Showing papers in "AIDS in 2005"

Review of sampling hard-to-reach and hidden populations for HIV surveillance

Abstract: Adequate surveillance of hard-to-reach and 'hidden' subpopulations is crucial to containing the HIV epidemic in low prevalence settings and in slowing the rate of transmission in high prevalence settings. For a variety of reasons, however, conventional facility and survey-based surveillance data collection strategies are ineffective for a number of key subpopulations, particularly those whose behaviors are illegal or illicit. This paper critically reviews alternative sampling strategies for undertaking behavioral or biological surveillance surveys of such groups. Non-probability sampling approaches such as facility-based sentinel surveillance and snowball sampling are the simplest to carry out, but are subject to a high risk of sampling/selection bias. Most of the probability sampling methods considered are limited in that they are adequate only under certain circumstances and for some groups. One relatively new method, respondent-driven sampling, an adaptation of chain-referral sampling, appears to be the most promising for general applications. However, as its applicability to HIV surveillance in resource-poor settings has yet to be established, further field trials are needed before a firm conclusion can be reached.

Young people's sexual health in South Africa: HIV prevalence and sexual behaviors from a nationally representative household survey

Abstract: The objectives were to determine the prevalence of HIV infection HIV risk factors and exposure to national HIV prevention programs and to identify factors associated with HIV infection among South African youth aged 15–24 years. Design: A cross-sectional nationally representative household survey. From March to August 2003 we conducted a national survey of HIV prevalence and sexual behavior among 11 904 15–24 year olds. Multivariable models for HIV infection were restricted to sexually experienced youth. Young women were significantly more likely to be infected with HIV in comparison with young men (15.5 versus 4.8%). Among men a history of genital ulcers in the past 12 months was associated with HIV infection [adjusted odds ratio (AOR) 1.91; 95% confidence interval (CI) 1.04–3.49) whereas among women a history of unusual vaginal discharge in the past 12 months was associated with HIV infection (AOR 1.75; 95% CI 1.26–2.44). Young women with older partners were also at increased risk of HIV infection. Among both men and women increasing partner numbers and inconsistent condom use were significantly associated with HIV infection. Males and females who reported participation in at least one loveLife program were less likely to be infected with HIV (AOR 0.60; 95% CI 0.40–0.89; AOR 0.61; 95% CI 0.43–0.85 respectively). This survey confirms the high HIV prevalence among young people in South Africa and in particular young women’s disproportionate risk. Programs for youth must continue to promote partner reduction consistent condom use and prompt treatment for sexually transmitted infections while also addressing contextual factors that make it difficult for them to implement behavior change. (authors)

Incidence and risk factors for immune reconstitution inflammatory syndrome during highly active antiretroviral therapy

Abstract: Background: There is little systematic information regarding the immune reconstitution inflammatory syndrome (IRIS). Objective: To determine the incidence, risk factors, and long-term outcome of IRIS in HIV-infected patients receiving highly active antiretroviral therapy (HAART) who were coinfected with one of three common opportunistic pathogens. Design: A retrospective cohort identified through a city-wide prospective surveillance program. Methods: A retrospective chart review was performed for 180 HIV-infected patients who received HAART and were coinfected with Mycobacterium tuberculosis, Mycobacterium avium complex, or Cryptococcus neoformans between 1997 and 2000. Medical records were reviewed for baseline demographics, receipt and type of HAART, response to antiretroviral therapy, development of IRIS, and long-term outcome. Results: In this cohort, 31.7% of patients who received HAART developed IRIS. Patients with IRIS were more likely to have initiated HAART nearer to the time of diagnosis of their opportunistic infection (P < 0.001), to have been antiretroviral naive at time of diagnosis of their opportunistic infection (P < 0.001), and to have a more rapid initial fall in HIV-1 RNA level in response to HAART (P < 0.001). Conclusions: IRIS is common among HIV-infected persons coinfected with M. tuberculosis, M. avium complex, or C. neoformans. Antiretroviral drug-naive patients who start HAART in close proximity to the diagnosis of an opportunistic infection and have a rapid decline in HIV-1 RNA level should be monitored for development of this disorder.

Early exclusive breastfeeding reduces the risk of postnatal HIV-1 transmission and increases HIV-free survival

Abstract: Objectives: The promotion of exclusive breastfeeding (EBF) to reduce the postnatal transmission (PNT) of HIV is based on limited data. In the context of a trial of postpartum vitamin A supplementation, we provided education and counseling about infant feeding and HIV, prospectively collected information on infant feeding practices, and measured associated infant infections and deaths. Design and methods: A total of 14 110 mother–newborn pairs were enrolled, randomly assigned to vitamin A treatment group after delivery, and followed for 2 years. At baseline, 6 weeks and 3 months, mothers were asked whether they were still breastfeeding, and whether any of 22 liquids or foods had been given to the infant. Breastfed infants were classified as exclusive, predominant, or mixed breastfed. Results: A total of 4495 mothers tested HIV positive at baseline; 2060 of their babies were alive, polymerase chain reaction negative at 6 weeks, and provided complete feeding information. All infants initiated breastfeeding. Overall PNT (defined by a positive HIV test after the 6-week negative test) was 12.1%, 68.2% of which occurred after 6 months. Compared with EBF, early mixed breastfeeding was associated with a 4.03 (95% CI 0.98, 16.61), 3.79 (95% CI 1.40–10.29), and 2.60 (95% CI 1.21–5.55) greater risk of PNT at 6, 12, and 18 months, respectively. Predominant breastfeeding was associated with a 2.63 (95% CI 0.59–11.67), 2.69 (95% CI 0.95–7.63) and 1.61 (95% CI 0.72–3.64) trend towards greater PNT risk at 6, 12, and 18 months, compared with EBF.

