. METHODS: We studied 3 patients who underwent HSCT after either reduced intensity conditioning or myeloablative conditioning regimen. We measured HIV antigens and antibodies (Ag/Ab), HIV-specific CD4 T-cell responses, HIV RNA, and DNA in plasma, peripheral blood mononuclear cells, isolated CD4 T cells from peripheral blood, and lymph node cells. The patients remained on antiretroviral therapy throughout the follow-up period. RESULTS: All patients have been in continued remission for 4-6 years post-HSCT. Analyses of HIV RNA and DNA levels showed substantial reductions in HIV reservoir-related measurements in all 3 patients, changes in immune response varied with pronounced reductions in 2 patients and a less dramatic reduction in 1 patient. One patient experienced unexpected viral rebound 4 years after HSCT. CONCLUSIONS: These 3 cases highlight the substantial changes to the HIV reservoir and the HIV immune response in patients undergoing allogeneic HSCT. The viral rebound observed in 1 patient indicates that replication competent HIV can re-emerge several years after HSCT despite these marked changes.

HIV-1 transmission amongst men who have sex with men: a probabilistic model incorporating antiretroviral treatment optimism-scepticism, sexual beliefs and sexual behaviour.

To explore the hypotheses that HIV-1 infected patients receiving suppressive antiretroviral therapy believe that they cannot transmit their virus, that this translates to increasing rates of unprotected anal intercourse and new infections, and that sexual practice may be influenced by the HIV-1 serostatus of one's sexual partner. We developed a Bernoulli model for HIV-1 transmission amongst a cross-sectional cohort of 119 HIV-1 positive treated and untreated men having sex with men attending a metropolitan HIV-1 clinic. The model included transmission probabilities for different types of anal intercourse, the local HIV-1 seroprevalence rate, and behavioural data from a validated sexual practice questionnaire and scales of treatment optimism-scepticism and sexual beliefs pertaining to the previous 3 months. Subjects reported partner serostatus as HIV-1 negative or unknown. There were no differences in optimism-scepticism score (p = 0.295) and total sexual belief scores (p = 0.211) according to antiretroviral therapy status. Sex with unknown serostatus partners was higher risk for transmission than sex with HIV-1 negative partners. Most unprotected anal intercourse was practiced by a minority of men, independent of antiretroviral treatment status. Compared to subjects with HIV-1 negative partners, subjects with unknown serostatus partners had more UAI, a 2-fold higher probability of transmitting HIV-1 and were responsible for 2.6 as many new infections. Overall, there were 4 times as many infections predicted to occur amongst unknown serostatus men cf. HIV-1 negative men. A sub-group reported frequent unprotected anal intercourse with their partners. Our model may be used to quantify risk behavior during individual counselling or to develop targeted prevention programmes at the public health level.

Correlates of unprotected anal intercourse in HIV positive men attending an HIV/AIDS clinic in Sydney.

We examined the impact of cognitive and biomedical variables on unprotected anal intercourse between HIV-1 infected men and casual sexual partners in a Sydney-based cohort. Participants answered questionnaires examining insertive and receptive intercourse with and without ejaculation. They completed a modified optimism-scepticism scale, a sexual beliefs scale and a clinical/demographics questionnaire. CD4 count, blood and semen VL were assessed. 43 of 109 reported anal intercourse with HIV+ partners, 33 with HIV- partners and 38 with partners of unknown status. With HIV+ partners past sexually transmittable infections were associated with receptive intercourse without ejaculation (p = 0.03) and insertive intercourse without ejaculation (p = 0.06) while sexual beliefs were associated with insertive intercourse without ejaculation (p = 0.038), receptive intercourse with ejaculation (p = 0.016) and insertive intercourse with ejaculation (p = 0.077). Sexual beliefs were found to have some association with unprotected receptive intercourse without ejaculation with HIV- partners (p = 0.071). With unknown serostatus partners, treatment-optimism (p = 0.026) had association with insertive intercourse with ejaculation while optimism (p = 0.002), sexual beliefs (p = 0.039) and recent VL (p = 0.059) had associations with insertive intercourse without ejaculation. Current STI had association with receptive intercourse with ejaculation with unknown status partners (p = 0.014). We found between-group differences in variables associated with different types of unprotected anal intercourse that may guide the development of prevention strategies.

