The effects of early syphilis on CD4 counts and HIV-1 RNA viral loads in blood and semen.

OBJECTIVE: To examine the effect of early syphilis on blood and semen plasma HIV-1 viral loads and CD4 counts. METHODS: In a retrospective case-control study, blood plasma HIV-1 viral loads and CD4 counts in cases during early syphilis (n = 63, 27 receiving antiretroviral therapy) were compared to those before and after syphilis and with controls with non-systemic acute sexually transmitted infections (STI) (n = 104, 39 receiving antiretroviral therapy). In a prospective substudy in those not receiving antiretroviral therapy, semen plasma viral loads during early syphilis (n = 13) were compared with those 1 month, 3 months, and 6 months after treatment for syphilis and with controls with no STIs (n = 20). RESULTS: Retrospective study: CD4 counts were similar in cases (median 410, n = 139 counts) during early syphilis compared to before (485, n = 80) and after (475, n = 88). In a secondary analysis, a drop in CD4 count (21%) among those with early latent syphilis was observed compared with controls. Blood plasma viral loads did not change significantly overall or in those with primary, secondary, or early latent syphilis. Effects were similar on or off antiretroviral therapy. Prospective study: blood and semen viral loads were slightly higher in cases compared with controls but treatment of early syphilis did not reduce either. CONCLUSIONS: We detected no association between early syphilis and changes in blood or semen viral load or CD4 count. Increased HIV-1 infectivity associated with early syphilis is unlikely to be associated with increased levels of HIV-1 RNA in blood or semen.

The effects of urethritis on seminal plasma HIV-1 RNA loads in homosexual men not receiving antiretroviral therapy.

OBJECTIVES: To examine the effects of urethritis and its treatment on semen plasma HIV-1 RNA load in HIV-1 infected men not receiving antiretroviral therapy (ART), in a developed world setting. METHODS: Prospective case-control study. HIV-1 infected homosexual men, not receiving ART for at least 3 months, with (cases) and without (controls) symptomatic urethritis, were recruited. Blood and semen were collected for HIV-1 RNA quantification at presentation, before antibiotic therapy, and at 1 and 2 weeks. RESULTS: 20 cases (13 gonococcal urethritis and/or chlamydial urethritis (GU/CU) and seven non-specific urethritis (NSU)) and 35 controls were recruited. Baseline characteristics and blood plasma viral load were similar in cases and controls. Mean log semen plasma viral loads were higher among those with GU/CU compared with controls (4.27 log versus 3.55 log respectively; p = 0.01) but not in those with NSU (3.48 log; p = 0.82). Following antibiotics, semen plasma viral loads fell by a mean of 0.25 log (95% CI: 0.03 to 0.47) in those with GU/CU. Semen plasma viral loads did not fall in those with NSU. CONCLUSIONS: In this study of 55 homosexual men not on ART, semen plasma viral loads were approximately fivefold higher in those with GU/CU, but not NSU, compared with controls. Treatment of GU/CU resulted in reduction in semen plasma viral loads. Although absolute effects were considerably lower when compared to patients from a similar study from sub-Saharan Africa, our data demonstrate the potential for sexually transmitted infections to enhance HIV infectivity of men not receiving ART in the developed world.

Lactic acidosis in HIV infected patients: a systematic review of published cases.

OBJECTIVE: To describe the clinical, epidemiological, and biochemical characteristics of published cases of lactic acidosis (LA) and to generate hypotheses concerning risk factors associated with this complication. METHODS: Systematic review of cases reported in the medical literature. RESULTS: 217 published cases were identified, 90 of which fulfilled the study definition and had sufficient individual data on potential risk factors to be included. The 90 patients had a mean age of 40.1 years (range 16-69) and 53% were female. All 90 patients were taking nucleoside reverse transcriptase inhibitors (NRTI) at the time of the episode. Among the 83 patients with details of their antiretroviral therapy (ART) regimen 51 patients were taking stavudine, 29 zidovudine, 27 didanosine, and 25 lamivudine. Around 50% of the patients had abdominal pain, nausea, or vomiting. Hepatic steatosis was consistently reported (53/90) and in 36 (68%) there was histological evidence. The case fatality rate was 48%. Six cases were rechallenged with NRTI and three developed a further LA episode. Using data on the numbers of HIV infected individuals receiving care in the United States, we estimate that the risk of LA could be 2.5 times higher for women than men. CONCLUSIONS: NRTI use and female sex appear to be risk factors for the development of LA. What other factors are involved is still not clear but might include duration of NRTI therapy, specific drug use, and genetic predisposition. A case-control study is needed to better define risk factors for severe LA.

Autologous apoptotic T cells interact with dendritic cells, but do not affect their surface phenotype or their ability to induce recall immune responses.

Dendritic cells (DCs) play an important role in determining immunogenicity and the subsequent immune response. They may also have a role in maintaining peripheral tolerance to self-antigens by initiating an immune response only in the context of danger signals released from cells during stress, damage or death. These signals may originate from surrounding T cells as well as from other cells. Therefore, in this study the effect of autologous T cell injury on DC morphology and function has been investigated. Co-incubation of apoptotic or necrotic T cells with immature DCs altered their morphology towards a more mature appearance, with more cells showing activation as judged by spreading and formation of arborizing long processes. The apoptotic autologous T cells were rarely phagocytosed by immature DCs, compared to macrophages. The DC surface phenotype was not affected by the co-incubation with autologous injured T cells. The ability of DCs to elicit a secondary immune response was not altered by exposure to autologous injured T cells. These findings suggest that DC can continue to function in T cell activation, rather than in tolerogenic mode, even in the presence of large numbers of dying autologous T cells, such as may be present in the aftermath of an acute antiviral response.