Hepatitis B and HIV: prevalence, AIDS progression, response to highly active antiretroviral therapy and increased mortality in the EuroSIDA cohort

Abstract: Background: Whether hepatitis B (HBV) coinfection affects outcome in HIV-1-infected patients remains unclear. Objective: To assess the prevalence of HBV (assessed as HBsAg) coinfection and its possible impact on progression to AIDS, all-cause deaths, liver-related deaths and response to highly active antiretroviral therapy (HAART) in the EuroSIDA cohort. Methods: Data on 9802 patients in 72 European HIV centres were analysed. Incidence rates of AIDS, global mortality and liver-related mortality, time to 25% CD4 cell count increase and time to viral load < 400 copies/ml after starting HAART were calculated and compared between HBsAg-positive and HBsAg-negative patients. Results: HBsAg was found in 498 (8.7%) patients. The incidence of new AIDS diagnosis was similar in HBsAg-positive and HBsAg-negative patients (3.3 and 3.4/100 person-years, respectively) even after adjustment for potential confounders: the incidence rate ratio (IRR) was 0.94 [95% confidence interval (CI), 0.74-1.19; P=0.61]. The incidences of all-cause and liver-related mortalities were significantly higher in HBsAg-positive subjects (3.7 and 0.7/100 person-years, respectively) compared with HBsAg-negative subjects (2.6 and 0.2/100 person-years, respectively). The adjusted IRR values were 1.53 for global (95% CI, 1.23-1.90; P = 0.0001) and 3.58 for liver-related (95% Cl, 2.09-6.16; P < 0.0001) mortality. HBsAg status did not influence viral or immunological responses among the 1679 patients starting HAART. Conclusions: The prevalence of HBV coinfection was 9% in the EuroSIDA cohort. Chronic HBV infection significantly increased liver-related mortality in HIV-1-infected patients but did not impact on progression to AIDS or on viral and immunological responses to HAART. (c) 2005 Lippincott Williams & Wilkins.

Efficacy of a brief case management intervention to link recently diagnosed HIV-infected persons to care.

Abstract: Objective The Antiretroviral Treatment Access Study (ARTAS) assessed a case management intervention to improve linkage to care for persons recently receiving an HIV diagnosis Methods Participants were recently diagnosed HIV-infected persons in Atlanta, Baltimore, Los Angeles and Miami They were randomized to either standard of care (SOC) passive referral or case management (CM) for linkage to nearby HIV clinics The SOC arm received information about HIV and local care resources; the CM intervention arm included up to five contacts with a case manager over a 90-day period The outcome measure was self-reported attendance at an HIV care clinic at least twice over a 12-month period Results A higher proportion of the 136 case-managed participants than the 137 SOC participants visited an HIV clinician at least once within 6 months [78 versus 60%; adjusted relative risk (RR(adj)), 136; P = 00005) and at least twice within 12 months (64 versus 49%; RR(adj), 141; P = 0006) Individuals older than 40 years, Hispanic participants, individuals enrolled within 6 months of an HIV-seropositive test result and participants without recent crack cocaine use were all significantly more likely to have made two visits to an HIV care provider We estimate the cost of such case management to be 600-1200 US dollars per client Conclusion A brief intervention by a case manager was associated with a significantly higher rate of successful linkage to HIV care Brief case management is an affordable and effective resource that can be offered to HIV-infected clients soon after their HIV diagnosis

The International HIV Dementia Scale: a new rapid screening test for HIV dementia.

Abstract: Objective: HIV dementia is an important neurological complication of advanced HIV infection. The use of a cross-cultural screening test to detect HIV dementia within the international community is critical for diagnosing this condition. The objective of this study was to evaluate the sensitivity and specificity of a new screening test for HIV dementia the International HIV Dementia Scale (IHDS) in cohorts from the US and Uganda. Design: Two cross-sectional cohort studies designed to evaluate for the presence of HIV dementia. Methods: Sixty-six HIV-positive individuals in the US and 81 HIV-positive individuals in Uganda received the IHDS and full standardized neurological and neuropsychological assessments. The sensitivity and specificity of varying cut-off scores of the IHDS were evaluated in the two cohorts. Results: In the US cohort the mean IHDS score for HIV-positive individuals without dementia and with dementia were 10.6 and 9.3 respectively (P < 0.001). Using the cut-off of = 10 the sensitivity and specificity for HIV dementia with the IHDS were 80% and 57% respectively in the US cohort and 80% and 55% respectively in the Uganda cohort. Conclusions: The IHDS may be a useful screening test to identify individuals at risk for HIV dementia in both the industrialized world and the developing world. Full neuropsychological testing should then be performed to confirm a diagnosis of HIV dementia. (authors)

Early mortality among adults accessing a community-based antiretroviral service in South Africa: implications for programme design.