Correlation between HIV-1 RNA load in blood and seminal plasma depending on antiretroviral treatment status, regimen and penetration of semen by antiretroviral drugs.

To assess the correlation between HIV-1 RNA load in blood and semen by antiretroviral therapy status and the relative penetration of antiretroviral drugs in seminal plasma. We performed a cross-sectional cohort study of 119 HIV-1 subjects divided into three groups according to treatment status. Blood and semen were collected concurrently. Seminal viral load determined by NucliSens HIV-1 QT PCR (BioMerieux). Viral suppression over time was assessed in a second semen sample collected from 10 treated subjects. Antiretroviral plasma concentrations were measured by high performance liquid chromatography and recovery experiments were performed on semen samples to validate quantitation in this matrix. All subjects taking non nucleoside reverse transcriptase inhibitors (n = 36, mean treatment 33 months +/- 14) or protease inhibitors (n = 45, mean treatment 31 months +/- 25) had blood viral load < 50 copies/mL and seminal viral load < 250 copies/mL. In untreated subjects (n = 38), blood and semen viral loads were positively correlated (Spearman's rho = 0.489, p = 0.002). Blood and semen nevirapine concentrations were positively correlated (r(2) = 0.795, p = 0.005) and therapeutic concentrations achieved in both compartments. Lopinavir and atazanavir also penetrated semen but efavirenz did not. We find that there is compartmentalisation of HIV-1 within the male genital tract and propose that new infections may originate from untreated men and that suppressive antiretroviral regimens may reduce the risk of sexual transmission.

Assays for the determination of HIV-1 load in semen: a review of indications, methods and performance in vitro.

Techniques for the quantification of HIV-1 load in semen include culture and nucleic acid amplification techniques. The latter tend to be used in the reproductive, public health and research settings due to speed, throughput, sensitivity and capacity to eliminate and control for contamination or inhibitory substances from semen. Commercially-available assays such as nucleic acid sequence-based amplification and reverse transcriptase polymerase chain reaction are equivalent in yielding more reliable and reproducible results than in-house, non-commercial assays, and should be used for the determination of HIV-1 load in semen. Sensitivity is increased when silica extraction methods are used.

Relationship between HIV-RNA load in blood and semen in antiretroviral-naïve and experienced men and effect of asymptomatic sexually transmissible infections.

We assessed the correlation between HIV-RNA viral load in blood (BPVL) and seminal plasma (SPVL) in a cross-sectional cohort of 119 asymptomatic, antiretroviral-naive and experienced HIV-1 subjects (BPVL < 50 copies/mL for minimum 12 months and stable on one drug regimen). The cohort was divided into 3 groups: 2 according to the non nucleoside reverse transcriptase inhibitor (NNRTI) and protease inhibitor (PI) used, and 1 untreated group. At the initial visit, subjects were screened for gonorrhoea, chlamydia and syphilis. Blood was collected for CD4 count, BPVL, and general biochemistry and haematology. Semen was collected concurrently and SPVL determined by the NucliSens HIV-1 QT PCR (BioMerieux, Boxtel, The Netherlands). At a subsequent visit, a second semen sample was obtained and SPVL was repeated for 10 subjects on ART. All NNRTI subjects (n = 36, mean treatment 33 months +/- 14) and PI subjects (n = 45, mean treatment 31 months +/- 25) had BPVL < 50 copies/mL and SPVL < 250 copies/mL at baseline and with repeat sampling. 9/119 subjects (8%) had an asymptomatic STI; 4 cases in the treated groups and 5 in the untreated group. Treated subjects were less likely to have an STI than untreated subjects. In conclusion, asymptomatic STIs had no effect on BPVL or SPVL in either treated group and SPVL remains undetectable over time. STIs minimally increase, or do not increase, SPVL in untreated patients. Our data supports the role of ART in lowering the risk of sexual transmission of HIV-1.

Things that go bump on the right.

