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Upon interruption of antiretroviral therapy, HIV-infected patients usually show viral load rebound to pre-treatment levels. Four patients, hereafter referred to as secondary controllers (SC), were identified who initiated therapy during chronic infection and, after stopping treatment, could control virus replication at undetectable levels for more than six months. In the present study we set out to unravel possible viral and immune parameters or mechanisms of this phenomenon by comparing secondary controllers with elite controllers and non-controllers, including patients under HAART. As candidate correlates of protection, virus growth kinetics, levels of intracellular viral markers, several aspects of HIV-specific CD4+ and CD8+ T cell function and HIV neutralizing antibodies were investigated. As expected all intracellular viral markers were lower in aviremic as compared to viremic subjects, but in addition both elite and secondary controllers had lower levels of viral unspliced RNA in PBMC as compared to patients on HAART. Ex vivo cultivation of the virus from CD4+ T cells of SC consistently failed in one patient and showed delayed kinetics in the three others. Formal in vitro replication studies of these three viruses showed low to absent growth in two cases and a virus with normal fitness in the third case. T cell responses toward HIV peptides, evaluated in IFN-γ ELISPOT, revealed no significant differences in breadth, magnitude or avidity between SC and all other patient groups. Neither was there a difference in polyfunctionality of CD4+ or CD8+ T cells, as evaluated with intracellular cytokine staining. However, secondary and elite controllers showed higher proliferative responses to Gag and Pol peptides. SC also showed the highest level of autologous neutralizing antibodies. These data suggest that higher T cell proliferative responses and lower replication kinetics might be instrumental in secondary viral control in the absence of treatment.

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CCR5-tropic viruses cause the vast majority of new HIV-1 infections while about half of the individuals infected with HIV-1 manifest a co-receptor switch (CCR5 (R5) to CXCR4 (X4)) prior to accelerated disease progression. The underlying biological mechanisms of X4 outgrowth in AIDS patients are still poorly understood. Although X4 viruses have been associated with increased "virulence" in vivo, in vitro replication and cytopathicity studies of X4 and R5 viruses have led to conflicting conclusions. We studied the replicative fitness of HIV-1 biological clones with different co-receptor tropism, isolated from four AIDS patients. On average, R5 and X4 clones replicated equally well in mitogen-activated T cells. In contrast, X4 variants were transferred more efficiently from dendritic cells to autologous CD4+ T cells. These observations suggest that interaction between X4 viruses, DC and T cells might contribute to the preferential outgrowth of X4 viruses in AIDS patients.

Though the HIV-1 subtypes infecting patients living in urban and semi-urban areas in Cameroon have been reported, information on the subtypes infecting patients in rural villages is lacking. To begin to understand the diversity of the HIV-1 group M subtypes infecting persons living in rural villages in the equatorial rain forest regions of Cameroon, 49 plasma samples from 14 rural villages in four provinces of Cameroon were analyzed using heteroduplex mobility analysis (HMA), DNA sequencing, and phylogenetic tree analysis on the basis of env C2V5, gag, or pol regions. Sixty-one percent of the group M infections were clade A or CRF02_AG-like as subtyped by env and gag. Of the remaining group M infections, 12% were either A or CRF02_AG-like or CRF01_AE-like in recombination with other clades; 25% were infections that were entirely non-A or non-CRF02_AG-like; and 2% were CRF11_cpx. The HIV-1 group M clades identified included A, D, F (F2), G, and H. The CRF strains identified were CRF02_AG-like, CRF01_AE-like, and CRF11_cpx. Two new intersubtype recombinant infections, H/G and A/F2, were identified. This study suggests that the HIV-1 diversity in rural villages in the equatorial rain forest of Cameroon is at least as broad as has been observed in major cities of Cameroon and that multiple HIV-1 group M subtypes are infecting persons living in the countryside of Cameroon.

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