Abstract: The objectives were to determine rates risk factors and causes of death among patients accessing a community-based antiretroviral treatment (ART) programme both prior to and following initiation of treatment. All in-programme deaths were ascertained between September 2002 and March 2005 among treatment-naive patients enrolled into a prospective communitybased ART cohort in Cape Town South Africa. Of 712 patients (median CD4 cell count 94 cells/ml) 578 (81%) started triple ART a median of 29 days after enrolment. 68 (9.5%) patients died during 563 personyears of observation. The high pretreatment mortality rate of 35.6 deaths/100 personyears [95% confidence interval (CI) 23.0-55.1) decreased to 2.5/100 person-years (95% CI 0.9-6.6) at 1 year among those who received ART. However within the first 90 days from enrolment 29 of 44 (66%) deaths occurred among patients awaiting ART; these would not be identified by an on-treatment analysis. Multivariate analysis showed that risk of death (both pre-treatment and on-treatment) was independently associated with baseline CD4 cell count and World Health Organization (WHO) clinical stage; stage 4 disease was the strongest risk factor. Major attributed causes of death were wasting syndrome tuberculosis acute bacterial infections malignancy and immune reconstitution disease. Most early in-programme deaths occurred among patients with advanced immunodeficiency but who had not yet started ART. Programme evaluation using ontreatment analyses greatly underestimated early mortality. This mortality would be reduced by minimizing unnecessary in-programme delays in treatment initiation and by starting ART before development of WHO stage 4 disease. (authors)

Anal intraepithelial neoplasia in the highly active antiretroviral therapy era among HIV-positive men who have sex with men.

Abstract: Objectives The incidence of anal cancer among men who have sex with men (MSM) has continued to increase since the introduction of highly active antiretroviral therapy (HAART). The prevalence of the putative anal cancer precursor, anal intraepithelial neoplasia (AIN) was high among HIV-positive MSM prior to the availability of HAART but little is known about AIN since HAART was introduced. We characterized the prevalence of AIN among HIV-positive MSM and examined the association between AIN and various factors including use of HAART. Design and methods A baseline point-prevalence analyses in a prospective cohort study of AIN was performed at a university-based research clinic. A total of 357 HIV-positive MSM with no history of anal cancer completed a questionnaire detailing behaviors and medical history, anal cytology and human papillomavirus (HPV) testing, and high-resolution anoscopy with biopsy for detection of AIN. Results Eighty-one percent of participants with available CD4+ cell counts at baseline had AIN of any grade; 52% had AIN 2 or 3; and 95% had anal HPV infection. In multivariate analysis, detection of > or = 6 HPV types [odds ratio (OR), 36; 95% confidence interval (CI), 7.4-171) and use of HAART (OR, 10; 95% CI, 2.6-38) were associated with AIN after adjustment for length of time participants were HIV-positive, CD4+ cell count and HIV viral load. Conclusions The prevalence of AIN has remained high among HIV-positive MSM after the introduction of HAART. Our data indicate that HAART is not associated with a reduced prevalence of AIN and support measures to prevent anal cancer among HIV-positive MSM whether or not they are using HAART.

Tuberculosis among HIV-infected patients receiving HAART: long term incidence and risk factors in a South African cohort.

Abstract: OBJECTIVES: To determine the long-term incidence of tuberculosis (TB) and associated risk factors among individuals receiving HAART in South Africa. DESIGN: Prospective cohort study. METHODS: Microbiologically or histologically confirmed incident TB was identified in a hospital-based cohort of 346 patients receiving HAART between 1996 and 2005 in Cape Town. RESULTS: The TB incidence density rate was 3.5/100 person-years in the first year and significantly decreased during follow-up, reaching 1.01/100 person-years in the fifth year (P = 0.002 for trend). TB incidence during the study was highest among patients with baseline CD4 cell counts < 100 cells/microl and those with World Health Organization (WHO) clinical stage 3 or 4 disease (5.71 and 3.88/100 person-years, respectively). Risk of TB was independently associated with CD4 cell count < 100 cells/microl (adjusted risk ratio [ARR], 2.38; 95% confidence interval (CI), 1.01-5.60; P = 0.04), WHO stage 3 or 4 disease (ARR, 3.60; 95% CI, 1.32-9.80; P = 0.01) and age < 33 years (ARR, 2.86; 95% CI, 1.29-6.34; P = 0.01). Risk of TB was not independently associated with plasma viral load, previous history of TB, low socioeconomic status or sex. Despite similar virological responses to HAART, blood CD4 cell count increases were much smaller among patients who developed TB than among those who remained free of TB. CONCLUSIONS: Incidence of TB continues to decrease during the first 5 years of HAART and so HAART may contribute more to TB control in low-income countries than was previously estimated from short-term follow-up. Patients with advanced pretreatment immunodeficiency had persistently increased risk of TB during HAART; this may reflect limited capacity for immune restoration among such patients.

