Determinants of HIV-1 transmission in men who have sex with men: a combined clinical, epidemiological and phylogenetic approach.

OBJECTIVES: To identify biological factors associated with HIV transmission in men who have sex with men (MSM). DESIGN: A longitudinal phylogenetic analysis of HIV-1 from an MSM cohort, incorporating clinical and epidemiological data. METHODS: Potential individuals were HIV-infected MSM attending a sexual health clinic between 2000 and 2006. Individuals were classified such that they could move from recent to chronic infection categories. HIV-1pol gene sequences were obtained from plasma virus or proviral DNA and clusters estimated by maximum likelihood and conservative genetic distance differences. The single most likely transmitter generating each recent infection was ascertained and risk factors around time of likely transmission explored using Poisson regression modelling. RESULTS: Out of 1144 HIV-infected MSM, pol sequence data were obtained for 859 (75%); 159 out of 859 (19%) were recently HIV infected at diagnosis. A single most likely transmitter was identified for 41 out of 159 (26%), of which 11 were recently infected (27%) and 30 chronically infected. Factors associated with transmission in multivariable analysis were: younger age {rate ratio per 5 years older 0.68 [95% confidence interval (CI) 0.54-0.86], P=0.0009}, higher viral load [rate ratio per log higher 1.61 (95% CI 1.15-2.25), P=0.005], recent infection [rate ratio 3.88 (95% CI 1.76-8.55), P=0.0008] and recent sexually transmitted disease [rate ratio 5.32 (95% CI 2.51-11.29), P=0.0001]. HAART was highly protective in a univariable model, RR 0.14 (95% CI 0.07-0.27, P=0.0001). CONCLUSION: Onward transmission of HIV among MSM is significantly associated with recent infection, sexually transmitted diseases and higher viral load, and reduced by effective HAART. The majority of new infections appear to occur from individuals whose infection was undiagnosed at the time of transmission.

Potential impact of early antiretroviral therapy on transmission.

PURPOSE OF REVIEW: In this review, we will discuss the potential of early highly active antiretroviral therapy (HAART) to reduce the sexual transmission of HIV on an individual and population level. We will focus on the biological plausibility and behavioural factors associated with HAART use and interventions that might influence such a strategy. RECENT FINDINGS: Empiric and phylogenetic studies support the view that recent HIV infection is a highly infectious disease stage. Evidence increasingly demonstrates that individuals on fully suppressive HAART are significantly less likely to transmit HIV to sexual partners and some even suggest that such individuals cannot transmit HIV. Changes in risk behaviour are associated with the availability of HAART but behavioural studies offer contradictory observations regarding the direction and magnitude of these changes. This in turn makes the intricate assumptions and therefore outcomes of many complex mathematical modelling studies less secure. Furthermore, there is evidence that it is those individuals with undiagnosed HIV infection who contribute significantly to onward sexual transmission. SUMMARY: At an individual level, HAART will reduce viral load and, therefore, infectiousness, although whether to zero or not remains controversial. At a population level, if recent infection and undiagnosed infections continue to drive onward transmission, earlier treatment will only alter the pandemic if accompanied by an improvement in diagnosing the undiagnosed and recognizing recent infection.

Serological testing algorithm shows rising HIV incidence in a UK cohort of men who have sex with men: 10 years application.

OBJECTIVES: To investigate whether combining clinical data with the serological testing algorithm for recent HIV seroconversion (STARHS) reliably identifies otherwise unrecognized recent infections and observe their trends. DESIGN: Incorporation of STARHS into routine HIV diagnosis. METHODS: STARHS was applied to serum collected between 1996 and 2005 at HIV diagnosis and routine clinical/laboratory markers of recent infections were determined. The recent infections were identified by conventional means, by STARHS, and by both combined. RESULTS: Of 1526 infections diagnosed, 812 were new. Of these, 604 were in men who have sex with men (MSM); 208 in heterosexuals; 88% had serum available for STARHS, which identified 88 incident infections that would otherwise have been unrecognized (12% of all new infections, 34% of all recent infections). Of these, 88% reported recent high-risk sex; 47% reported seroconversion symptoms. STARHS confirmed recent infections in 71 of 74 (96%) known to be infected within 6 months by conventional methods. Combining both approaches, recent infections increased over time from 26% (1996) to 45% (2005) [P < 0.001]. STARHS results from 3% new diagnoses and 8% previous diagnoses were deemed false incident (associated with antiretroviral therapy, advanced disease or undetectable viral load). False incident results were only inexplicable in two individuals. CONCLUSION: Adjunctive use of STARHS with clinical data identified a high and increasing proportion of new HIV diagnoses as recent infections, confirming significant ongoing transmission. Since 2002, 50% of new diagnoses among MSM were recent infections. Identification of additional recent infections by STARHS enables effective intervention that may benefit the individual and reduce onward transmission.

Transmission of HIV-1 during primary infection: relationship to sexual risk and sexually transmitted infections.