Groin masses are common and the differential diagnosis is wide. It is important to distinguish surgical and medical causes. A rare surgical cause--that may be associated with cryptorchidism--is presented here.

Quantification of antiretroviral drugs for HIV-1 in the male genital tract: current data, limitations and implications for laboratory analysis.

Antiretroviral therapy has reduced the morbidity and mortality associated with HIV-1/AIDS in developed countries. Viral replication in blood plasma is suppressed by antiretroviral drugs, whereas virus in the male genital tract is genetically and phenotypically unique and may not be suppressed. This viral compartmentalization affects antiretroviral drug penetration of the male genital tract and capacity for antiretroviral therapy to reduce sexual transmission. The problem of having two distinct viral populations within any given individual is compounded by the fact that antiretroviral drugs penetrate semen to varying degrees. Incomplete suppression of genital tract virus may yield drug-resistant virus and increase the risk of sexual transmission. This review critically appraises current studies of antiretroviral drug quantification in semen and suggests recommendations to address observed limitations.

Pathophysiology of HIV-1 in semen: current evidence for compartmentalisation and penetration by antiretroviral drugs.

Sexual transmission of HIV-1 is dependent on the semen viral load. Seminal viral load may fluctuate and is increased by several HIV-1 related factors and prevailing conditions within the male genital tract. The precise reservoirs of virus production within the male genital tract, whether cell-associated of cell-free, are undefined. The ability of antiretroviral drugs to penetrate the male genital tract and reach therapeutic concentrations is correlated with the degree of viral suppression and therefore relative infectivity. The basic physicochemical properties of the drugs themselves do not predict penetration of semen and other factors, such as active drug transport, may be involved. Measurement of seminal viral load and antiretroviral drug concentration are affected by the physiology of semen and non-standardised methodology (type of test used, specimen collection methods, data presentation issues, and pharmacokinetic assumptions) between studies.

Factors affecting sexual transmission of HIV-1: current evidence and implications for prevention.

The predominant mode of HIV-1 transmission globally is from sexual practices. The risk of HIV-1 transmission by sexual means is a function of infectivity, susceptibility and mode of transmission (type of sexual practice). In addition, transmission may be significantly increased or decreased by factors relating to the HIV-1 per se, sexual behaviour, other sexually transmissible infections (STIs), antiretroviral therapy (ART), spermicidal microbicides and HIV-1 vaccines, the host immune system, genital anatomy and nutritional deficiencies. Current research into the factors affecting sexual transmission of HIV-1 appears to benefit developed nations more than developing nations because of structured public health systems and the capacity to translate research findings into prevention strategies. A redistribution of global aid funding would do much to alleviate the pandemic in developed countries.

Syphilis and HIV co-infection: when is lumbar puncture indicated?

The rate of syphilis/HIV co-infection amongst men who have sex with men (MSM) in large urban regions ranges from 20 to 70%. Concurrent HIV infection can alter the clinical presentation of syphilis, the response to treatment, and complicate the diagnosis and clinical course of neurosyphilis. Therefore whether to perform a lumbar puncture (LP) on every co-infected patient in order to diagnose neurosyphilis is controversial. Current clinical guidelines specify the indications for LP, but fall short of recommending LP in certain clinical situations such as early syphilis without neurological involvement. This article reviews the current literature on the relative utility and indications for LP in syphilis/HIV co-infected patients and new research in this area.

HIV-1 superinfection: evidence and impact.

Superinfection is defined as infection by a second virus during an immunologic steady state, following infection by a primary virus. It is now well established that superinfection with HIV-1 occurs in humans. Detection of an increasing number of circulating recombinant forms, which result from infection of a cell by two or more clades, suggests that superinfection occurs more frequently than previously thought. The second virus (from a different clade or the same clade as the primary virus) can superinfect some time after the first and this is associated with rapid viral rebound and immune decline. Primary infection with a specific clade appears not to provide cross-protection against superinfection with a different clade or the same clade. Estimating the overall impact of HIV-1 superinfection on pathogenesis and attempts to create a broadly protective prophylactic HIV-1 vaccine is complicated by our inability to quantify the true incidence and prevalence.