Predisposition to nevirapine hypersensitivity associated with HLA-DRB1*0101 and abrogated by low CD4 T-cell counts

Abstract: Genetic (human leukocyte antigen), disease-related and demographic risk factors for nevirapine reactions were examined in a nevirapine-exposed cohort. Cases involving combinations of hepatitis, fever or rash were associated with an interaction between HLA-DRB1*0101 and the percentage of CD4, whereas no associations were detected for isolated rash. These data suggest that HLA-DRB1*0101 and the CD4 status may determine susceptibility to nevirapine hypersensitivity, consistent with a CD4 T-cell-dependent immune response to nevirapine-specific antigens.

Sexual harm reduction practices of HIV-seropositive gay and bisexual men: serosorting, strategic positioning, and withdrawal before ejaculation.

Abstract: This study assessed unprotected anal and oral sex behaviors of HIV-positive gay and bisexual men in New York City and San Francisco with their main and nonmain sexual partners. Here we focus on the use of three harm reduction strategies (serosorting strategic positioning and withdrawal before ejaculation) in order to decrease transmission risk. The data from a baseline assessment of 1168 HIV-positive gay and bisexual men in the two cities were utilized. Men were recruited from a variety of community-based venues through advertising and other techniques. City differences were identified with more men in San Francisco reporting sexual risk behaviors across all partner types compared with men in New York City. Serosorting was identified with men reporting significantly more oral and anal sex acts with other HIV-positive partners than with HIV-negative partners. However men also reported more unprotected sex with partners of unknown status compared with their other partners. Some evidence of strategic positioning was identified although differences were noted across cities and across different types of partners. Men in both cities reported more acts of oral sex without ejaculation than with ejaculation but the use of withdrawal as a harm reduction strategy for anal sex was more common among men from San Francisco. Overall evidence for harm reduction was identified; however significant differences across the two cities were found. The complicated nature of the sexual practices of gay and bisexual men are discussed and the findings have important implications for prevention efforts and future research studies. (authors)

Association between highly active antiretroviral therapy and hypertension in a large cohort of men followed from 1984 to 2003.

Abstract: negative men to have SH [odds ratio (OR), 0.79; 95% confidence interval (CI), 0.70‐ 0.89], as were men taking mono/combination therapy (OR, 0.69; 95% CI, 0.59‐0.80). The prevalence of SH among men taking highly active antiretroviral therapy (HAART) for less than 2 years was similar to that among HIV negative men (OR, 1.06; 95% CI, 0.87‐1.30), but was significantly higher thereafter; for 2 to 5 years of HAART (OR, 1.51; 95% CI, 1.25‐1.82) and for more than 5 years of HAART (OR, 1.70; 95% CI, 1.34‐ 2.16). In contrast, DH was not significantly higher among men with prolonged HAART use compared to that among HIV negative controls. Conclusions: Prolonged HAART use was significantly associated with a higher prevalence of SH. This finding suggests that individuals taking HAART may be at increased risk of developing hypertension-related conditions and underscores the importance of blood pressure monitoring among these individuals.

Incidence and risk factors of immune reconstitution inflammatory syndrome complicating HIV-associated cryptococcosis in France.

Abstract: Background: Immune reconstitution inflammatory syndrome (IRIS) in association with cryptococcosis has been anecdotically reported following administration of highly active antiretroviral therapy (HAART). Objective: To analyse the incidence and risk factors for IRIS-associated cryptococcosis among HIV-infected patients. Design: Retrospective multicentre study between 1996 and 2000 through the French Cryptococcosis Database. Methods: Subsequent occurrence of IRIS examined in 120 HIV-infected adult patients treated with HAARTand experiencing a first episode of culture-confirmed cryptococcosis. Results: Ten patients developed IRIS during the study period, giving an incidence of 10/239, or 4.2/100 person-years [95% confidence interval (Cl), 2.2-7.8]. IRIS consisted of acute symptoms consistent with inflammation occurring within a median of 8 months (range, 2 -3 7) after the diagnosis of cryptococcosis in the context of negative cultures and immunological and/or virological response to HAART. Radiology and histopathology detected features compatible with inflammation. Symptom severity required transfer into intensive care units for three patients and use of anti-inflammatory drugs for four. Three patients with evolutive IRIS died. Compared with patients without IRIS for whom complete clinical and microbiological information were available at baseline, previously unknown HIV infection [odds ratio (OR), 4.8; 95% Cl, 1.0-21.7], CD4 cell count < 7 x 106 cells/I (OR, 4.0; 95% CI, 0.9-17.2), fungaemia (OR, 6.1; 95% Cl, 1.1-35.2) and HAART initiation within 2 months of cryptococcosis diagnosis (OR, 5.50; 95% CI, 1.0-29.6) were independently associated with the risk of subsequent IRIS. Conclusions: IRIS-related cryptococcosis was observed more frequently in severely immunocompromised patients with disseminated infection and HAART initiation soon after the diagnosis.