OBJECTIVE: To study primary HIV-1 infections (PHI) using molecular and epidemiological approaches in order to assess correlates of transmission in this population. METHODS: Individuals with PHI were recruited prospectively from a discrete cohort of 1235 individuals under follow-up in a well-defined geographical area between 1999 and 2003. PHI was diagnosed by one of the following: negative HIV antibody test within 18 months, evolving antibody response, or application of the serological testing algorithm for recent HIV seroconversion. The pol gene was sequenced to identify genotypic resistance and facilitate molecular epidemiological analysis. Clinical data were collected and linked in an irretrievable fashion when informed consent was obtained. RESULTS: A total of 103 individuals with PHI diagnosed between 1999 and 2003 were included in the study; 99 (96%) were male and 90 (91%) were men who have sex with men. Viruses from 35 out of 103 (34%) appeared within 15 phylogenetically related clusters. Significant associations with clustering were: young age, high CD4 cell count, number of sexual contacts, and unprotected anal intercourse (UAI) in the 3 months before diagnosis (P < 0.05 for all). High rates of acute sexually transmitted infections (STI) were observed in both groups with a trend towards higher rates in those individuals with viruses within a cluster (42.9 versus 27.9%; P = 0.13). CONCLUSION: High rates of partner change, UAI and STI are factors that facilitate onward transmission during PHI. More active identification of individuals during PHI, the management of STI and highly active antiretroviral therapy may all be useful methods to break transmission networks.

Long-term persistence of primary genotypic resistance after HIV-1 seroconversion.

Primary infection with drug-resistant HIV-1 is well documented. We have followed up patients infected with such viruses to determine the stability of resistance-associated mutations. Fourteen patients who experienced primary infection with genotypic evidence of resistance were followed for up to 3 years. Drug resistance-associated mutations persisted over time in most patients studied. In particular, M41L, T69N, K103N, and T215 variants within reverse transcriptase (RT) and multidrug resistance demonstrated little reversion to wild-type virus. By contrast, Y181C and K219Q in RT, occurring alone, disappeared within 25 and 9 months, respectively. Multidrug resistance in 2 patients was found to be stable for up to 18 months, the maximum period studied. We conclude that certain resistance-associated mutations are highly stable and these data support the recommendation that all new HIV diagnoses in areas where primary resistance may occur should undergo genotyping irrespective of whether the date of seroconversion is known.

Cost savings and effectiveness of outpatient treatment with low molecular weight heparin of deep vein thrombosis in a community hospital.

UNLABELLED: This study was conducted at Centenary Health Centre of the Rouge Valley Health System, a community based hospital in Toronto. In January 1997, a new treatment was introduced for the management of patients with uncomplicated deep vein thrombosis (DVT). Eligible patients presenting at the ER were placed on LMWH (tinzaparin) and followed at home. Previously the patients had been hospitalized and treated with intravenous heparin until they reached a therapeutic international normalized ratio (INR). The intent of this study was to evaluate the patient outcomes and cost-savings of the new approach. METHODS: Data from all patients eligible for home care, treated in 1996 were assembled and compared with those from all eligible patients treated from April 1, 1997 to March 31, 1998. The data was collected by chart review and consisted of patient outcomes and costs during the period of heparin treatment. Costs for hospitalized patients were based on a per diem. For home care patients, the costs were itemized according to service and medication usage. All costs were calculated in 1999 Canadian dollars. RESULTS: In each one year period, 39 cases were treated. There was no serious adversity and the outcomes were compatible with what has been reported in the literature. The mean cost per patient for the 1996 hospitalized cohort was $3,266 compared to $584 for the subsequent home care cohort. The difference was statistically significant (p<0.00001). CONCLUSION: Home care with tinzaparin compared to hospital care with IV heparin resulted in a large mean saving per patient with no difference in outcome.

Management issues in syphilis.

Syphilis is a sexually transmitted infection which is systemic from the outset and has increased in incidence worldwide over the last decade. There has been concern as to whether or not co-infection with HIV can modify the clinical presentation of syphilis and, as a genital ulcer disease, it can facilitate the transmission of HIV infection. Diagnosis is based on the microscopic identification of the causative treponeme and serological testing. Recommendations for the treatment of syphilis have been based on expert opinion, case series, some clinical trials and 50 years of clinical experience. Penicillin, given intramuscularly, is the mainstay of treatment and the favoured preparations for early infectious syphilis are benzathine penicillin as a single injection or a course of daily procaine penicillin injections for 10 to 14 days. The duration of treatment is longer for late syphilis. There has been concern that benzathine penicillin may not prevent the development of neurosyphilis but that is a rare outcome with this therapy. The main alternative to penicillin is doxycycline, but the place of azithromycin and ceftriaxone is yet to be established. It is not necessary to carry out examination of the cerebrospinal fluid in patients with early infectious syphilis but it should be performed in those with neurological or ocular signs, psychiatric signs or symptoms, when there is evidence of treatment failure and in those who are co-infected with HIV. Follow-up is an essential part of management and should be particularly assiduous, for at least 24 months, in those co-infected with HIV. Partner notification should be mandatory to try to contain the spread of infection.