RESUMO
Natural killer (NK) cells may be important in modulating HIV replication in early course of HIV infection. The effector function of NK cells is finely tuned by a balance between signals delivered by activating and inhibitory receptors. However, the influence of expression of these receptors on the early course of HIV replication and subsequent disease progression is not explored in the context of HIV-1C infection. The expression pattern of activating (NKp46, NKp44, NKp30, NKG2D, and NKG2C) and inhibitory (CD158b, NKG2A, and ILT2) receptors was determined in 20 patients with recent HIV-1C infection within 3-7 months of acquiring HIV infection and was compared with the expression pattern in individuals with progressive (N = 12), non-progressive HIV-1C infection (LTNPs, N = 12) and healthy seronegative individuals (N = 20). The association of the expression of these receptors on the rate of disease progression was assessed using viral load set point of recently infected individuals as a marker of disease progression. The study showed that higher cytotoxic potency of NK cells was associated with low viral load set point in recent HIV infection (r = -0.701; p = 0.0006) and higher CD4 counts (r = 0.720; p = 0.001). The expression of activating receptors (NKp46, NKp30, and NKG2D) on cytotoxic NK cells but not on regulatory NK cells was also significantly associated with low viral set point (p < 0.01) and viral load in LTNPs and progressors (p < 0.01). The study also indicated that cytotoxic NK cells might show the ability to specifically lyse HIV infected CD4 cells. This data collectively showed that early and sustained higher expression of activating receptors on cytotoxic NK cells could be responsible for increased cytotoxicity, reduced viral burden, and thus delaying the disease progression. The study to identify the molecular mechanism of the expression of these receptors in HIV infection will be helpful in further understanding of NK cell mediated control in early HIV infection.
RESUMO
BACKGROUND: This paper presents an evaluation of Avahan, a large scale HIV prevention program that was implemented using peer-mediated strategies, condom distribution and sexually transmitted infection (STI) clinical services among high-risk men who have sex with men (HR-MSM) and male to female transgender persons (TGs) in six high-prevalence state of Tamil Nadu, in southern India. METHODS: Two rounds of large scale cross-sectional bio-behavioural surveys among HR-MSM and TGs and routine program monitoring data were used to assess changes in program coverage, condom use and prevalence of STIs (including HIV) and their association to program exposure. RESULTS: The Avahan program for HR-MSM and TGs in Tamil Nadu was significantly scaled up and contacts by peer educators reached 77 percent of the estimated denominator by the end of the program's fourth year. Exposure to the program increased between the two rounds of surveys for both HR-MSM (from 66 percent to 90 percent; AOR = 4.6; p < 0.001) and TGs (from 74.5 percent to 83 percent; AOR = 1.82; p < 0.06). There was an increase in consistent condom use by HR-MSM with their regular male partners (from 33 percent to 46 percent; AOR = 1.9; p < 0.01). Last time condom use with paying male partners (up from 81 percent to 94 percent; AOR = 3.6; p < 0.001) also showed an increase. Among TGs, the increase in condom use with casual male partners (18 percent to 52 percent; AOR = 1.8; p < 0.27) was not significant, and last time condom use declined significantly with paying male partners (93 percent to 80 percent; AOR = 0.32; p < 0.015). Syphilis declined significantly among both HR-MSM (14.3 percent to 6.8 percent; AOR = 0.37; p < 0.001) and TGs (16.6 percent to 4.2 percent; AOR = 0.34; p < 0.012), while change in HIV prevalence was not found to be significant for HR-MSM (9.7 percent to 10.9 percent) and TGs (12 percent to 9.8 percent). For both groups, change in condom use with commercial and non-commercial partners was found to be strongly linked with exposure to the Avahan program. CONCLUSION: The Avahan program for HR-MSM and TGs in Tamil Nadu achieved a high coverage, resulting in improved condom use by HR-MSM with their regular and commercial male partners. Declining STI prevalence and stable HIV prevalence reflect the positive effects of the prevention strategy. Outcomes from the program logic model indiacte the effectiveness of the program for HR-MSM and TGs in Tamil Nadu.