Brain deposition of beta-amyloid is a common pathologic feature in HIV positive patients.

Abstract: Background We planned to analyze the prevalence and distribution of beta-amyloid deposition in the HIV+ brain in the HAART era. Our working hypothesis is that long term survival, aging and the secondary effects of HAART may contribute to increased beta-amyloid accumulation in this patient population. Methods Paraffin embedded archival brain autopsy tissues were assessed by immunocytochemistry for beta-amyloid. Detailed in-vivo neuro-behavioral assessments and ApoE genotyping were available for a subset of the studied population. Results Immunoreactivity with the antibodies 4G8 and 6E10 was found predominantly in neuronal soma and dystrophic axonal processes. Extracellular, often perivascular plaques were also identified in many cases. Conclusions We propose that prolonged HAART and aging may contribute to an overall increase in amyloid deposition, potentially mediated by inhibition of insulin degradation enzyme (IDE) or disruption of the axonal transport of the amyloid precursor protein.

Atazanavir plus ritonavir or saquinavir, and lopinavir/ritonavir in patients experiencing multiple virological failures.

Abstract: OBJECTIVE: To evaluate atazanavir/ritonavir (ATV/RTV) (300/100 mg) once daily, atazanavir/saquinavir (ATV/SQV) (400/1200 mg) once daily, and lopinavir/ritonavir (LPV/RTV) (400/100 mg) twice daily, each with tenofovir (300 mg) once daily and a nucleoside reverse transcriptase inhibitor in treatment-experienced HIV-infected patients. METHODS: Randomized, open-label, 48-week multicenter trial of 358 randomized adult patients who had failed two or more prior HAART regimens with baseline HIV RNA > or = 1000 copies/ml and CD4 cell count > or = 50 x 10(6) cells/l. RESULTS: The primary efficacy endpoint [plasma HIV RNA reduction assessed by time-averaged difference (TAD)] was similar for ATV/RTV and LPV/RTV [TAD 0.13; 97.5% confidence interval, -0.12 to 0.39] at 48 weeks. Mean reductions from baseline for ATV/RTV and LPV/RTV were comparable at 1.93 and 1.87 log10 copies/ml, respectively. Mean CD4 cell count increases were 110 and 121 x 10(6) cells/l for ATV/RTV, and LPV/RTV, respectively. The efficacy of ATV/SQV was lower than LPV/RTV by both these parameters. Declines in total cholesterol and fasting triglycerides were greater with ATV/RTV and ATV/SQV than with LPV/RTV (P < or = 0.005). Lipids in the LPV/RTV arm at week 48 generally increased from baseline. Lipid-lowering agents were used more frequently in the LPV/RTV arm than in the ATV arms (P < 0.05 versus ATV/RTV), as were antidiarrheal agents (P < or = 0.04 versus both ATV treatments). No new or unique safety findings emerged. CONCLUSIONS: ATV boosted with RTV is as effective and well tolerated as LPV/RTV in treatment-experienced patients, with a more favorable impact on serum lipids. Pharmacokinetically enhanced ATV provides a suitable choice for therapy of treatment-experienced HIV-infected patients.

Cumulative exposure to nucleoside analogue reverse transcriptase inhibitors is associated with insulin resistance markers in the Multicenter AIDS Cohort Study

Abstract: Objective:To estimate insulin resistance and its relationship to antiretroviral therapy (ART) in a cohort of HIV-infected persons with comparison to HIV-seronegative controls.Design:Prospective cohort of 533 HIV-infected and 755 HIV-seronegative men in the Multicenter AIDS Cohort Study evaluated at

A cluster of acute hepatitis C virus infection among men who have sex with men--results from contact tracing and public health implications.

Abstract: Objective An acute hepatitis C virus (HCV) infection in an HIV-positive man who had sex with men (MSM) was notified. In the period of his seroconversion he was also diagnosed with a rectal lymphogranuloma venereum (LGV) infection, and was part of a cluster of 15 LGV cases in 2003. Our aim was to investigate HCV transmission and to search for potential spread among sexual contacts and known LGV patients. Methods Our case series included the index, two recent contacts, and 14 LGV cases. They were interviewed about parenteral exposure for HCV, history of sexually transmitted diseases(STDs), sexual behaviour and drug use. Laboratory investigations included anti-HCV antibodies, HCV-polymerase chain reaction, and HCV genotyping. Results Seven out of 17 MSM recently seroconverted for HCV (41%). Three genotypes were found. Parenteral risk factors were excluded. Six out of seven had LGV proctitis coinciding with HCV seroconversion, six (86%) were HIV infected. Unprotected anal contact was practised by both HCV uninfected and infected cases. Unprotected active and passive fisting was reported by all seven HCV infected men, compared with two of nine uninfected men (P = 0.003). Non-intravenous drug use during sexual activities was common among all MSM. Numerous, often anonymous, sexual contacts in various European countries were reported. Conclusions A cluster of acute HCV infection is reported among mostly HIV-positive MSM, with multiple partners throughout Europe. Sexual techniques potentially leading to mucosal damage (fisting), concomitant STDs such as LGV and drug use seem facilitating factors for spread. Extensive case finding and partner tracing is advocated as well as targeted prevention messages.

