Suppressed cellular alloimmune responses in HIV-exposed seronegative female sex workers.

Particular human leucocyte antigen (HLA) polymorphisms have been associated with a reduced risk of HIV transmission. However, protective alloimmune responses expected to result from such a genetic predisposition have not been demonstrated. To this end, we analysed and compared cellular and humoral alloimmune responses in a cohort of female sex workers who remained human immunodeficiency virus (HIV)-seronegative despite more than 3 years of high-risk sexual activity (ESN FSWs) with those of low-risk HIV-seronegative female blood donors in Abidjan, Côte d'Ivoire. ESN FSWs showed significantly lower allostimulated CD69 expression and secretion of interferon-gamma, macrophage inflammatory protein (MIP)-1beta and RANTES (regulated upon activation, normal T-cell expressed and secreted) by lymphocytes than controls. In contrast, ESN FSWs showed significantly higher mitogen-stimulated CD69 expression and secretion of tumour necrosis factor-alpha and MIP-1beta than controls. Suppression of cellular alloimmune responses among ESN FSWs was associated with a higher self-reported frequency of unprotected sex. Levels of anti-HLA class I alloantibodies in plasma were not significantly different between ESN FSWs and controls. These findings indicate that frequent sexual exposure to multiple partners results in suppression rather than activation of cellular alloimmune responses. Our data support the hypothesis that suppressed cellular alloimmune responses may play a role in protection against HIV infection.

Assessment of CD8 T cell immune activation markers to monitor response to antiretroviral therapy among HIV-1 infected patients in Côte d'Ivoire.

Because of the paucity of plasma HIV RNA viral load (VL) tests in resource-poor settings, the CD4(+) T cell count is often used as the sole laboratory marker to evaluate the effectiveness of antiretroviral therapy (ART) in HIV-infected patients. In untreated patients, the level of activated T cells is positively correlated with VL and represents a prognostic marker of HIV infection. However, little is known about its value to predict early drug failure, taking into account the relatively high non-specific immune activation background observed in many resource-limited tropical countries. We assessed the use of immune activation markers (expression of CD38 and/or human leucocyte antigen-DR on CD8(+) lymphocytes) to predict virological response to ART in a cohort of HIV-1 infected patients in Abidjan, Côte d'Ivoire. Correlations between VL, absolute CD4(+) T cell counts and immune activation levels were examined in 111 HIV patient samples at baseline and after 6 and 12 months of therapy. The percentage of CD38(+) CD8(+) T cells appeared to be the best correlate of VL. In contrast, changes in CD4(+) T cell counts provided a poor correlate of virological response to ART. Unfortunately, CD38(+) CD8(+) percentages lacked specificity for the determination of early virological drug failure and did not appear to be reliable surrogates of RNA viral load. CD38(+) CD8(+) T cell percentages may, rather, provide a sensitive estimate of the overall immune recovery, and be a useful extra laboratory parameter to CD4 counts that would contribute to improve the clinical management of HIV-infected people when VL testing facilities are lacking.

Comparison of NucliSens and Amplicor monitor assays for quantification of human immunodeficiency virus type 1 (HIV-1) RNA in plasma of persons with HIV-1 subtype A infection in Abidjan, Côte d'Ivoire.

We compared the sensitivity and accuracy of the NucliSens assay and those of both the standard and modified (addition of a new primer set, primer mix 1, supplied by Roche) Amplicor HIV Monitor assays to quantify human immunodeficiency virus type 1 (HIV-1) RNA in persons infected with HIV-1 subtype A in Abidjan, Côte d'Ivoire. Seventy-one plasma samples from HIV-1-seropositive persons at different stages of HIV infection and 15 samples from HIV antibody-negative persons were analyzed. The HIV-1 genetic subtype was determined either by DNA sequencing or by a restriction fragment length polymorphism assay. Of the 71 samples, 70 (98%) were subtype A and 1 was subtype G. Of the 70 subtype A samples, the proportion of RNA-positive plasma samples and mean HIV-1 RNA levels were significantly higher by the modified HIV Monitor assay (n = 67 [96%]; mean RNA levels, 5.2 log10 HIV-1 RNA copies/ml) than the NucliSens assay (n = 56 [80%]; 4.3 log10 HIV-1 RNA copies/ml) or the standard HIV Monitor assay (n = 44 [63%]; mean RNA levels, 3.8 log10 HIV-1 RNA copies/ml) (all P values were <0.05). The HIV-1 RNA levels by the modified HIV Monitor assay correlated significantly with those by the NucliSens assay (r = 0.76; P < 0.001) and the standard HIV Monitor assay (r = 0.57; P < 0.001), as did the RNA levels by the NucliSens and the standard HIV Monitor assays (r = 0.60; P < 0. 001). Lower CD4 cell counts were significantly correlated with higher HIV-1 RNA levels by all three assays (r = -0.47 for the NucliSens assay, -0.45 for the standard HIV Monitor assay, and -0.62 for the modified HIV Monitor assay). These results indicate that the modified HIV Monitor assay has the highest sensitivity and efficiency at quantifying the levels of RNA in persons infected with HIV-1 subtype A and thus constitutes a valuable tool for the monitoring of RNA levels in areas of Africa were HIV-1 subtype A is predominant.