Gay men who look for sex on the Internet: is there more HIV/STI risk with online partners?

Abstract: Objective: To examine whether the excess risk for HIV and sexually transmitted infection (STI) seen among gay men who look for sex through the Internet occurs with men they meet online (through the Internet) rather than offline (in bars, clubs, etc).Methods: In 2002-2003, 4225 London gay men were surveyed in an HIV treatment clinic, HIV testing clinic, gyms and on UK Internet sites (gaydar and gay.com). All men completed a self-administered questionnaire concerning Internet use and sexual risk behaviour. Unprotected anal intercourse (UAI) with a partner of unknown or discordant HIV status was classified as non-concordant.Results: Between 40 and 50% of men surveyed in the clinics and gyms used the Internet to look for sex. HIV-positive men who looked for sex through the Internet were more likely to report UAI with HIV-positive casual partners they met online rather than offline (clinic sample: met online only 9.9%, met offline only 3.8%, McNemar P < 0.05). Regardless of HIV status, however, men who looked for sex through the Internet were no more likely to report UAI with non-concordant casual partners they met online than offline (eg, HIV-negative men, Internet sample: met online only 9.71%, offline only 11.1%, McNemar P = 0.6).Conclusions: In London, HIV-positive gay men appear to meet casual UAI partners of the same status through the Internet. This presents a risk for STI transmission. However, gay men were no more likely to meet casual UAI partners of unknown or discordant HIV status - which presents a risk for HIV transmission - online rather than offline. (c) 2005 Lippincott Williams & Wilkins.

Field efficacy of zidovudine, lamivudine and single-dose nevirapine to prevent peripartum HIV transmission.

Abstract: OBJECTIVES: In Africa, single-dose nevirapine (NVPsd), short regimens of zidovudine (ZDV) or ZDV + lamivudine (3TC) are recommended to prevent peripartum mother-to-child HIV transmission (PMTCT). We evaluated the 6-week field efficacy of two more PMTCT drug combinations. DESIGN: An open-label intervention cohort in Abidjan. METHODS: In 2001-2002, consenting women started oral ZDV 300 mg twice daily (bid) at > or =36 weeks of gestation, with 600 mg of ZDV + 200 mg NVPsd orally at beginning of labour. In 2002-2003, the antepartum regimen at > or =32 weeks comprised ZDV as previously + 3TC 150 mg bid; the labour dose comprised ZDV + NVPsd as previously + 300 mg 3TC orally. Neonates received ZDV syrup (2 mg/kg per 6 h) for 7 days + NVPsd syrup (2 mg/kg) on day 2 in both periods. Each woman was assisted to either use breast milk substitutes or breastfeed exclusively. Paediatric HIV infection was diagnosed by plasma HIV RNA viral load at 4 weeks, confirmed at 6 weeks. The reference group was a cohort receiving a short regimen of ZDV > or = 36-38 weeks in 1995-2000 in the same population. RESULTS: A total of 1144 HIV-infected pregnant women were included: 351 with ZDV, 420 with ZDV + NVPsd and 373 with ZDV + 3TC + NVPsd; 1010 livebirths were eligible for analysis; 79 children were HIV-infected peripartum. Six-week transmission probability was 6.5% [95% confidence interval (CI), 3.9-9.1%) with ZDV + NVPsd, a 72% reduction compared with ZDV alone (95% CI, 52-88%; P = 0.0002 adjusted on maternal CD4, clinical stage and breastfeeding). It was 4.7% (95% CI, 2.4-7.0%) with ZDV + 3TC + NVPsd (P = 0.34 compared with ZDV + NVPsd). CONCLUSIONS: A short-course of ZDV + NVPsd prevents most peripartum HIV transmission in Africa. This regimen could be added to international guidelines.

CPG 7909 adjuvant improves hepatitis B virus vaccine seroprotection in antiretroviral-treated HIV-infected adults.

Abstract: Background: HIV patients are vaccine hyporesponsive. Methods: We evaluated CPG 7909, a synthetic oligodeoxynucleotide containing immunostimulatory CpG motifs, as an adjuvant to Engerix-B. A randomized, double-blind controlled trial was conducted to determine safety and hepatitis B virus (HBV) immunogenicity in adult HIV subjects on effective antiretroviral therapy. HBVsusceptible subjects, half of whom had failed previous vaccination, were vaccinated at 0, 1 and 2 months with a double dose of Engerix-B with/without (� ) 1 mg CPG 7909. HBV immune subjects (anti-HBsAg titres � 10 mIU/l) received either CPG 7909 alone or saline. Safety, anti-HBs titres and lymphocyte proliferation response (LPR) to HBsAg were assessed over 12 months.

HIV infection and sexually transmitted infections among men who have sex with men in Senegal.

Abstract: No epidemiological study has been conducted on HIV and vulnerability to sexually transmitted diseases (STI) among men who have sex with men (MSM) in sub-Saharan Africa. A survey including questionnaire physical examination and detection of HIV and STI was carried out among 463 MSM aged 18-52 years recruited through the snowball technique in five urban sites throughout Senegal. A total of 21.5% of men were found to be infected with HIV [95% confidence interval (CI) 17.8-25.6]. Active syphilis positive serology for herpes simplex virus (HSV)-2 and polymerase chain reaction detection in urine of Chlamydia and gonorrhea infections were recorded in 4.8 22.3 4.1 and 5.4% of participants respectively. Most respondents reported sex with women (94.1%). In the month preceding the interview 24% reported at least one unprotected insertive anal intercourse with a male partner 20% at least one unprotected receptive anal intercourse and 18% at least one unprotected intercourse with a female partner. Genital examination showed that 5% of participants had at least one clinical sign of STI. Factors associated with HIV infection were age group the reporting of more than nine lifetime male partners [odds ratio (OR) 3.76; 95% CI 1.61-8.79] being a waiter or bartender (OR 3.33; 95% CI 1.41-7.84) and living in Dakar (OR 3.33; 95% CI 1.07-3.43). Men who have sex with men in Senegal are highly infected with HIV and other STI. Intervention programs targeting this population are urgently needed given their particular vulnerability and because infections are likely to disseminate into the general population given the high proportion of bisexual activity in this community. (authors)

Couple-focused support to improve HIV medication adherence: a randomized controlled trial

Abstract: The objective was to assess the efficacy of a couple-based intervention to improve medication-taking behavior in a clinic population with demonstrated adherence problems. Design: A randomized controlled trial (SMART Couples Study) conducted between August 2000 and January 2004. Setting: Two HIV/AIDS outpatient clinics in New York City. Participants: Heterosexual and homosexual HIV-serodiscordant couples (n ¼ 215) in which the HIV-seropositive partner had 80% > 90% or > 95%) when compared with controls. However in most cases effects diminished with time as seen at follow-up at 3 and 6 months. The SMART Couples program significantly improved medication adherence over usual care although the level of improved adherence for many participants was still suboptimal and the effect was attenuated over time. (authors)

No room for complacency about adherence to antiretroviral therapy in sub-Saharan Africa.

Abstract: Medication adherence is essential to successful treatment of HIV/AIDS. Maintaining high adherence will likely prove a major challenge in Africa -- just as it has in developed nations. Despite early reports suggesting that adherence would not pose a major barrier to treatment success, more recent research shows that adherence rates in Africa are quite variable and often poor. Given the large number of patients whose disease will progress if adherence is suboptimal, research is urgently needed to determine patient-level behavioral barriers to adherence and the most effective and appropriate methods for assessing adherence in African cohorts.

Amphetamine use is associated with increased HIV incidence among men who have sex with men in San Francisco.

Abstract: We examined the association between amphetamine use and HIV incidence for 2991 men who have sex with men (MSM) who tested anonymously for HIV in San Francisco. HIV incidence among 290 amphetamine users was 6.3% per year (95% CI 1.9-10.6%), compared with 2.1% per year (95% CI 1.3-2.9%) among 2701 non-users (RR 3.0, 95% CI 1.4-6.5). HIV prevention programmes in San Francisco should include efforts to reduce amphetamine use and associated high-risk sexual behaviors.

Glucose metabolism, lipid, and body fat changes in antiretroviral-naive subjects randomized to nelfinavir or efavirenz plus dual nucleosides.

Abstract: Objective: To determine if particular components of antiretroviral drug regimens are associated with greater insulin resistance, dyslipidemia, and peripheral lipoatrophy. Methods: Metabolic and body composition variables were measured prospectively over 64 weeks in 334 antiretroviral-naive, HIV-infected subjects who were randomized to receive nelfinavir, efavirenz, or both, combined with zidovudine/lamivudine or didanosine/stavudine in a factorial design, multicenter trial. Subjects assigned to efavirenz (n = 110) were compared with those assigned to nelfinavir (n = 99); subjects assigned to zidovudine/lamivudine (n = 154) were compared with those assigned to didanosine/stavudine (n = 180). A subset of 157 subjects had serial dual-energy X-ray absorptiometry (DEXA) scans. Results: Lipid measures increased in all groups. Greater increases in high density lipoprotein (HDL) cholesterol occurred with efavirenz than with nelfinavir. Greater increases in total cholesterol, non-HDL cholesterol and HDL cholesterol occurred with stavudine and didanosine than with zidovudine/lamivudine. There were no differences in insulin resistance in the comparisons. After initial increases in the first 16 weeks, median limb fat decreased. Greater changes in percentage changes in limb fat occurred with didanosine/stavudine (-16.8%) than with zidovudine/lamivudine (+4.0%; P < 0.001 for overall change from baseline) and with nelfinavir (-13.1%) compared with efavirenz (+1.8%; P = 0.003). Conclusions: Over 64 weeks, all regimens were associated with increases in lipids but insulin resistance did not differ between groups. Regimens containing didanosine/ stavudine and regimens containing nelfinavir were associated with greater loss of limb fat.

Clinical and immunogenetic correlates of abacavir hypersensitivity.

Abstract: A patch test (PT) may be useful in defining true abacavir hypersensitivity syndrome (AHS). Seven previously PT-positive patients remote from the original AHS were shown to have robust 24 h responses, supporting PT durability. HLA-B*5701 was present in all seven PT-positive versus one of 11 controls tolerating abacavir (P < 0.001). Five of seven PT (71%) versus one of 11 controls (9%) (P = 0.005) showed significant abacavir-specific CD8 proliferation, suggesting a direct role for HLA-B*5701-restricted CD8 cells in the pathophysiology of AHS.

Surplus men, sex work, and the spread of HIV in China.

Abstract: While 70% of HIV positive individuals live in sub-Saharan Africa it is widely believed that the future of the epidemic depends on the magnitude of HIV spread in India and China the world’s most populous countries. China’s 1.3 billion people are in the midst of significant social transformation which will impact future sexual disease transmission. Soon approximately 8.5 million ‘surplus men’ unmarried and disproportionately poor and migrant will come of age in China’s cities and rural areas. Meanwhile many millions of Chinese sex workers appear to represent a broad range of prices places and related HIV risk behaviors. Using demographic and behavioral data this paper describes the combined effect of sexual practices sex work and a true male surplus on HIV transmission. Alongside a rapid increase in sexually transmitted disease incidence across developed parts of urban China surplus men could become a significant new HIV risk group. The anticipated high sexual risk among many surplus men and injecting drug use use among a subgroup of surplus men may create bridging populations from high to low risk individuals. Prevention strategies that emphasize traditional measures – condom promotion sex education medical training – must be reinforced by strategies which acknowledge surplus men and sex workers. Reform within female sex worker mandatory re-education centers and site specific interventions at construction sites military areas or unemployment centers may hold promise in curbing HIV/sexually transmitted infections. From a sociological perspective we believe that surplus men and sex workers will have a profound effect on the future of HIV spread in China and on the success or failure of future interventions. (authors)

Hepatic steatosis and antiretroviral drug use among adults coinfected with HIV and hepatitis C virus.

Abstract: Objective: To ascertain the prevalence and severity of hepatic steatosis among patients coinfected with HIV and hepatitis C virus (HCV) who had been taking antiretroviral therapy (ART); to investigate if steatosis is associated with more advanced liver disease, and to identify factors that might contribute to the process. Methods: Steatosis was assessed among a randomly selected subset of HIV-HCV-coinfected patients who had received at least 2 years of ART in a cohort study at the Johns Hopkins University HIV clinic. Liver histology was evaluated by a single pathologist. The primary outcome measure was the hepatic steatosis grade, which was classified on a 5 point scale: 0, none; 1, steatosis involving 60%. Results: Liver histology was assessed in 112 patients, 74% of whom were taking ART at the time of biopsy. The median cumulative exposure to nucleoside reverse transcriptase inhibitors and protease inhibitors was 5.8 and 3.7 years, respectively. No steatosis was detected in 60%; grades 2-4 steatosis was recognized in 18%. In multivariate analysis, steatosis was independently associated with Caucasian race, weight > 86 kg, hyperglycemia, and stavudine use. Patients with steatosis also were more likely to have greater hepatic fibrosis (P= 0.02) and necroinflammatory activity (P= 0.005). Conclusions: Steatosis was observed in 40% of HIV-HCV-coinfected patients with extensive ART exposure and was associated with more severe HCV-related liver disease. Metabolic abnormalities (excess weight and hyperglycemia) and stavudine use were modifiable risk factors for steatosis in this population.

HIV-1 Tat inhibits neprilysin and elevates amyloid beta.

Abstract: Objective Aging is a risk factor for amyloid beta (Abeta) accumulation and dementia. Since highly active antiretroviral therapies have effectively lengthened the life expectancy of individuals infected with HIV-1, we investigated the affect of HIV-1 Tat, a viral transactivating transcription factor, on Abeta degradation in the brain by neprilysin (NEP), a neuronal endopeptidase. Design and methods Using neural cell membrane fractions from human brain aggregates, Tat inhibition of NEP activity was assessed in a fluorescence assay. Following treatment with Tat, conditioned medium of human brain aggregate cultures was assayed for Abeta1-40 by ELISA. We evaluated the potential consequence of Tat inhibition of NEP by immunostaining cortex sections from postmortem human brain for Abeta. Results In an in vitro assay, Tat inhibited NEP activity by 80%. The cysteine-rich domain of Tat was essential for NEP inhibition. Recombinant Tat added directly to brain cultures, resulted in a 125% increase in soluble Abeta. Postmortem human brain sections from patients with HIV-1 infection (n = 14; 31-58 years old) had a significant increase in Abeta, compared to controls (n = 5; 30-52 years old). Correlative analysis identified a statistically significant relationship between Abeta load and duration of HIV-1 seropositive status. Conclusion We have shown that Tat, which is found in the brains of patients with HIV-1 infection, inhibits the Abeta-degrading enzyme, NEP. Abeta staining was significantly increased in human brain sections from individuals with HIV-1 infection compared to controls. These results have important implications for individuals living and aging with HIV-1 infection.